Endo 2012

HOUSTON – Laparoscopic sleeve gastrectomy with ileal interposition sent diabetes into remission in 20 of 43 adults and reduced the need for diabetes medications in the other 23 patients during an average of 20 months of follow-up.

Among the 30 obese (defined as having a body mass index greater than 27 kg/m²) patients in the study, 26 showed remission of diabetes – an 86% success rate that’s similar to results reported for gastric bypass surgery, Dr. Kirtikumar D. Modi said in a press briefing at the annual meeting of the Endocrine Society.

Patients had an average disease duration of 10 years and an average BMI of 33. In laparoscopic sleeve gastrectomy with ileal interposition, stapling reduces the size of the stomach, and a segment of the ileum is shifted to the jejunal area closer to the stomach. The average BMI fell to 26 after surgery. Among 30 patients who had hypertension before surgery, 27 had no hypertension postoperatively.

The surgery seemed to have no significant effect on lipid levels, "maybe because [the patients] were already on lipid-lowering drugs," said Dr. Modi, chief endocrinologist at Medwin Hospital in Hyderabad, India.

There were few complications; approximately 25% of patients had nausea and loss of appetite during the first postoperative month. Difficulty with rapid swallowing in six patients subsided over 2 weeks.

In a second series, Dr. Modi and his associates performed a laparoscopic diverted sleeve gastrectomy with ileal interposition on 17 additional patients who were not obese and had had diabetes longer than 10 years – the characteristics of patients who responded less well to the sleeve gastrectomy with ileal interposition in the first series.

Laparoscopic diverted sleeve gastrectomy diverts food away from parts of the small intestine, including the duodenum, where the absorption of nutrients begins, and the ileal segment is shifted more proximally. Patients who underwent this procedure had had diabetes for 15 years on average, and they had an average BMI of 29 as well as stimulated C-peptide levels greater than 4 ng/mL.

As expected, the mean BMI decreased to 23 over 18 months, he said. Of the eight patients who had hypertension before surgery, seven (88%) had no hypertension afterward. This time, treatment produced significant decreases in glycemic, lipid, and microalbuminuria levels.

At 9 months after surgery, diabetes was in remission in 12 (70%) of the 17 patients, and the other 5 patients needed fewer oral hyperglycemic medications than did those in the first series.

All patients in both studies had poorly controlled diabetes. The investigators defined diabetes remission as a hemoglobin A_1c level less than 6.5% and no further need for insulin or oral hypoglycemic agents.

The reduction in hemoglobin A_1c was disproportionately greater than the decline in BMI, suggesting benefits that are "much more than the weight improvement," he said.

More complications were seen in the second series, including three patients with minor intraoperative complications. Another patient developed ileus with ileal perforation 2 weeks after surgery and underwent laparotomy for repair. Three patients experienced nausea and anorexia for 2 weeks. Two patients developed vitamin B₁₂ deficiency at 12 months.

A previous study of 150 patients with uncontrolled type 2 diabetes reported better glycemic control in patients who were randomized to 12 months of medical therapy plus bariatric surgery (sleeve gastrectomy or Roux-en-Y gastric bypass), compared with those on medical treatment alone, Dr. Modi noted (N. Engl. J. Med. 2012;366:1567-76).

A separate retrospective study of 271,726 patients in the Bariatric Outcomes Longitudinal Database found that the efficacy and safety of laparoscopic sleeve gastrectomy fell between those of gastric banding and laparoscopic gastric bypass.

Dr. Modi reported having no financial disclosures.

HOUSTON – Laparoscopic sleeve gastrectomy with ileal interposition sent diabetes into remission in 20 of 43 adults and reduced the need for diabetes medications in the other 23 patients during an average of 20 months of follow-up.

Among the 30 obese (defined as having a body mass index greater than 27 kg/m²) patients in the study, 26 showed remission of diabetes – an 86% success rate that’s similar to results reported for gastric bypass surgery, Dr. Kirtikumar D. Modi said in a press briefing at the annual meeting of the Endocrine Society.

Patients had an average disease duration of 10 years and an average BMI of 33. In laparoscopic sleeve gastrectomy with ileal interposition, stapling reduces the size of the stomach, and a segment of the ileum is shifted to the jejunal area closer to the stomach. The average BMI fell to 26 after surgery. Among 30 patients who had hypertension before surgery, 27 had no hypertension postoperatively.

The surgery seemed to have no significant effect on lipid levels, "maybe because [the patients] were already on lipid-lowering drugs," said Dr. Modi, chief endocrinologist at Medwin Hospital in Hyderabad, India.

There were few complications; approximately 25% of patients had nausea and loss of appetite during the first postoperative month. Difficulty with rapid swallowing in six patients subsided over 2 weeks.

In a second series, Dr. Modi and his associates performed a laparoscopic diverted sleeve gastrectomy with ileal interposition on 17 additional patients who were not obese and had had diabetes longer than 10 years – the characteristics of patients who responded less well to the sleeve gastrectomy with ileal interposition in the first series.

Laparoscopic diverted sleeve gastrectomy diverts food away from parts of the small intestine, including the duodenum, where the absorption of nutrients begins, and the ileal segment is shifted more proximally. Patients who underwent this procedure had had diabetes for 15 years on average, and they had an average BMI of 29 as well as stimulated C-peptide levels greater than 4 ng/mL.

As expected, the mean BMI decreased to 23 over 18 months, he said. Of the eight patients who had hypertension before surgery, seven (88%) had no hypertension afterward. This time, treatment produced significant decreases in glycemic, lipid, and microalbuminuria levels.

At 9 months after surgery, diabetes was in remission in 12 (70%) of the 17 patients, and the other 5 patients needed fewer oral hyperglycemic medications than did those in the first series.

All patients in both studies had poorly controlled diabetes. The investigators defined diabetes remission as a hemoglobin A_1c level less than 6.5% and no further need for insulin or oral hypoglycemic agents.

The reduction in hemoglobin A_1c was disproportionately greater than the decline in BMI, suggesting benefits that are "much more than the weight improvement," he said.

More complications were seen in the second series, including three patients with minor intraoperative complications. Another patient developed ileus with ileal perforation 2 weeks after surgery and underwent laparotomy for repair. Three patients experienced nausea and anorexia for 2 weeks. Two patients developed vitamin B₁₂ deficiency at 12 months.

A previous study of 150 patients with uncontrolled type 2 diabetes reported better glycemic control in patients who were randomized to 12 months of medical therapy plus bariatric surgery (sleeve gastrectomy or Roux-en-Y gastric bypass), compared with those on medical treatment alone, Dr. Modi noted (N. Engl. J. Med. 2012;366:1567-76).

