Jeff Evans

PRAGUE — Elective cesarean sections that are carried out near the end of term may be more likely to result in neonatal respiratory morbidity than planned vaginal births, Dr. Anne Kirkeby Hansen reported at the 20th European Congress of Perinatal Medicine.

Using data from the prospective Århus Birth Cohort, Dr. Hansen and her colleagues identified 2,438 singleton neonates born in 1998–2005 by elective cesarean section at a gestational age of greater than 36 weeks.

Overall, 403 (17%) of these infants had respiratory morbidity classified as respiratory distress syndrome, transient tachypnea of the newborn, or persistent pulmonary hypertension of the newborn, said Dr. Hansen of the Perinatal Epidemiology Research Unit at Århus (Denmark) University Hospital.

Respiratory morbidity occurred significantly more often among infants who were delivered by elective C-section at 37 weeks (4.5%) or 38 weeks (3.4%) than among those who were born via an intended vaginal delivery (1.4% and 1%, respectively). The relative risk of respiratory morbidity was 3.2 and 3.6 times higher if an elective C-section was performed at those gestational ages instead of an intended vaginal delivery, which included deliveries by vacuum, forceps, and emergency C-section.

Elective C-section at 37 weeks was associated with a significant, nearly sixfold higher relative risk of respiratory morbidity than among infants born by intended vaginal delivery at a gestational age of 40 weeks, 0.8% of whom had respiratory morbidity. The relative risk of respiratory morbidity for those born by C-section at 38 weeks was 4.4 times higher than that of neonates who were intended to be born vaginally.

Infants born by elective C-section at 37 weeks were 3.6 times more likely and those born at 38 weeks were 2.7 times more likely to have respiratory morbidity than infants born by elective C-section at 39 weeks.

The incidence of respiratory morbidity did not differ significantly between neonates in either category at a gestational age of 39 or 40 weeks.

“Both way of delivery and timing of elective cesarean section influence the risk of respiratory morbidity,” Dr. Hansen said.

“These results indicate that elective cesarean section is associated with an increased risk of respiratory morbidity regardless of gestational age. Timing of elective C-section is crucial as the risk of respiratory morbidity increases with decreasing gestational age,” she said.

PRAGUE — Elective cesarean sections that are carried out near the end of term may be more likely to result in neonatal respiratory morbidity than planned vaginal births, Dr. Anne Kirkeby Hansen reported at the 20th European Congress of Perinatal Medicine.

Using data from the prospective Århus Birth Cohort, Dr. Hansen and her colleagues identified 2,438 singleton neonates born in 1998–2005 by elective cesarean section at a gestational age of greater than 36 weeks.

Overall, 403 (17%) of these infants had respiratory morbidity classified as respiratory distress syndrome, transient tachypnea of the newborn, or persistent pulmonary hypertension of the newborn, said Dr. Hansen of the Perinatal Epidemiology Research Unit at Århus (Denmark) University Hospital.

Respiratory morbidity occurred significantly more often among infants who were delivered by elective C-section at 37 weeks (4.5%) or 38 weeks (3.4%) than among those who were born via an intended vaginal delivery (1.4% and 1%, respectively). The relative risk of respiratory morbidity was 3.2 and 3.6 times higher if an elective C-section was performed at those gestational ages instead of an intended vaginal delivery, which included deliveries by vacuum, forceps, and emergency C-section.

Elective C-section at 37 weeks was associated with a significant, nearly sixfold higher relative risk of respiratory morbidity than among infants born by intended vaginal delivery at a gestational age of 40 weeks, 0.8% of whom had respiratory morbidity. The relative risk of respiratory morbidity for those born by C-section at 38 weeks was 4.4 times higher than that of neonates who were intended to be born vaginally.

Infants born by elective C-section at 37 weeks were 3.6 times more likely and those born at 38 weeks were 2.7 times more likely to have respiratory morbidity than infants born by elective C-section at 39 weeks.

The incidence of respiratory morbidity did not differ significantly between neonates in either category at a gestational age of 39 or 40 weeks.

“Both way of delivery and timing of elective cesarean section influence the risk of respiratory morbidity,” Dr. Hansen said.

“These results indicate that elective cesarean section is associated with an increased risk of respiratory morbidity regardless of gestational age. Timing of elective C-section is crucial as the risk of respiratory morbidity increases with decreasing gestational age,” she said.

PRAGUE — Elective cesarean sections that are carried out near the end of term may be more likely to result in neonatal respiratory morbidity than planned vaginal births, Dr. Anne Kirkeby Hansen reported at the 20th European Congress of Perinatal Medicine.

Using data from the prospective Århus Birth Cohort, Dr. Hansen and her colleagues identified 2,438 singleton neonates born in 1998–2005 by elective cesarean section at a gestational age of greater than 36 weeks.

Overall, 403 (17%) of these infants had respiratory morbidity classified as respiratory distress syndrome, transient tachypnea of the newborn, or persistent pulmonary hypertension of the newborn, said Dr. Hansen of the Perinatal Epidemiology Research Unit at Århus (Denmark) University Hospital.

Respiratory morbidity occurred significantly more often among infants who were delivered by elective C-section at 37 weeks (4.5%) or 38 weeks (3.4%) than among those who were born via an intended vaginal delivery (1.4% and 1%, respectively). The relative risk of respiratory morbidity was 3.2 and 3.6 times higher if an elective C-section was performed at those gestational ages instead of an intended vaginal delivery, which included deliveries by vacuum, forceps, and emergency C-section.

Elective C-section at 37 weeks was associated with a significant, nearly sixfold higher relative risk of respiratory morbidity than among infants born by intended vaginal delivery at a gestational age of 40 weeks, 0.8% of whom had respiratory morbidity. The relative risk of respiratory morbidity for those born by C-section at 38 weeks was 4.4 times higher than that of neonates who were intended to be born vaginally.

Infants born by elective C-section at 37 weeks were 3.6 times more likely and those born at 38 weeks were 2.7 times more likely to have respiratory morbidity than infants born by elective C-section at 39 weeks.

The incidence of respiratory morbidity did not differ significantly between neonates in either category at a gestational age of 39 or 40 weeks.

“Both way of delivery and timing of elective cesarean section influence the risk of respiratory morbidity,” Dr. Hansen said.

“These results indicate that elective cesarean section is associated with an increased risk of respiratory morbidity regardless of gestational age. Timing of elective C-section is crucial as the risk of respiratory morbidity increases with decreasing gestational age,” she said.

SAN FRANCISCO — Few morbidly obese adolescents are referred for bariatric surgery, despite the high rate of failure with conservative interventions. But short-term outcomes and compliance in teens undergoing Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or biliopancreatic diversion are as good as those of older patients, according to findings from a series of small retrospective studies presented at the annual meeting of the American Society for Bariatric Surgery.

Those who object to doing bariatric surgery in adolescents question “whether teenagers will comply with the treatment regimen,” said Dr. George A. Fielding of the surgical weight loss program at New York University, New York. “It's been postulated that kids won't do this just by the nature of being a teenager.”

While in Dr. Fielding's care at the NYU Medical Center, 81 adolescents have received laparoscopic adjustable gastric banding (LAGB). Five of the patients were aged 12–13 years, 55 were aged 14–17 years, and 21 were aged 18–19 years. Most (60) were girls and weighed an average of 137 kg with a mean body mass index (BMI) of 48 kg/m

After 1 year of follow-up in 32 patients, the patients lost 57% of their excess weight on average and had a mean BMI of 34. All comorbidities were resolved, except for two patients who needed to maintain antidepressant therapy.

Banding adjustments at follow-up visits is a “key issue to the management of all LAGB patients, and it's no different with children,” Dr. Fielding pointed out.

During the first year of follow-up in 27 patients aged 14–17 years, an average of 6.5 banding adjustments were made during 10 visits. This led to an average of 64% excess weight lost; only 2 of these 27 patients lost less than 50% of their excess weight, Dr. Fielding said.

Most patients reported that they were much less hungry and were eating a substantially smaller volume of food than they had been preoperatively. Very few had a desire to binge eat, he said.

The decision to undergo LAGB had been made mostly by the adolescents rather than by their parents, Dr. Fielding said. When performing LAGB in adolescents in Australia and in New York, he has taken a hands-off approach. “If you tell teenagers they can do pretty much what they like, they'll rear back in shock and usually do what you ask them to,” he said.

In a separate report, Dr. Jose S. Pinheiro of the Hospital São Camilo, São Paulo, Brazil, reviewed his center's experience in performing laparoscopic Roux-en-Y gastric bypass surgery in 49 adolescents with a mean age of 16 years. The patients, 35 of whom were male, all received preoperative psychiatric evaluations and had full parental support.

The laparoscopic RYGBs involved an antecolic, antegastric approach and used a 50-cm biliary limb and a 150-cm alimentary limb. No patients died or had complications during surgery, and their average hospital stay was 30 hours.

The patients' mean BMI dropped from 45 before surgery to 23.5 at a mean follow-up of 48 months. All obesity-related comorbidities resolved after surgery.

Dr. Pinheiro and his colleagues are still collecting quality of life data, but he said that all of the patients are happy with the surgery and are committed to becoming healthier. “The patients were extremely compliant with treatment,” Dr. Pinheiro said, noting that all of them exercised on a regular basis. “Gastric bypass should be offered as an option in the treatment of obese adolescents,” he added.

When adolescents are referred for bariatric surgery, they are usually offered a restrictive procedure, said Dr. Francesco S. Papadia of the department of surgery at the University of Genoa (Italy). Malabsorptive procedures such as biliopancreatic diversion (BPD) are “considered unsuitable a priori despite the lack of any evidence” against its safety or effectiveness in adolescents.

During 1976–2005, 76 adolescents received BPD surgery at the University of Genoa. Excluding 7 patients with Prader-Willi syndrome and 1 with Turner's syndrome, the remaining 68 had a mean of 11 years of follow-up, ranging from 2 to 23 years. On average, the patients were nearly 17 years of age at the time of the operation, weighed 125 kg, and had a BMI of 46. No patients died during surgery, and one had a wound dehiscence.

At their longest point of follow-up, patients lost a mean of 78% of their excess weight. Four patients lost less than 50% of excess weight. Of those, three underwent a revision and one was converted from a vertical banded gastroplasty with a preoperative BMI of 26.

Obesity-related comorbidities resolved in a significant percentage of patients; hypertension was reduced from 49% to 9%, dyslipidemia from 16% to 0%, and glucose-intolerant or type 2 diabetes from 7% to 0%.

Twelve patients developed protein malnutrition at some point 1–10 years after surgery, and two patients had recurrent protein malnutrition. Those who experienced protein malnutrition after surgery had significantly higher initial body weight and BMI than did those who did not have malnutrition.

The incidence of protein malnutrition decreased steadily during the 30-year period of the study from 30% in the first few years to 2% in the last few years. The length of the common limb remained 50 cm, but as the surgeons gained experience, they adapted alimentary limb lengths to individual characteristics, and gastric sizes were not restricted to prevent protein malnutrition, Dr. Papadia said.

In a range of 4–18 years after BPD surgery, 18 women gave birth to 28 healthy infants. One infant was mentally retarded. Another two women died of severe protein malnutrition at the end of their pregnancies.

A total of 19 reoperations were performed in 14 patients, including 5 elongations and 2 restorations. Overall, three patients in the cohort died (4%)—two from protein malnutrition during pregnancy and one from acute pancreatitis.

SAN FRANCISCO — Few morbidly obese adolescents are referred for bariatric surgery, despite the high rate of failure with conservative interventions. But short-term outcomes and compliance in teens undergoing Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or biliopancreatic diversion are as good as those of older patients, according to findings from a series of small retrospective studies presented at the annual meeting of the American Society for Bariatric Surgery.

Those who object to doing bariatric surgery in adolescents question “whether teenagers will comply with the treatment regimen,” said Dr. George A. Fielding of the surgical weight loss program at New York University, New York. “It's been postulated that kids won't do this just by the nature of being a teenager.”

