Obesity

ILLUSTRATIVE CASE

A 57-year-old man who was given a diagnosis of T2D a year ago presents for an office visit. His hemoglobin A1C level at diagnosis was 8.3%. He is otherwise healthy and has been adhering well to a plan of metformin 1000 mg twice daily, regular exercise, and a low-­carbohydrate diet you recommended. His most recent hemoglobin A1C is 7.3%. He is pleased with his progress, so he is discouraged when you tell him that he is not yet at goal. He asks if there are other things that he can do to further lower his hemoglobin A1C. What can you recommend for him?

According to the National Diabetes Statistics Report, 2020 from the Centers for Disease Control and Prevention, approximately 34.1 million US adults ≥ 18 years of age (13% of the adult population) have diabetes, 50% of whom have a hemoglobin A1C > 7%. The report also states that approximately 88 million US adults—more than one-third of the population—have prediabetes.²

The American Diabetes Association (ADA) estimated that diabetes-related health care costs in the United States for 2017 totaled $237 billion, an increase of 26% from 2012. More than $30 billion of this expense comes directly from diabetes medications; the remainder of these costs are related to lost wages, clinic visits, hospitalizations, and treatment for diabetic complications and comorbidities. After controlling for age and gender, medical expenditures for people with diabetes are 2.3 times higher than for those without diabetes.³

The 2019 ADA Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report makes general recommendations concerning fiber intake for patients with diabetes or prediabetes, stating that these patients should consume approximately 14 g of fiber for every 1000 kcal consumed, giving preference to whole-food sources rather than supplements.⁴ The report indicates that some studies have shown hemoglobin A1C reductions of 0.2% to 0.3% with daily fiber intake exceeding 50 g. However, this level of intake can cause unpleasant gastrointestinal adverse effects, including bloating, diarrhea, and flatulence.^4,5

STUDY SUMMARY

Effect on A1C exceeded the FDA threshold for new drugs

This systematic review and meta-analysis searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials that studied the effects of viscous fiber supplementation on glycemic control in patients with T2D. Eligible studies included those that: (1) had a duration ≥ 3 weeks; (2) allowed isolation of the viscous fiber effects; and (3) reported at least 1 of the following glycemic measures: hemoglobin A1C (n = 1148 patients), fasting glucose (n = 1394), fasting insulin (n = 228), homeostatic model assessment of insulin resistance (HOMA-IR; n = 652), and fructosamine (n = 23).

As an adjunct to standard of care, viscous fiber supplements significantly improved hemoglobin A1C and other glycemic markers in patients with T2D.

Data were pooled using the generic inverse variance method and expressed as mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified (Cochran Q and I² statistics, respectively). I² ≥ 50% indicates substantial heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall strength of evidence.

Twenty-eight eligible studies were compared. The median age of included patients was 60 years. The median dose of viscous fiber was 13.1 g/d (range, 2.55-21). Viscous fiber type varied between the studies and included psyllium, guar gum, β-glucan, and konjac, and was consumed in powder, tablet, capsule, and limited food-based forms (in 1 of the included studies). The median trial duration was 8 weeks, with 11 trials lasting ≥ 12 weeks.

Continue to: The study found...

The study found moderate-grade evidence that, when added to standard of care, viscous fiber supplementation reduced hemoglobin A1C (MD = –0.58%; 95% CI, –0.88 to –0.28; P = .0002; I² = 91%), fasting glucose (MD = –14.8 mg/dL; 95% CI, –23.8 to –5.58; P = .001; I² = 92%), and HOMA-IR (MD = –1.89; 95% CI, –3.45 to –0.33; P = .02; I² = 94%) compared with control. The effect on hemoglobin A1C exceeds the ≥ 0.3% threshold established by the US Food and Drug Administration for new antihyperglycemic drug development. There was no significant effect on fasting insulin or fructosamine, although the sample size for fructosamine was small. No significant evidence of a dose-dependent response effect was found. The studies had substantial heterogeneity. No evaluation of potential or real harm was noted in the analysis.

WHAT’S NEW

Potential glycemic benefit without large dietary increase

The glucose-lowering effects of increased fiber intake have often been hypothesized, but this meta-analysis is the first to focus specifically on the effect of viscous fiber supplements in patients with T2D. Prior meta-analyses, including those cited in the 2019 ADA recommendations mentioned above, included primarily whole-food dietary sources of fiber in the treatment arms and generally had more modest effects on outcomes.^4,6,7

By focusing on viscous fiber supplements, this study isolated the effect of these supplements vs fiber-rich dietary changes. It illustrates a greater potential benefit with supplements than whole-food dietary ­sources of fiber, and at a lower dose of fiber than was seen in prior studies without requiring substantial increases in caloric intake. Viscous fiber supplementation is a potential adjunct to the usual evidence-based standards of care for glycemic control in patients with T2D.

CAVEATS

Limited study durations may raise uncertainty about long-term benefits

This meta-analysis does have its limitations. The heterogeneity among the studies analyzed makes it difficult to establish a single recommendation regarding dose, type, and brand of fiber to be used. Only 11 of the 28 studies lasted longer than 12 weeks, with a median duration of 8 weeks, making any long-term effects on hemoglobin A1C unknown. No adverse effects or reactions were described to evaluate safety and tolerability of the viscous fiber supplementation. No patient-oriented outcomes were reported.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to supplement with viscous fiber

The biggest challenge to implementation is patient compliance. Some forms of supplemental fiber are less palatable than others and may cause unpleasant gastrointestinal adverse effects, which may be an impediment for some patients. Cost may also be an issue for some patients. Diabetes medications can be expensive; however, they are often covered, at least partially, by medical insurance. Over-the-counter supplements are unlikely to be covered for most patients.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 57-year-old man who was given a diagnosis of T2D a year ago presents for an office visit. His hemoglobin A1C level at diagnosis was 8.3%. He is otherwise healthy and has been adhering well to a plan of metformin 1000 mg twice daily, regular exercise, and a low-­carbohydrate diet you recommended. His most recent hemoglobin A1C is 7.3%. He is pleased with his progress, so he is discouraged when you tell him that he is not yet at goal. He asks if there are other things that he can do to further lower his hemoglobin A1C. What can you recommend for him?

According to the National Diabetes Statistics Report, 2020 from the Centers for Disease Control and Prevention, approximately 34.1 million US adults ≥ 18 years of age (13% of the adult population) have diabetes, 50% of whom have a hemoglobin A1C > 7%. The report also states that approximately 88 million US adults—more than one-third of the population—have prediabetes.²

The American Diabetes Association (ADA) estimated that diabetes-related health care costs in the United States for 2017 totaled $237 billion, an increase of 26% from 2012. More than $30 billion of this expense comes directly from diabetes medications; the remainder of these costs are related to lost wages, clinic visits, hospitalizations, and treatment for diabetic complications and comorbidities. After controlling for age and gender, medical expenditures for people with diabetes are 2.3 times higher than for those without diabetes.³

The 2019 ADA Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report makes general recommendations concerning fiber intake for patients with diabetes or prediabetes, stating that these patients should consume approximately 14 g of fiber for every 1000 kcal consumed, giving preference to whole-food sources rather than supplements.⁴ The report indicates that some studies have shown hemoglobin A1C reductions of 0.2% to 0.3% with daily fiber intake exceeding 50 g. However, this level of intake can cause unpleasant gastrointestinal adverse effects, including bloating, diarrhea, and flatulence.^4,5

STUDY SUMMARY

Effect on A1C exceeded the FDA threshold for new drugs

This systematic review and meta-analysis searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials that studied the effects of viscous fiber supplementation on glycemic control in patients with T2D. Eligible studies included those that: (1) had a duration ≥ 3 weeks; (2) allowed isolation of the viscous fiber effects; and (3) reported at least 1 of the following glycemic measures: hemoglobin A1C (n = 1148 patients), fasting glucose (n = 1394), fasting insulin (n = 228), homeostatic model assessment of insulin resistance (HOMA-IR; n = 652), and fructosamine (n = 23).

As an adjunct to standard of care, viscous fiber supplements significantly improved hemoglobin A1C and other glycemic markers in patients with T2D.

Data were pooled using the generic inverse variance method and expressed as mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified (Cochran Q and I² statistics, respectively). I² ≥ 50% indicates substantial heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall strength of evidence.

Twenty-eight eligible studies were compared. The median age of included patients was 60 years. The median dose of viscous fiber was 13.1 g/d (range, 2.55-21). Viscous fiber type varied between the studies and included psyllium, guar gum, β-glucan, and konjac, and was consumed in powder, tablet, capsule, and limited food-based forms (in 1 of the included studies). The median trial duration was 8 weeks, with 11 trials lasting ≥ 12 weeks.

Continue to: The study found...

The study found moderate-grade evidence that, when added to standard of care, viscous fiber supplementation reduced hemoglobin A1C (MD = –0.58%; 95% CI, –0.88 to –0.28; P = .0002; I² = 91%), fasting glucose (MD = –14.8 mg/dL; 95% CI, –23.8 to –5.58; P = .001; I² = 92%), and HOMA-IR (MD = –1.89; 95% CI, –3.45 to –0.33; P = .02; I² = 94%) compared with control. The effect on hemoglobin A1C exceeds the ≥ 0.3% threshold established by the US Food and Drug Administration for new antihyperglycemic drug development. There was no significant effect on fasting insulin or fructosamine, although the sample size for fructosamine was small. No significant evidence of a dose-dependent response effect was found. The studies had substantial heterogeneity. No evaluation of potential or real harm was noted in the analysis.

WHAT’S NEW

Potential glycemic benefit without large dietary increase

The glucose-lowering effects of increased fiber intake have often been hypothesized, but this meta-analysis is the first to focus specifically on the effect of viscous fiber supplements in patients with T2D. Prior meta-analyses, including those cited in the 2019 ADA recommendations mentioned above, included primarily whole-food dietary sources of fiber in the treatment arms and generally had more modest effects on outcomes.^4,6,7

By focusing on viscous fiber supplements, this study isolated the effect of these supplements vs fiber-rich dietary changes. It illustrates a greater potential benefit with supplements than whole-food dietary ­sources of fiber, and at a lower dose of fiber than was seen in prior studies without requiring substantial increases in caloric intake. Viscous fiber supplementation is a potential adjunct to the usual evidence-based standards of care for glycemic control in patients with T2D.

CAVEATS

Limited study durations may raise uncertainty about long-term benefits

This meta-analysis does have its limitations. The heterogeneity among the studies analyzed makes it difficult to establish a single recommendation regarding dose, type, and brand of fiber to be used. Only 11 of the 28 studies lasted longer than 12 weeks, with a median duration of 8 weeks, making any long-term effects on hemoglobin A1C unknown. No adverse effects or reactions were described to evaluate safety and tolerability of the viscous fiber supplementation. No patient-oriented outcomes were reported.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to supplement with viscous fiber

The biggest challenge to implementation is patient compliance. Some forms of supplemental fiber are less palatable than others and may cause unpleasant gastrointestinal adverse effects, which may be an impediment for some patients. Cost may also be an issue for some patients. Diabetes medications can be expensive; however, they are often covered, at least partially, by medical insurance. Over-the-counter supplements are unlikely to be covered for most patients.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 57-year-old man who was given a diagnosis of T2D a year ago presents for an office visit. His hemoglobin A1C level at diagnosis was 8.3%. He is otherwise healthy and has been adhering well to a plan of metformin 1000 mg twice daily, regular exercise, and a low-­carbohydrate diet you recommended. His most recent hemoglobin A1C is 7.3%. He is pleased with his progress, so he is discouraged when you tell him that he is not yet at goal. He asks if there are other things that he can do to further lower his hemoglobin A1C. What can you recommend for him?

According to the National Diabetes Statistics Report, 2020 from the Centers for Disease Control and Prevention, approximately 34.1 million US adults ≥ 18 years of age (13% of the adult population) have diabetes, 50% of whom have a hemoglobin A1C > 7%. The report also states that approximately 88 million US adults—more than one-third of the population—have prediabetes.²

The American Diabetes Association (ADA) estimated that diabetes-related health care costs in the United States for 2017 totaled $237 billion, an increase of 26% from 2012. More than $30 billion of this expense comes directly from diabetes medications; the remainder of these costs are related to lost wages, clinic visits, hospitalizations, and treatment for diabetic complications and comorbidities. After controlling for age and gender, medical expenditures for people with diabetes are 2.3 times higher than for those without diabetes.³

The 2019 ADA Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report makes general recommendations concerning fiber intake for patients with diabetes or prediabetes, stating that these patients should consume approximately 14 g of fiber for every 1000 kcal consumed, giving preference to whole-food sources rather than supplements.⁴ The report indicates that some studies have shown hemoglobin A1C reductions of 0.2% to 0.3% with daily fiber intake exceeding 50 g. However, this level of intake can cause unpleasant gastrointestinal adverse effects, including bloating, diarrhea, and flatulence.^4,5

STUDY SUMMARY

Effect on A1C exceeded the FDA threshold for new drugs

This systematic review and meta-analysis searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials that studied the effects of viscous fiber supplementation on glycemic control in patients with T2D. Eligible studies included those that: (1) had a duration ≥ 3 weeks; (2) allowed isolation of the viscous fiber effects; and (3) reported at least 1 of the following glycemic measures: hemoglobin A1C (n = 1148 patients), fasting glucose (n = 1394), fasting insulin (n = 228), homeostatic model assessment of insulin resistance (HOMA-IR; n = 652), and fructosamine (n = 23).