A separate retrospective study of 271,726 patients in the Bariatric Outcomes Longitudinal Database found that the efficacy and safety of laparoscopic sleeve gastrectomy fell between those of gastric banding and laparoscopic gastric bypass.

Dr. Modi reported having no financial disclosures.

HOUSTON – Laparoscopic sleeve gastrectomy with ileal interposition sent diabetes into remission in 20 of 43 adults and reduced the need for diabetes medications in the other 23 patients during an average of 20 months of follow-up.

Among the 30 obese (defined as having a body mass index greater than 27 kg/m²) patients in the study, 26 showed remission of diabetes – an 86% success rate that’s similar to results reported for gastric bypass surgery, Dr. Kirtikumar D. Modi said in a press briefing at the annual meeting of the Endocrine Society.

Patients had an average disease duration of 10 years and an average BMI of 33. In laparoscopic sleeve gastrectomy with ileal interposition, stapling reduces the size of the stomach, and a segment of the ileum is shifted to the jejunal area closer to the stomach. The average BMI fell to 26 after surgery. Among 30 patients who had hypertension before surgery, 27 had no hypertension postoperatively.

The surgery seemed to have no significant effect on lipid levels, "maybe because [the patients] were already on lipid-lowering drugs," said Dr. Modi, chief endocrinologist at Medwin Hospital in Hyderabad, India.

There were few complications; approximately 25% of patients had nausea and loss of appetite during the first postoperative month. Difficulty with rapid swallowing in six patients subsided over 2 weeks.

In a second series, Dr. Modi and his associates performed a laparoscopic diverted sleeve gastrectomy with ileal interposition on 17 additional patients who were not obese and had had diabetes longer than 10 years – the characteristics of patients who responded less well to the sleeve gastrectomy with ileal interposition in the first series.

Laparoscopic diverted sleeve gastrectomy diverts food away from parts of the small intestine, including the duodenum, where the absorption of nutrients begins, and the ileal segment is shifted more proximally. Patients who underwent this procedure had had diabetes for 15 years on average, and they had an average BMI of 29 as well as stimulated C-peptide levels greater than 4 ng/mL.

As expected, the mean BMI decreased to 23 over 18 months, he said. Of the eight patients who had hypertension before surgery, seven (88%) had no hypertension afterward. This time, treatment produced significant decreases in glycemic, lipid, and microalbuminuria levels.

At 9 months after surgery, diabetes was in remission in 12 (70%) of the 17 patients, and the other 5 patients needed fewer oral hyperglycemic medications than did those in the first series.

All patients in both studies had poorly controlled diabetes. The investigators defined diabetes remission as a hemoglobin A_1c level less than 6.5% and no further need for insulin or oral hypoglycemic agents.

The reduction in hemoglobin A_1c was disproportionately greater than the decline in BMI, suggesting benefits that are "much more than the weight improvement," he said.

More complications were seen in the second series, including three patients with minor intraoperative complications. Another patient developed ileus with ileal perforation 2 weeks after surgery and underwent laparotomy for repair. Three patients experienced nausea and anorexia for 2 weeks. Two patients developed vitamin B₁₂ deficiency at 12 months.

A previous study of 150 patients with uncontrolled type 2 diabetes reported better glycemic control in patients who were randomized to 12 months of medical therapy plus bariatric surgery (sleeve gastrectomy or Roux-en-Y gastric bypass), compared with those on medical treatment alone, Dr. Modi noted (N. Engl. J. Med. 2012;366:1567-76).

A separate retrospective study of 271,726 patients in the Bariatric Outcomes Longitudinal Database found that the efficacy and safety of laparoscopic sleeve gastrectomy fell between those of gastric banding and laparoscopic gastric bypass.

Dr. Modi reported having no financial disclosures.

HOUSTON – Hypoparathyroidism may soon lose its status as the only endocrine deficiency disease for which the missing hormone isn’t available as an approved replacement therapy.

That change may come as a result of the positive findings of the REPLACE study of the investigational recombinant human parathyroid hormone (1-84), known as Natpara.

REPLACE was a double-blind, randomized, multinational, dose-escalation clinical trial of 134 adults with hypoparathyroidism. After an average 10-week stabilization period in which participants’ oral calcium and active vitamin D doses were adjusted to maintain optimal biochemical control of their disease as defined by serum calcium concentrations of 8.0-9.0 mg/dL for 2 weeks, they were randomized 2:1 to once-daily self-injected subcutaneous recombinant human parathyroid hormone (rhPTH) or placebo for 24 weeks.

The starting dose of rhPTH was 50 mcg. Subjects underwent staged reductions in their calcium and vitamin D supplementation while maintaining a serum calcium level in the target range. In order to accomplish this, patients could be up-titrated to 75 mcg and if need be 100 mcg per day over 6-8 weeks, Dr. Michael Mannstadt explained at the annual meeting of the Endocrine Society.

The primary end point in the REPLACE study was at least a 50% reduction in oral calcium and vitamin D requirements at week 24 compared with baseline, along with maintenance of serum calcium in the target range. This combined end point was achieved in 53% of patients on rhPTH, compared with 2% of controls, reported Dr. Mannstadt, of Harvard Medical School and Massachusetts General Hospital, both in Boston.

At week 24, 43% of patients in the rhPTH arm no longer required vitamin D supplementation and could be maintained on an oral calcium dose of 500 mg/day or less of calcipotriol. This secondary end point was achieved in only 5% of controls.

The mean dose of active vitamin D was reduced by 78% compared with baseline in the rhPTH group and by 30% in controls. The mean dose of oral calcium was lowered by 52% in the rhPTH group, compared with a 5.7% increase over baseline in controls.

Natpara was generally well tolerated, with adverse event rates and profiles similar to those of the placebo arm. An ongoing extension phase of the REPLACE trial is looking at the effects of treatment beyond 24 weeks.

The REPLACE participants were similar to the patients typically encountered in clinical practice. They averaged 48 years of age and had a 13-year history of hypoparathyroidism; 78% were women; and their hormone deficiency resulted from surgery in three-quarters of cases.

Symptoms of hypoparathyroidism include paresthesias, uncontrollable muscle spasms, fatigue, laryngospasm, depression, and even seizures. The impetus for developing Natpara as the first replacement therapy for hypothyroidism stems from the high rate of serious complications resulting from current therapy, which entails large doses of calcium and vitamin D. High-dose calcium supplementation can result in major swings in serum calcium levels and, long term, as calcium builds up extraskeletally, in coronary artery calcification, renal damage, and neurocognitive abnormalities, Dr. Mannstadt noted.