While in Dr. Fielding's care at the NYU Medical Center, 81 adolescents have received laparoscopic adjustable gastric banding (LAGB). Five of the patients were aged 12–13 years, 55 were aged 14–17 years, and 21 were aged 18–19 years. Most (60) were girls and weighed an average of 137 kg with a mean body mass index (BMI) of 48 kg/m

After 1 year of follow-up in 32 patients, the patients lost 57% of their excess weight on average and had a mean BMI of 34. All comorbidities were resolved, except for two patients who needed to maintain antidepressant therapy.

Banding adjustments at follow-up visits is a “key issue to the management of all LAGB patients, and it's no different with children,” Dr. Fielding pointed out.

During the first year of follow-up in 27 patients aged 14–17 years, an average of 6.5 banding adjustments were made during 10 visits. This led to an average of 64% excess weight lost; only 2 of these 27 patients lost less than 50% of their excess weight, Dr. Fielding said.

Most patients reported that they were much less hungry and were eating a substantially smaller volume of food than they had been preoperatively. Very few had a desire to binge eat, he said.

The decision to undergo LAGB had been made mostly by the adolescents rather than by their parents, Dr. Fielding said. When performing LAGB in adolescents in Australia and in New York, he has taken a hands-off approach. “If you tell teenagers they can do pretty much what they like, they'll rear back in shock and usually do what you ask them to,” he said.

In a separate report, Dr. Jose S. Pinheiro of the Hospital São Camilo, São Paulo, Brazil, reviewed his center's experience in performing laparoscopic Roux-en-Y gastric bypass surgery in 49 adolescents with a mean age of 16 years. The patients, 35 of whom were male, all received preoperative psychiatric evaluations and had full parental support.

The laparoscopic RYGBs involved an antecolic, antegastric approach and used a 50-cm biliary limb and a 150-cm alimentary limb. No patients died or had complications during surgery, and their average hospital stay was 30 hours.

The patients' mean BMI dropped from 45 before surgery to 23.5 at a mean follow-up of 48 months. All obesity-related comorbidities resolved after surgery.

Dr. Pinheiro and his colleagues are still collecting quality of life data, but he said that all of the patients are happy with the surgery and are committed to becoming healthier. “The patients were extremely compliant with treatment,” Dr. Pinheiro said, noting that all of them exercised on a regular basis. “Gastric bypass should be offered as an option in the treatment of obese adolescents,” he added.

When adolescents are referred for bariatric surgery, they are usually offered a restrictive procedure, said Dr. Francesco S. Papadia of the department of surgery at the University of Genoa (Italy). Malabsorptive procedures such as biliopancreatic diversion (BPD) are “considered unsuitable a priori despite the lack of any evidence” against its safety or effectiveness in adolescents.

During 1976–2005, 76 adolescents received BPD surgery at the University of Genoa. Excluding 7 patients with Prader-Willi syndrome and 1 with Turner's syndrome, the remaining 68 had a mean of 11 years of follow-up, ranging from 2 to 23 years. On average, the patients were nearly 17 years of age at the time of the operation, weighed 125 kg, and had a BMI of 46. No patients died during surgery, and one had a wound dehiscence.

At their longest point of follow-up, patients lost a mean of 78% of their excess weight. Four patients lost less than 50% of excess weight. Of those, three underwent a revision and one was converted from a vertical banded gastroplasty with a preoperative BMI of 26.

Obesity-related comorbidities resolved in a significant percentage of patients; hypertension was reduced from 49% to 9%, dyslipidemia from 16% to 0%, and glucose-intolerant or type 2 diabetes from 7% to 0%.

Twelve patients developed protein malnutrition at some point 1–10 years after surgery, and two patients had recurrent protein malnutrition. Those who experienced protein malnutrition after surgery had significantly higher initial body weight and BMI than did those who did not have malnutrition.

The incidence of protein malnutrition decreased steadily during the 30-year period of the study from 30% in the first few years to 2% in the last few years. The length of the common limb remained 50 cm, but as the surgeons gained experience, they adapted alimentary limb lengths to individual characteristics, and gastric sizes were not restricted to prevent protein malnutrition, Dr. Papadia said.

In a range of 4–18 years after BPD surgery, 18 women gave birth to 28 healthy infants. One infant was mentally retarded. Another two women died of severe protein malnutrition at the end of their pregnancies.

A total of 19 reoperations were performed in 14 patients, including 5 elongations and 2 restorations. Overall, three patients in the cohort died (4%)—two from protein malnutrition during pregnancy and one from acute pancreatitis.

SAN FRANCISCO — Few morbidly obese adolescents are referred for bariatric surgery, despite the high rate of failure with conservative interventions. But short-term outcomes and compliance in teens undergoing Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, or biliopancreatic diversion are as good as those of older patients, according to findings from a series of small retrospective studies presented at the annual meeting of the American Society for Bariatric Surgery.

Those who object to doing bariatric surgery in adolescents question “whether teenagers will comply with the treatment regimen,” said Dr. George A. Fielding of the surgical weight loss program at New York University, New York. “It's been postulated that kids won't do this just by the nature of being a teenager.”

While in Dr. Fielding's care at the NYU Medical Center, 81 adolescents have received laparoscopic adjustable gastric banding (LAGB). Five of the patients were aged 12–13 years, 55 were aged 14–17 years, and 21 were aged 18–19 years. Most (60) were girls and weighed an average of 137 kg with a mean body mass index (BMI) of 48 kg/m

After 1 year of follow-up in 32 patients, the patients lost 57% of their excess weight on average and had a mean BMI of 34. All comorbidities were resolved, except for two patients who needed to maintain antidepressant therapy.

Banding adjustments at follow-up visits is a “key issue to the management of all LAGB patients, and it's no different with children,” Dr. Fielding pointed out.

During the first year of follow-up in 27 patients aged 14–17 years, an average of 6.5 banding adjustments were made during 10 visits. This led to an average of 64% excess weight lost; only 2 of these 27 patients lost less than 50% of their excess weight, Dr. Fielding said.

Most patients reported that they were much less hungry and were eating a substantially smaller volume of food than they had been preoperatively. Very few had a desire to binge eat, he said.

The decision to undergo LAGB had been made mostly by the adolescents rather than by their parents, Dr. Fielding said. When performing LAGB in adolescents in Australia and in New York, he has taken a hands-off approach. “If you tell teenagers they can do pretty much what they like, they'll rear back in shock and usually do what you ask them to,” he said.

In a separate report, Dr. Jose S. Pinheiro of the Hospital São Camilo, São Paulo, Brazil, reviewed his center's experience in performing laparoscopic Roux-en-Y gastric bypass surgery in 49 adolescents with a mean age of 16 years. The patients, 35 of whom were male, all received preoperative psychiatric evaluations and had full parental support.

The laparoscopic RYGBs involved an antecolic, antegastric approach and used a 50-cm biliary limb and a 150-cm alimentary limb. No patients died or had complications during surgery, and their average hospital stay was 30 hours.

The patients' mean BMI dropped from 45 before surgery to 23.5 at a mean follow-up of 48 months. All obesity-related comorbidities resolved after surgery.

Dr. Pinheiro and his colleagues are still collecting quality of life data, but he said that all of the patients are happy with the surgery and are committed to becoming healthier. “The patients were extremely compliant with treatment,” Dr. Pinheiro said, noting that all of them exercised on a regular basis. “Gastric bypass should be offered as an option in the treatment of obese adolescents,” he added.

When adolescents are referred for bariatric surgery, they are usually offered a restrictive procedure, said Dr. Francesco S. Papadia of the department of surgery at the University of Genoa (Italy). Malabsorptive procedures such as biliopancreatic diversion (BPD) are “considered unsuitable a priori despite the lack of any evidence” against its safety or effectiveness in adolescents.

During 1976–2005, 76 adolescents received BPD surgery at the University of Genoa. Excluding 7 patients with Prader-Willi syndrome and 1 with Turner's syndrome, the remaining 68 had a mean of 11 years of follow-up, ranging from 2 to 23 years. On average, the patients were nearly 17 years of age at the time of the operation, weighed 125 kg, and had a BMI of 46. No patients died during surgery, and one had a wound dehiscence.

At their longest point of follow-up, patients lost a mean of 78% of their excess weight. Four patients lost less than 50% of excess weight. Of those, three underwent a revision and one was converted from a vertical banded gastroplasty with a preoperative BMI of 26.

Obesity-related comorbidities resolved in a significant percentage of patients; hypertension was reduced from 49% to 9%, dyslipidemia from 16% to 0%, and glucose-intolerant or type 2 diabetes from 7% to 0%.

Twelve patients developed protein malnutrition at some point 1–10 years after surgery, and two patients had recurrent protein malnutrition. Those who experienced protein malnutrition after surgery had significantly higher initial body weight and BMI than did those who did not have malnutrition.

The incidence of protein malnutrition decreased steadily during the 30-year period of the study from 30% in the first few years to 2% in the last few years. The length of the common limb remained 50 cm, but as the surgeons gained experience, they adapted alimentary limb lengths to individual characteristics, and gastric sizes were not restricted to prevent protein malnutrition, Dr. Papadia said.

In a range of 4–18 years after BPD surgery, 18 women gave birth to 28 healthy infants. One infant was mentally retarded. Another two women died of severe protein malnutrition at the end of their pregnancies.

A total of 19 reoperations were performed in 14 patients, including 5 elongations and 2 restorations. Overall, three patients in the cohort died (4%)—two from protein malnutrition during pregnancy and one from acute pancreatitis.

WASHINGTON — Which comes first, diabetes or depression?

The data on this temporal relationship are mixed. Although findings from previous studies suggest that depression precedes diabetes, findings from another investigation, presented at the annual scientific sessions of the American Diabetes Association, propose that there is no time correlation between the two diagnoses.

This chicken-or-egg question is important because depression has a reported prevalence ranging from 11% to 33% in patients with diabetes, which is twice as high as it is in people without diabetes, said Dr. Lawrence S. Phillips, professor of medicine in the division of endocrinology and metabolism at Emory University, Atlanta.

Dr. Phillips and his colleagues conducted a cross-sectional study of 573 people (about half were white and half were African American) who said that they did not have diabetes. Each person received a 75-g oral glucose tolerance test after an 8-hour overnight fast, and screening for depression with a well-validated tool, the Patient Health Questionnaire.

Normal glucose tolerance (NGT) occurred in 65% of the participants, whereas 15% had impaired fasting glucose (IFG), 8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 4% had diabetes. Some participants had received (11%) or were currently receiving (12%) treatment for depression.

The PHQ scores rose in a statistically significant trend from being low among those who never underwent treatment for depression to being higher in people who received depression treatment in the past and highest in individuals who were currently receiving depression treatment.

But there was no relationship between the different categories of glucose tolerance and PHQ score, the prevalence of any depressive syndrome or major depressive disorder, or the severity of depression, Dr. Phillips said. In multivariate analyses, higher body mass index and current receipt of depression treatment significantly increased the risk of having any depressive syndrome, but this risk was not increased within any category of glucose tolerance.

An audience member asked Dr. Phillips how he viewed the results of his study given that a poster presented at last year's ADA meeting found that patients with IGT in the Diabetes Prevention Program had a significantly increased risk for depression, suggesting depression may have preceded IGT. “It's possible that among people who are depressed, there are neuroendocrine changes that lead to diabetes. There's room in human biology for both processes,” he said.

But he argued that the situation in which depression precedes the development of diabetes is unlikely given the lack of an association between depression and unrecognized IGT in his study and the fact that patients in the Diabetes Prevention Program were told that they had IGT and were at risk for diabetes, which could possibly have had a negative psychosocial effect.

Firm conclusions favoring either side of the issue, however, may have to wait for research into the dynamics of neurohormonal changes, which are believed to underlie some of the association between depression and the development of diabetes, said Dr. Sherita Hill Golden of the division of endocrinology and metabolism at Johns Hopkins University, Baltimore.

Melancholic depression increases the activation of the hypothalamic pituitary adrenal (HPA) axis, which leads to a simultaneous activation of the sympathetic nervous system, Dr. Golden said. In the tightly regulated feedback loop of the HPA axis, the hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal gland to release cortisol. Cortisol levels in turn regulate the production and release of CRH.