As an adjunct to standard of care, viscous fiber supplements significantly improved hemoglobin A1C and other glycemic markers in patients with T2D.

Data were pooled using the generic inverse variance method and expressed as mean difference (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed and quantified (Cochran Q and I² statistics, respectively). I² ≥ 50% indicates substantial heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the overall strength of evidence.

Twenty-eight eligible studies were compared. The median age of included patients was 60 years. The median dose of viscous fiber was 13.1 g/d (range, 2.55-21). Viscous fiber type varied between the studies and included psyllium, guar gum, β-glucan, and konjac, and was consumed in powder, tablet, capsule, and limited food-based forms (in 1 of the included studies). The median trial duration was 8 weeks, with 11 trials lasting ≥ 12 weeks.

Continue to: The study found...

The study found moderate-grade evidence that, when added to standard of care, viscous fiber supplementation reduced hemoglobin A1C (MD = –0.58%; 95% CI, –0.88 to –0.28; P = .0002; I² = 91%), fasting glucose (MD = –14.8 mg/dL; 95% CI, –23.8 to –5.58; P = .001; I² = 92%), and HOMA-IR (MD = –1.89; 95% CI, –3.45 to –0.33; P = .02; I² = 94%) compared with control. The effect on hemoglobin A1C exceeds the ≥ 0.3% threshold established by the US Food and Drug Administration for new antihyperglycemic drug development. There was no significant effect on fasting insulin or fructosamine, although the sample size for fructosamine was small. No significant evidence of a dose-dependent response effect was found. The studies had substantial heterogeneity. No evaluation of potential or real harm was noted in the analysis.

WHAT’S NEW

Potential glycemic benefit without large dietary increase

The glucose-lowering effects of increased fiber intake have often been hypothesized, but this meta-analysis is the first to focus specifically on the effect of viscous fiber supplements in patients with T2D. Prior meta-analyses, including those cited in the 2019 ADA recommendations mentioned above, included primarily whole-food dietary sources of fiber in the treatment arms and generally had more modest effects on outcomes.^4,6,7

By focusing on viscous fiber supplements, this study isolated the effect of these supplements vs fiber-rich dietary changes. It illustrates a greater potential benefit with supplements than whole-food dietary ­sources of fiber, and at a lower dose of fiber than was seen in prior studies without requiring substantial increases in caloric intake. Viscous fiber supplementation is a potential adjunct to the usual evidence-based standards of care for glycemic control in patients with T2D.

CAVEATS

Limited study durations may raise uncertainty about long-term benefits

This meta-analysis does have its limitations. The heterogeneity among the studies analyzed makes it difficult to establish a single recommendation regarding dose, type, and brand of fiber to be used. Only 11 of the 28 studies lasted longer than 12 weeks, with a median duration of 8 weeks, making any long-term effects on hemoglobin A1C unknown. No adverse effects or reactions were described to evaluate safety and tolerability of the viscous fiber supplementation. No patient-oriented outcomes were reported.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to supplement with viscous fiber

The biggest challenge to implementation is patient compliance. Some forms of supplemental fiber are less palatable than others and may cause unpleasant gastrointestinal adverse effects, which may be an impediment for some patients. Cost may also be an issue for some patients. Diabetes medications can be expensive; however, they are often covered, at least partially, by medical insurance. Over-the-counter supplements are unlikely to be covered for most patients.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Chronic kidney disease (CKD) is a significant comorbidity of diabetes mellitus. The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation defines CKD as the presence of kidney damage or decreased kidney function for ≥ 3 months. CKD caused by diabetes is called diabetic kidney disease (DKD), which is 1 of 3 principal microvascular complications of diabetes. DKD can progress to end-stage renal disease (ESRD), requiring kidney replacement therapy, and is the leading cause of CKD and ESRD in the United States.^1-3 Studies have also shown that, particularly in patients with diabetes, CKD considerably increases the risk of cardiovascular events, which often occur prior to ESRD.^1,4

This article provides the latest recommendations for evaluating and managing DKD to help you prevent or slow its progression.

Defining and categorizing diabetic kidney disease

CKD is defined as persistently elevated excretion of urinary albumin (albuminuria) and decreased estimated glomerular filtration rate (eGFR), or as the presence of signs of progressive kidney damage.^5,6 DKD, also known as diabetic nephropathy, is CKD attributed to long-term diabetes. A patient’s eGFR is the established basis for assignment to a stage (1, 2, 3a, 3b, 4, or 5) of CKD (TABLE 1⁷) and, along with the category of albuminuria (A1, A2, or A3), can indicate prognosis.

Taking its toll in diabetes

As many as 40% of patients with diabetes develop DKD.^8-10 Most studies of DKD have been conducted in patients with type 1 diabetes (T1D), because the time of clinical onset is typically known.

Type 1 diabetes. DKD usually occurs 10 to 15 years, or later, after the onset of diabetes.⁶ As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.^5,11 After approximately 22.5 years without albuminuria, patients with T1D have approximately a 1% annual risk of DKD.¹²

Type 2 diabetes (T2D). DKD is often present at diagnosis, likely due to a delay in diagnosis and briefer clinical exposure, compared to T1D. Albuminuria has been reported in as many as 40% of patients with T2D approximately 10 years after onset of diabetes.^12,13

Multiple risk factors with no standout “predictor”

Genetic susceptibility, ethnicity, glycemic control, smoking, blood pressure (BP), and the eGFR have been identified as risk factors for renal involvement in diabetes; obesity, oral contraceptives, and age can also contribute. Although each risk factor increases the risk of DKD, no single factor is adequately predictive. Moderately increased albuminuria, the earliest sign of DKD, is associated with progressive nephropathy.¹²

Continue to: How great is the risk?

How great is the risk? From disease onset to proteinuria and from proteinuria to ESRD, the risk of DKD in T1D and T2D is similar. With appropriate treatment, albuminuria can regress, and the risk of ESRD can be < 20% at 10 years in T1D.¹² As in T1D, good glycemic control might result in regression of albuminuria in T2D.¹⁴

As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.

For unknown reasons, the degree of albuminuria can exist independent of the progression of DKD. Factors responsible for a progressive decline in eGFR in DKD without albuminuria are unknown.^12,15

Patient evaluation with an eye toward comorbidities

A comprehensive initial medical evaluation for DKD includes a review of microvascular complications; visits to specialists; lifestyle and behavior patterns (eg, diet, sleep, substance use, and social support); and medication adherence, adverse drug effects, and alternative medicines. Although DKD is often a clinical diagnosis, it can be ruled in by persistent albuminuria or decreased eGFR, or both, in established diabetes or diabetic retinopathy when other causes are unlikely (see “Recommended DKD screening protocol,” below).

Screening for mental health conditions and barriers to self-management is also key.⁶

Comorbidities, of course, can complicate disease management in patients with diabetes.^16-20 Providers and patients therefore need to be aware of potential diabetic comorbidities. For example, DKD and even moderately increased albuminuria significantly increase the risk of cardiovascular disease (CVD).¹² Other possible comorbidities include (but are not limited to) nonalcoholic steatohepatitis, fracture, hearing impairment, cancer (eg, liver, pancreas, endometrium, colon, rectum, breast, and bladder), pancreatitis, hypogonadism, obstructive sleep apnea, periodontal disease, anxiety, depression, and eating disorders.⁶

Continue to: Recommended DKD screening protocol

 

 

Recommended DKD screening protocol

In all cases of T2D, in cases of T1D of ≥ 5 years’ duration, and in patients with diabetes and comorbid hypertension, perform annual screening for albuminuria, an elevated creatinine level, and a decline in eGFR.

Screen for potential comorbidities of DKD: For example, the risk of cardiovascular disease is significantly elevated in even moderately increased albuminuria.

To confirm the diagnosis of DKD, at least 2 of 3 urine specimens must demonstrate an elevated urinary albumin:creatinine ratio (UACR) over a 3- to 6-month period.²¹ Apart from renal damage, exercise within 24 hours before specimen collection, infection, fever, congestive heart failure, hyperglycemia, menstruation, and hypertension can elevate the UACR.⁶

Levels of the UACR are established as follows²²:

• Normal UACR is defined as < 30 milligrams of albumin per gram of creatinine (expressed as “mg/g”).
• Increased urinary albumin excretion is defined as ≥ 30 mg/g.
• Moderately increased albuminuria, a predictor of potential nephropathy, is the excretion of 30 to 300 mg/g.
• Severely increased albuminuria is excretion > 300 mg/g; it is often followed by a gradual decline in eGFR that, without treatment, eventually leads to ESRD.

The rate of decline in eGFR once albuminuria is severely increased is equivalent in T1D and T2D.¹² Without intervention, the time from severely increased albuminuria to ESRD in T1D and T2D averages approximately 6 or 7 years.

Clinical features

DKD is typically a clinical diagnosis seen in patients with longstanding diabetes, albuminuria, retinopathy, or a reduced eGFR in the absence of another primary cause of kidney damage. In patients with T1D and DKD, signs of retinopathy and neuropathy are almost always present at diagnosis, unless a diagnosis is made early in the course of diabetes.¹² Therefore, the presence of retinopathy suggests that diabetes is the likely cause of CKD.

Continue to: The presence of microvascular disease...

The presence of microvascular disease in patients with T2D and DKD is less predictable.¹² In T2D patients who do not have retinopathy, consider causes of CKD other than DKD. Features suggesting that the cause of CKD is an underlying condition other than diabetes are rapidly increasing albuminuria or decreasing eGFR; urinary sediment comprising red blood cells or white blood cells; and nephrotic syndrome.⁶

As the prevalence of diabetes increases, it has become more common to diagnose DKD by eGFR without albuminuria—underscoring the importance of routine monitoring of eGFR in patients with diabetes.⁶

Sources of expert guidance. The Chronic Kidney Disease Epidemiology Collaboration equation²³ is preferred for calculating eGFR from serum creatinine: An eGFR < 60 mL/min/1.73 m² is considered abnormal.^3,12 At these rates, the prevalence of complications related to CKD rises and screening for complications becomes necessary.

A more comprehensive classification of the stages of CKD, incorporating albuminuria and progression of CKD, has been recommended by Kidney Disease: Improving Global Outcomes (KDIGO).⁷ Because eGFR and excretion of albumin vary, abnormal test results need to be verified over time to stage the degree of CKD.^3,12 Kidney damage often manifests as albuminuria, but also as hematuria, other types of abnormal urinary sediment, radiographic abnormalities, and other abnormal presentations.

Management

Nutritional factors

Excessive protein intake has been shown to increase albuminuria, worsen renal function, and increase CVD mortality in DKD.^24-26 Therefore, daily dietary protein intake of 0.8 g/kg body weight is recommended for patients who are not on dialysis.³ Patients on dialysis might require higher protein intake to preserve muscle mass caused by protein-energy wasting, which is common in dialysis patients.⁶

Continue to: Low sodium intake

Low sodium intake in CKD patients has been shown to decrease BP and thus slow the progression of renal disease and lower the risk of CVD. The recommended dietary sodium intake in CKD patients is 1500-3000 mg/d.³

Low potassium intake. Hyperkalemia is a serious complication of CKD. A low-potassium diet is recommended in ESRD patients who have a potassium level > 5.5 mEq/L.⁶

Blood pressure

Preventing and treating hypertension is critical to slowing the progression of CKD and reducing cardiovascular risk. BP should be measured at every clinic visit. Aside from lifestyle changes, medication might be needed to reach target BP.

The American Diabetes Association recommends a BP goal of ≤ 140/90 mm Hg for hypertensive patients with diabetes, although they do state that a lower BP target (≤ 130/80 mm Hg) might be more appropriate for patients with DKD.²⁷

The American College of Cardiology recommends that hypertensive patients with CKD have a BP target of ≤ 130/80 mm Hg.²⁸

Continue to: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have renoprotective benefits. These agents are recommended as first-line medications for patients with diabetes, hypertension, and an eGFR < 60 mL/min/1.73 m² and a UACR > 300 mg/g.^29-31 Evidence also supports their use when the UACR is 30 to 299 mg/g.