This study was sponsored by NPS Pharmaceuticals. Dr. Mannstadt reported that he is on the company’s advisory board.

*CORRECTION 8/2/12:  Natpara was misspelled in the headline in a previous version of this story. This version reflects the corrected headline.

HOUSTON – Hypoparathyroidism may soon lose its status as the only endocrine deficiency disease for which the missing hormone isn’t available as an approved replacement therapy.

That change may come as a result of the positive findings of the REPLACE study of the investigational recombinant human parathyroid hormone (1-84), known as Natpara.

REPLACE was a double-blind, randomized, multinational, dose-escalation clinical trial of 134 adults with hypoparathyroidism. After an average 10-week stabilization period in which participants’ oral calcium and active vitamin D doses were adjusted to maintain optimal biochemical control of their disease as defined by serum calcium concentrations of 8.0-9.0 mg/dL for 2 weeks, they were randomized 2:1 to once-daily self-injected subcutaneous recombinant human parathyroid hormone (rhPTH) or placebo for 24 weeks.

The starting dose of rhPTH was 50 mcg. Subjects underwent staged reductions in their calcium and vitamin D supplementation while maintaining a serum calcium level in the target range. In order to accomplish this, patients could be up-titrated to 75 mcg and if need be 100 mcg per day over 6-8 weeks, Dr. Michael Mannstadt explained at the annual meeting of the Endocrine Society.

The primary end point in the REPLACE study was at least a 50% reduction in oral calcium and vitamin D requirements at week 24 compared with baseline, along with maintenance of serum calcium in the target range. This combined end point was achieved in 53% of patients on rhPTH, compared with 2% of controls, reported Dr. Mannstadt, of Harvard Medical School and Massachusetts General Hospital, both in Boston.

At week 24, 43% of patients in the rhPTH arm no longer required vitamin D supplementation and could be maintained on an oral calcium dose of 500 mg/day or less of calcipotriol. This secondary end point was achieved in only 5% of controls.

The mean dose of active vitamin D was reduced by 78% compared with baseline in the rhPTH group and by 30% in controls. The mean dose of oral calcium was lowered by 52% in the rhPTH group, compared with a 5.7% increase over baseline in controls.

Natpara was generally well tolerated, with adverse event rates and profiles similar to those of the placebo arm. An ongoing extension phase of the REPLACE trial is looking at the effects of treatment beyond 24 weeks.

The REPLACE participants were similar to the patients typically encountered in clinical practice. They averaged 48 years of age and had a 13-year history of hypoparathyroidism; 78% were women; and their hormone deficiency resulted from surgery in three-quarters of cases.

Symptoms of hypoparathyroidism include paresthesias, uncontrollable muscle spasms, fatigue, laryngospasm, depression, and even seizures. The impetus for developing Natpara as the first replacement therapy for hypothyroidism stems from the high rate of serious complications resulting from current therapy, which entails large doses of calcium and vitamin D. High-dose calcium supplementation can result in major swings in serum calcium levels and, long term, as calcium builds up extraskeletally, in coronary artery calcification, renal damage, and neurocognitive abnormalities, Dr. Mannstadt noted.

This study was sponsored by NPS Pharmaceuticals. Dr. Mannstadt reported that he is on the company’s advisory board.

*CORRECTION 8/2/12:  Natpara was misspelled in the headline in a previous version of this story. This version reflects the corrected headline.

HOUSTON – Hypoparathyroidism may soon lose its status as the only endocrine deficiency disease for which the missing hormone isn’t available as an approved replacement therapy.

That change may come as a result of the positive findings of the REPLACE study of the investigational recombinant human parathyroid hormone (1-84), known as Natpara.

REPLACE was a double-blind, randomized, multinational, dose-escalation clinical trial of 134 adults with hypoparathyroidism. After an average 10-week stabilization period in which participants’ oral calcium and active vitamin D doses were adjusted to maintain optimal biochemical control of their disease as defined by serum calcium concentrations of 8.0-9.0 mg/dL for 2 weeks, they were randomized 2:1 to once-daily self-injected subcutaneous recombinant human parathyroid hormone (rhPTH) or placebo for 24 weeks.

The starting dose of rhPTH was 50 mcg. Subjects underwent staged reductions in their calcium and vitamin D supplementation while maintaining a serum calcium level in the target range. In order to accomplish this, patients could be up-titrated to 75 mcg and if need be 100 mcg per day over 6-8 weeks, Dr. Michael Mannstadt explained at the annual meeting of the Endocrine Society.

The primary end point in the REPLACE study was at least a 50% reduction in oral calcium and vitamin D requirements at week 24 compared with baseline, along with maintenance of serum calcium in the target range. This combined end point was achieved in 53% of patients on rhPTH, compared with 2% of controls, reported Dr. Mannstadt, of Harvard Medical School and Massachusetts General Hospital, both in Boston.

At week 24, 43% of patients in the rhPTH arm no longer required vitamin D supplementation and could be maintained on an oral calcium dose of 500 mg/day or less of calcipotriol. This secondary end point was achieved in only 5% of controls.

The mean dose of active vitamin D was reduced by 78% compared with baseline in the rhPTH group and by 30% in controls. The mean dose of oral calcium was lowered by 52% in the rhPTH group, compared with a 5.7% increase over baseline in controls.

Natpara was generally well tolerated, with adverse event rates and profiles similar to those of the placebo arm. An ongoing extension phase of the REPLACE trial is looking at the effects of treatment beyond 24 weeks.

The REPLACE participants were similar to the patients typically encountered in clinical practice. They averaged 48 years of age and had a 13-year history of hypoparathyroidism; 78% were women; and their hormone deficiency resulted from surgery in three-quarters of cases.

Symptoms of hypoparathyroidism include paresthesias, uncontrollable muscle spasms, fatigue, laryngospasm, depression, and even seizures. The impetus for developing Natpara as the first replacement therapy for hypothyroidism stems from the high rate of serious complications resulting from current therapy, which entails large doses of calcium and vitamin D. High-dose calcium supplementation can result in major swings in serum calcium levels and, long term, as calcium builds up extraskeletally, in coronary artery calcification, renal damage, and neurocognitive abnormalities, Dr. Mannstadt noted.

This study was sponsored by NPS Pharmaceuticals. Dr. Mannstadt reported that he is on the company’s advisory board.