There is evidence to suggest that subclinical hypercortisolism, defined as having two of three abnormalities in HPA axis function (increased 24-hour urine free cortisol, failure of the dexamethasone suppression test, and decreased levels of ACTH), may contribute to the development of type 2 diabetes, Dr. Golden said.

A study of 12 patients with adrenal incidentalomas and subclinical hypercortisolism found that such patients had a higher prevalence of insulin resistance, impaired glucose tolerance, and type 2 diabetes, as well as greater central adiposity, than did 29 patients with a nonfunctioning adrenal incidentaloma and no subclinical hypercortisolism (J. Clin. Endocrinol. Metab. 2002;87:998–1003).

Dr. Golden's research has centered on determining which measures of neuroendocrine activity provide the most reliable results and on understanding how that activity correlates with metabolic parameters. Preliminary results of an extensive 3-day series of tests in 15 healthy African American women have indicated that static measures of HPA axis activity, such as salivary cortisol sampling, do not correlate well with more dynamic measurements, such as 24-hour urine-free cortisol levels. Other analyses in the patient group suggested CT scan measurements of adrenal gland volume and the results of dexamethasone suppression testing are correlated strongly with body mass index, high-density lipoprotein cholesterol, and systolic blood pressure.

The results of studies measuring the effect of neuroendocrine changes on metabolic parameters are beginning to suggest that “modification of the neurohormonal response may provide a novel approach to the primary prevention of type 2 diabetes,” Dr. Golden said, adding that such an approach “would be complementary to our already established measures.”

WASHINGTON — Which comes first, diabetes or depression?

The data on this temporal relationship are mixed. Although findings from previous studies suggest that depression precedes diabetes, findings from another investigation, presented at the annual scientific sessions of the American Diabetes Association, propose that there is no time correlation between the two diagnoses.

This chicken-or-egg question is important because depression has a reported prevalence ranging from 11% to 33% in patients with diabetes, which is twice as high as it is in people without diabetes, said Dr. Lawrence S. Phillips, professor of medicine in the division of endocrinology and metabolism at Emory University, Atlanta.

Dr. Phillips and his colleagues conducted a cross-sectional study of 573 people (about half were white and half were African American) who said that they did not have diabetes. Each person received a 75-g oral glucose tolerance test after an 8-hour overnight fast, and screening for depression with a well-validated tool, the Patient Health Questionnaire.

Normal glucose tolerance (NGT) occurred in 65% of the participants, whereas 15% had impaired fasting glucose (IFG), 8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 4% had diabetes. Some participants had received (11%) or were currently receiving (12%) treatment for depression.

The PHQ scores rose in a statistically significant trend from being low among those who never underwent treatment for depression to being higher in people who received depression treatment in the past and highest in individuals who were currently receiving depression treatment.

But there was no relationship between the different categories of glucose tolerance and PHQ score, the prevalence of any depressive syndrome or major depressive disorder, or the severity of depression, Dr. Phillips said. In multivariate analyses, higher body mass index and current receipt of depression treatment significantly increased the risk of having any depressive syndrome, but this risk was not increased within any category of glucose tolerance.

An audience member asked Dr. Phillips how he viewed the results of his study given that a poster presented at last year's ADA meeting found that patients with IGT in the Diabetes Prevention Program had a significantly increased risk for depression, suggesting depression may have preceded IGT. “It's possible that among people who are depressed, there are neuroendocrine changes that lead to diabetes. There's room in human biology for both processes,” he said.

But he argued that the situation in which depression precedes the development of diabetes is unlikely given the lack of an association between depression and unrecognized IGT in his study and the fact that patients in the Diabetes Prevention Program were told that they had IGT and were at risk for diabetes, which could possibly have had a negative psychosocial effect.

Firm conclusions favoring either side of the issue, however, may have to wait for research into the dynamics of neurohormonal changes, which are believed to underlie some of the association between depression and the development of diabetes, said Dr. Sherita Hill Golden of the division of endocrinology and metabolism at Johns Hopkins University, Baltimore.

Melancholic depression increases the activation of the hypothalamic pituitary adrenal (HPA) axis, which leads to a simultaneous activation of the sympathetic nervous system, Dr. Golden said. In the tightly regulated feedback loop of the HPA axis, the hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal gland to release cortisol. Cortisol levels in turn regulate the production and release of CRH.

There is evidence to suggest that subclinical hypercortisolism, defined as having two of three abnormalities in HPA axis function (increased 24-hour urine free cortisol, failure of the dexamethasone suppression test, and decreased levels of ACTH), may contribute to the development of type 2 diabetes, Dr. Golden said.

A study of 12 patients with adrenal incidentalomas and subclinical hypercortisolism found that such patients had a higher prevalence of insulin resistance, impaired glucose tolerance, and type 2 diabetes, as well as greater central adiposity, than did 29 patients with a nonfunctioning adrenal incidentaloma and no subclinical hypercortisolism (J. Clin. Endocrinol. Metab. 2002;87:998–1003).

Dr. Golden's research has centered on determining which measures of neuroendocrine activity provide the most reliable results and on understanding how that activity correlates with metabolic parameters. Preliminary results of an extensive 3-day series of tests in 15 healthy African American women have indicated that static measures of HPA axis activity, such as salivary cortisol sampling, do not correlate well with more dynamic measurements, such as 24-hour urine-free cortisol levels. Other analyses in the patient group suggested CT scan measurements of adrenal gland volume and the results of dexamethasone suppression testing are correlated strongly with body mass index, high-density lipoprotein cholesterol, and systolic blood pressure.

The results of studies measuring the effect of neuroendocrine changes on metabolic parameters are beginning to suggest that “modification of the neurohormonal response may provide a novel approach to the primary prevention of type 2 diabetes,” Dr. Golden said, adding that such an approach “would be complementary to our already established measures.”

WASHINGTON — Which comes first, diabetes or depression?

The data on this temporal relationship are mixed. Although findings from previous studies suggest that depression precedes diabetes, findings from another investigation, presented at the annual scientific sessions of the American Diabetes Association, propose that there is no time correlation between the two diagnoses.

This chicken-or-egg question is important because depression has a reported prevalence ranging from 11% to 33% in patients with diabetes, which is twice as high as it is in people without diabetes, said Dr. Lawrence S. Phillips, professor of medicine in the division of endocrinology and metabolism at Emory University, Atlanta.

Dr. Phillips and his colleagues conducted a cross-sectional study of 573 people (about half were white and half were African American) who said that they did not have diabetes. Each person received a 75-g oral glucose tolerance test after an 8-hour overnight fast, and screening for depression with a well-validated tool, the Patient Health Questionnaire.

Normal glucose tolerance (NGT) occurred in 65% of the participants, whereas 15% had impaired fasting glucose (IFG), 8% had impaired glucose tolerance (IGT), 8% had both IFG and IGT, and 4% had diabetes. Some participants had received (11%) or were currently receiving (12%) treatment for depression.

The PHQ scores rose in a statistically significant trend from being low among those who never underwent treatment for depression to being higher in people who received depression treatment in the past and highest in individuals who were currently receiving depression treatment.

But there was no relationship between the different categories of glucose tolerance and PHQ score, the prevalence of any depressive syndrome or major depressive disorder, or the severity of depression, Dr. Phillips said. In multivariate analyses, higher body mass index and current receipt of depression treatment significantly increased the risk of having any depressive syndrome, but this risk was not increased within any category of glucose tolerance.

An audience member asked Dr. Phillips how he viewed the results of his study given that a poster presented at last year's ADA meeting found that patients with IGT in the Diabetes Prevention Program had a significantly increased risk for depression, suggesting depression may have preceded IGT. “It's possible that among people who are depressed, there are neuroendocrine changes that lead to diabetes. There's room in human biology for both processes,” he said.

But he argued that the situation in which depression precedes the development of diabetes is unlikely given the lack of an association between depression and unrecognized IGT in his study and the fact that patients in the Diabetes Prevention Program were told that they had IGT and were at risk for diabetes, which could possibly have had a negative psychosocial effect.

Firm conclusions favoring either side of the issue, however, may have to wait for research into the dynamics of neurohormonal changes, which are believed to underlie some of the association between depression and the development of diabetes, said Dr. Sherita Hill Golden of the division of endocrinology and metabolism at Johns Hopkins University, Baltimore.

Melancholic depression increases the activation of the hypothalamic pituitary adrenal (HPA) axis, which leads to a simultaneous activation of the sympathetic nervous system, Dr. Golden said. In the tightly regulated feedback loop of the HPA axis, the hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal gland to release cortisol. Cortisol levels in turn regulate the production and release of CRH.

There is evidence to suggest that subclinical hypercortisolism, defined as having two of three abnormalities in HPA axis function (increased 24-hour urine free cortisol, failure of the dexamethasone suppression test, and decreased levels of ACTH), may contribute to the development of type 2 diabetes, Dr. Golden said.

A study of 12 patients with adrenal incidentalomas and subclinical hypercortisolism found that such patients had a higher prevalence of insulin resistance, impaired glucose tolerance, and type 2 diabetes, as well as greater central adiposity, than did 29 patients with a nonfunctioning adrenal incidentaloma and no subclinical hypercortisolism (J. Clin. Endocrinol. Metab. 2002;87:998–1003).

Dr. Golden's research has centered on determining which measures of neuroendocrine activity provide the most reliable results and on understanding how that activity correlates with metabolic parameters. Preliminary results of an extensive 3-day series of tests in 15 healthy African American women have indicated that static measures of HPA axis activity, such as salivary cortisol sampling, do not correlate well with more dynamic measurements, such as 24-hour urine-free cortisol levels. Other analyses in the patient group suggested CT scan measurements of adrenal gland volume and the results of dexamethasone suppression testing are correlated strongly with body mass index, high-density lipoprotein cholesterol, and systolic blood pressure.

The results of studies measuring the effect of neuroendocrine changes on metabolic parameters are beginning to suggest that “modification of the neurohormonal response may provide a novel approach to the primary prevention of type 2 diabetes,” Dr. Golden said, adding that such an approach “would be complementary to our already established measures.”

SAN FRANCISCO — Bariatric surgery may be safe for older patients and provide weight loss benefits and improved comorbidities similar to those achieved by younger patients, according to three new studies presented at the annual meeting of the American Society for Bariatric Surgery.

In February, the Centers for Medicare and Medicaid Services extended coverage for bariatric surgery to beneficiaries of all ages, provided that the surgery was performed at certified facilities.

And although a recent review of Medicare beneficiaries reported significantly higher mortality in patients aged 65 years and older than in younger patients (JAMA 2005;294:1903–8), the new studies do not support that finding.

In a study of 340 Medicare patients who underwent bariatric surgery, individuals aged 65 years and older had similar rates of major and minor complications but lower mortality after surgery than did those younger than 65 years, reported Dr. David A. Provost of the University of Texas Southwestern Medical Center, Dallas.

No deaths occurred in 65 older adult patients who received either laparoscopic adjustable gastric banding (LAGB) or open or laparoscopic Roux-en-Y gastric bypass (RYGB), but 3 (0.1%) of 275 younger patients died. The overall complication rate for patients aged 65 years and older was similar to that observed for patients under 65 years of age.

In a separate retrospective study of 55 patients aged at least 60 years, laparoscopic bariatric procedures caused no deaths and few complications, reported Dr. David Hazzan of the division of minimally invasive surgery at Mount Sinai School of Medicine, New York.

In the first 30 days after surgery, 4 (7%) patients developed complications: upper GI bleeding, an empyema, a urinary tract infection, and a wound infection. No patients had died at 90 days after surgery.

All patients underwent a contrast swallow study on the first day after surgery, and more than 70% were monitored in the surgical or postanesthesia ICU for the first 24 hours after surgery, based on their comorbidities and cardiovascular status.

Another study found that RYGB surgery in patients aged 60 years and older could be safe and effective in resolving comorbidities, even though the older patients lost less excess weight and had more comorbidities than their younger counterparts.