Studies have shown that, in patients with DKD, ACE inhibitors and ARBs can slow the progression of renal disease.^29,30,32 There is no difference between ACE inhibitors and ARBs in their effectiveness for preventing progression of DKD.⁶ There is no added benefit in combining an ACE inhibitor and an ARB³³; notably, combination ACE inhibitor and ARB therapy can increase the risk of adverse events, such as hyperkalemia and acute kidney injury, especially in patients with DKD.³³

There is no evidence for starting an ACE inhibitor or ARB to prevent CKD in patients with diabetes who are not hypertensive.⁵

ACE inhibitors and ARBs should be used with caution in women of childbearing age, who should use a reliable form of contraception if taking one of these drugs.

Diuretics. Thiazide-type and loop diuretics might potentiate the positive effects of ACE inhibitors and ARBs. KDOQI guidelines recommend that, in patients who require a second agent to control BP, a diuretic should be considered in combination with an ACE inhibitor or an ARB.²⁰ A loop diuretic is preferred if the eGFR is < 30 mL/min/1.73 m².

Continue to: Nondihydropyridine calcium-channel blockers

Nondihydropyridine calcium-channel blockers (CCBs), such as diltiazem and verapamil, have been shown to be more effective then dihydrophyridine CCBs, such as amlodipine and nifedipine, in slowing the progression of renal disease because of their antiproteinuric effects. However, the antiproteinuric effects of nondihydropyridine CCBs are not as strong as those of ACE inhibitors or ARBs, and these drugs do not appear to potentiate the effects of an ACE inhibitor or ARB when used in combination.²⁰

Confirmation of suspected DKD requires an elevated albumin:creatinine ratio in at least 2 of 3 urine specimens over a 3- to 6-month period.

Nondihydropyridine CCBs might be a reasonable alternative in patients who cannot tolerate an ACE inhibitor or an ARB.

Mineralocorticoid receptor antagonists in combination with an ACE inhibitor or ARB have been demonstrated to reduce albuminuria in short-term studies.^34,35

Glycemic levels

Studies conducted in patients with T1D, and others in patients with T2D, have shown that tight glycemic control can delay the onset and slow the progression of albuminuria and a decline in the eGFR.^10,36-39 The target glycated hemoglobin (A1C) should be < 7% to prevent or slow progression of DKD.⁴⁰ However, patients with DKD have an increased risk of hypoglycemic events and increased mortality with more intensive glycemic control.^40,41 Given those findings, some patients with DKD and significant comorbidities, ESRD, or limited life expectancy might need to have an A1C target set at 8%.^6,42

Adjustments to antidiabetes medications in DKD

In patients with stages 3 to 5 DKD, several common antidiabetic medications might need to be adjusted or discontinued because they decrease creatinine clearance.

Continue to: First-generation sulfonylureas

First-generation sulfonylureas should be avoided in DKD. Glipizide and gliclazide are preferred among second-generation sulfonylureas because they do not increase the risk of hypoglycemia in DKD patients, although patients taking these medications still require close monitoring of their blood glucose level.²⁰

Metformin. In 2016, recommendations changed for the use of metformin in patients with DKD: The eGFR, not the serum creatinine level, should guide treatment.⁴³ Metformin can be used safely in patients with (1) an eGFR of < 60 mL/min/1.73 m² and (2) an eGFR of 30 mL/min/1.73 m² with close monitoring. Metformin should not be initiated if the eGFR is < 45 mL/min/1.73 m².⁴³ 

Antidiabetes medications with direct effect on the kidney

Several antidiabetes medications have a direct effect on the kidney apart from their effect on the blood glucose level.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce albuminuria and slow the decrease of eGFR independent of glycemic control. In addition, SGLT2 inhibitors have also been shown to have cardiovascular benefits in patients with DKD.^44,45 

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to delay and decrease the progression of DKD.^46-48 Also, similar to what is seen with SGLT2 inhibitors, GLP-1 agonists have demonstrable cardiovascular benefit in patients with DKD.^46,48

Continue to: Dyslipidemia and DKD

 

 

Dyslipidemia and DKD

Because the risk of CVD is increased in patients with DKD, addressing other modifiable risk factors, including dyslipidemia, is recommended in these patients. Patients with diabetes and stages 1 to 4 DKD should be treated with a high-intensity statin or a combination of a statin and ezetimibe.^49,50

Tight glycemic control in T1D and T2D can delay the onset, and slow the progression, of albuminuria and a decline in the eGFR.

If a patient is taking a statin and starting dialysis, it’s important to discuss with him or her whether to continue the statin, based on perceived benefits and risks. It is not recommended that statins be initiated in patients on dialysis unless there is a specific cardiovascular indication for doing so. Risk reduction with a statin has been shown to be significantly less in dialysis patients than in patients who are not being treated with dialysis.⁴⁹

Complications of CKD

Anemia is a common complication of CKD. KDIGO recommends measuring the ­hemoglobin concentration annually in DKD stage 3 patients without anemia; at least every 6 months in stage 4 patients; and at least every 3 months in stage 5. DKD patients with anemia should have additional laboratory testing: the absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate.⁵¹

Mineral and bone disorder should be screened for in patients with DKD. TABLE 2⁵² outlines when clinical laboratory tests should be ordered to assess for mineral bone disease.

When to refer to a nephrologist

Refer patients with stage 4 or 5 CKD (eGFR, ≤ 30 mL/min/1.73 m²) to a nephrologist for discussion of kidney replacement therapy.⁶ Patients with stage 3a CKD and severely increased albuminuria or with stage 3b CKD and moderately or severely increased albuminuria should also be referred to a nephrologist for intervention to delay disease progression.

Continue to: Identifying the need for early referral...

Nutritional control is important in DKD: A lowsodium diet can slow progression of DKD, and a low-potassium diet can prevent hyperkalemia in end-stage renal disease.

Identifying the need for early referral to a nephrologist has been shown to reduce the cost, and improve the quality, of care.⁵³ Other indications for earlier referral include uncertainty about the etiology of renal disease, persistent or severe albuminuria, persistent hematuria, a rapid decline in eGFR, and acute kidney injury. Additionally, referral at an earlier stage of DKD might be needed to assist with complications associated with DKD, such as anemia, secondary hyperparathyroidism, mineral and bone disorder, resistant hypertension, fluid overload, and electrolyte disturbances.⁶

ACKNOWLEDGEMENT
The authors thank Colleen Colbert, PhD, and Iqbal Ahmad, PhD, for their review and critique of the manuscript of this article. They also thank Christopher Babiuch, MD, for his guidance in the preparation of the manuscript.

CORRESPONDENCE
Faraz Ahmad, MD, MPH, Care Point East Family Medicine, 543 Taylor Avenue, 2nd floor, Columbus, OH 43203; faraz. ahmad@osumc.edu.

Chronic kidney disease (CKD) is a significant comorbidity of diabetes mellitus. The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation defines CKD as the presence of kidney damage or decreased kidney function for ≥ 3 months. CKD caused by diabetes is called diabetic kidney disease (DKD), which is 1 of 3 principal microvascular complications of diabetes. DKD can progress to end-stage renal disease (ESRD), requiring kidney replacement therapy, and is the leading cause of CKD and ESRD in the United States.^1-3 Studies have also shown that, particularly in patients with diabetes, CKD considerably increases the risk of cardiovascular events, which often occur prior to ESRD.^1,4

This article provides the latest recommendations for evaluating and managing DKD to help you prevent or slow its progression.

Defining and categorizing diabetic kidney disease

CKD is defined as persistently elevated excretion of urinary albumin (albuminuria) and decreased estimated glomerular filtration rate (eGFR), or as the presence of signs of progressive kidney damage.^5,6 DKD, also known as diabetic nephropathy, is CKD attributed to long-term diabetes. A patient’s eGFR is the established basis for assignment to a stage (1, 2, 3a, 3b, 4, or 5) of CKD (TABLE 1⁷) and, along with the category of albuminuria (A1, A2, or A3), can indicate prognosis.

Taking its toll in diabetes

As many as 40% of patients with diabetes develop DKD.^8-10 Most studies of DKD have been conducted in patients with type 1 diabetes (T1D), because the time of clinical onset is typically known.

Type 1 diabetes. DKD usually occurs 10 to 15 years, or later, after the onset of diabetes.⁶ As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.^5,11 After approximately 22.5 years without albuminuria, patients with T1D have approximately a 1% annual risk of DKD.¹²

Type 2 diabetes (T2D). DKD is often present at diagnosis, likely due to a delay in diagnosis and briefer clinical exposure, compared to T1D. Albuminuria has been reported in as many as 40% of patients with T2D approximately 10 years after onset of diabetes.^12,13

Multiple risk factors with no standout “predictor”

Genetic susceptibility, ethnicity, glycemic control, smoking, blood pressure (BP), and the eGFR have been identified as risk factors for renal involvement in diabetes; obesity, oral contraceptives, and age can also contribute. Although each risk factor increases the risk of DKD, no single factor is adequately predictive. Moderately increased albuminuria, the earliest sign of DKD, is associated with progressive nephropathy.¹²

Continue to: How great is the risk?

How great is the risk? From disease onset to proteinuria and from proteinuria to ESRD, the risk of DKD in T1D and T2D is similar. With appropriate treatment, albuminuria can regress, and the risk of ESRD can be < 20% at 10 years in T1D.¹² As in T1D, good glycemic control might result in regression of albuminuria in T2D.¹⁴

As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.

For unknown reasons, the degree of albuminuria can exist independent of the progression of DKD. Factors responsible for a progressive decline in eGFR in DKD without albuminuria are unknown.^12,15

Patient evaluation with an eye toward comorbidities

A comprehensive initial medical evaluation for DKD includes a review of microvascular complications; visits to specialists; lifestyle and behavior patterns (eg, diet, sleep, substance use, and social support); and medication adherence, adverse drug effects, and alternative medicines. Although DKD is often a clinical diagnosis, it can be ruled in by persistent albuminuria or decreased eGFR, or both, in established diabetes or diabetic retinopathy when other causes are unlikely (see “Recommended DKD screening protocol,” below).

Screening for mental health conditions and barriers to self-management is also key.⁶

Comorbidities, of course, can complicate disease management in patients with diabetes.^16-20 Providers and patients therefore need to be aware of potential diabetic comorbidities. For example, DKD and even moderately increased albuminuria significantly increase the risk of cardiovascular disease (CVD).¹² Other possible comorbidities include (but are not limited to) nonalcoholic steatohepatitis, fracture, hearing impairment, cancer (eg, liver, pancreas, endometrium, colon, rectum, breast, and bladder), pancreatitis, hypogonadism, obstructive sleep apnea, periodontal disease, anxiety, depression, and eating disorders.⁶

Continue to: Recommended DKD screening protocol

 

 

Recommended DKD screening protocol

In all cases of T2D, in cases of T1D of ≥ 5 years’ duration, and in patients with diabetes and comorbid hypertension, perform annual screening for albuminuria, an elevated creatinine level, and a decline in eGFR.

Screen for potential comorbidities of DKD: For example, the risk of cardiovascular disease is significantly elevated in even moderately increased albuminuria.

To confirm the diagnosis of DKD, at least 2 of 3 urine specimens must demonstrate an elevated urinary albumin:creatinine ratio (UACR) over a 3- to 6-month period.²¹ Apart from renal damage, exercise within 24 hours before specimen collection, infection, fever, congestive heart failure, hyperglycemia, menstruation, and hypertension can elevate the UACR.⁶

Levels of the UACR are established as follows²²:

• Normal UACR is defined as < 30 milligrams of albumin per gram of creatinine (expressed as “mg/g”).
• Increased urinary albumin excretion is defined as ≥ 30 mg/g.
• Moderately increased albuminuria, a predictor of potential nephropathy, is the excretion of 30 to 300 mg/g.
• Severely increased albuminuria is excretion > 300 mg/g; it is often followed by a gradual decline in eGFR that, without treatment, eventually leads to ESRD.

The rate of decline in eGFR once albuminuria is severely increased is equivalent in T1D and T2D.¹² Without intervention, the time from severely increased albuminuria to ESRD in T1D and T2D averages approximately 6 or 7 years.

Clinical features

DKD is typically a clinical diagnosis seen in patients with longstanding diabetes, albuminuria, retinopathy, or a reduced eGFR in the absence of another primary cause of kidney damage. In patients with T1D and DKD, signs of retinopathy and neuropathy are almost always present at diagnosis, unless a diagnosis is made early in the course of diabetes.¹² Therefore, the presence of retinopathy suggests that diabetes is the likely cause of CKD.

Continue to: The presence of microvascular disease...

The presence of microvascular disease in patients with T2D and DKD is less predictable.¹² In T2D patients who do not have retinopathy, consider causes of CKD other than DKD. Features suggesting that the cause of CKD is an underlying condition other than diabetes are rapidly increasing albuminuria or decreasing eGFR; urinary sediment comprising red blood cells or white blood cells; and nephrotic syndrome.⁶

As the prevalence of diabetes increases, it has become more common to diagnose DKD by eGFR without albuminuria—underscoring the importance of routine monitoring of eGFR in patients with diabetes.⁶

Sources of expert guidance. The Chronic Kidney Disease Epidemiology Collaboration equation²³ is preferred for calculating eGFR from serum creatinine: An eGFR < 60 mL/min/1.73 m² is considered abnormal.^3,12 At these rates, the prevalence of complications related to CKD rises and screening for complications becomes necessary.