*CORRECTION 8/2/12:  Natpara was misspelled in the headline in a previous version of this story. This version reflects the corrected headline.

HOUSTON – Physical fitness nearly halved the risk of death in men with type 2 diabetes, regardless of whether they had left ventricular hypertrophy, a longitudinal study of 866 patients found.

During a follow-up period as long as 24 years (with a median 9-year follow-up), 236 men who had left ventricular hypertrophy and were within the lower 50th percentile of physical fitness were 20% more likely to die, compared with 225 men in a reference group who did not have left ventricular hypertrophy and also had a low level of fitness. The difference in mortality risk between these two groups did not reach statistical significance.

In contrast, compared with the reference group, the risk of death was 41% lower in 218 men who were physically fit (in the upper 50th percentile) and did not have left ventricular hypertrophy and 43% lower in 187 men who were fit and did have left ventricular hypertrophy, Dr. Khaled Alswat and his associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The risk reductions in the two fit groups were statistically significant.

"We, as doctors, do a lot of testing, and one of those tests should be an exercise test" for patients with diabetes who have an increased risk for heart disease, said Dr. Alswat, an endocrinology fellow at Veterans Affairs Medical Center and George Washington University, Washington. An exercise stress test provides objective measures that physicians can use to work with patients on improving their physical fitness, he said in an interview.

The patients underwent a standardized exercise stress test and echocardiographic evaluation at the VA Medical Center during 1986-2011. Those who had a peak exercise capacity of at least six metabolic equivalence tasks (METs) were considered fit, and the rest were defined as having a low level of fitness (within the lower 50th percentile).

Left ventricular hypertrophy was defined by a left ventricular mass index, calculated by dividing left ventricular mass by height in meters to the power of 2.7. A left ventricular mass index greater than 48 g/m^2.7 indicated left ventricular hypertrophy.

During follow-up, 346 patients died, for an annual death rate of 4%.

Smoking significantly increased mortality risk by 54%, a multivariate Cox proportional hazards analysis showed. The study controlled for the potential influences of age, body mass index, hypertension, smoking, and medications.

The adjusted mortality risk declined by 17% for every one-MET increase in fitness, Dr. Alswat reported.

Previous studies had shown that higher exercise capacity was associated with lower mortality risk in people with diabetes, but it had not been clear whether this applies to people with diabetes and left ventricular hypertrophy, he said.

Dr. Alswat reported having no relevant financial disclosures.

HOUSTON – Physical fitness nearly halved the risk of death in men with type 2 diabetes, regardless of whether they had left ventricular hypertrophy, a longitudinal study of 866 patients found.

During a follow-up period as long as 24 years (with a median 9-year follow-up), 236 men who had left ventricular hypertrophy and were within the lower 50th percentile of physical fitness were 20% more likely to die, compared with 225 men in a reference group who did not have left ventricular hypertrophy and also had a low level of fitness. The difference in mortality risk between these two groups did not reach statistical significance.

In contrast, compared with the reference group, the risk of death was 41% lower in 218 men who were physically fit (in the upper 50th percentile) and did not have left ventricular hypertrophy and 43% lower in 187 men who were fit and did have left ventricular hypertrophy, Dr. Khaled Alswat and his associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The risk reductions in the two fit groups were statistically significant.

"We, as doctors, do a lot of testing, and one of those tests should be an exercise test" for patients with diabetes who have an increased risk for heart disease, said Dr. Alswat, an endocrinology fellow at Veterans Affairs Medical Center and George Washington University, Washington. An exercise stress test provides objective measures that physicians can use to work with patients on improving their physical fitness, he said in an interview.

The patients underwent a standardized exercise stress test and echocardiographic evaluation at the VA Medical Center during 1986-2011. Those who had a peak exercise capacity of at least six metabolic equivalence tasks (METs) were considered fit, and the rest were defined as having a low level of fitness (within the lower 50th percentile).

Left ventricular hypertrophy was defined by a left ventricular mass index, calculated by dividing left ventricular mass by height in meters to the power of 2.7. A left ventricular mass index greater than 48 g/m^2.7 indicated left ventricular hypertrophy.

During follow-up, 346 patients died, for an annual death rate of 4%.

Smoking significantly increased mortality risk by 54%, a multivariate Cox proportional hazards analysis showed. The study controlled for the potential influences of age, body mass index, hypertension, smoking, and medications.

The adjusted mortality risk declined by 17% for every one-MET increase in fitness, Dr. Alswat reported.

Previous studies had shown that higher exercise capacity was associated with lower mortality risk in people with diabetes, but it had not been clear whether this applies to people with diabetes and left ventricular hypertrophy, he said.

Dr. Alswat reported having no relevant financial disclosures.

HOUSTON – Physical fitness nearly halved the risk of death in men with type 2 diabetes, regardless of whether they had left ventricular hypertrophy, a longitudinal study of 866 patients found.

During a follow-up period as long as 24 years (with a median 9-year follow-up), 236 men who had left ventricular hypertrophy and were within the lower 50th percentile of physical fitness were 20% more likely to die, compared with 225 men in a reference group who did not have left ventricular hypertrophy and also had a low level of fitness. The difference in mortality risk between these two groups did not reach statistical significance.

In contrast, compared with the reference group, the risk of death was 41% lower in 218 men who were physically fit (in the upper 50th percentile) and did not have left ventricular hypertrophy and 43% lower in 187 men who were fit and did have left ventricular hypertrophy, Dr. Khaled Alswat and his associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The risk reductions in the two fit groups were statistically significant.

"We, as doctors, do a lot of testing, and one of those tests should be an exercise test" for patients with diabetes who have an increased risk for heart disease, said Dr. Alswat, an endocrinology fellow at Veterans Affairs Medical Center and George Washington University, Washington. An exercise stress test provides objective measures that physicians can use to work with patients on improving their physical fitness, he said in an interview.

The patients underwent a standardized exercise stress test and echocardiographic evaluation at the VA Medical Center during 1986-2011. Those who had a peak exercise capacity of at least six metabolic equivalence tasks (METs) were considered fit, and the rest were defined as having a low level of fitness (within the lower 50th percentile).

Left ventricular hypertrophy was defined by a left ventricular mass index, calculated by dividing left ventricular mass by height in meters to the power of 2.7. A left ventricular mass index greater than 48 g/m^2.7 indicated left ventricular hypertrophy.

During follow-up, 346 patients died, for an annual death rate of 4%.

Smoking significantly increased mortality risk by 54%, a multivariate Cox proportional hazards analysis showed. The study controlled for the potential influences of age, body mass index, hypertension, smoking, and medications.