Of 1,002 patients who received bariatric surgery at the Geisinger Medical Center, Danville, Pa., during 2001–2005, 61 patients aged at least 60 years (mean, 62 years old) and 941 younger patients (mean, 43 years old) received laparoscopic or open RYGB surgery, said Dr. Stephanie E. Dunkle-Blatter, of the center.

Surgeons performed laparoscopic RYGB surgery in 32% of the older patients and in 53% of the younger patients. Postoperative body mass index was similar between the two groups (about 36 kg/m

Rates of major complications were 13% in older adults and 12% in younger patients, while rates of minor complications were 27% and 21%, respectively. However, 90-day mortality rates were similar in the two groups (1.6% vs. 0.53%, respectively).

More bariatric surgery is likely to be performed in older adults in the future, given the aging population and climbing rate of obesity, several speakers noted.

SAN FRANCISCO — Bariatric surgery may be safe for older patients and provide weight loss benefits and improved comorbidities similar to those achieved by younger patients, according to three new studies presented at the annual meeting of the American Society for Bariatric Surgery.

In February, the Centers for Medicare and Medicaid Services extended coverage for bariatric surgery to beneficiaries of all ages, provided that the surgery was performed at certified facilities.

And although a recent review of Medicare beneficiaries reported significantly higher mortality in patients aged 65 years and older than in younger patients (JAMA 2005;294:1903–8), the new studies do not support that finding.

In a study of 340 Medicare patients who underwent bariatric surgery, individuals aged 65 years and older had similar rates of major and minor complications but lower mortality after surgery than did those younger than 65 years, reported Dr. David A. Provost of the University of Texas Southwestern Medical Center, Dallas.

No deaths occurred in 65 older adult patients who received either laparoscopic adjustable gastric banding (LAGB) or open or laparoscopic Roux-en-Y gastric bypass (RYGB), but 3 (0.1%) of 275 younger patients died. The overall complication rate for patients aged 65 years and older was similar to that observed for patients under 65 years of age.

In a separate retrospective study of 55 patients aged at least 60 years, laparoscopic bariatric procedures caused no deaths and few complications, reported Dr. David Hazzan of the division of minimally invasive surgery at Mount Sinai School of Medicine, New York.

In the first 30 days after surgery, 4 (7%) patients developed complications: upper GI bleeding, an empyema, a urinary tract infection, and a wound infection. No patients had died at 90 days after surgery.

All patients underwent a contrast swallow study on the first day after surgery, and more than 70% were monitored in the surgical or postanesthesia ICU for the first 24 hours after surgery, based on their comorbidities and cardiovascular status.

Another study found that RYGB surgery in patients aged 60 years and older could be safe and effective in resolving comorbidities, even though the older patients lost less excess weight and had more comorbidities than their younger counterparts.

Of 1,002 patients who received bariatric surgery at the Geisinger Medical Center, Danville, Pa., during 2001–2005, 61 patients aged at least 60 years (mean, 62 years old) and 941 younger patients (mean, 43 years old) received laparoscopic or open RYGB surgery, said Dr. Stephanie E. Dunkle-Blatter, of the center.

Surgeons performed laparoscopic RYGB surgery in 32% of the older patients and in 53% of the younger patients. Postoperative body mass index was similar between the two groups (about 36 kg/m

Rates of major complications were 13% in older adults and 12% in younger patients, while rates of minor complications were 27% and 21%, respectively. However, 90-day mortality rates were similar in the two groups (1.6% vs. 0.53%, respectively).

More bariatric surgery is likely to be performed in older adults in the future, given the aging population and climbing rate of obesity, several speakers noted.

SAN FRANCISCO — Bariatric surgery may be safe for older patients and provide weight loss benefits and improved comorbidities similar to those achieved by younger patients, according to three new studies presented at the annual meeting of the American Society for Bariatric Surgery.

In February, the Centers for Medicare and Medicaid Services extended coverage for bariatric surgery to beneficiaries of all ages, provided that the surgery was performed at certified facilities.

And although a recent review of Medicare beneficiaries reported significantly higher mortality in patients aged 65 years and older than in younger patients (JAMA 2005;294:1903–8), the new studies do not support that finding.

In a study of 340 Medicare patients who underwent bariatric surgery, individuals aged 65 years and older had similar rates of major and minor complications but lower mortality after surgery than did those younger than 65 years, reported Dr. David A. Provost of the University of Texas Southwestern Medical Center, Dallas.

No deaths occurred in 65 older adult patients who received either laparoscopic adjustable gastric banding (LAGB) or open or laparoscopic Roux-en-Y gastric bypass (RYGB), but 3 (0.1%) of 275 younger patients died. The overall complication rate for patients aged 65 years and older was similar to that observed for patients under 65 years of age.

In a separate retrospective study of 55 patients aged at least 60 years, laparoscopic bariatric procedures caused no deaths and few complications, reported Dr. David Hazzan of the division of minimally invasive surgery at Mount Sinai School of Medicine, New York.

In the first 30 days after surgery, 4 (7%) patients developed complications: upper GI bleeding, an empyema, a urinary tract infection, and a wound infection. No patients had died at 90 days after surgery.

All patients underwent a contrast swallow study on the first day after surgery, and more than 70% were monitored in the surgical or postanesthesia ICU for the first 24 hours after surgery, based on their comorbidities and cardiovascular status.

Another study found that RYGB surgery in patients aged 60 years and older could be safe and effective in resolving comorbidities, even though the older patients lost less excess weight and had more comorbidities than their younger counterparts.

Of 1,002 patients who received bariatric surgery at the Geisinger Medical Center, Danville, Pa., during 2001–2005, 61 patients aged at least 60 years (mean, 62 years old) and 941 younger patients (mean, 43 years old) received laparoscopic or open RYGB surgery, said Dr. Stephanie E. Dunkle-Blatter, of the center.

Surgeons performed laparoscopic RYGB surgery in 32% of the older patients and in 53% of the younger patients. Postoperative body mass index was similar between the two groups (about 36 kg/m

Rates of major complications were 13% in older adults and 12% in younger patients, while rates of minor complications were 27% and 21%, respectively. However, 90-day mortality rates were similar in the two groups (1.6% vs. 0.53%, respectively).

More bariatric surgery is likely to be performed in older adults in the future, given the aging population and climbing rate of obesity, several speakers noted.

LOUISVILLE, KY. — Extension of the Roux limb in Roux-en-Y gastric bypass procedures for “super obese” patients may provide good long-term weight loss and resolution of comorbidities with an acceptable rate of complications, Wayne K. Nelson reported at the annual meeting of the Central Surgical Association.

Surgeons at the Mayo Clinic, Rochester, Minn., developed and refined the very, very long-limb Roux-en-Y gastric bypass (RYGBP) to meet the needs of their large referral practice in bariatric surgery, which accepts patients who are more overweight and have worse comorbidities than are typically seen.

The more commonly performed RYGBP operations for super obese patients—the distal gastric bypass and the biliopancreatic diversion with or without duodenal switch—both leave a relatively short Roux limb, a relatively long biliopancreatic limb, and a short (100-cm) common channel where food and digestive enzymes mix.

The proximal anatomy of the very, very long-limb RYGBP is similar to that of the distal RYGBP, but the Roux limb is much longer (typically 400–500 cm). This leaves a longer transit and greater ability to absorb water, minerals, and vitamins, said Mr. Nelson, a student at the Mayo Medical School in Rochester.

The common channel is the same 100-cm length, whereas the biliopancreatic limb is typically shorter—around 50–70 cm—than in other RYGBP procedures.

“Remember, this isn't a typical Roux-en-Y gastric bypass,” he said.

Of 1,435 bariatric procedures performed at the Mayo Clinic during 1985–2003, 257 were performed with the very, very long-limb RYGBP. These 257 consecutive patients were 45 years old on average, and had an average body mass index (kg/m

When the investigators began their study, they sent a detailed survey to patients to gather data in addition to what had been captured at normal follow-up visits; 73% of the patients responded to the survey.

After an average of 45 months of follow-up, the patients' BMI had dropped to a mean of 37, and 82% had lost more than 50% of their excess body weight, an amount commonly considered as a marker of success in bariatric surgery. The patients who did not lose greater than 50% of their excess body weight still lost a lot of weight, Mr. Nelson said, but many of them needed to lose hundreds of pounds to reach their ideal body weight. On average, patients lost 66% of their excess body weight.

Medical comorbidities resolved without the need for further treatment in many of the patients after the operation, including type 2 diabetes in 95% of the patients, hypertension in 65%, sleep apnea in 48%, and asthma in 30%. In the survey, 90% of the patients reported that they were satisfied with the results of the operation, and 93% said that they would recommend the procedure to others.

Procedural complications included two deaths, four staple-line leaks (one required reoperation), two intraabdominal abscesses, five wound dehiscences, 22 wound infections, and two pulmonary emboli.

About 82% of the patients reported some food intolerance, and 70% had occasional loose or watery stools. The more serious complication of malnutrition resulting from protein or caloric deficiency developed in 4%; this was resolved with a proximal relocation of the jejunoileostomy to lengthen the common channel to 200–300 cm. Other problems included oxalate nephrolithiasis in 16% of the patients, and gross steatorrhea in 5%.

“Because of the potential metabolic sequelae, [the very, very long-limb RYGBP] should not be offered” to patients who are medically naive, noncompliant, or unreliable regarding follow-up, or to those who have extremely abnormal preoperative amounts of urinary oxalate, Mr. Nelson said.

Emily Brannan, Illustration

LOUISVILLE, KY. — Extension of the Roux limb in Roux-en-Y gastric bypass procedures for “super obese” patients may provide good long-term weight loss and resolution of comorbidities with an acceptable rate of complications, Wayne K. Nelson reported at the annual meeting of the Central Surgical Association.

Surgeons at the Mayo Clinic, Rochester, Minn., developed and refined the very, very long-limb Roux-en-Y gastric bypass (RYGBP) to meet the needs of their large referral practice in bariatric surgery, which accepts patients who are more overweight and have worse comorbidities than are typically seen.

The more commonly performed RYGBP operations for super obese patients—the distal gastric bypass and the biliopancreatic diversion with or without duodenal switch—both leave a relatively short Roux limb, a relatively long biliopancreatic limb, and a short (100-cm) common channel where food and digestive enzymes mix.

The proximal anatomy of the very, very long-limb RYGBP is similar to that of the distal RYGBP, but the Roux limb is much longer (typically 400–500 cm). This leaves a longer transit and greater ability to absorb water, minerals, and vitamins, said Mr. Nelson, a student at the Mayo Medical School in Rochester.

The common channel is the same 100-cm length, whereas the biliopancreatic limb is typically shorter—around 50–70 cm—than in other RYGBP procedures.

“Remember, this isn't a typical Roux-en-Y gastric bypass,” he said.

Of 1,435 bariatric procedures performed at the Mayo Clinic during 1985–2003, 257 were performed with the very, very long-limb RYGBP. These 257 consecutive patients were 45 years old on average, and had an average body mass index (kg/m

When the investigators began their study, they sent a detailed survey to patients to gather data in addition to what had been captured at normal follow-up visits; 73% of the patients responded to the survey.

After an average of 45 months of follow-up, the patients' BMI had dropped to a mean of 37, and 82% had lost more than 50% of their excess body weight, an amount commonly considered as a marker of success in bariatric surgery. The patients who did not lose greater than 50% of their excess body weight still lost a lot of weight, Mr. Nelson said, but many of them needed to lose hundreds of pounds to reach their ideal body weight. On average, patients lost 66% of their excess body weight.

Medical comorbidities resolved without the need for further treatment in many of the patients after the operation, including type 2 diabetes in 95% of the patients, hypertension in 65%, sleep apnea in 48%, and asthma in 30%. In the survey, 90% of the patients reported that they were satisfied with the results of the operation, and 93% said that they would recommend the procedure to others.

Procedural complications included two deaths, four staple-line leaks (one required reoperation), two intraabdominal abscesses, five wound dehiscences, 22 wound infections, and two pulmonary emboli.

About 82% of the patients reported some food intolerance, and 70% had occasional loose or watery stools. The more serious complication of malnutrition resulting from protein or caloric deficiency developed in 4%; this was resolved with a proximal relocation of the jejunoileostomy to lengthen the common channel to 200–300 cm. Other problems included oxalate nephrolithiasis in 16% of the patients, and gross steatorrhea in 5%.