A more comprehensive classification of the stages of CKD, incorporating albuminuria and progression of CKD, has been recommended by Kidney Disease: Improving Global Outcomes (KDIGO).⁷ Because eGFR and excretion of albumin vary, abnormal test results need to be verified over time to stage the degree of CKD.^3,12 Kidney damage often manifests as albuminuria, but also as hematuria, other types of abnormal urinary sediment, radiographic abnormalities, and other abnormal presentations.

Management

Nutritional factors

Excessive protein intake has been shown to increase albuminuria, worsen renal function, and increase CVD mortality in DKD.^24-26 Therefore, daily dietary protein intake of 0.8 g/kg body weight is recommended for patients who are not on dialysis.³ Patients on dialysis might require higher protein intake to preserve muscle mass caused by protein-energy wasting, which is common in dialysis patients.⁶

Continue to: Low sodium intake

Low sodium intake in CKD patients has been shown to decrease BP and thus slow the progression of renal disease and lower the risk of CVD. The recommended dietary sodium intake in CKD patients is 1500-3000 mg/d.³

Low potassium intake. Hyperkalemia is a serious complication of CKD. A low-potassium diet is recommended in ESRD patients who have a potassium level > 5.5 mEq/L.⁶

Blood pressure

Preventing and treating hypertension is critical to slowing the progression of CKD and reducing cardiovascular risk. BP should be measured at every clinic visit. Aside from lifestyle changes, medication might be needed to reach target BP.

The American Diabetes Association recommends a BP goal of ≤ 140/90 mm Hg for hypertensive patients with diabetes, although they do state that a lower BP target (≤ 130/80 mm Hg) might be more appropriate for patients with DKD.²⁷

The American College of Cardiology recommends that hypertensive patients with CKD have a BP target of ≤ 130/80 mm Hg.²⁸

Continue to: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have renoprotective benefits. These agents are recommended as first-line medications for patients with diabetes, hypertension, and an eGFR < 60 mL/min/1.73 m² and a UACR > 300 mg/g.^29-31 Evidence also supports their use when the UACR is 30 to 299 mg/g.

Studies have shown that, in patients with DKD, ACE inhibitors and ARBs can slow the progression of renal disease.^29,30,32 There is no difference between ACE inhibitors and ARBs in their effectiveness for preventing progression of DKD.⁶ There is no added benefit in combining an ACE inhibitor and an ARB³³; notably, combination ACE inhibitor and ARB therapy can increase the risk of adverse events, such as hyperkalemia and acute kidney injury, especially in patients with DKD.³³

There is no evidence for starting an ACE inhibitor or ARB to prevent CKD in patients with diabetes who are not hypertensive.⁵

ACE inhibitors and ARBs should be used with caution in women of childbearing age, who should use a reliable form of contraception if taking one of these drugs.

Diuretics. Thiazide-type and loop diuretics might potentiate the positive effects of ACE inhibitors and ARBs. KDOQI guidelines recommend that, in patients who require a second agent to control BP, a diuretic should be considered in combination with an ACE inhibitor or an ARB.²⁰ A loop diuretic is preferred if the eGFR is < 30 mL/min/1.73 m².

Continue to: Nondihydropyridine calcium-channel blockers

Nondihydropyridine calcium-channel blockers (CCBs), such as diltiazem and verapamil, have been shown to be more effective then dihydrophyridine CCBs, such as amlodipine and nifedipine, in slowing the progression of renal disease because of their antiproteinuric effects. However, the antiproteinuric effects of nondihydropyridine CCBs are not as strong as those of ACE inhibitors or ARBs, and these drugs do not appear to potentiate the effects of an ACE inhibitor or ARB when used in combination.²⁰

Confirmation of suspected DKD requires an elevated albumin:creatinine ratio in at least 2 of 3 urine specimens over a 3- to 6-month period.

Nondihydropyridine CCBs might be a reasonable alternative in patients who cannot tolerate an ACE inhibitor or an ARB.

Mineralocorticoid receptor antagonists in combination with an ACE inhibitor or ARB have been demonstrated to reduce albuminuria in short-term studies.^34,35

Glycemic levels

Studies conducted in patients with T1D, and others in patients with T2D, have shown that tight glycemic control can delay the onset and slow the progression of albuminuria and a decline in the eGFR.^10,36-39 The target glycated hemoglobin (A1C) should be < 7% to prevent or slow progression of DKD.⁴⁰ However, patients with DKD have an increased risk of hypoglycemic events and increased mortality with more intensive glycemic control.^40,41 Given those findings, some patients with DKD and significant comorbidities, ESRD, or limited life expectancy might need to have an A1C target set at 8%.^6,42

Adjustments to antidiabetes medications in DKD

In patients with stages 3 to 5 DKD, several common antidiabetic medications might need to be adjusted or discontinued because they decrease creatinine clearance.

Continue to: First-generation sulfonylureas

First-generation sulfonylureas should be avoided in DKD. Glipizide and gliclazide are preferred among second-generation sulfonylureas because they do not increase the risk of hypoglycemia in DKD patients, although patients taking these medications still require close monitoring of their blood glucose level.²⁰

Metformin. In 2016, recommendations changed for the use of metformin in patients with DKD: The eGFR, not the serum creatinine level, should guide treatment.⁴³ Metformin can be used safely in patients with (1) an eGFR of < 60 mL/min/1.73 m² and (2) an eGFR of 30 mL/min/1.73 m² with close monitoring. Metformin should not be initiated if the eGFR is < 45 mL/min/1.73 m².⁴³ 

Antidiabetes medications with direct effect on the kidney

Several antidiabetes medications have a direct effect on the kidney apart from their effect on the blood glucose level.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce albuminuria and slow the decrease of eGFR independent of glycemic control. In addition, SGLT2 inhibitors have also been shown to have cardiovascular benefits in patients with DKD.^44,45 

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to delay and decrease the progression of DKD.^46-48 Also, similar to what is seen with SGLT2 inhibitors, GLP-1 agonists have demonstrable cardiovascular benefit in patients with DKD.^46,48

Continue to: Dyslipidemia and DKD

 

 

Dyslipidemia and DKD

Because the risk of CVD is increased in patients with DKD, addressing other modifiable risk factors, including dyslipidemia, is recommended in these patients. Patients with diabetes and stages 1 to 4 DKD should be treated with a high-intensity statin or a combination of a statin and ezetimibe.^49,50

Tight glycemic control in T1D and T2D can delay the onset, and slow the progression, of albuminuria and a decline in the eGFR.

If a patient is taking a statin and starting dialysis, it’s important to discuss with him or her whether to continue the statin, based on perceived benefits and risks. It is not recommended that statins be initiated in patients on dialysis unless there is a specific cardiovascular indication for doing so. Risk reduction with a statin has been shown to be significantly less in dialysis patients than in patients who are not being treated with dialysis.⁴⁹

Complications of CKD

Anemia is a common complication of CKD. KDIGO recommends measuring the ­hemoglobin concentration annually in DKD stage 3 patients without anemia; at least every 6 months in stage 4 patients; and at least every 3 months in stage 5. DKD patients with anemia should have additional laboratory testing: the absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate.⁵¹

Mineral and bone disorder should be screened for in patients with DKD. TABLE 2⁵² outlines when clinical laboratory tests should be ordered to assess for mineral bone disease.

When to refer to a nephrologist

Refer patients with stage 4 or 5 CKD (eGFR, ≤ 30 mL/min/1.73 m²) to a nephrologist for discussion of kidney replacement therapy.⁶ Patients with stage 3a CKD and severely increased albuminuria or with stage 3b CKD and moderately or severely increased albuminuria should also be referred to a nephrologist for intervention to delay disease progression.

Continue to: Identifying the need for early referral...

Nutritional control is important in DKD: A lowsodium diet can slow progression of DKD, and a low-potassium diet can prevent hyperkalemia in end-stage renal disease.

Identifying the need for early referral to a nephrologist has been shown to reduce the cost, and improve the quality, of care.⁵³ Other indications for earlier referral include uncertainty about the etiology of renal disease, persistent or severe albuminuria, persistent hematuria, a rapid decline in eGFR, and acute kidney injury. Additionally, referral at an earlier stage of DKD might be needed to assist with complications associated with DKD, such as anemia, secondary hyperparathyroidism, mineral and bone disorder, resistant hypertension, fluid overload, and electrolyte disturbances.⁶

ACKNOWLEDGEMENT
The authors thank Colleen Colbert, PhD, and Iqbal Ahmad, PhD, for their review and critique of the manuscript of this article. They also thank Christopher Babiuch, MD, for his guidance in the preparation of the manuscript.

CORRESPONDENCE
Faraz Ahmad, MD, MPH, Care Point East Family Medicine, 543 Taylor Avenue, 2nd floor, Columbus, OH 43203; faraz. ahmad@osumc.edu.

Chronic kidney disease (CKD) is a significant comorbidity of diabetes mellitus. The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation defines CKD as the presence of kidney damage or decreased kidney function for ≥ 3 months. CKD caused by diabetes is called diabetic kidney disease (DKD), which is 1 of 3 principal microvascular complications of diabetes. DKD can progress to end-stage renal disease (ESRD), requiring kidney replacement therapy, and is the leading cause of CKD and ESRD in the United States.^1-3 Studies have also shown that, particularly in patients with diabetes, CKD considerably increases the risk of cardiovascular events, which often occur prior to ESRD.^1,4

This article provides the latest recommendations for evaluating and managing DKD to help you prevent or slow its progression.

Defining and categorizing diabetic kidney disease

CKD is defined as persistently elevated excretion of urinary albumin (albuminuria) and decreased estimated glomerular filtration rate (eGFR), or as the presence of signs of progressive kidney damage.^5,6 DKD, also known as diabetic nephropathy, is CKD attributed to long-term diabetes. A patient’s eGFR is the established basis for assignment to a stage (1, 2, 3a, 3b, 4, or 5) of CKD (TABLE 1⁷) and, along with the category of albuminuria (A1, A2, or A3), can indicate prognosis.

Taking its toll in diabetes

As many as 40% of patients with diabetes develop DKD.^8-10 Most studies of DKD have been conducted in patients with type 1 diabetes (T1D), because the time of clinical onset is typically known.

Type 1 diabetes. DKD usually occurs 10 to 15 years, or later, after the onset of diabetes.⁶ As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.^5,11 After approximately 22.5 years without albuminuria, patients with T1D have approximately a 1% annual risk of DKD.¹²

Type 2 diabetes (T2D). DKD is often present at diagnosis, likely due to a delay in diagnosis and briefer clinical exposure, compared to T1D. Albuminuria has been reported in as many as 40% of patients with T2D approximately 10 years after onset of diabetes.^12,13

Multiple risk factors with no standout “predictor”

Genetic susceptibility, ethnicity, glycemic control, smoking, blood pressure (BP), and the eGFR have been identified as risk factors for renal involvement in diabetes; obesity, oral contraceptives, and age can also contribute. Although each risk factor increases the risk of DKD, no single factor is adequately predictive. Moderately increased albuminuria, the earliest sign of DKD, is associated with progressive nephropathy.¹²

Continue to: How great is the risk?

How great is the risk? From disease onset to proteinuria and from proteinuria to ESRD, the risk of DKD in T1D and T2D is similar. With appropriate treatment, albuminuria can regress, and the risk of ESRD can be < 20% at 10 years in T1D.¹² As in T1D, good glycemic control might result in regression of albuminuria in T2D.¹⁴

As many as 30% of people with T1D have albuminuria approximately 15 years after onset of diabetes; almost one-half of those develop DKD.

For unknown reasons, the degree of albuminuria can exist independent of the progression of DKD. Factors responsible for a progressive decline in eGFR in DKD without albuminuria are unknown.^12,15

Patient evaluation with an eye toward comorbidities

A comprehensive initial medical evaluation for DKD includes a review of microvascular complications; visits to specialists; lifestyle and behavior patterns (eg, diet, sleep, substance use, and social support); and medication adherence, adverse drug effects, and alternative medicines. Although DKD is often a clinical diagnosis, it can be ruled in by persistent albuminuria or decreased eGFR, or both, in established diabetes or diabetic retinopathy when other causes are unlikely (see “Recommended DKD screening protocol,” below).