The adjusted mortality risk declined by 17% for every one-MET increase in fitness, Dr. Alswat reported.

Previous studies had shown that higher exercise capacity was associated with lower mortality risk in people with diabetes, but it had not been clear whether this applies to people with diabetes and left ventricular hypertrophy, he said.

Dr. Alswat reported having no relevant financial disclosures.

HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.

"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.

For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.

Sherry Boschert/IMNG Medical Media

The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.

The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.

Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."

The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).

A Look at the Data

Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.

In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.

Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.

Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.

Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.

The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.

Animal In Utero Studies

In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.

"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.

The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.

Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.

A third study randomized 23 pregnant rats to low levels of a mix of polychlorinated biphenyls (PCBs) and 22 to an inactive substance. Researchers found that these EDCs disrupted five genes that are critical to the normal hypothalamic control of reproduction. Compared with the control group, the EDC group showed delayed puberty in male offspring and disrupted reproductive cycles in adult female offspring.

The data collectively suggest that determinations of the potential risks or safety of any EDCs should be particular to specific age groups, Dr. Park said.

The EDCs identified so far are just the tip of the iceberg, she added. "Many more chemicals will be found" to be EDCs, she predicted.

Many products contain EDCs. Phthalates are part of some vinyl floor tiles, toys, blood transfusion bags, medical tubing, perfumes, lotions, cosmetics, air fresheners, laundry products, and more. BPA is found in many hard plastic bottles, cash register receipts, and the epoxy resin that lines canned goods. PCBs had been used in plastics, floor finishes, and electrical equipment before being banned in 1979 but are still present in air, water, and soil.

Tools for Clinicians

Dr. Gore and Dr. Taylor recommended these resources for clinicians who are wondering what and how to advise patients about EDCs in their environment:

• The Collaborative on Health and the Environment.

• Environment and Human Health.

Some other resources are available from the University of California's program on reproductive health and the environment.

The speakers reported having no relevant financial disclosures.

HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.

"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.

For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.

Sherry Boschert/IMNG Medical Media

The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.

The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.

Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."

The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).

A Look at the Data

Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.

In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.

Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.

Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.

Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.

The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.

Animal In Utero Studies

In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.

"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.

The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.

Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.

A third study randomized 23 pregnant rats to low levels of a mix of polychlorinated biphenyls (PCBs) and 22 to an inactive substance. Researchers found that these EDCs disrupted five genes that are critical to the normal hypothalamic control of reproduction. Compared with the control group, the EDC group showed delayed puberty in male offspring and disrupted reproductive cycles in adult female offspring.

The data collectively suggest that determinations of the potential risks or safety of any EDCs should be particular to specific age groups, Dr. Park said.

The EDCs identified so far are just the tip of the iceberg, she added. "Many more chemicals will be found" to be EDCs, she predicted.

Many products contain EDCs. Phthalates are part of some vinyl floor tiles, toys, blood transfusion bags, medical tubing, perfumes, lotions, cosmetics, air fresheners, laundry products, and more. BPA is found in many hard plastic bottles, cash register receipts, and the epoxy resin that lines canned goods. PCBs had been used in plastics, floor finishes, and electrical equipment before being banned in 1979 but are still present in air, water, and soil.

Tools for Clinicians

Dr. Gore and Dr. Taylor recommended these resources for clinicians who are wondering what and how to advise patients about EDCs in their environment:

• The Collaborative on Health and the Environment.

• Environment and Human Health.

Some other resources are available from the University of California's program on reproductive health and the environment.

The speakers reported having no relevant financial disclosures.

HOUSTON – The U.S. Environmental Protection Agency and other groups that evaluate chemicals need to assess endocrine-disrupting chemicals during critical life periods and strengthen screening programs to identify such chemicals, according to recommendations from the Endocrine Society.

"We believe now that the science behind endocrine-disrupting chemicals [EDCs] is incredibly strong," said Andrea C. Gore, Ph.D., professor of pharmacology and toxicology at the University of Texas, Austin. "The current regulatory process is not up to the standards that endocrinologists would use in their own labs," added Dr. Gore, one of the authors of a statement from the society.

For those reasons, the society released a set of principles calling for acknowledgement that changes in hormone action from EDC exposure during development are not correctable, and that they permanently and adversely affect cognitive function and other aspects of health. In addition, the newly released principles call for an acknowledgement that people are exposed to multiple EDCs in daily life, and that these exposures can have a cumulative effect.

Sherry Boschert/IMNG Medical Media

The Endocrine Society also recommended a simplified definition of endocrine-disrupting chemicals in light of mounting evidence of potential harm from exposure to them. By that definition, an EDC would be defined as an exogenous chemical (or mixture of chemicals) that interferes with any aspect of hormone action, Dr. Gore said at the annual meeting of the Endocrine Society.

The ability of a chemical to interfere with any aspect of hormone action is a clear predictor of adverse outcomes if a person is exposed during critical periods or developmental processes, said Dr. Gore.

Furthermore, "low-dose testing is absolutely critical," she said. "There is no safe dose, studies suggest."

The society released the statement of principles online in advance of publication in the journal Endocrinology (2012 June 25 [doi:10.1210/en.2012-1422]). The document updates the society’s first scientific statement about EDCs in 2009 (Endocrine Reviews 30:293-342).

A Look at the Data

Studies presented at the society’s annual meeting – along with hundreds of others in the last few years – prompted the new definition and principles.

In the first study presented at the meeting, children with higher levels of the EDC di(2-ethylhexyl) phthalate (DEHP) were more likely to be obese. In addition, serum levels of DEHP were associated with weight in a dose-dependent fashion, according to findings from the prospective study of 204 Korean schoolchildren, aged 6-13 years, including 105 obese children and 99 nonobese controls, Dr. Mi Jung Park reported at a press briefing.

Compared with the lowest quartile of serum DEHP, the risk of obesity increased by 25% in the second quartile, nearly quadrupled in the third quartile, and increased fivefold in the highest quartile after adjustment for the effects of age, sex, physical activity, household income, and daily caloric intake.

Mean serum DEHP levels were 107 ng/mL, significantly higher than the mean of 54 ng/mL in control children, said Dr. Park, a pediatric endocrinologist at Sanggye Paik Hospital in Seoul, Korea.

Serum DEHP levels showed significant positive correlations with body mass index, serum ALT, body fat mass, and uric acid levels, but did not correlate significantly with HDL cholesterol level, triglycerides, fasting blood sugar level, or fasting insulin level.