“Because of the potential metabolic sequelae, [the very, very long-limb RYGBP] should not be offered” to patients who are medically naive, noncompliant, or unreliable regarding follow-up, or to those who have extremely abnormal preoperative amounts of urinary oxalate, Mr. Nelson said.

Emily Brannan, Illustration

LOUISVILLE, KY. — Extension of the Roux limb in Roux-en-Y gastric bypass procedures for “super obese” patients may provide good long-term weight loss and resolution of comorbidities with an acceptable rate of complications, Wayne K. Nelson reported at the annual meeting of the Central Surgical Association.

Surgeons at the Mayo Clinic, Rochester, Minn., developed and refined the very, very long-limb Roux-en-Y gastric bypass (RYGBP) to meet the needs of their large referral practice in bariatric surgery, which accepts patients who are more overweight and have worse comorbidities than are typically seen.

The more commonly performed RYGBP operations for super obese patients—the distal gastric bypass and the biliopancreatic diversion with or without duodenal switch—both leave a relatively short Roux limb, a relatively long biliopancreatic limb, and a short (100-cm) common channel where food and digestive enzymes mix.

The proximal anatomy of the very, very long-limb RYGBP is similar to that of the distal RYGBP, but the Roux limb is much longer (typically 400–500 cm). This leaves a longer transit and greater ability to absorb water, minerals, and vitamins, said Mr. Nelson, a student at the Mayo Medical School in Rochester.

The common channel is the same 100-cm length, whereas the biliopancreatic limb is typically shorter—around 50–70 cm—than in other RYGBP procedures.

“Remember, this isn't a typical Roux-en-Y gastric bypass,” he said.

Of 1,435 bariatric procedures performed at the Mayo Clinic during 1985–2003, 257 were performed with the very, very long-limb RYGBP. These 257 consecutive patients were 45 years old on average, and had an average body mass index (kg/m

When the investigators began their study, they sent a detailed survey to patients to gather data in addition to what had been captured at normal follow-up visits; 73% of the patients responded to the survey.

After an average of 45 months of follow-up, the patients' BMI had dropped to a mean of 37, and 82% had lost more than 50% of their excess body weight, an amount commonly considered as a marker of success in bariatric surgery. The patients who did not lose greater than 50% of their excess body weight still lost a lot of weight, Mr. Nelson said, but many of them needed to lose hundreds of pounds to reach their ideal body weight. On average, patients lost 66% of their excess body weight.

Medical comorbidities resolved without the need for further treatment in many of the patients after the operation, including type 2 diabetes in 95% of the patients, hypertension in 65%, sleep apnea in 48%, and asthma in 30%. In the survey, 90% of the patients reported that they were satisfied with the results of the operation, and 93% said that they would recommend the procedure to others.

Procedural complications included two deaths, four staple-line leaks (one required reoperation), two intraabdominal abscesses, five wound dehiscences, 22 wound infections, and two pulmonary emboli.

About 82% of the patients reported some food intolerance, and 70% had occasional loose or watery stools. The more serious complication of malnutrition resulting from protein or caloric deficiency developed in 4%; this was resolved with a proximal relocation of the jejunoileostomy to lengthen the common channel to 200–300 cm. Other problems included oxalate nephrolithiasis in 16% of the patients, and gross steatorrhea in 5%.

“Because of the potential metabolic sequelae, [the very, very long-limb RYGBP] should not be offered” to patients who are medically naive, noncompliant, or unreliable regarding follow-up, or to those who have extremely abnormal preoperative amounts of urinary oxalate, Mr. Nelson said.

Emily Brannan, Illustration

SAN FRANCISCO — Pregnancy soon after bariatric surgery does not appear to pose safety concerns for the mother or newborn, Dr. Tuoc N. Dao reported at the annual meeting of the American Society for Bariatric Surgery.

Surgeons have generally recommended that bariatric surgery patients should not become pregnant until 12–18 months after the procedure because of a perceived risk to the fetus or the woman during the period of large weight loss and limited calorie and nutrient intake following the surgery, said Dr. Dao, a surgical resident at Baylor University Medical Center at Dallas.

Although her review of 24 patients indicated that “the desire for pregnancy should not be a deterrent to Roux-en-Y gastric bypass as a weight-loss procedure,” she and her colleagues still recommend that bariatric surgery patients wait 12–18 months before becoming pregnant “due to the psychological component of trying to undergo all of these changes at one time. Trying to lose weight and deal with a pregnancy at the same time I think would be too much for people.”

Several previous studies have not reported any major adverse events or outcomes in women who became pregnant after bariatric surgery. In a study of 298 deliveries, no adverse perinatal outcomes were reported in women who had restrictive or malabsorptive surgery, although Roux-en-Y gastric bypass (RYGB) was associated with an increased risk of premature rupture of membranes, labor induction, and fetal macrosomia (Am. J. Obstet. Gynecol. 2004;190:1335–40).

A separate review of 18 pregnancies after gastric bypass showed few metabolic problems or deficiencies in vitamin B₁₂ or iron (South. Med. J. 1989;82:1319–20). In another group of 46 deliveries, four of seven preterm infants were born to mothers who became pregnant within 16 months of their surgery. Pregnancy was safe outside of that time period (Am. Surg. 1982;48:363–5).

Pregnancy during the period of rapid weight loss immediately after surgery can cause deficiencies in iron, folate, calcium, and vitamin B₁₂. It also has been questioned whether women will be able to lose additional weight post partum during the early postoperative phase. Fetal and maternal deaths have been reported in a few cases of postoperative small bowel herniations and ischemia, but other reports have recorded good outcomes with early detection and treatment of this complication, Dr. Dao said.

In her review of 2,532 patients who underwent RYGB at Baylor during 2001–2005, 24 became pregnant within 1 year after the surgery. These patients were 32 years old with a body mass index of 49 kg/m

The patients' mean body mass index dropped from 34 kg/m

The 24 women had 26 pregnancies, 2 of which were early miscarriages in women who soon became pregnant again and carried to term. Of three other miscarriages, two occurred in the first trimester and one at a gestational age of 20 weeks. Another patient had an ectopic pregnancy.

One patient had mild iron deficiency during pregnancy that resolved with iron supplementation. One patient had symptomatic cholelithiasis and underwent laparoscopic cholecystectomy after the delivery of her baby. An internal hernia in one patient was detected early and repaired without any incident. Another patient with a gastrogastric fistula was treated conservatively until her delivery. Two patients had preterm labor. One patient had preeclampsia and one had mild hypertension that was much improved since her last pregnancy before bariatric surgery.

The 21 babies (including one set of twins) had an average birth weight of 2,874 g. Three neonates, including the twins, had a low birth weight (less than 2,500 g). One infant had intrauterine growth restriction (born to the mother with an internal hernia). Another infant had intrauterine growth restriction plus a low birth weight (born to the mother with a gastrogastric fistula). No infants had any congenital or developmental defects.

In five of the women who had pregnancies before their RYGB surgery, there were fewer instances of diabetes, hypertension, and complications during postsurgery pregnancies than in those that occurred before the operation.

Dr. Dao did not know how many of the other patients who received RYGB in the cohort were lost to follow-up, but she said that patients who report pregnancy at clinical visits or on follow-up surveys are interviewed to gather information.

SAN FRANCISCO — Pregnancy soon after bariatric surgery does not appear to pose safety concerns for the mother or newborn, Dr. Tuoc N. Dao reported at the annual meeting of the American Society for Bariatric Surgery.

Surgeons have generally recommended that bariatric surgery patients should not become pregnant until 12–18 months after the procedure because of a perceived risk to the fetus or the woman during the period of large weight loss and limited calorie and nutrient intake following the surgery, said Dr. Dao, a surgical resident at Baylor University Medical Center at Dallas.

Although her review of 24 patients indicated that “the desire for pregnancy should not be a deterrent to Roux-en-Y gastric bypass as a weight-loss procedure,” she and her colleagues still recommend that bariatric surgery patients wait 12–18 months before becoming pregnant “due to the psychological component of trying to undergo all of these changes at one time. Trying to lose weight and deal with a pregnancy at the same time I think would be too much for people.”

Several previous studies have not reported any major adverse events or outcomes in women who became pregnant after bariatric surgery. In a study of 298 deliveries, no adverse perinatal outcomes were reported in women who had restrictive or malabsorptive surgery, although Roux-en-Y gastric bypass (RYGB) was associated with an increased risk of premature rupture of membranes, labor induction, and fetal macrosomia (Am. J. Obstet. Gynecol. 2004;190:1335–40).

A separate review of 18 pregnancies after gastric bypass showed few metabolic problems or deficiencies in vitamin B₁₂ or iron (South. Med. J. 1989;82:1319–20). In another group of 46 deliveries, four of seven preterm infants were born to mothers who became pregnant within 16 months of their surgery. Pregnancy was safe outside of that time period (Am. Surg. 1982;48:363–5).

Pregnancy during the period of rapid weight loss immediately after surgery can cause deficiencies in iron, folate, calcium, and vitamin B₁₂. It also has been questioned whether women will be able to lose additional weight post partum during the early postoperative phase. Fetal and maternal deaths have been reported in a few cases of postoperative small bowel herniations and ischemia, but other reports have recorded good outcomes with early detection and treatment of this complication, Dr. Dao said.

In her review of 2,532 patients who underwent RYGB at Baylor during 2001–2005, 24 became pregnant within 1 year after the surgery. These patients were 32 years old with a body mass index of 49 kg/m

The patients' mean body mass index dropped from 34 kg/m

The 24 women had 26 pregnancies, 2 of which were early miscarriages in women who soon became pregnant again and carried to term. Of three other miscarriages, two occurred in the first trimester and one at a gestational age of 20 weeks. Another patient had an ectopic pregnancy.

One patient had mild iron deficiency during pregnancy that resolved with iron supplementation. One patient had symptomatic cholelithiasis and underwent laparoscopic cholecystectomy after the delivery of her baby. An internal hernia in one patient was detected early and repaired without any incident. Another patient with a gastrogastric fistula was treated conservatively until her delivery. Two patients had preterm labor. One patient had preeclampsia and one had mild hypertension that was much improved since her last pregnancy before bariatric surgery.

The 21 babies (including one set of twins) had an average birth weight of 2,874 g. Three neonates, including the twins, had a low birth weight (less than 2,500 g). One infant had intrauterine growth restriction (born to the mother with an internal hernia). Another infant had intrauterine growth restriction plus a low birth weight (born to the mother with a gastrogastric fistula). No infants had any congenital or developmental defects.

In five of the women who had pregnancies before their RYGB surgery, there were fewer instances of diabetes, hypertension, and complications during postsurgery pregnancies than in those that occurred before the operation.

Dr. Dao did not know how many of the other patients who received RYGB in the cohort were lost to follow-up, but she said that patients who report pregnancy at clinical visits or on follow-up surveys are interviewed to gather information.

SAN FRANCISCO — Pregnancy soon after bariatric surgery does not appear to pose safety concerns for the mother or newborn, Dr. Tuoc N. Dao reported at the annual meeting of the American Society for Bariatric Surgery.

Surgeons have generally recommended that bariatric surgery patients should not become pregnant until 12–18 months after the procedure because of a perceived risk to the fetus or the woman during the period of large weight loss and limited calorie and nutrient intake following the surgery, said Dr. Dao, a surgical resident at Baylor University Medical Center at Dallas.

Although her review of 24 patients indicated that “the desire for pregnancy should not be a deterrent to Roux-en-Y gastric bypass as a weight-loss procedure,” she and her colleagues still recommend that bariatric surgery patients wait 12–18 months before becoming pregnant “due to the psychological component of trying to undergo all of these changes at one time. Trying to lose weight and deal with a pregnancy at the same time I think would be too much for people.”

Several previous studies have not reported any major adverse events or outcomes in women who became pregnant after bariatric surgery. In a study of 298 deliveries, no adverse perinatal outcomes were reported in women who had restrictive or malabsorptive surgery, although Roux-en-Y gastric bypass (RYGB) was associated with an increased risk of premature rupture of membranes, labor induction, and fetal macrosomia (Am. J. Obstet. Gynecol. 2004;190:1335–40).