Screening for mental health conditions and barriers to self-management is also key.⁶

Comorbidities, of course, can complicate disease management in patients with diabetes.^16-20 Providers and patients therefore need to be aware of potential diabetic comorbidities. For example, DKD and even moderately increased albuminuria significantly increase the risk of cardiovascular disease (CVD).¹² Other possible comorbidities include (but are not limited to) nonalcoholic steatohepatitis, fracture, hearing impairment, cancer (eg, liver, pancreas, endometrium, colon, rectum, breast, and bladder), pancreatitis, hypogonadism, obstructive sleep apnea, periodontal disease, anxiety, depression, and eating disorders.⁶

Continue to: Recommended DKD screening protocol

 

 

Recommended DKD screening protocol

In all cases of T2D, in cases of T1D of ≥ 5 years’ duration, and in patients with diabetes and comorbid hypertension, perform annual screening for albuminuria, an elevated creatinine level, and a decline in eGFR.

Screen for potential comorbidities of DKD: For example, the risk of cardiovascular disease is significantly elevated in even moderately increased albuminuria.

To confirm the diagnosis of DKD, at least 2 of 3 urine specimens must demonstrate an elevated urinary albumin:creatinine ratio (UACR) over a 3- to 6-month period.²¹ Apart from renal damage, exercise within 24 hours before specimen collection, infection, fever, congestive heart failure, hyperglycemia, menstruation, and hypertension can elevate the UACR.⁶

Levels of the UACR are established as follows²²:

• Normal UACR is defined as < 30 milligrams of albumin per gram of creatinine (expressed as “mg/g”).
• Increased urinary albumin excretion is defined as ≥ 30 mg/g.
• Moderately increased albuminuria, a predictor of potential nephropathy, is the excretion of 30 to 300 mg/g.
• Severely increased albuminuria is excretion > 300 mg/g; it is often followed by a gradual decline in eGFR that, without treatment, eventually leads to ESRD.

The rate of decline in eGFR once albuminuria is severely increased is equivalent in T1D and T2D.¹² Without intervention, the time from severely increased albuminuria to ESRD in T1D and T2D averages approximately 6 or 7 years.

Clinical features

DKD is typically a clinical diagnosis seen in patients with longstanding diabetes, albuminuria, retinopathy, or a reduced eGFR in the absence of another primary cause of kidney damage. In patients with T1D and DKD, signs of retinopathy and neuropathy are almost always present at diagnosis, unless a diagnosis is made early in the course of diabetes.¹² Therefore, the presence of retinopathy suggests that diabetes is the likely cause of CKD.

Continue to: The presence of microvascular disease...

The presence of microvascular disease in patients with T2D and DKD is less predictable.¹² In T2D patients who do not have retinopathy, consider causes of CKD other than DKD. Features suggesting that the cause of CKD is an underlying condition other than diabetes are rapidly increasing albuminuria or decreasing eGFR; urinary sediment comprising red blood cells or white blood cells; and nephrotic syndrome.⁶

As the prevalence of diabetes increases, it has become more common to diagnose DKD by eGFR without albuminuria—underscoring the importance of routine monitoring of eGFR in patients with diabetes.⁶

Sources of expert guidance. The Chronic Kidney Disease Epidemiology Collaboration equation²³ is preferred for calculating eGFR from serum creatinine: An eGFR < 60 mL/min/1.73 m² is considered abnormal.^3,12 At these rates, the prevalence of complications related to CKD rises and screening for complications becomes necessary.

A more comprehensive classification of the stages of CKD, incorporating albuminuria and progression of CKD, has been recommended by Kidney Disease: Improving Global Outcomes (KDIGO).⁷ Because eGFR and excretion of albumin vary, abnormal test results need to be verified over time to stage the degree of CKD.^3,12 Kidney damage often manifests as albuminuria, but also as hematuria, other types of abnormal urinary sediment, radiographic abnormalities, and other abnormal presentations.

Management

Nutritional factors

Excessive protein intake has been shown to increase albuminuria, worsen renal function, and increase CVD mortality in DKD.^24-26 Therefore, daily dietary protein intake of 0.8 g/kg body weight is recommended for patients who are not on dialysis.³ Patients on dialysis might require higher protein intake to preserve muscle mass caused by protein-energy wasting, which is common in dialysis patients.⁶

Continue to: Low sodium intake

Low sodium intake in CKD patients has been shown to decrease BP and thus slow the progression of renal disease and lower the risk of CVD. The recommended dietary sodium intake in CKD patients is 1500-3000 mg/d.³

Low potassium intake. Hyperkalemia is a serious complication of CKD. A low-potassium diet is recommended in ESRD patients who have a potassium level > 5.5 mEq/L.⁶

Blood pressure

Preventing and treating hypertension is critical to slowing the progression of CKD and reducing cardiovascular risk. BP should be measured at every clinic visit. Aside from lifestyle changes, medication might be needed to reach target BP.

The American Diabetes Association recommends a BP goal of ≤ 140/90 mm Hg for hypertensive patients with diabetes, although they do state that a lower BP target (≤ 130/80 mm Hg) might be more appropriate for patients with DKD.²⁷

The American College of Cardiology recommends that hypertensive patients with CKD have a BP target of ≤ 130/80 mm Hg.²⁸

Continue to: ACE inhibitors and ARBs

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have renoprotective benefits. These agents are recommended as first-line medications for patients with diabetes, hypertension, and an eGFR < 60 mL/min/1.73 m² and a UACR > 300 mg/g.^29-31 Evidence also supports their use when the UACR is 30 to 299 mg/g.

Studies have shown that, in patients with DKD, ACE inhibitors and ARBs can slow the progression of renal disease.^29,30,32 There is no difference between ACE inhibitors and ARBs in their effectiveness for preventing progression of DKD.⁶ There is no added benefit in combining an ACE inhibitor and an ARB³³; notably, combination ACE inhibitor and ARB therapy can increase the risk of adverse events, such as hyperkalemia and acute kidney injury, especially in patients with DKD.³³

There is no evidence for starting an ACE inhibitor or ARB to prevent CKD in patients with diabetes who are not hypertensive.⁵

ACE inhibitors and ARBs should be used with caution in women of childbearing age, who should use a reliable form of contraception if taking one of these drugs.

Diuretics. Thiazide-type and loop diuretics might potentiate the positive effects of ACE inhibitors and ARBs. KDOQI guidelines recommend that, in patients who require a second agent to control BP, a diuretic should be considered in combination with an ACE inhibitor or an ARB.²⁰ A loop diuretic is preferred if the eGFR is < 30 mL/min/1.73 m².

Continue to: Nondihydropyridine calcium-channel blockers

Nondihydropyridine calcium-channel blockers (CCBs), such as diltiazem and verapamil, have been shown to be more effective then dihydrophyridine CCBs, such as amlodipine and nifedipine, in slowing the progression of renal disease because of their antiproteinuric effects. However, the antiproteinuric effects of nondihydropyridine CCBs are not as strong as those of ACE inhibitors or ARBs, and these drugs do not appear to potentiate the effects of an ACE inhibitor or ARB when used in combination.²⁰

Confirmation of suspected DKD requires an elevated albumin:creatinine ratio in at least 2 of 3 urine specimens over a 3- to 6-month period.

Nondihydropyridine CCBs might be a reasonable alternative in patients who cannot tolerate an ACE inhibitor or an ARB.

Mineralocorticoid receptor antagonists in combination with an ACE inhibitor or ARB have been demonstrated to reduce albuminuria in short-term studies.^34,35

Glycemic levels

Studies conducted in patients with T1D, and others in patients with T2D, have shown that tight glycemic control can delay the onset and slow the progression of albuminuria and a decline in the eGFR.^10,36-39 The target glycated hemoglobin (A1C) should be < 7% to prevent or slow progression of DKD.⁴⁰ However, patients with DKD have an increased risk of hypoglycemic events and increased mortality with more intensive glycemic control.^40,41 Given those findings, some patients with DKD and significant comorbidities, ESRD, or limited life expectancy might need to have an A1C target set at 8%.^6,42

Adjustments to antidiabetes medications in DKD

In patients with stages 3 to 5 DKD, several common antidiabetic medications might need to be adjusted or discontinued because they decrease creatinine clearance.

Continue to: First-generation sulfonylureas

First-generation sulfonylureas should be avoided in DKD. Glipizide and gliclazide are preferred among second-generation sulfonylureas because they do not increase the risk of hypoglycemia in DKD patients, although patients taking these medications still require close monitoring of their blood glucose level.²⁰

Metformin. In 2016, recommendations changed for the use of metformin in patients with DKD: The eGFR, not the serum creatinine level, should guide treatment.⁴³ Metformin can be used safely in patients with (1) an eGFR of < 60 mL/min/1.73 m² and (2) an eGFR of 30 mL/min/1.73 m² with close monitoring. Metformin should not be initiated if the eGFR is < 45 mL/min/1.73 m².⁴³ 

Antidiabetes medications with direct effect on the kidney

Several antidiabetes medications have a direct effect on the kidney apart from their effect on the blood glucose level.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce albuminuria and slow the decrease of eGFR independent of glycemic control. In addition, SGLT2 inhibitors have also been shown to have cardiovascular benefits in patients with DKD.^44,45 

Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to delay and decrease the progression of DKD.^46-48 Also, similar to what is seen with SGLT2 inhibitors, GLP-1 agonists have demonstrable cardiovascular benefit in patients with DKD.^46,48

Continue to: Dyslipidemia and DKD

 

 

Dyslipidemia and DKD

Because the risk of CVD is increased in patients with DKD, addressing other modifiable risk factors, including dyslipidemia, is recommended in these patients. Patients with diabetes and stages 1 to 4 DKD should be treated with a high-intensity statin or a combination of a statin and ezetimibe.^49,50

Tight glycemic control in T1D and T2D can delay the onset, and slow the progression, of albuminuria and a decline in the eGFR.

If a patient is taking a statin and starting dialysis, it’s important to discuss with him or her whether to continue the statin, based on perceived benefits and risks. It is not recommended that statins be initiated in patients on dialysis unless there is a specific cardiovascular indication for doing so. Risk reduction with a statin has been shown to be significantly less in dialysis patients than in patients who are not being treated with dialysis.⁴⁹

Complications of CKD

Anemia is a common complication of CKD. KDIGO recommends measuring the ­hemoglobin concentration annually in DKD stage 3 patients without anemia; at least every 6 months in stage 4 patients; and at least every 3 months in stage 5. DKD patients with anemia should have additional laboratory testing: the absolute reticulocyte count, serum ferritin, serum transferrin saturation, vitamin B12, and folate.⁵¹

Mineral and bone disorder should be screened for in patients with DKD. TABLE 2⁵² outlines when clinical laboratory tests should be ordered to assess for mineral bone disease.

When to refer to a nephrologist

Refer patients with stage 4 or 5 CKD (eGFR, ≤ 30 mL/min/1.73 m²) to a nephrologist for discussion of kidney replacement therapy.⁶ Patients with stage 3a CKD and severely increased albuminuria or with stage 3b CKD and moderately or severely increased albuminuria should also be referred to a nephrologist for intervention to delay disease progression.

Continue to: Identifying the need for early referral...

Nutritional control is important in DKD: A lowsodium diet can slow progression of DKD, and a low-potassium diet can prevent hyperkalemia in end-stage renal disease.

Identifying the need for early referral to a nephrologist has been shown to reduce the cost, and improve the quality, of care.⁵³ Other indications for earlier referral include uncertainty about the etiology of renal disease, persistent or severe albuminuria, persistent hematuria, a rapid decline in eGFR, and acute kidney injury. Additionally, referral at an earlier stage of DKD might be needed to assist with complications associated with DKD, such as anemia, secondary hyperparathyroidism, mineral and bone disorder, resistant hypertension, fluid overload, and electrolyte disturbances.⁶

ACKNOWLEDGEMENT
The authors thank Colleen Colbert, PhD, and Iqbal Ahmad, PhD, for their review and critique of the manuscript of this article. They also thank Christopher Babiuch, MD, for his guidance in the preparation of the manuscript.

CORRESPONDENCE
Faraz Ahmad, MD, MPH, Care Point East Family Medicine, 543 Taylor Avenue, 2nd floor, Columbus, OH 43203; faraz. ahmad@osumc.edu.

Home-based preventive interventions not only improve healthy eating habits and self-regulation in toddlers but also guide their parents toward better food presentation and response to picky behaviors, reported Robert L. Nix, PhD, of the University of Wisconsin, Madison, and his associates.

In a small, randomized controlled trial of 73 families with toddlers aged 18-36 months enrolled in home-based Early Head Start (EHS), the researchers evaluated four protective factors, including toddlers’ healthy eating habits, toddlers’ self-regulation, parents’ responsive feeding practices, and parents’ sensitive scaffolding. The study, conducted from April to October 2013, is the first clinical trial of Recipe 4 Success, a preschool-focused intervention created by administrators and home visitors of EHS that promotes healthy eating and self-regulation in toddlers living in poverty who may otherwise face weight challenges and obesity later in life. Integrating the intervention into EHS allowed the researchers to take full advantage of its national infrastructure and to make dissemination more efficient.