The worldwide epidemic in obesity over the past 40 years cannot be fully explained by overeating and inactivity and parallels increased use of chemicals in our societies, Dr. Park said. She called for prospective studies to determine whether DEHP exposure is a cause of childhood obesity.

Animal In Utero Studies

In the second study, eight pregnant mice exposed to the ubiquitous EDC bisphenol A (BPA) demonstrated "major and permanent changes in gene expression" in female offspring that became apparent only when they were exposed to estrogen through puberty or estrogen treatment, Dr. Hugh S. Taylor reported at the briefing.

"It seems the BPA exposure in utero was programming their response to estrogen later in life" by permanently altering the expression of more than 400 genes, said Dr. Taylor, professor of ob.gyn. and reproductive sciences and chief of reproductive endocrinology and infertility at Yale University, New Haven, Conn.

The changes may help explain the increased incidence of estrogen-related disorders seen after exposure to EDCs, he said.

Pregnant women should minimize their exposure to BPA, and their physicians should advise them on this, he added. "I think it’s something that we don’t do enough of right now as obstetricians or pediatricians. ... It’s important that all obstetricians be educated in endocrine disruptors. It’s not part of any formal medical school curriculum or obstetrics and gynecology training program," but should be, he said.

A third study randomized 23 pregnant rats to low levels of a mix of polychlorinated biphenyls (PCBs) and 22 to an inactive substance. Researchers found that these EDCs disrupted five genes that are critical to the normal hypothalamic control of reproduction. Compared with the control group, the EDC group showed delayed puberty in male offspring and disrupted reproductive cycles in adult female offspring.

The data collectively suggest that determinations of the potential risks or safety of any EDCs should be particular to specific age groups, Dr. Park said.

The EDCs identified so far are just the tip of the iceberg, she added. "Many more chemicals will be found" to be EDCs, she predicted.

Many products contain EDCs. Phthalates are part of some vinyl floor tiles, toys, blood transfusion bags, medical tubing, perfumes, lotions, cosmetics, air fresheners, laundry products, and more. BPA is found in many hard plastic bottles, cash register receipts, and the epoxy resin that lines canned goods. PCBs had been used in plastics, floor finishes, and electrical equipment before being banned in 1979 but are still present in air, water, and soil.

Tools for Clinicians

Dr. Gore and Dr. Taylor recommended these resources for clinicians who are wondering what and how to advise patients about EDCs in their environment:

• The Collaborative on Health and the Environment.

• Environment and Human Health.

Some other resources are available from the University of California's program on reproductive health and the environment.

The speakers reported having no relevant financial disclosures.

HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.

The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB₂), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB₂, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB₂ per mg of creatinine.

The men had a mean age of 49 years and a mean body mass index of 34 kg/m². They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.

The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB₂ per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.

Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA_1C) measurements.

Patients with aspirin resistance had a mean HbA_1c of 8.1%, compared with 7.7% in those without aspirin resistance.

Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.

Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.

Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.

Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.

Dr. Yaturu reported having no financial disclosures.

HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.

The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB₂), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB₂, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB₂ per mg of creatinine.

The men had a mean age of 49 years and a mean body mass index of 34 kg/m². They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.

The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB₂ per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.

Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA_1C) measurements.

Patients with aspirin resistance had a mean HbA_1c of 8.1%, compared with 7.7% in those without aspirin resistance.

Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.

Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.

Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.

Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.

Dr. Yaturu reported having no financial disclosures.

HOUSTON – In all, 53% of 142 young men with type 2 diabetes were resistant to the anticlotting effects of aspirin in a retrospective analysis, suggesting that they may need higher-than-usual doses of prophylactic aspirin to prevent heart attacks and strokes.

The study shows that aspirin resistance is common in men with type 2 diabetes, even in those with good glycemic control, Dr. Subhashini Yaturu and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

The investigators combined test results and information that had been gathered at one institution for a previous study with supplemental analyses of urine samples in order to measure concentrations of 11-dehydro-thromboxane beta-2 (11-DH-TXB₂), a major urinary metabolite of thromboxane that is formed during blood clotting. High urinary levels of 11-DH-TXB₂, measured using an enzyme immunoassay kit, indicate resistance to aspirin. Aspirin resistance was defined as a urine level of at least 1,500 pg 11-DH-TXB₂ per mg of creatinine.

The men had a mean age of 49 years and a mean body mass index of 34 kg/m². They’d had diabetes for a mean of 8 years; 88% of them had hypertension, and 23% had a history of coronary artery disease.

The investigators had hypothesized that aspirin resistance might be associated with high insulin levels and inflammatory markers. They found that 11-DH-TXB₂ per creatinine levels correlated with a history of coronary artery disease, abdominal fat content, and interleukin-6 levels. Levels were highest in patients with a longer duration of diabetes and increased urinary microalbumin levels, an indicator of early kidney disease in diabetes, said Dr. Yaturu, section chief of the endocrinology and metabolism department at the Albany (N.Y.) Stratton Veterans Affairs Medical Center.

Although high blood pressure and greater abdominal-fat distribution conventionally are associated with increased risk of cardiovascular disease, these were not associated with aspirin resistance in this study. Patients with or without aspirin resistance did not differ significantly in age, BMI, history of hypertension, or waist-to-hip ratio. They also did not differ significantly in biochemical parameters such as creatinine, thyroid function tests, lipid parameters, or glycosylated hemoglobin (HbA_1C) measurements.

Patients with aspirin resistance had a mean HbA_1c of 8.1%, compared with 7.7% in those without aspirin resistance.

Knowing that aspirin resistance is so common is important clinically because it may allow for additional measures. Giving patients higher medication doses or additional prophylactic therapy might be considered to prevent heart attacks and strokes, Dr. Yaturu said.

Identifying patients with aspirin resistance isn’t easy, however, given the lack of correlation with obvious clinical markers, she said in an interview. The measures used in the study are still a research tool. But if aspirin resistance is identified in a patient, consider doubling the standard low dose of aspirin, she suggested.

Cardiovascular risk in patients with type 2 diabetes is equivalent to that of patients without diabetes who have had a coronary event, she noted. The American Diabetes Association recommends enteric-coated aspirin at a dosage of 81-325 mg/day for the prevention of cardiovascular events in high-risk patients with diabetes, including those older than 40 years or patients with risk factors other than diabetes, such as hypertension, smoking, dyslipidemia, albuminuria, or a family history of cardiovascular disease.

Causes of aspirin resistance include concurrent use of NSAIDs that may compete with aspirin at the cyclooxygenase-1 receptor site; polymorphisms in the COX1 gene; poor glucose control; body weight; and conditions associated with a high turnover of platelets, she said.

