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SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
SAN FRANCISCO – and by the time those with youth-onset diabetes reach their early 20s, they are beset with disease-related complications usually seen in older populations, findings from the RISE and TODAY2 studies have demonstrated.
“Additional research is urgently needed to better understand the reasons for this more serious trajectory,” Philip Zeitler, MD, PhD, of Children’s Hospital Colorado, Aurora, said at the annual scientific sessions of the American Diabetes Association. The hope is to identify at-risk children and prevent the disease, but at this point “we don’t know the answer.”
In the meantime, “we are getting more aggressive with bariatric surgery at our center, because nothing else is working as well. It would be nice to move away from that, but these kids are going to die,” he added.
Steven Kahn, MD, of the diabetes Research Center at the University of Washington, Seattle, presented the findings from a comparison of outcomes from the Restoring Insulin Secretion (RISE) studies in adolescents aged 10-19 years and in adults. The RISE Pediatric Medication Study (Diabetes Care. 2018; 41[8]:1717-25) and RISE Adult Medication Study were parallel investigations treatments to preserve or improve beta-cell function.
“This is the first-ever true comparison of outcomes in youth versus adults,” he said. Both arms had the same design and lab measurements, but the differences in outcomes were “very scary,” he added. “The disease is much more aggressive in youth than in adults.”
Among other things, the RISE youth-versus-adult study compared the outcomes after 3 months of insulin glargine followed by 9 months of metformin, or 12 months of metformin in 132 obese adults and 91 obese adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes. The treatments were stopped after 12 months, and the participants were reevaluated at 15 months. Hyperglycemic clamps were conducted at baseline, 12 months, and 3 months after treatment cessation (Diabetes. 2019 Jun 9. doi: 10.2337/db19-0299).
In adults, treatment improved insulin sensitivity and beta-cell response, but after treatment cessation, they reverted to baseline by the 15-month evaluation. However, there was no improvement in insulin sensitivity and beta-cell response in adolescents, either during treatment or after cessation, and in fact, they were worse off at 15 months than they had been at baseline, with lower insulin secretion and higher hemoglobin A1c.
Those stark differences in outcomes between the adolescents and adults were indicative of a more aggressive disease trajectory for younger patients.
Compliance was not the issue, with more than 80% of both adults and children taking more than 80% of their medications, Dr. Kahn said.
He suggested that adolescents might have a different underlying pathology that makes it worse to develop diabetes during puberty, which is already an insulin-resistant state. But, whatever the case, there is an “urgent need” to better understand the differences between adolescents and adults and to find better treatments for younger patients with diabetes, he said.
In regard to using weight loss as a means of treatment or prevention, Dr. Zeitler emphasized that type 2 diabetes in younger patients “occurs in a context of very low socioeconomic status, family dysfunction, and a great deal of stress and [family] illness. It’s often a complex situation and it’s difficult to accomplish effective lifestyle change when families are struggling to have afford quality food, facing challenges of family and neighborhood violence, and working multiple jobs.”
The RISE findings of a more aggressive deterioration in beta-cell function for younger patients were reflected in outcomes in the TODAY2 study, which found that adolescents who are diagnosed with type 2 diabetes face severe renal, cardiovascular, eye, and nerve complications by the time they reach their early 20s.
TODAY2 was an 8-year follow-up to the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial published in 2012 (N Engl J Med. 2012;366:2247-56). Data from the original study of patients aged 10-17 years with type 2 diabetes showed that after a roughly 4-year follow-up, almost half of all participants had experienced loss of glycemic control on their original treatment assignment, a rate much higher than that reported in adults. Metformin plus rosiglitazone was superior to metformin alone in maintaining durable glycemic control and metformin plus an intensive lifestyle intervention was intermediate to the other groups, but not significantly different from them. In addition, metformin alone was found to be least effective in non-Hispanic black patients, metformin and rosiglitazone was most effective in girls.
Overall, 517 participants of the original study’s 669 participants are still being followed as part of the TODAY2 trial. They are managed in community practices now and are in their early 20s, on average.
But, less than 10 years down the road from TODAY, the young adults “have problems you’d expect in your grandparents. Target-organ damage is already evident, and serious cardiovascular events are occurring,” Dr. Zeitler said.
Cardiovascular complications
The cardiovascular event rate in TODAY 2 was about the same as is seen in older adults with type 1 diabetes. Overall, there were 38 cardiovascular events in 19 patients for an event rate of 6.4/1,000 patients per year. Those events included heart failure, arrhythmia, coronary artery disease or myocardial infarction, deep venous thrombosis, stroke or transient ischemic attack, and vascular insufficiency.