A separate review of 18 pregnancies after gastric bypass showed few metabolic problems or deficiencies in vitamin B₁₂ or iron (South. Med. J. 1989;82:1319–20). In another group of 46 deliveries, four of seven preterm infants were born to mothers who became pregnant within 16 months of their surgery. Pregnancy was safe outside of that time period (Am. Surg. 1982;48:363–5).

Pregnancy during the period of rapid weight loss immediately after surgery can cause deficiencies in iron, folate, calcium, and vitamin B₁₂. It also has been questioned whether women will be able to lose additional weight post partum during the early postoperative phase. Fetal and maternal deaths have been reported in a few cases of postoperative small bowel herniations and ischemia, but other reports have recorded good outcomes with early detection and treatment of this complication, Dr. Dao said.

In her review of 2,532 patients who underwent RYGB at Baylor during 2001–2005, 24 became pregnant within 1 year after the surgery. These patients were 32 years old with a body mass index of 49 kg/m

The patients' mean body mass index dropped from 34 kg/m

The 24 women had 26 pregnancies, 2 of which were early miscarriages in women who soon became pregnant again and carried to term. Of three other miscarriages, two occurred in the first trimester and one at a gestational age of 20 weeks. Another patient had an ectopic pregnancy.

One patient had mild iron deficiency during pregnancy that resolved with iron supplementation. One patient had symptomatic cholelithiasis and underwent laparoscopic cholecystectomy after the delivery of her baby. An internal hernia in one patient was detected early and repaired without any incident. Another patient with a gastrogastric fistula was treated conservatively until her delivery. Two patients had preterm labor. One patient had preeclampsia and one had mild hypertension that was much improved since her last pregnancy before bariatric surgery.

The 21 babies (including one set of twins) had an average birth weight of 2,874 g. Three neonates, including the twins, had a low birth weight (less than 2,500 g). One infant had intrauterine growth restriction (born to the mother with an internal hernia). Another infant had intrauterine growth restriction plus a low birth weight (born to the mother with a gastrogastric fistula). No infants had any congenital or developmental defects.

In five of the women who had pregnancies before their RYGB surgery, there were fewer instances of diabetes, hypertension, and complications during postsurgery pregnancies than in those that occurred before the operation.

Dr. Dao did not know how many of the other patients who received RYGB in the cohort were lost to follow-up, but she said that patients who report pregnancy at clinical visits or on follow-up surveys are interviewed to gather information.

PRAGUE — Normative values for mean blood glucose levels during the first trimester may be much lower than what has been reported previously, Dr. Yariv Yogev reported at the 20th European Congress of Perinatal Medicine.

This lower-than-expected glycemic profile may suggest new targets for glycemic control during pregnancy complicated by diabetes, said Dr. Yogev of the department of obstetrics and gynecology at Rabin Medical Center, Petah Tikva, Israel.

Before this study, there was little information on the definition of normal blood glucose levels during pregnancy, especially during the first trimester, he said. Most of the previous information had come from “very limited studies” of 10–25 patients, mostly in the third trimester, who were placed on a strict diet and hospitalized to evaluate their glycemic profile.

The current study included 62 healthy, nondiabetic women in their first trimester of pregnancy (average of 10 weeks' gestation). The investigators fit the women with continuous glucose monitoring devices that measured their blood glucose levels every 5 minutes for 72 hours. Patients were asked not to modify their lifestyles or nutritional habits.

Because of the difficulty of performing continuous glucose monitoring in nondiabetic women with a normal pregnancy, the study did not involve a specific cohort of patients but instead mostly included doctors' wives, midwives, and nurses.

The women's overall mean blood glucose (79.3 mg/dL) and mean fasting blood glucose levels (75 mg/dL) were “much, much lower than was previously reported by others” Dr. Yogev said.

Mean nighttime blood glucose levels (66 mg/dL) “almost represented hypoglycemia,” but such values may actually represent “normal physiology during the first trimester in nondiabetic patients,” he said.

The postprandial glycemic profile of the women was the same after each meal. Mean blood glucose values started at 79 mg/dL just before a meal and rose to 106 mg/dL 60 minutes after the meal; it reached a high of 112 mg/dL 74 minutes after the meal. The values reached 99 mg/dL at 2 hours and 82 mg/dL at 3 hours.

The fasting and overall mean blood glucose levels were similar in 18 obese (defined as a body mass index greater than 27.3 kg/m

The obese patients were characterized by a higher postprandial peak value, a longer time interval to reach the postprandial peak value, and higher mean blood glucose levels during the 3 hours after each meal, Dr. Yogev said.

PRAGUE — Normative values for mean blood glucose levels during the first trimester may be much lower than what has been reported previously, Dr. Yariv Yogev reported at the 20th European Congress of Perinatal Medicine.

This lower-than-expected glycemic profile may suggest new targets for glycemic control during pregnancy complicated by diabetes, said Dr. Yogev of the department of obstetrics and gynecology at Rabin Medical Center, Petah Tikva, Israel.

Before this study, there was little information on the definition of normal blood glucose levels during pregnancy, especially during the first trimester, he said. Most of the previous information had come from “very limited studies” of 10–25 patients, mostly in the third trimester, who were placed on a strict diet and hospitalized to evaluate their glycemic profile.

The current study included 62 healthy, nondiabetic women in their first trimester of pregnancy (average of 10 weeks' gestation). The investigators fit the women with continuous glucose monitoring devices that measured their blood glucose levels every 5 minutes for 72 hours. Patients were asked not to modify their lifestyles or nutritional habits.

Because of the difficulty of performing continuous glucose monitoring in nondiabetic women with a normal pregnancy, the study did not involve a specific cohort of patients but instead mostly included doctors' wives, midwives, and nurses.

The women's overall mean blood glucose (79.3 mg/dL) and mean fasting blood glucose levels (75 mg/dL) were “much, much lower than was previously reported by others” Dr. Yogev said.

Mean nighttime blood glucose levels (66 mg/dL) “almost represented hypoglycemia,” but such values may actually represent “normal physiology during the first trimester in nondiabetic patients,” he said.

The postprandial glycemic profile of the women was the same after each meal. Mean blood glucose values started at 79 mg/dL just before a meal and rose to 106 mg/dL 60 minutes after the meal; it reached a high of 112 mg/dL 74 minutes after the meal. The values reached 99 mg/dL at 2 hours and 82 mg/dL at 3 hours.

The fasting and overall mean blood glucose levels were similar in 18 obese (defined as a body mass index greater than 27.3 kg/m

The obese patients were characterized by a higher postprandial peak value, a longer time interval to reach the postprandial peak value, and higher mean blood glucose levels during the 3 hours after each meal, Dr. Yogev said.

PRAGUE — Normative values for mean blood glucose levels during the first trimester may be much lower than what has been reported previously, Dr. Yariv Yogev reported at the 20th European Congress of Perinatal Medicine.

This lower-than-expected glycemic profile may suggest new targets for glycemic control during pregnancy complicated by diabetes, said Dr. Yogev of the department of obstetrics and gynecology at Rabin Medical Center, Petah Tikva, Israel.

Before this study, there was little information on the definition of normal blood glucose levels during pregnancy, especially during the first trimester, he said. Most of the previous information had come from “very limited studies” of 10–25 patients, mostly in the third trimester, who were placed on a strict diet and hospitalized to evaluate their glycemic profile.

The current study included 62 healthy, nondiabetic women in their first trimester of pregnancy (average of 10 weeks' gestation). The investigators fit the women with continuous glucose monitoring devices that measured their blood glucose levels every 5 minutes for 72 hours. Patients were asked not to modify their lifestyles or nutritional habits.

Because of the difficulty of performing continuous glucose monitoring in nondiabetic women with a normal pregnancy, the study did not involve a specific cohort of patients but instead mostly included doctors' wives, midwives, and nurses.

The women's overall mean blood glucose (79.3 mg/dL) and mean fasting blood glucose levels (75 mg/dL) were “much, much lower than was previously reported by others” Dr. Yogev said.

Mean nighttime blood glucose levels (66 mg/dL) “almost represented hypoglycemia,” but such values may actually represent “normal physiology during the first trimester in nondiabetic patients,” he said.

The postprandial glycemic profile of the women was the same after each meal. Mean blood glucose values started at 79 mg/dL just before a meal and rose to 106 mg/dL 60 minutes after the meal; it reached a high of 112 mg/dL 74 minutes after the meal. The values reached 99 mg/dL at 2 hours and 82 mg/dL at 3 hours.

The fasting and overall mean blood glucose levels were similar in 18 obese (defined as a body mass index greater than 27.3 kg/m

The obese patients were characterized by a higher postprandial peak value, a longer time interval to reach the postprandial peak value, and higher mean blood glucose levels during the 3 hours after each meal, Dr. Yogev said.

WASHINGTON — Corneal confocal microscopy can be used to noninvasively diagnose neuropathy early on in diabetic patients and to follow the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements.

Skin nerve biopsies can provide much information, but are “highly invasive,” she said.

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.

Patients who undergo the procedure are given an anesthetic drop on the cornea to make it easier to then place a gel on the cornea to reduce excessive reflections between the cornea and the instrument.

She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.

They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

Significant reductions in these measures were found even among diabetic patients without neuropathy, Ms. Tavakoli said.

The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.

Corneal confocal microscopy “may act as a good surrogate marker to diagnose and follow the progression” of neuropathy during interventions and follow-up, she said.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.

At 6 months after transplantation, repeat scans performed in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly.

Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.

In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.

Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology among patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap.

The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside.

Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).

Other researchers have reported that it takes 5 years for corneal nerves to completely recover after LASIK (Am. J. Ophthalmol. 2005;140:1059–64).

“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.

Two second-generation corneal confocal microscopes are available, the $80,000 ConfoScan4 (Nidek Co.) and the $60,000 confocal laser microscope (Heidelberg Engineering GmbH), said Dr. Efron, who has no commercial interest in either device.

The Nidek microscope uses a white light source whereas the Heidelberg uses a laser light source, which provides “much better contrast” and is recommended by Dr. Efron, although it is a “little less user friendly.”

Corneal confocal microscopy offers a noninvasive alternative to many traditional diagnostics. This micrograph demonstrates nerves in a control patient without neuropathy.

Diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity, nerve fiber density (above), nerve branch density, and nerve fiber length. PHOTOS COURTESY MITRA TAVAKOLI

WASHINGTON — Corneal confocal microscopy can be used to noninvasively diagnose neuropathy early on in diabetic patients and to follow the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements.

Skin nerve biopsies can provide much information, but are “highly invasive,” she said.

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.

Patients who undergo the procedure are given an anesthetic drop on the cornea to make it easier to then place a gel on the cornea to reduce excessive reflections between the cornea and the instrument.

She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.

They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

Significant reductions in these measures were found even among diabetic patients without neuropathy, Ms. Tavakoli said.

The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.

Corneal confocal microscopy “may act as a good surrogate marker to diagnose and follow the progression” of neuropathy during interventions and follow-up, she said.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.

At 6 months after transplantation, repeat scans performed in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly.

Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.

In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.

Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology among patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap.

The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside.

Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).

Other researchers have reported that it takes 5 years for corneal nerves to completely recover after LASIK (Am. J. Ophthalmol. 2005;140:1059–64).

“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.

Two second-generation corneal confocal microscopes are available, the $80,000 ConfoScan4 (Nidek Co.) and the $60,000 confocal laser microscope (Heidelberg Engineering GmbH), said Dr. Efron, who has no commercial interest in either device.

The Nidek microscope uses a white light source whereas the Heidelberg uses a laser light source, which provides “much better contrast” and is recommended by Dr. Efron, although it is a “little less user friendly.”

Corneal confocal microscopy offers a noninvasive alternative to many traditional diagnostics. This micrograph demonstrates nerves in a control patient without neuropathy.

Diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity, nerve fiber density (above), nerve branch density, and nerve fiber length. PHOTOS COURTESY MITRA TAVAKOLI

WASHINGTON — Corneal confocal microscopy can be used to noninvasively diagnose neuropathy early on in diabetic patients and to follow the course of the disease during treatment, several speakers said at the annual scientific sessions of the American Diabetes Association.

By comparison, the clinical neurologic exam may be easier than corneal confocal microscopy but it lacks sensitivity, said Mitra Tavakoli, a doctoral student at the University of Manchester (England).

Nerve conduction studies are time-consuming and are reliable only in measuring the function of large nerve fibers. Quantitative sensory testing also is easier to do, but relies on the patient's response to take measurements.

Skin nerve biopsies can provide much information, but are “highly invasive,” she said.

Using a first-generation corneal confocal microscope, the ConfoScan P4 (Tomey Corp.), Ms. Tavakoli and her colleagues are able to obtain in vivo, real-time micrographs of the cornea at up to 680 times magnification without directly contacting the eye.

Patients who undergo the procedure are given an anesthetic drop on the cornea to make it easier to then place a gel on the cornea to reduce excessive reflections between the cornea and the instrument.

She and her coinvestigators studied 183 people including control patients without diabetes, diabetic patients without neuropathy, and diabetic patients with mild, moderate, or severe neuropathy.

They found that diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity (as measured by noncontact corneal aesthesiometry), nerve fiber density, nerve branch density, and nerve fiber length. Nerve fiber tortuosity also became progressively worse as the severity of neuropathy worsened.

Significant reductions in these measures were found even among diabetic patients without neuropathy, Ms. Tavakoli said.

The measurements of corneal nerve morphology obtained with confocal microscopy correlated well with assessments of corneal sensitivity and neuropathy severity, as measured by the Neuropathy Disability Score.

Corneal confocal microscopy “may act as a good surrogate marker to diagnose and follow the progression” of neuropathy during interventions and follow-up, she said.

In a poster presented at the meeting, Ms. Tavakoli and her colleagues used corneal confocal microscopy to show the effectiveness of pancreatic transplantation in improving neuropathy in 20 patients with type 1 diabetes who had an average age of 41 years.

Before transplantation, the diabetic patients had significantly reduced corneal sensitivity as well as significantly lower nerve fiber density, nerve branch density, and nerve fiber length on corneal confocal micrographs, compared with 18 individuals without neuropathy who had an average age of 55 years.

At 6 months after transplantation, repeat scans performed in 11 of the patients who had neuropathy showed that nerve fiber density and length had improved significantly.

Other posttransplantation studies that have employed electrophysiology and quantitative sensory testing have been able to detect improvements in large fiber function after 3–4 years, unlike the early detection of small fiber repair at 6 months in this study, Ms. Tavakoli reported.

In the laboratory of Nathan Efron, Ph.D.—one of Ms. Tavakoli's collaborators—the microscopy technique has proved to have sensitivity (71%) and specificity (77%) comparable with the histopathologic examination of skin punch biopsy specimens (59% and 90%, respectively) when both are compared with the “gold standard” Neuropathic Disability Score.

Dr. Efron has used confocal microscopy to monitor longitudinal changes in corneal morphology among patients who have received myopic laser in situ keratomileusis (LASIK), which involves cutting a flap of the cornea, irradiating the corneal stroma with a laser, and replacing the flap.

The LASIK procedure severs corneal nerves in the subbasal nerve plexus where most of the corneal nerves reside.

Several weeks after the surgery, confocal microscopy shows a “hazy image” devoid of any nerve fibers. At 3 months, a few nerve fragments can be seen, and at 6 months a few continuous nerves begin to appear (Optom. Vis. Sci. 2003;80:690–7).

Other researchers have reported that it takes 5 years for corneal nerves to completely recover after LASIK (Am. J. Ophthalmol. 2005;140:1059–64).

“Certainly, this has implications with respect to diabetic patients who are having this LASIK procedure,” said Dr. Efron, research professor at Queensland University of Technology, Brisbane, Australia.

Two second-generation corneal confocal microscopes are available, the $80,000 ConfoScan4 (Nidek Co.) and the $60,000 confocal laser microscope (Heidelberg Engineering GmbH), said Dr. Efron, who has no commercial interest in either device.

The Nidek microscope uses a white light source whereas the Heidelberg uses a laser light source, which provides “much better contrast” and is recommended by Dr. Efron, although it is a “little less user friendly.”

Corneal confocal microscopy offers a noninvasive alternative to many traditional diagnostics. This micrograph demonstrates nerves in a control patient without neuropathy.

Diabetic neuropathy was associated with progressive, significant reductions in corneal sensitivity, nerve fiber density (above), nerve branch density, and nerve fiber length. PHOTOS COURTESY MITRA TAVAKOLI

SAN FRANCISCO — African American patients, especially women, appear to lose a smaller percentage of excess weight after laparoscopic adjustable gastric banding than their white counterparts, despite similar resolution of comorbidities, Dr. Manish S. Parikh reported at the annual meeting of the American Society for Bariatric Surgery.

“It's unclear what impact race has on outcomes after bariatric surgery. There have been conflicting reports of decreased mean excess weight loss among African Americans after bariatric surgery, most of which involved gastric bypasses,” said Dr. Parikh, of the department of surgery at New York University, New York.

In a previously published review of 630 white and 61 African American patients, Dr. Parikh and his colleagues found a significant difference in mean excess weight loss between whites and African Americans at 3 years of follow-up (54% and 38%, respectively) after laparoscopic adjustable gastric banding (LABG). But that study did not examine any differences in age, body mass index, or prevalence of comorbidities (Surg. Endosc. 2005;19:1631–5).

To investigate more thoroughly any racial differences in LABG outcomes, Dr. Parikh and his colleagues used prospectively collected data on 959 patients who underwent the procedure during 2001–2004. They retrospectively matched 65 white patients with 58 African American patients based on age (mean 37 years), sex (104 females), and preoperative BMI (47 kg/m

Compared with African American patients, white patients on average lost a significantly higher percentage of excess weight at 1 year (39% vs. 49%), 2 years (44% vs. 55%), and 3 years of follow-up (41% vs. 52%). But the obesity-related comorbidities of type 2 diabetes, hypertension, obstructive sleep apnea, and hyperlipidemia resolved in a similar percentage of patients in both groups at each time point.

At baseline, 64% of African Americans and 55% of whites had obesity-related comorbidities. A decrease in the dose or number of medications was seen in 77% of African Americans and 61% of whites while obesity-related comorbidities completely resolved (medications were discontinued) in 32% of African Americans and in 29% of whites.

The follow-up rates at 3 years were 60% for African Americans and 74% for whites.

“This is a very small study with preliminary data. Larger studies are needed to delineate ethnic differences in outcomes after bariatric surgery,” Dr. Parikh said.

Physicians should look at such data “with a little bit of caution, especially the types of studies that may foster far-reaching implications,” said Dr. Titus D. Duncan, a scheduled discussant. “Insurance companies and other entities get these papers as well; and they can—and have—historically denied access to patients” based on studies that have not reached final conclusions.

It's important to consider “difficult-to-study” variables, such as social support issues, social negotiation skills, personal life experiences, conditioned preferences and avoidances, role models, and body image, which influence the overall outcomes in African American patients, said Dr. Duncan, director of minimally invasive and bariatric surgery at the Atlanta Medical Center.

Taking those variables into consideration in postoperative care plans, Dr. Duncan said that his group has found no significant racial differences in weight loss parameters or resolution of comorbidities in 3,500 bariatric procedures performed at their institution (including more than 800 African American patients).

SAN FRANCISCO — African American patients, especially women, appear to lose a smaller percentage of excess weight after laparoscopic adjustable gastric banding than their white counterparts, despite similar resolution of comorbidities, Dr. Manish S. Parikh reported at the annual meeting of the American Society for Bariatric Surgery.

“It's unclear what impact race has on outcomes after bariatric surgery. There have been conflicting reports of decreased mean excess weight loss among African Americans after bariatric surgery, most of which involved gastric bypasses,” said Dr. Parikh, of the department of surgery at New York University, New York.

In a previously published review of 630 white and 61 African American patients, Dr. Parikh and his colleagues found a significant difference in mean excess weight loss between whites and African Americans at 3 years of follow-up (54% and 38%, respectively) after laparoscopic adjustable gastric banding (LABG). But that study did not examine any differences in age, body mass index, or prevalence of comorbidities (Surg. Endosc. 2005;19:1631–5).

To investigate more thoroughly any racial differences in LABG outcomes, Dr. Parikh and his colleagues used prospectively collected data on 959 patients who underwent the procedure during 2001–2004. They retrospectively matched 65 white patients with 58 African American patients based on age (mean 37 years), sex (104 females), and preoperative BMI (47 kg/m

Compared with African American patients, white patients on average lost a significantly higher percentage of excess weight at 1 year (39% vs. 49%), 2 years (44% vs. 55%), and 3 years of follow-up (41% vs. 52%). But the obesity-related comorbidities of type 2 diabetes, hypertension, obstructive sleep apnea, and hyperlipidemia resolved in a similar percentage of patients in both groups at each time point.

At baseline, 64% of African Americans and 55% of whites had obesity-related comorbidities. A decrease in the dose or number of medications was seen in 77% of African Americans and 61% of whites while obesity-related comorbidities completely resolved (medications were discontinued) in 32% of African Americans and in 29% of whites.

The follow-up rates at 3 years were 60% for African Americans and 74% for whites.

“This is a very small study with preliminary data. Larger studies are needed to delineate ethnic differences in outcomes after bariatric surgery,” Dr. Parikh said.

Physicians should look at such data “with a little bit of caution, especially the types of studies that may foster far-reaching implications,” said Dr. Titus D. Duncan, a scheduled discussant. “Insurance companies and other entities get these papers as well; and they can—and have—historically denied access to patients” based on studies that have not reached final conclusions.

It's important to consider “difficult-to-study” variables, such as social support issues, social negotiation skills, personal life experiences, conditioned preferences and avoidances, role models, and body image, which influence the overall outcomes in African American patients, said Dr. Duncan, director of minimally invasive and bariatric surgery at the Atlanta Medical Center.

Taking those variables into consideration in postoperative care plans, Dr. Duncan said that his group has found no significant racial differences in weight loss parameters or resolution of comorbidities in 3,500 bariatric procedures performed at their institution (including more than 800 African American patients).

SAN FRANCISCO — African American patients, especially women, appear to lose a smaller percentage of excess weight after laparoscopic adjustable gastric banding than their white counterparts, despite similar resolution of comorbidities, Dr. Manish S. Parikh reported at the annual meeting of the American Society for Bariatric Surgery.

“It's unclear what impact race has on outcomes after bariatric surgery. There have been conflicting reports of decreased mean excess weight loss among African Americans after bariatric surgery, most of which involved gastric bypasses,” said Dr. Parikh, of the department of surgery at New York University, New York.

In a previously published review of 630 white and 61 African American patients, Dr. Parikh and his colleagues found a significant difference in mean excess weight loss between whites and African Americans at 3 years of follow-up (54% and 38%, respectively) after laparoscopic adjustable gastric banding (LABG). But that study did not examine any differences in age, body mass index, or prevalence of comorbidities (Surg. Endosc. 2005;19:1631–5).

To investigate more thoroughly any racial differences in LABG outcomes, Dr. Parikh and his colleagues used prospectively collected data on 959 patients who underwent the procedure during 2001–2004. They retrospectively matched 65 white patients with 58 African American patients based on age (mean 37 years), sex (104 females), and preoperative BMI (47 kg/m

Compared with African American patients, white patients on average lost a significantly higher percentage of excess weight at 1 year (39% vs. 49%), 2 years (44% vs. 55%), and 3 years of follow-up (41% vs. 52%). But the obesity-related comorbidities of type 2 diabetes, hypertension, obstructive sleep apnea, and hyperlipidemia resolved in a similar percentage of patients in both groups at each time point.

At baseline, 64% of African Americans and 55% of whites had obesity-related comorbidities. A decrease in the dose or number of medications was seen in 77% of African Americans and 61% of whites while obesity-related comorbidities completely resolved (medications were discontinued) in 32% of African Americans and in 29% of whites.