Of the families selected to participate, all of whom were living below the Federal poverty threshold, 66 were retained through post treatment. Most participating parents were biological mothers; 61% were single; 29% were not high school graduates; just 11% were employed full time. The toddlers averaged 30.72 months; 44% were female. Roughly 48% of families were non-Hispanic White; 29% were Black; and 23% were Hispanic or Latinx, the investigators reported in Pediatrics. More than three-quarters of participants were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children or the Supplemental Nutrition Assistance Program.
 

The program allowed parents to transform toddler eating habits quickly

The study, which was designed to evaluate for posttreatment differences in the primary outcomes, involved 10 consecutive weekly lessons implemented by regularly assigned EHS home visitors. Parents were required to adhere to feeding practices carefully targeted with sensitive, structured scaffolding designed to keep toddlers from becoming overwhelmed. Parents were guided to understand, for instance, that toddlers frequently need to be exposed to a new food 10-20 times before eating it, and that poor sleep can have a detrimental influence on emotional and behavioral controls that can progress to weight gain.

Parent recall of what food and drinks their toddlers consumed in the previous 24-hour period was collected by interviewers. The percentage of all meals that included a fruit and/or vegetable, a protein source, and the absence of sweets and junk food were noted. Toddler self-regulation was assessed in accordance with delay of gratification, task orientation, and emotional/behavioral control. Parents were asked to rate toddler ability to cease desired activities to comply with parental requests. Parental responsive feeding practices were also recorded to observe how they introduce unique healthy foods and how they responded to their toddlers’ reactions. Parental sensitive scaffolding was similarly observed for their ability to structure activities in a developmentally appropriate manner promoting self-regulation.

The researchers noted no statistically significant differences between families in the treatment and control groups, nor were there differences in outcome measures or covariates. Study findings showed that, compared with toddlers who continued to receive just EHS support, the toddlers randomly assigned to Recipe 4 Success were more likely to consume snacks and meals that contained fruits, vegetables, protein, and no sweets or junk food.

As the results of this study and others have shown, early food preferences offer the strongest indication of later diet and healthy eating habits throughout life. The program targeted in this study is significant in its ability to accelerate the adoption of better toddler eating habits in just a 10-week period.

Recipe 4 Success along with other successful preventive interventions for young children are most effective when parents drive the change. “In the present trial, the quality of parenting was most highly related to healthy eating habits and self-regulation at baseline,” the researchers noted.

Specifically, the authors attributed the success of the program to “targeting specific interrelated outcomes with an integrated, theoretically driven intervention model,” which allowed Recipe 4 Success to boost the effectiveness of EHS substantially “in just 10 weeks with a minimal increase in funding,” the authors added.

The authors noted several weaknesses as well as strengths of the study. Its primary weakness was a baseline-posttreatment design, which made it impossible to assert that intervention effects can be sustained. The study was also limited to English-speaking families. Given that most home visitors attended to families in both Recipe 4 Success and EHS, the researchers noted the possibility for contamination across conditions, but they added that this would have actually reduced the intervention effects. The study’s primary strength was the evidenced-based nature of the randomized control. That Recipe 4 Success was operated as an intervention only strengthen the benefits of normal EHS visits.
 

Patient parents who promote self-regulation have the best chance of success

“This small study emphasizes the importance of parent education and support in setting the toddlers’ palate for lifelong eating habits and self-regulation,” observed Silver Spring, MD, private practice pediatrician and associate clinical professor of pediatrics at George Washington University, Washington, Lillian M. Beard, MD, in a separate interview.

“With the goal of promoting eating habits and self-regulation, I try to guide parents’ choices of what they offer to their toddler. I applaud parents’ patience as I encourage them not to give in and quickly resort to offering salty or sweet snacks. I suggest that if during the course of a day, a palette of colorful healthy choices is offered, most toddlers will graze independently as they go about their play. The challenge is to really support the parent through this quirky stage of their child’s development,” she explained.

“The ultimate challenge today with so much food insecurity, COVID-19 related job losses, and shrinking dollars to feed families is that too many families are feeling a food crisis! A program such as Recipe 4 Success can provide invaluable education for families on how to best stretch their few dollars, with knowledge of which items to seek from their community food pantries, how to best utilize items from the State WIC programs and still seek nutrition tips from their pediatricians while avoiding expensive fast foods that only offer immediate satiety and gratification. The Recipe 4 Success educator, pediatrician, or any community educator can give recommendations about which fresh produce may be inexpensive, but nutritional,” Dr. Beard suggested.

Dr. Nix and colleagues as well as Dr. Beard had no conflicts of interest and no relevant financial disclosures.
 

Home-based preventive interventions not only improve healthy eating habits and self-regulation in toddlers but also guide their parents toward better food presentation and response to picky behaviors, reported Robert L. Nix, PhD, of the University of Wisconsin, Madison, and his associates.

In a small, randomized controlled trial of 73 families with toddlers aged 18-36 months enrolled in home-based Early Head Start (EHS), the researchers evaluated four protective factors, including toddlers’ healthy eating habits, toddlers’ self-regulation, parents’ responsive feeding practices, and parents’ sensitive scaffolding. The study, conducted from April to October 2013, is the first clinical trial of Recipe 4 Success, a preschool-focused intervention created by administrators and home visitors of EHS that promotes healthy eating and self-regulation in toddlers living in poverty who may otherwise face weight challenges and obesity later in life. Integrating the intervention into EHS allowed the researchers to take full advantage of its national infrastructure and to make dissemination more efficient.

Of the families selected to participate, all of whom were living below the Federal poverty threshold, 66 were retained through post treatment. Most participating parents were biological mothers; 61% were single; 29% were not high school graduates; just 11% were employed full time. The toddlers averaged 30.72 months; 44% were female. Roughly 48% of families were non-Hispanic White; 29% were Black; and 23% were Hispanic or Latinx, the investigators reported in Pediatrics. More than three-quarters of participants were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children or the Supplemental Nutrition Assistance Program.
 

The program allowed parents to transform toddler eating habits quickly

The study, which was designed to evaluate for posttreatment differences in the primary outcomes, involved 10 consecutive weekly lessons implemented by regularly assigned EHS home visitors. Parents were required to adhere to feeding practices carefully targeted with sensitive, structured scaffolding designed to keep toddlers from becoming overwhelmed. Parents were guided to understand, for instance, that toddlers frequently need to be exposed to a new food 10-20 times before eating it, and that poor sleep can have a detrimental influence on emotional and behavioral controls that can progress to weight gain.

Parent recall of what food and drinks their toddlers consumed in the previous 24-hour period was collected by interviewers. The percentage of all meals that included a fruit and/or vegetable, a protein source, and the absence of sweets and junk food were noted. Toddler self-regulation was assessed in accordance with delay of gratification, task orientation, and emotional/behavioral control. Parents were asked to rate toddler ability to cease desired activities to comply with parental requests. Parental responsive feeding practices were also recorded to observe how they introduce unique healthy foods and how they responded to their toddlers’ reactions. Parental sensitive scaffolding was similarly observed for their ability to structure activities in a developmentally appropriate manner promoting self-regulation.

The researchers noted no statistically significant differences between families in the treatment and control groups, nor were there differences in outcome measures or covariates. Study findings showed that, compared with toddlers who continued to receive just EHS support, the toddlers randomly assigned to Recipe 4 Success were more likely to consume snacks and meals that contained fruits, vegetables, protein, and no sweets or junk food.

As the results of this study and others have shown, early food preferences offer the strongest indication of later diet and healthy eating habits throughout life. The program targeted in this study is significant in its ability to accelerate the adoption of better toddler eating habits in just a 10-week period.

Recipe 4 Success along with other successful preventive interventions for young children are most effective when parents drive the change. “In the present trial, the quality of parenting was most highly related to healthy eating habits and self-regulation at baseline,” the researchers noted.

Specifically, the authors attributed the success of the program to “targeting specific interrelated outcomes with an integrated, theoretically driven intervention model,” which allowed Recipe 4 Success to boost the effectiveness of EHS substantially “in just 10 weeks with a minimal increase in funding,” the authors added.

The authors noted several weaknesses as well as strengths of the study. Its primary weakness was a baseline-posttreatment design, which made it impossible to assert that intervention effects can be sustained. The study was also limited to English-speaking families. Given that most home visitors attended to families in both Recipe 4 Success and EHS, the researchers noted the possibility for contamination across conditions, but they added that this would have actually reduced the intervention effects. The study’s primary strength was the evidenced-based nature of the randomized control. That Recipe 4 Success was operated as an intervention only strengthen the benefits of normal EHS visits.
 

Patient parents who promote self-regulation have the best chance of success

“This small study emphasizes the importance of parent education and support in setting the toddlers’ palate for lifelong eating habits and self-regulation,” observed Silver Spring, MD, private practice pediatrician and associate clinical professor of pediatrics at George Washington University, Washington, Lillian M. Beard, MD, in a separate interview.

“With the goal of promoting eating habits and self-regulation, I try to guide parents’ choices of what they offer to their toddler. I applaud parents’ patience as I encourage them not to give in and quickly resort to offering salty or sweet snacks. I suggest that if during the course of a day, a palette of colorful healthy choices is offered, most toddlers will graze independently as they go about their play. The challenge is to really support the parent through this quirky stage of their child’s development,” she explained.

“The ultimate challenge today with so much food insecurity, COVID-19 related job losses, and shrinking dollars to feed families is that too many families are feeling a food crisis! A program such as Recipe 4 Success can provide invaluable education for families on how to best stretch their few dollars, with knowledge of which items to seek from their community food pantries, how to best utilize items from the State WIC programs and still seek nutrition tips from their pediatricians while avoiding expensive fast foods that only offer immediate satiety and gratification. The Recipe 4 Success educator, pediatrician, or any community educator can give recommendations about which fresh produce may be inexpensive, but nutritional,” Dr. Beard suggested.

Dr. Nix and colleagues as well as Dr. Beard had no conflicts of interest and no relevant financial disclosures.
 

Home-based preventive interventions not only improve healthy eating habits and self-regulation in toddlers but also guide their parents toward better food presentation and response to picky behaviors, reported Robert L. Nix, PhD, of the University of Wisconsin, Madison, and his associates.

In a small, randomized controlled trial of 73 families with toddlers aged 18-36 months enrolled in home-based Early Head Start (EHS), the researchers evaluated four protective factors, including toddlers’ healthy eating habits, toddlers’ self-regulation, parents’ responsive feeding practices, and parents’ sensitive scaffolding. The study, conducted from April to October 2013, is the first clinical trial of Recipe 4 Success, a preschool-focused intervention created by administrators and home visitors of EHS that promotes healthy eating and self-regulation in toddlers living in poverty who may otherwise face weight challenges and obesity later in life. Integrating the intervention into EHS allowed the researchers to take full advantage of its national infrastructure and to make dissemination more efficient.

Of the families selected to participate, all of whom were living below the Federal poverty threshold, 66 were retained through post treatment. Most participating parents were biological mothers; 61% were single; 29% were not high school graduates; just 11% were employed full time. The toddlers averaged 30.72 months; 44% were female. Roughly 48% of families were non-Hispanic White; 29% were Black; and 23% were Hispanic or Latinx, the investigators reported in Pediatrics. More than three-quarters of participants were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children or the Supplemental Nutrition Assistance Program.
 

The program allowed parents to transform toddler eating habits quickly

The study, which was designed to evaluate for posttreatment differences in the primary outcomes, involved 10 consecutive weekly lessons implemented by regularly assigned EHS home visitors. Parents were required to adhere to feeding practices carefully targeted with sensitive, structured scaffolding designed to keep toddlers from becoming overwhelmed. Parents were guided to understand, for instance, that toddlers frequently need to be exposed to a new food 10-20 times before eating it, and that poor sleep can have a detrimental influence on emotional and behavioral controls that can progress to weight gain.

Parent recall of what food and drinks their toddlers consumed in the previous 24-hour period was collected by interviewers. The percentage of all meals that included a fruit and/or vegetable, a protein source, and the absence of sweets and junk food were noted. Toddler self-regulation was assessed in accordance with delay of gratification, task orientation, and emotional/behavioral control. Parents were asked to rate toddler ability to cease desired activities to comply with parental requests. Parental responsive feeding practices were also recorded to observe how they introduce unique healthy foods and how they responded to their toddlers’ reactions. Parental sensitive scaffolding was similarly observed for their ability to structure activities in a developmentally appropriate manner promoting self-regulation.

The researchers noted no statistically significant differences between families in the treatment and control groups, nor were there differences in outcome measures or covariates. Study findings showed that, compared with toddlers who continued to receive just EHS support, the toddlers randomly assigned to Recipe 4 Success were more likely to consume snacks and meals that contained fruits, vegetables, protein, and no sweets or junk food.

As the results of this study and others have shown, early food preferences offer the strongest indication of later diet and healthy eating habits throughout life. The program targeted in this study is significant in its ability to accelerate the adoption of better toddler eating habits in just a 10-week period.