Dr. Yaturu reported having no financial disclosures.

HOUSTON – Glipizide, glyburide, and glimepiride were independently associated with 59%-68% greater all-cause mortality risks than metformin in a retrospective study of nearly 24,000 type 2 diabetic patients on monotherapy for control of blood sugar.

Notably, among the 2,721 subjects with documented coronary artery disease (CAD), glipizide and glyburide carried an increased overall mortality risk compared with metformin, but glimepiride did not, according to Dr. Kevin M. Pantalone of Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"Metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes. Our results suggest that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred sulfonylurea in those with known coronary artery disease," he said at the annual meeting of the Endocrine Society.

Given that this was a retrospective study, it has to be viewed as hypothesis generating. A prospective study is warranted to establish the causal mechanism for the observed increase in mortality risk associated with these three widely prescribed sulfonylureas.

"The Food and Drug Administration now requires all drugs for the treatment of diabetes to have a cardiovascular safety study. These older drugs, which are considered tier 1, core-validated therapies by the American Diabetes Association, appear to have been given a free pass in terms of their cardiovascular risk," the endocrinologist observed.

He reported on 23,915 patients with type 2 diabetes who began monotherapy with metformin or one of the three sulfonylureas. The study was conducted using data from the Cleveland Clinic’s electronic health record system. Patients were followed for a median of 2.2 years, during which 2,546 deaths occurred in 58,513 person-years of follow-up.

In a multivariate Cox regression analysis adjusted for 16 variables, glipizide was independently associated with a 64% greater relative risk of all-cause mortality than was metformin. Glyburide was linked to a 59% increased risk, and glimepiride was associated with a 68% increased risk.

Among 2,721 diabetic patients with documented baseline CAD, there were 419 deaths during 5,980 person-years of follow-up. In this subgroup with CAD, glipizide had a 41% increased overall mortality risk, and glyburide had a 38% greater risk than metformin.

The clinical implications of these study findings are huge, Dr. Pantalone said. An estimated 26 million Americans have diabetes, and most of them either have known CAD or are at elevated risk for it. The four antidiabetic drugs examined in the study are among the most widely prescribed agents for blood glucose control, and all four are available in generic versions at bargain basement prices.

Dr. Alvin Powers commented that controversy surrounding the safety of sulfonylureas dates back several decades. As far as he’s concerned the issue remains unresolved, given the limitations of Dr. Pantalone’s retrospective study design.

"I think we really need a prospective comparison. I think metformin remains the primary drug, and when we add a second-line drug, the studies would show that glipizide and glimepiride are probably preferred over glyburide because of the length of time they’ve been studied. But I think that because glycemic control is important, the second-line drug still can be a sulfonylurea," said Dr. Powers, professor of medicine at Vanderbilt University, Nashville, Tenn., and director of the Vanderbilt Diabetes Center.

Dr. Pantalone’s study was supported by a research grant from AstraZeneca.

HOUSTON – Glipizide, glyburide, and glimepiride were independently associated with 59%-68% greater all-cause mortality risks than metformin in a retrospective study of nearly 24,000 type 2 diabetic patients on monotherapy for control of blood sugar.

Notably, among the 2,721 subjects with documented coronary artery disease (CAD), glipizide and glyburide carried an increased overall mortality risk compared with metformin, but glimepiride did not, according to Dr. Kevin M. Pantalone of Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"Metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes. Our results suggest that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred sulfonylurea in those with known coronary artery disease," he said at the annual meeting of the Endocrine Society.

Given that this was a retrospective study, it has to be viewed as hypothesis generating. A prospective study is warranted to establish the causal mechanism for the observed increase in mortality risk associated with these three widely prescribed sulfonylureas.

"The Food and Drug Administration now requires all drugs for the treatment of diabetes to have a cardiovascular safety study. These older drugs, which are considered tier 1, core-validated therapies by the American Diabetes Association, appear to have been given a free pass in terms of their cardiovascular risk," the endocrinologist observed.

He reported on 23,915 patients with type 2 diabetes who began monotherapy with metformin or one of the three sulfonylureas. The study was conducted using data from the Cleveland Clinic’s electronic health record system. Patients were followed for a median of 2.2 years, during which 2,546 deaths occurred in 58,513 person-years of follow-up.

In a multivariate Cox regression analysis adjusted for 16 variables, glipizide was independently associated with a 64% greater relative risk of all-cause mortality than was metformin. Glyburide was linked to a 59% increased risk, and glimepiride was associated with a 68% increased risk.

Among 2,721 diabetic patients with documented baseline CAD, there were 419 deaths during 5,980 person-years of follow-up. In this subgroup with CAD, glipizide had a 41% increased overall mortality risk, and glyburide had a 38% greater risk than metformin.

The clinical implications of these study findings are huge, Dr. Pantalone said. An estimated 26 million Americans have diabetes, and most of them either have known CAD or are at elevated risk for it. The four antidiabetic drugs examined in the study are among the most widely prescribed agents for blood glucose control, and all four are available in generic versions at bargain basement prices.

Dr. Alvin Powers commented that controversy surrounding the safety of sulfonylureas dates back several decades. As far as he’s concerned the issue remains unresolved, given the limitations of Dr. Pantalone’s retrospective study design.

"I think we really need a prospective comparison. I think metformin remains the primary drug, and when we add a second-line drug, the studies would show that glipizide and glimepiride are probably preferred over glyburide because of the length of time they’ve been studied. But I think that because glycemic control is important, the second-line drug still can be a sulfonylurea," said Dr. Powers, professor of medicine at Vanderbilt University, Nashville, Tenn., and director of the Vanderbilt Diabetes Center.

Dr. Pantalone’s study was supported by a research grant from AstraZeneca.

HOUSTON – Glipizide, glyburide, and glimepiride were independently associated with 59%-68% greater all-cause mortality risks than metformin in a retrospective study of nearly 24,000 type 2 diabetic patients on monotherapy for control of blood sugar.

Notably, among the 2,721 subjects with documented coronary artery disease (CAD), glipizide and glyburide carried an increased overall mortality risk compared with metformin, but glimepiride did not, according to Dr. Kevin M. Pantalone of Summa Western Reserve Hospital in Cuyahoga Falls, Ohio.

"Metformin, when not contraindicated, should be the first-line agent used to control blood sugar levels in patients with type 2 diabetes. Our results suggest that if a sulfonylurea is required to control blood sugar levels, glimepiride may be the preferred sulfonylurea in those with known coronary artery disease," he said at the annual meeting of the Endocrine Society.