The follow-up rates at 3 years were 60% for African Americans and 74% for whites.

“This is a very small study with preliminary data. Larger studies are needed to delineate ethnic differences in outcomes after bariatric surgery,” Dr. Parikh said.

Physicians should look at such data “with a little bit of caution, especially the types of studies that may foster far-reaching implications,” said Dr. Titus D. Duncan, a scheduled discussant. “Insurance companies and other entities get these papers as well; and they can—and have—historically denied access to patients” based on studies that have not reached final conclusions.

It's important to consider “difficult-to-study” variables, such as social support issues, social negotiation skills, personal life experiences, conditioned preferences and avoidances, role models, and body image, which influence the overall outcomes in African American patients, said Dr. Duncan, director of minimally invasive and bariatric surgery at the Atlanta Medical Center.

Taking those variables into consideration in postoperative care plans, Dr. Duncan said that his group has found no significant racial differences in weight loss parameters or resolution of comorbidities in 3,500 bariatric procedures performed at their institution (including more than 800 African American patients).

WASHINGTON – Tight glycemic control early in the course of type 1 diabetes does not result in later cognitive decline, according to new findings from two studies with an average of 18 years of follow-up data.

“Because of the length of follow-up and extent of cognitive testing, this study strongly supports the safety of intensive diabetes therapy,” Dr. Alan M. Jacobson said at the annual scientific sessions of the American Diabetes Association.

The results should allay the serious concerns that have been raised about whether tight glycemic control might lead to more severe hypoglycemic episodes and subsequent decreased cognitive ability, said Dr. Jacobson, head of the behavioral and mental health research section at the Joslin Diabetes Center, Boston.

But the recurrent, severe hypoglycemic events that are more likely to occur with tight glycemic control could still possibly have a negative cognitive effect on older adults, very young children, or those with a longer disease duration, he added.

The results from the multicenter, randomized Diabetes Control and Complications Trial (DCCT) and its continuation in the long-term observational Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that patients who received intensive glycemic control during the DCCT did not have any differences in cognition, compared with conventional treatment, as measured by an extensive test battery involving eight cognitive domains (problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency, and motor speed), Dr. Jacobson reported.

The 18 years of combined follow-up make the DCCT and the EDIC the largest, longest-term prospective study that has implemented a cognitive assessment of patients with any clinical condition, he said.

Among patients in either group, there were no differences in cognitive functioning in those who had no hypoglycemic episodes, one to five episodes, or more than five episodes.

Control of HbA_1c (glycosylated hemoglobin) values to less than 7.9% similarly showed no significant effects, except in sparing patients from small reductions in psychomotor efficiency and in improving motor speed. The “very modest” declines in psychomotor efficiency and motor speed that were associated with higher HbA_1c values (7.9% or greater) were “consistent with emerging literature on the effects of persistent hyperglycemia on mental and motor slowing,” Dr. Jacobson said.

The results did not change when the investigators removed 28 patients with potentially confounding illnesses–strokes, decreased vision, renal insufficiency–from the analysis, except that patients who had prior tight glycemic control in the DCCT had a significantly lower decline in psychomotor efficiency than did patients who received conventional treatment.

All of the analyses were adjusted to account for the confounding variables of baseline age, gender, years of education, length of follow-up, and the number of cognitive tests taken. (Patients took different numbers of tests because they entered the DCCT at different times.)

The initial results at the end of the DCCT showed that maintenance of near normal glycemic control reduced the risk of developing–or the progression of–microvascular complications.

After 10 years of additional follow-up in the EDIC study, the patients who had prior intensive treatment still had reduced progression of retinopathy, nephropathy, neuropathy, and cardiovascular events.

As patients in the intensive treatment arm of the DCCT finished the trial and entered the EDIC study, they did not maintain the same level of glycemic control during the ensuing years, whereas individuals who were in the conventional treatment arm of the DCCT received training on how to maintain tight glycemic control and soon began doing so on their own. Both groups had a mean HbA_1c value of 7.8% at the end of 12 years of follow-up in the EDIC study, which includes more than 90% of the original DCCT patients.

At the end of those 12 years, a significantly greater percentage of the 583 patients who were in the intensive treatment arm of the DCCT had one or more severe hypoglycemic events leading to coma or seizures than did the 553 patients who received conventional treatment (44%, or 258 patients with 880 events, vs. 34%, or 187 patients with 452 events).

Most (97%) of the participants were white and were 27 years old on average when they entered the DCCT, where they received a mean of 6.5 years of intervention; they were 45 years old on average after 12 years of follow-up in the EDIC trial. At the last follow-up, all of the participants were adults and about 50% were employed as professionals.

The patients in the study were “unusually healthy and subject to careful follow-up, which may suggest that those in worse control may show worse cognitive outcomes,” he said.

WASHINGTON – Tight glycemic control early in the course of type 1 diabetes does not result in later cognitive decline, according to new findings from two studies with an average of 18 years of follow-up data.

“Because of the length of follow-up and extent of cognitive testing, this study strongly supports the safety of intensive diabetes therapy,” Dr. Alan M. Jacobson said at the annual scientific sessions of the American Diabetes Association.

The results should allay the serious concerns that have been raised about whether tight glycemic control might lead to more severe hypoglycemic episodes and subsequent decreased cognitive ability, said Dr. Jacobson, head of the behavioral and mental health research section at the Joslin Diabetes Center, Boston.

But the recurrent, severe hypoglycemic events that are more likely to occur with tight glycemic control could still possibly have a negative cognitive effect on older adults, very young children, or those with a longer disease duration, he added.

The results from the multicenter, randomized Diabetes Control and Complications Trial (DCCT) and its continuation in the long-term observational Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that patients who received intensive glycemic control during the DCCT did not have any differences in cognition, compared with conventional treatment, as measured by an extensive test battery involving eight cognitive domains (problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency, and motor speed), Dr. Jacobson reported.

The 18 years of combined follow-up make the DCCT and the EDIC the largest, longest-term prospective study that has implemented a cognitive assessment of patients with any clinical condition, he said.

Among patients in either group, there were no differences in cognitive functioning in those who had no hypoglycemic episodes, one to five episodes, or more than five episodes.

Control of HbA_1c (glycosylated hemoglobin) values to less than 7.9% similarly showed no significant effects, except in sparing patients from small reductions in psychomotor efficiency and in improving motor speed. The “very modest” declines in psychomotor efficiency and motor speed that were associated with higher HbA_1c values (7.9% or greater) were “consistent with emerging literature on the effects of persistent hyperglycemia on mental and motor slowing,” Dr. Jacobson said.

The results did not change when the investigators removed 28 patients with potentially confounding illnesses–strokes, decreased vision, renal insufficiency–from the analysis, except that patients who had prior tight glycemic control in the DCCT had a significantly lower decline in psychomotor efficiency than did patients who received conventional treatment.

All of the analyses were adjusted to account for the confounding variables of baseline age, gender, years of education, length of follow-up, and the number of cognitive tests taken. (Patients took different numbers of tests because they entered the DCCT at different times.)

The initial results at the end of the DCCT showed that maintenance of near normal glycemic control reduced the risk of developing–or the progression of–microvascular complications.

After 10 years of additional follow-up in the EDIC study, the patients who had prior intensive treatment still had reduced progression of retinopathy, nephropathy, neuropathy, and cardiovascular events.

As patients in the intensive treatment arm of the DCCT finished the trial and entered the EDIC study, they did not maintain the same level of glycemic control during the ensuing years, whereas individuals who were in the conventional treatment arm of the DCCT received training on how to maintain tight glycemic control and soon began doing so on their own. Both groups had a mean HbA_1c value of 7.8% at the end of 12 years of follow-up in the EDIC study, which includes more than 90% of the original DCCT patients.

At the end of those 12 years, a significantly greater percentage of the 583 patients who were in the intensive treatment arm of the DCCT had one or more severe hypoglycemic events leading to coma or seizures than did the 553 patients who received conventional treatment (44%, or 258 patients with 880 events, vs. 34%, or 187 patients with 452 events).

Most (97%) of the participants were white and were 27 years old on average when they entered the DCCT, where they received a mean of 6.5 years of intervention; they were 45 years old on average after 12 years of follow-up in the EDIC trial. At the last follow-up, all of the participants were adults and about 50% were employed as professionals.

The patients in the study were “unusually healthy and subject to careful follow-up, which may suggest that those in worse control may show worse cognitive outcomes,” he said.

WASHINGTON – Tight glycemic control early in the course of type 1 diabetes does not result in later cognitive decline, according to new findings from two studies with an average of 18 years of follow-up data.

“Because of the length of follow-up and extent of cognitive testing, this study strongly supports the safety of intensive diabetes therapy,” Dr. Alan M. Jacobson said at the annual scientific sessions of the American Diabetes Association.

The results should allay the serious concerns that have been raised about whether tight glycemic control might lead to more severe hypoglycemic episodes and subsequent decreased cognitive ability, said Dr. Jacobson, head of the behavioral and mental health research section at the Joslin Diabetes Center, Boston.

But the recurrent, severe hypoglycemic events that are more likely to occur with tight glycemic control could still possibly have a negative cognitive effect on older adults, very young children, or those with a longer disease duration, he added.

The results from the multicenter, randomized Diabetes Control and Complications Trial (DCCT) and its continuation in the long-term observational Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that patients who received intensive glycemic control during the DCCT did not have any differences in cognition, compared with conventional treatment, as measured by an extensive test battery involving eight cognitive domains (problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency, and motor speed), Dr. Jacobson reported.

The 18 years of combined follow-up make the DCCT and the EDIC the largest, longest-term prospective study that has implemented a cognitive assessment of patients with any clinical condition, he said.

Among patients in either group, there were no differences in cognitive functioning in those who had no hypoglycemic episodes, one to five episodes, or more than five episodes.

Control of HbA_1c (glycosylated hemoglobin) values to less than 7.9% similarly showed no significant effects, except in sparing patients from small reductions in psychomotor efficiency and in improving motor speed. The “very modest” declines in psychomotor efficiency and motor speed that were associated with higher HbA_1c values (7.9% or greater) were “consistent with emerging literature on the effects of persistent hyperglycemia on mental and motor slowing,” Dr. Jacobson said.

The results did not change when the investigators removed 28 patients with potentially confounding illnesses–strokes, decreased vision, renal insufficiency–from the analysis, except that patients who had prior tight glycemic control in the DCCT had a significantly lower decline in psychomotor efficiency than did patients who received conventional treatment.

All of the analyses were adjusted to account for the confounding variables of baseline age, gender, years of education, length of follow-up, and the number of cognitive tests taken. (Patients took different numbers of tests because they entered the DCCT at different times.)

The initial results at the end of the DCCT showed that maintenance of near normal glycemic control reduced the risk of developing–or the progression of–microvascular complications.

After 10 years of additional follow-up in the EDIC study, the patients who had prior intensive treatment still had reduced progression of retinopathy, nephropathy, neuropathy, and cardiovascular events.

As patients in the intensive treatment arm of the DCCT finished the trial and entered the EDIC study, they did not maintain the same level of glycemic control during the ensuing years, whereas individuals who were in the conventional treatment arm of the DCCT received training on how to maintain tight glycemic control and soon began doing so on their own. Both groups had a mean HbA_1c value of 7.8% at the end of 12 years of follow-up in the EDIC study, which includes more than 90% of the original DCCT patients.

At the end of those 12 years, a significantly greater percentage of the 583 patients who were in the intensive treatment arm of the DCCT had one or more severe hypoglycemic events leading to coma or seizures than did the 553 patients who received conventional treatment (44%, or 258 patients with 880 events, vs. 34%, or 187 patients with 452 events).

Most (97%) of the participants were white and were 27 years old on average when they entered the DCCT, where they received a mean of 6.5 years of intervention; they were 45 years old on average after 12 years of follow-up in the EDIC trial. At the last follow-up, all of the participants were adults and about 50% were employed as professionals.

The patients in the study were “unusually healthy and subject to careful follow-up, which may suggest that those in worse control may show worse cognitive outcomes,” he said.