Recipe 4 Success along with other successful preventive interventions for young children are most effective when parents drive the change. “In the present trial, the quality of parenting was most highly related to healthy eating habits and self-regulation at baseline,” the researchers noted.

Specifically, the authors attributed the success of the program to “targeting specific interrelated outcomes with an integrated, theoretically driven intervention model,” which allowed Recipe 4 Success to boost the effectiveness of EHS substantially “in just 10 weeks with a minimal increase in funding,” the authors added.

The authors noted several weaknesses as well as strengths of the study. Its primary weakness was a baseline-posttreatment design, which made it impossible to assert that intervention effects can be sustained. The study was also limited to English-speaking families. Given that most home visitors attended to families in both Recipe 4 Success and EHS, the researchers noted the possibility for contamination across conditions, but they added that this would have actually reduced the intervention effects. The study’s primary strength was the evidenced-based nature of the randomized control. That Recipe 4 Success was operated as an intervention only strengthen the benefits of normal EHS visits.
 

Patient parents who promote self-regulation have the best chance of success

“This small study emphasizes the importance of parent education and support in setting the toddlers’ palate for lifelong eating habits and self-regulation,” observed Silver Spring, MD, private practice pediatrician and associate clinical professor of pediatrics at George Washington University, Washington, Lillian M. Beard, MD, in a separate interview.

“With the goal of promoting eating habits and self-regulation, I try to guide parents’ choices of what they offer to their toddler. I applaud parents’ patience as I encourage them not to give in and quickly resort to offering salty or sweet snacks. I suggest that if during the course of a day, a palette of colorful healthy choices is offered, most toddlers will graze independently as they go about their play. The challenge is to really support the parent through this quirky stage of their child’s development,” she explained.

“The ultimate challenge today with so much food insecurity, COVID-19 related job losses, and shrinking dollars to feed families is that too many families are feeling a food crisis! A program such as Recipe 4 Success can provide invaluable education for families on how to best stretch their few dollars, with knowledge of which items to seek from their community food pantries, how to best utilize items from the State WIC programs and still seek nutrition tips from their pediatricians while avoiding expensive fast foods that only offer immediate satiety and gratification. The Recipe 4 Success educator, pediatrician, or any community educator can give recommendations about which fresh produce may be inexpensive, but nutritional,” Dr. Beard suggested.

Dr. Nix and colleagues as well as Dr. Beard had no conflicts of interest and no relevant financial disclosures.
 

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

A version of this article first appeared on Medscape.com.

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

A version of this article first appeared on Medscape.com.

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

A version of this article first appeared on Medscape.com.

In a recent New York Times opinion article, author Aubrey Gordon claims that since a visit to her pediatrician in fourth grade she has felt like an “enemy combatant in the nation’s war on childhood obesity.” (“Leave Fat Kids Alone,” Nov. 13, 2020).

At that unfortunate encounter, she recalls being told that “You’ll be thin and beautiful ... If you can just stay the same weight.” In retrospect she feels that the comment by her well-meaning but misguided physician “planted the seeds of depression” that have plagued her ever since.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

In a recent New York Times opinion article, author Aubrey Gordon claims that since a visit to her pediatrician in fourth grade she has felt like an “enemy combatant in the nation’s war on childhood obesity.” (“Leave Fat Kids Alone,” Nov. 13, 2020).

At that unfortunate encounter, she recalls being told that “You’ll be thin and beautiful ... If you can just stay the same weight.” In retrospect she feels that the comment by her well-meaning but misguided physician “planted the seeds of depression” that have plagued her ever since.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

In a recent New York Times opinion article, author Aubrey Gordon claims that since a visit to her pediatrician in fourth grade she has felt like an “enemy combatant in the nation’s war on childhood obesity.” (“Leave Fat Kids Alone,” Nov. 13, 2020).

At that unfortunate encounter, she recalls being told that “You’ll be thin and beautiful ... If you can just stay the same weight.” In retrospect she feels that the comment by her well-meaning but misguided physician “planted the seeds of depression” that have plagued her ever since.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

For too long, eating disorders have been considered a disease that afflicted mostly affluent white teenage girls, but there really is no type for eating disorders, said Laurie L. Hornberger, MD, MPH, lead author of a new clinical report on eating disorders in children and adolescents prepared by the American Academy of Pediatrics Committee on Adolescence.

FatCamera/E+

In a separate interview with Pediatric News, Dr. Hornberger, associate professor of pediatrics, University of Missouri–Kansas City, explained that eating disorders occur across the spectrum of races, ethnicities, sexes, and socioeconomic statuses, so “getting caught up in that stereotype can cause you to overlook kids with significant problems.” Pediatricians are on the front line in identifying and referring eating disorders for treatment, which is crucial to earlier detection, intervention, and better outcomes, she said.

“Once you become familiar with the signs and symptoms of EDs [eating disorders] and actively start screening for them, you realize how common they are,” she noted, adding that pediatricians should be inquiring routinely about body image, attempts at weight management and what was involved in that weight management. Efforts to restrict calories, limit food choices/groups, exercise excessively, force vomiting, abuse laxatives, etc., are all signs. If the child/adolescent experiences guilt with eating, feels the need to compensate for their eating with exercise or purging, is preoccupied with thoughts of food or calorie counting, feels he/she has lost control of their eating, or experiences uncontrollable binges where they are unable to stop eating despite feeling full and wanting to stop, these are all further evidence of an eating disorder, she added.

There are also physical clues to alert pediatricians. Abrupt or sharp increases or decreases in weight, as measured in growth charts, should be monitored and questioned, Dr. Hornberger cautioned. Physicians should be careful to hold compliments on weight loss until learning how the weight loss was achieved. “Vital signs, such as a resting bradycardia and orthostatic tachycardia, can reflect malnutrition, as can other physical findings. Although lab screening is frequently normal, it should not, by itself, rule out an [eating disorder]. Pediatricians should also be aware of the signs and symptoms of medical instability in an [eating disorder] patient that warrant hospitalization for renourishment,” she explained.
 

Number of eating disorders increased in 2020

Current pandemic conditions have shown an uptick in the number of referrals and long wait lists for eating disorder centers, noted Dr. Hornberger. Having a formal eating disorder treatment program nearby is a luxury not all communities have, so being able to call upon primary care pediatricians to be an active part of a treatment team, which ideally includes a mental health provider and dietitian, both experienced in eating disorders, is pretty important. In coordination with the team, pediatricians are responsible for monitoring physical recovery and remaining alert for signs of struggle to recover and the need for a higher level of care.

In a separate interview with Pediatric News, Margaret Thew, DNP, FNP-BC, medical director of adolescent medicine at the Medical College of Wisconsin, Milwaukee, observed, “COVID-19 has created a surge of children and adolescents struggling with eating disorders. Eating disorder numbers have been associated with social media promoting the avoidance of COVID-19–related weight gain and influencers promoting thin body image. The abrupt end of face-to-face learning, sports participation, and generalized anxiety have further influenced mental health and disordered eating behaviors. Early in the pandemic, the true impact on the psychosocial well-being of children and teens was not known. We are only now seeing the impact months into this pandemic. The timeliness of the American Association of Pediatrics guidelines on the identification and management of children and teens presenting with an eating disorder is pivotal to recognition and treatment,” she said.

“I applaud the AAP for presenting timely guidelines on the evaluation and management of eating disorders for the general pediatrician, yet feel the authors fell short in recognizing the challenges of mitigating management of an eating disorder,” Ms. Thew added.

“Treatment of disordered eating requires all parties to accept the diagnosis and no longer support unhealthy eating patterns. The environment rationalizing the disordered eating may require changes to reduce behaviors and improve nutrition,” she cautioned.
 

New guidelines offer a range of diagnostic and treatment resources

In preparing the current report, the authors included the most recent definitions of eating disorders outlined in the “Diagnostic and Statistical Manual of Mental Disorders,” 5th Edition (DSM-5). Special attention was paid to four classifications of eating disorders in particular – anorexia nervosa (AN), avoidant/restrictive food intake disorder (ARFID); binge-eating disorder (BED); and bulimia nervosa (BN) – because so many disorders are subclassified under these.

Beyond providing a list of comprehensive definitions, the guidance reviews prevalence data for eating disorders, and provides detailed screening, assessment, and laboratory evaluation guidelines. Medical complications, including psychological, neurologic, dermatologic, dental and/or oral, cardiovascular, gastrointestinal, renal and electrolyte, and endocrine effects are discussed in detail as are treatment principles, financial considerations, and prognosis. Besides the important prevention and advocacy roles the authors identify for pediatricians, the guidelines highlight four key areas where pediatricians play a key role in the screening and management of eating disorders, as touched on previously by the guidance authors in this article.

In a separate AAP press release, Margo Lane, MD, coauthor of the report, noted, “As pediatricians, there is much we can also do outside the clinic to advocate for our patients, through legislation and policy that support services, including medical care, nutritional intervention, mental health treatment, and care coordination.” Physicians can also play an important role in reprograming familial and societal attitudes and behaviors by encouraging more positive language that deemphasizes weight and embraces and celebrates kids of all shapes and sizes, added Dr. Lane.

Dr. Hornberger and colleagues as well as Ms. Thew had no conflicts of interest and no relevant financial disclosures.

SOURCE: Pediatrics. 2021;147(1):e2020040279. doi: 10.1542/peds.2020-040279.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Obese women may benefit from a higher dose of magnesium sulfate to protect against preeclampsia, based on data from a randomized trial.

Pharmacokinetic models have shown that, “in women who received a 4-g intravenous loading dose followed by a 2-g/h IV maintenance dose, obese women took approximately twice as long as women of mean body weight in the sample to achieve these previously accepted therapeutic serum magnesium concentrations,” which suggests the need for alternate dosing based on body mass index, wrote Kathleen F. Brookfield, MD, of Oregon Health & Science University, Portland, and colleagues.

In a study published in Obstetrics & Gynecology, the researchers randomized 37 women aged 15-45 years with a BMI of 35 kg/m² or higher who were at least 32 weeks’ gestation to receive the standard Zuspan regimen of magnesium sulfate (4 g intravenous loading dose, followed by a 1-g/hour infusion) or to higher dosing (6 g IV loading dose, followed by a 2-g/hour infusion).
 

Higher dose increases effectiveness

Serum magnesium concentrations were measured at baseline, and after administration of magnesium sulfate at 1 hour, 4 hours, and delivery; the primary outcome was the proportion of women with subtherapeutic serum magnesium concentrations (less than 4.8 mg/dL) 4 hours after administration.

After 4 hours, the average magnesium sulfate concentrations were significantly higher for women in the high-dose group vs. the standard group (4.41 mg/dL vs. 3.53 mg/dL). In addition, 100% of women in the standard group had subtherapeutic serum magnesium concentrations compared with 63% of the high-dose group.

No significant differences in maternal side effects or neonatal outcomes occurred between the groups. However, rates of nausea and flushing were higher in the higher dose group, compared with the standard group (10.5% vs. 5.5% and 5.2% vs. 0%, respectively).

The study findings were limited by several factors including the lack of statistical power to evaluate clinical outcomes and lack of generalizability to extremely obese patients, as well as to settings in which the higher-dose regimen is already the standard treatment, the researchers noted. However, the results were strengthened by the use of prospective pharmacokinetic data to determine dosing.

The researchers also noted that the study was not powered to examine preeclampsia as an outcome “and there is no evidence to date to suggest women in the United States with higher BMIs are more likely to experience eclampsia,” they said. “Therefore, we caution against universally applying the study findings to obese women without also considering the potential for increased toxicity with higher dosing regimens,” they added.

Current results may not affect practice

The study objectives are unclear, as they do not change the dosing for magnesium sulfate already in use, said Baha M. Sibai, MD, of the University of Texas Health Science Center at Houston, in an interview.

Dr. Sibai said he was not surprised by the findings. “This information has been known for almost 30 years as to serum levels with different dosing irrespective of BMI,” he said. Based on current evidence, Dr. Sibai advised clinicians “not to change your practice, since there are no therapeutic levels for preventing seizures.” In fact, “the largest trial that included 10,000 women showed no difference in the rate of eclampsia between 4 grams loading with 1 g/hour [magnesium sulfate] and 6 g loading and 2 g/hour,” he explained.

Future research should focus on different outcomes, said Dr. Sibai. “The outcome should be eclampsia and not serum levels. This requires studying over 6,000 women,” he emphasized.

The study was supported by the National Institutes of Health Loan Repayment Program and a Mission Support Award from Oregon Health & Science University to Dr. Brookfield and by the Oregon Clinical & Translational Research Institute grant. Dr. Brookfield also disclosed funding from the World Health Organization. Dr. Sibai had no financial conflicts to disclose.