Over that time, the cumulative incidence of elevated LDL cholesterol increased from 3% in the TODAY report to 26% for TODAY2, and for triglycerides, it went from 18% to 35%. The cumulative incidence of hypertension increased from 19% to 55%.
Decline renal function
In regard to renal complications, the cumulative incident curve for microalbuminuria went from 8% at baseline to 40% at 12 years, while macroalbuminuria prevalence increased from 1.5% to 11% during the same time. The cumulative incidence of hyperfiltration increased from 12% to 48%. Risk factors for hyperfiltration included female sex, Hispanic ethnicity, loss of glycemic control, and hypertension, although body mass index was actually associated with lower risk.
So far, there have been four renal events in two patients, who both had chronic kidney disease and end-stage renal failure, for an event rate of 0.7/1,000 patients per year.
Pregnancy outcomes
Women in the cohort – about two-thirds of the study population – have had high rates of maternal complications, and their offspring also face complications after birth.
There were 306 pregnancies reported, of which there are known outcomes for 53 (TODAY) and 236 (TODAY2). In all, 5% of the total cohort had voluntary elective termination; 9% and 12% of patients, respectively, suffered a miscarriage before 20 weeks; and 4% of pregnancies in the total cohort ended in stillbirth.
Preterm live births more than doubled from 11% to 24%, and full-term deliveries decreased from 62% to 46% in the TODAY2 patients.
In regard to offspring characteristics, average birth weight in the total cohort was just over 4.5 pounds (national average, 7.3 pounds), and the prevalence of very low birth weight more than doubled from 8% to 16% at the 12-year mark. The prevalence of macrosomia was 19% for the cohort, more than double the national average of 8%. In all, 5% and 7% of offspring were small for gestational age, whereas 22% and 26% of offspring were large for gestational age.
Among other complications, respiratory distress occurred in 8% and 14% of offspring, and cardiac anomalies occurred in 10% and 9%, which, although they held steady across the cohorts, were significantly higher than the national average of 1%. Similarly, neonatal hypoglycemia occurred in 17% and 29% of offspring, again, notably higher than the national average of 2%. Offspring outcomes were worse in mothers with loss of glycemic control.
In regard to maternal pregnancy complications, the rate of hospitalization before delivery increased from 25% to 36%; hypertension increased in prevalence from 19% to 36%; and while macroalbuminuria held steady at 9.4%, microalbuminuria increased from 6% to 8%. Thirty-three percent of the TODAY2 cohort had a hemoglobin A1c level of more than 8%.
Retinopathy
Serious eye problems were common, with notable progression seen in diabetic retinopathy in patients who had fundus photos taken in 2011 (TODAY) and 2018 (TODAY2). Among the patients, 86% and 51%, respectively, of 371 patients had no definitive diabetic retinopathy; 14% and 22% of patients had very mild nonproliferative diabetic retinopathy (NPDR); and 0% and 16% of patients had mild NPDR. None of the TODAY patients had early or high-risk proliferative diabetic retinopathy, compared with 3% and 1%, respectively, in TODAY2. Risk factors included loss of glycemic control (hazard ratio, 19.23; 95% confidence interval, 4.62-80.07).
None of the TODAY patients had macular edema, whereas it occurred in 4% of TODAY2 patients. In all, there were 142 adjudicated eye-related events reported for 92 patients, for an event rate of 15.5/1,000 patients per year. The events included NPDR, proliferative diabetic retinopathy, macular edema, cataracts, glaucoma, and vitreous hemorrhage).
Neuropathy
The prevalence of diabetic neuropathy also increased over the duration of follow-up, rising to 28%-33% based on Michigan Neuropathy Screening Instrument scores. There were 14 adjudicated events reported for 12 patients (2.4 events/1,000 patients per year), including peripheral diabetic neuropathy, autonomic neuropathy, and diabetic mononeuropathy.
“We’ve had a number of amputations; quite a number of toes are now missing in this group of kids,” Dr. Zeitler said.
There have been five deaths so far: one heart attack, one renal failure, one overwhelming sepsis, one postop cardiac arrest, and a drug overdose.
Dr. Zeitler was the senior author on 2018 updated ADA guidelines for managing youth-onset type 2 diabetes. The recommendations where extensively shaped by the TODAY findings and were more aggressive than those previously put forward, suggesting, among other things, hemoglobin A1c targets of 6.5%-7%; earlier treatment with insulin; and stricter management of hypertension, dyslipidemia, and proteinuria (Diabetes Care. 2018;41[12]:2648-68).
The National Institute of Diabetes & Kidney disease funded the studies. The presenters reported no relevant disclosures or conflicts of interest.
This article was updated 7/22/19.
EXPERT ANALYSIS FROM ADA 2019