SOURCE: Brookfield KF et al. Obstet Gynecol. 2020 Dec. doi: 10.1097/AOG.0000000000004137.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with obesity who lost weight as a result of bariatric surgery and who subsequently contracted COVID-19 were less likely to be admitted to the hospital for COVID, and the disease was less severe than among COVID patients with obesity who had not undergone the surgery, a new retrospective analysis shows.

The research was published in Surgery for Obesity and Related Diseases.

Because obesity is a well-known risk factor for poor COVID-19 outcomes, Ali Aminian, MD, Bariatric and Metabolic Institute, Cleveland Clinic, and colleagues decided to study whether weight-loss surgery had a bearing on outcomes of patients with COVID-19.

They matched 33 COVID-19 patients who had undergone metabolic surgery with 330 control patients with obesity who were infected with the virus during the first wave of the pandemic.

Surgery was associated with a 69% reduction in the risk of being hospitalized as a result of COVID-19. None of the surgery patients required intensive care, mechanical ventilation, or dialysis, and none died.

“Patients after bariatric surgery become significantly healthier and can fight the virus better,” said Dr. Aminian in a statement from his institution. “If confirmed by future studies, this can be added to the long list of health benefits of bariatric surgery.”
 

COVID-19 is a wake-up call for the consequences of obesity

Dr. Aminian said in an interview that COVID-19 is a “wake-up call to show the public and health care professionals that obesity is a major health problem and has multiple health consequences.”

More than 300 articles in the literature show that obesity is a major risk factor for poor outcomes following COVID-19 infection. Dr. Aminian said the pandemic has “improved public awareness about the consequences of obesity.”

Compared with last year at his institution, the intake of new patients “who would like to join a program to have surgery or have some tools to help them to lose weight is almost double,” he noted.

Furthermore, referrals to their unit from primary care physicians, as well as from endocrinologists and cardiologists, for bariatric surgery nearly doubled in recent months.

Although the unit had to stop all bariatric surgeries for around 6 weeks in April because of COVID-19, it has performed the same number of procedures this year as in 2019 and 2018.

Because of the recent surge in COVID cases in Ohio, bariatric procedures are once again on hold. “Elective operations that require hospital beds after surgery have been paused to provide beds for patients who have COVID-19,” he explained.
 

Small sample size, study should be repeated

For their study, Dr. Aminian and colleagues examined the records of 4,365 patients at the Cleveland Clinic Health System who tested positive for the virus between March 8 and July 22, 2020.

Of these, 1,003 had a body mass index of at least 35 mg/kg2; 482 had a BMI of at least 40. The team identified 33 patients who had previously undergone metabolic surgery, comprising 20 sleeve gastrectomies and 13 Roux-en-Y gastric bypasses.

The surgical patients were propensity matched in a 1:10 ratio with nonsurgical control patients with a BMI of at least 40. The patients were matched on the basis of age, sex, ethnicity, location, smoking status, and history of chronic obstructive pulmonary disease.

The mean BMI of surgical patients was 49.1 before their procedure. It fell to 37.2 by the time they tested positive for COVID-19. This compares with an average of 46.7 in the control group at the time they tested positive for the virus.

The team found that 18.2% of metabolic surgery patients were admitted to hospital versus 42.1% of control patients (P = .013).

Moreover, metabolic surgery patients did not require admission to the intensive care unit, nor did they require mechanical ventilation or dialysis, and none died. This compares with 13.0% (P = .021), 6.7% (P = .24), 1.5%, and 2.4%, respectively, of patients in the control group.

Multivariate analysis indicated that prior metabolic surgery was associated with lower hospital admission, at an odds ratio of 0.31 (P = .028), in comparison with control patients with obesity.

Acknowledging the limited sample size of their study, the team wrote: “As this study reflects findings early in the course of the pandemic, it will be of interest to repeat this study with larger data sets and later in the course of the pandemic.”
 

Continue as many aspects of obesity management as possible during pandemic

Dr. Aminian underlined that, for him, the take-home message from the study is that health care professionals should “ideally” continue all aspects of obesity management during the pandemic, including “medical management, behavioral therapy, lifestyle changes, and access to bariatric surgery.”

This is despite the fact that insurance coverage for bariatric surgery has “always been a challenge for many patients, since many insurance plans do not cover” bariatric procedures, he noted.

In July, the American Society for Metabolic and Bariatric Surgery issued a statement declaring that obesity surgery should not be considered an elective procedure and should be resumed as soon as it’s safe to do so during any resurgence of the COVID-19 pandemic.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with obesity who lost weight as a result of bariatric surgery and who subsequently contracted COVID-19 were less likely to be admitted to the hospital for COVID, and the disease was less severe than among COVID patients with obesity who had not undergone the surgery, a new retrospective analysis shows.

The research was published in Surgery for Obesity and Related Diseases.

Because obesity is a well-known risk factor for poor COVID-19 outcomes, Ali Aminian, MD, Bariatric and Metabolic Institute, Cleveland Clinic, and colleagues decided to study whether weight-loss surgery had a bearing on outcomes of patients with COVID-19.

They matched 33 COVID-19 patients who had undergone metabolic surgery with 330 control patients with obesity who were infected with the virus during the first wave of the pandemic.

Surgery was associated with a 69% reduction in the risk of being hospitalized as a result of COVID-19. None of the surgery patients required intensive care, mechanical ventilation, or dialysis, and none died.

“Patients after bariatric surgery become significantly healthier and can fight the virus better,” said Dr. Aminian in a statement from his institution. “If confirmed by future studies, this can be added to the long list of health benefits of bariatric surgery.”
 

COVID-19 is a wake-up call for the consequences of obesity

Dr. Aminian said in an interview that COVID-19 is a “wake-up call to show the public and health care professionals that obesity is a major health problem and has multiple health consequences.”

More than 300 articles in the literature show that obesity is a major risk factor for poor outcomes following COVID-19 infection. Dr. Aminian said the pandemic has “improved public awareness about the consequences of obesity.”

Compared with last year at his institution, the intake of new patients “who would like to join a program to have surgery or have some tools to help them to lose weight is almost double,” he noted.

Furthermore, referrals to their unit from primary care physicians, as well as from endocrinologists and cardiologists, for bariatric surgery nearly doubled in recent months.

Although the unit had to stop all bariatric surgeries for around 6 weeks in April because of COVID-19, it has performed the same number of procedures this year as in 2019 and 2018.

Because of the recent surge in COVID cases in Ohio, bariatric procedures are once again on hold. “Elective operations that require hospital beds after surgery have been paused to provide beds for patients who have COVID-19,” he explained.
 

Small sample size, study should be repeated

For their study, Dr. Aminian and colleagues examined the records of 4,365 patients at the Cleveland Clinic Health System who tested positive for the virus between March 8 and July 22, 2020.

Of these, 1,003 had a body mass index of at least 35 mg/kg2; 482 had a BMI of at least 40. The team identified 33 patients who had previously undergone metabolic surgery, comprising 20 sleeve gastrectomies and 13 Roux-en-Y gastric bypasses.

The surgical patients were propensity matched in a 1:10 ratio with nonsurgical control patients with a BMI of at least 40. The patients were matched on the basis of age, sex, ethnicity, location, smoking status, and history of chronic obstructive pulmonary disease.

The mean BMI of surgical patients was 49.1 before their procedure. It fell to 37.2 by the time they tested positive for COVID-19. This compares with an average of 46.7 in the control group at the time they tested positive for the virus.

The team found that 18.2% of metabolic surgery patients were admitted to hospital versus 42.1% of control patients (P = .013).

Moreover, metabolic surgery patients did not require admission to the intensive care unit, nor did they require mechanical ventilation or dialysis, and none died. This compares with 13.0% (P = .021), 6.7% (P = .24), 1.5%, and 2.4%, respectively, of patients in the control group.

Multivariate analysis indicated that prior metabolic surgery was associated with lower hospital admission, at an odds ratio of 0.31 (P = .028), in comparison with control patients with obesity.

Acknowledging the limited sample size of their study, the team wrote: “As this study reflects findings early in the course of the pandemic, it will be of interest to repeat this study with larger data sets and later in the course of the pandemic.”
 

Continue as many aspects of obesity management as possible during pandemic

Dr. Aminian underlined that, for him, the take-home message from the study is that health care professionals should “ideally” continue all aspects of obesity management during the pandemic, including “medical management, behavioral therapy, lifestyle changes, and access to bariatric surgery.”

This is despite the fact that insurance coverage for bariatric surgery has “always been a challenge for many patients, since many insurance plans do not cover” bariatric procedures, he noted.

In July, the American Society for Metabolic and Bariatric Surgery issued a statement declaring that obesity surgery should not be considered an elective procedure and should be resumed as soon as it’s safe to do so during any resurgence of the COVID-19 pandemic.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with obesity who lost weight as a result of bariatric surgery and who subsequently contracted COVID-19 were less likely to be admitted to the hospital for COVID, and the disease was less severe than among COVID patients with obesity who had not undergone the surgery, a new retrospective analysis shows.

The research was published in Surgery for Obesity and Related Diseases.

Because obesity is a well-known risk factor for poor COVID-19 outcomes, Ali Aminian, MD, Bariatric and Metabolic Institute, Cleveland Clinic, and colleagues decided to study whether weight-loss surgery had a bearing on outcomes of patients with COVID-19.

They matched 33 COVID-19 patients who had undergone metabolic surgery with 330 control patients with obesity who were infected with the virus during the first wave of the pandemic.

Surgery was associated with a 69% reduction in the risk of being hospitalized as a result of COVID-19. None of the surgery patients required intensive care, mechanical ventilation, or dialysis, and none died.

“Patients after bariatric surgery become significantly healthier and can fight the virus better,” said Dr. Aminian in a statement from his institution. “If confirmed by future studies, this can be added to the long list of health benefits of bariatric surgery.”
 

COVID-19 is a wake-up call for the consequences of obesity

Dr. Aminian said in an interview that COVID-19 is a “wake-up call to show the public and health care professionals that obesity is a major health problem and has multiple health consequences.”

More than 300 articles in the literature show that obesity is a major risk factor for poor outcomes following COVID-19 infection. Dr. Aminian said the pandemic has “improved public awareness about the consequences of obesity.”

Compared with last year at his institution, the intake of new patients “who would like to join a program to have surgery or have some tools to help them to lose weight is almost double,” he noted.

Furthermore, referrals to their unit from primary care physicians, as well as from endocrinologists and cardiologists, for bariatric surgery nearly doubled in recent months.

Although the unit had to stop all bariatric surgeries for around 6 weeks in April because of COVID-19, it has performed the same number of procedures this year as in 2019 and 2018.

Because of the recent surge in COVID cases in Ohio, bariatric procedures are once again on hold. “Elective operations that require hospital beds after surgery have been paused to provide beds for patients who have COVID-19,” he explained.
 

Small sample size, study should be repeated

For their study, Dr. Aminian and colleagues examined the records of 4,365 patients at the Cleveland Clinic Health System who tested positive for the virus between March 8 and July 22, 2020.

Of these, 1,003 had a body mass index of at least 35 mg/kg2; 482 had a BMI of at least 40. The team identified 33 patients who had previously undergone metabolic surgery, comprising 20 sleeve gastrectomies and 13 Roux-en-Y gastric bypasses.

The surgical patients were propensity matched in a 1:10 ratio with nonsurgical control patients with a BMI of at least 40. The patients were matched on the basis of age, sex, ethnicity, location, smoking status, and history of chronic obstructive pulmonary disease.

The mean BMI of surgical patients was 49.1 before their procedure. It fell to 37.2 by the time they tested positive for COVID-19. This compares with an average of 46.7 in the control group at the time they tested positive for the virus.

The team found that 18.2% of metabolic surgery patients were admitted to hospital versus 42.1% of control patients (P = .013).

Moreover, metabolic surgery patients did not require admission to the intensive care unit, nor did they require mechanical ventilation or dialysis, and none died. This compares with 13.0% (P = .021), 6.7% (P = .24), 1.5%, and 2.4%, respectively, of patients in the control group.

Multivariate analysis indicated that prior metabolic surgery was associated with lower hospital admission, at an odds ratio of 0.31 (P = .028), in comparison with control patients with obesity.

Acknowledging the limited sample size of their study, the team wrote: “As this study reflects findings early in the course of the pandemic, it will be of interest to repeat this study with larger data sets and later in the course of the pandemic.”
 

Continue as many aspects of obesity management as possible during pandemic

Dr. Aminian underlined that, for him, the take-home message from the study is that health care professionals should “ideally” continue all aspects of obesity management during the pandemic, including “medical management, behavioral therapy, lifestyle changes, and access to bariatric surgery.”

This is despite the fact that insurance coverage for bariatric surgery has “always been a challenge for many patients, since many insurance plans do not cover” bariatric procedures, he noted.

In July, the American Society for Metabolic and Bariatric Surgery issued a statement declaring that obesity surgery should not be considered an elective procedure and should be resumed as soon as it’s safe to do so during any resurgence of the COVID-19 pandemic.

The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.