Given that this was a retrospective study, it has to be viewed as hypothesis generating. A prospective study is warranted to establish the causal mechanism for the observed increase in mortality risk associated with these three widely prescribed sulfonylureas.

"The Food and Drug Administration now requires all drugs for the treatment of diabetes to have a cardiovascular safety study. These older drugs, which are considered tier 1, core-validated therapies by the American Diabetes Association, appear to have been given a free pass in terms of their cardiovascular risk," the endocrinologist observed.

He reported on 23,915 patients with type 2 diabetes who began monotherapy with metformin or one of the three sulfonylureas. The study was conducted using data from the Cleveland Clinic’s electronic health record system. Patients were followed for a median of 2.2 years, during which 2,546 deaths occurred in 58,513 person-years of follow-up.

In a multivariate Cox regression analysis adjusted for 16 variables, glipizide was independently associated with a 64% greater relative risk of all-cause mortality than was metformin. Glyburide was linked to a 59% increased risk, and glimepiride was associated with a 68% increased risk.

Among 2,721 diabetic patients with documented baseline CAD, there were 419 deaths during 5,980 person-years of follow-up. In this subgroup with CAD, glipizide had a 41% increased overall mortality risk, and glyburide had a 38% greater risk than metformin.

The clinical implications of these study findings are huge, Dr. Pantalone said. An estimated 26 million Americans have diabetes, and most of them either have known CAD or are at elevated risk for it. The four antidiabetic drugs examined in the study are among the most widely prescribed agents for blood glucose control, and all four are available in generic versions at bargain basement prices.

Dr. Alvin Powers commented that controversy surrounding the safety of sulfonylureas dates back several decades. As far as he’s concerned the issue remains unresolved, given the limitations of Dr. Pantalone’s retrospective study design.

"I think we really need a prospective comparison. I think metformin remains the primary drug, and when we add a second-line drug, the studies would show that glipizide and glimepiride are probably preferred over glyburide because of the length of time they’ve been studied. But I think that because glycemic control is important, the second-line drug still can be a sulfonylurea," said Dr. Powers, professor of medicine at Vanderbilt University, Nashville, Tenn., and director of the Vanderbilt Diabetes Center.

Dr. Pantalone’s study was supported by a research grant from AstraZeneca.

HOUSTON – Nearly one-third of obese patients who had type 2 diabetes and were randomized to an extended-release formulation of phentermine plus topiramate for 1 year achieved a rigorous composite diabetes management end point comprising greater-than-10% weight loss, an HbA_1c level lower than 6.5%, and systolic blood pressure lower than 130 mm Hg.

Moreover, almost 40% of patients who were randomized to the full dose of the drug combo achieved a less-rigorous trifecta consisting of the same blood pressure and HbA1c targets, plus a greater-than-5% weight loss, Dr. Donna H. Ryan reported at the annual meeting of the Endocrine Society.

On the basis of favorable feedback from the Food and Drug Administration, she expects the combination drug (brand name, Qnexa) will receive marketing approval before year’s end and perhaps as early as mid-July.

In late February, the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa. The FDA is expected to issue its decision by July 17.

The approved indication will be for medical weight loss in the treatment of obesity in patients with either a body mass index of at least 30 kg/m², or a BMI of 27 plus a comorbid condition, such as type 2 diabetes, according to Dr. Ryan of the Pennington Biomedical Research Center in Baton Rouge, La.

If approved, Qnexa would join lorcaserin (Belviq), which was approved by the FDA in late June and which also is indicated for patients with either a BMI of at least 30, or a BMI of at least 27 plus weight-related comorbidities.

More than 25 million Americans have type 2 diabetes, and most of them are obese.

Because both the FDA and Vivus Inc. (Qnexa’s developer) want to avoid the widespread abuse that often has been a problem with diet medications, the drug will be subject to a risk-management program. It will be available only through certified mail-order pharmacies that will collect patient data.

"This won’t be something you can get over the Internet. Patients won’t be able to go to a doc-in-a-box and say, ‘I want a diet drug; give me a prescription for this drug I read about in the newspaper.’ It won’t be like that," she said.

Dr. Ryan presented a secondary analysis from the randomized, double-blind, phase III CONQUER trial that involved roughly 2,500 obese patients (Lancet 2011;377:1341-52).

Her new substudy focused on the 388 CONQUER participants with type 2 diabetes. Like all participants in CONQUER, the diabetic patients were placed on a well-known, structured, lifestyle/behavioral modification program known as the LEARN (lifestyle, exercise, attitudes, relationships, nutrition) program for weight management. In addition, they were randomized to phentermine 7.5 mg/topiramate 46 mg, to phentermine 15 mg/topiramate 92 mg, or to placebo once daily. The subjects had relatively well-controlled diabetes and were on metformin as their sole antidiabetic medication at baseline.

At 56 weeks, the composite goal of a greater-than-5% weight loss from baseline, an HbA_1c level lower than 6.5%, and a systolic blood pressure lower than 130 mm Hg was met by 12% of patients on lifestyle modification plus placebo, by 27% of those on the lifestyle program and the lower dose, and by 39% of those on the full dose. The tougher goal, which involved a greater-than-10% weight loss, was achieved in 4% of controls, 14% on the lower dose, and 31% on the full dose, which suggests that the drug plus lifestyle modification was roughly eightfold more effective than lifestyle modification alone.

The mean weight loss from baseline was 2% in controls, 7% in patients on the lower dose, and 9% in those on full-dose therapy.

To reach the composite goals, 12% of control subjects required a net increase in antidiabetic medications, as did 2% of those on the low dose and 0.6% of those on the full dose.

Both phentermine and topiramate have been on the market as individual drugs for many years, and their side effects in the CONQUER diabetic subgroup were the familiar ones associated with those agents. Dry mouth and paresthesia each occurred in about 8% of patients on the lower dose, and constipation occurred in 15%. Because the side effects are dose related, it’s quite likely that phentermine 7.5 mg/topiramate 46 mg will be the recommended starting dose, according to Dr. Ryan.

Topiramate is a known teratogen with a risk of four or five cases of cleft palate per 1,000 exposures during pregnancy. For this reason, the combination drug will be a category X drug.

In an interview, Dr. Ryan said that she could see physicians setting up contracts with their patients to take the drug for at least a year, then stopping it in order to see if lifestyle modification efforts enable them to avoid weight regain. If the pounds start piling up, they’ll restart the drug.

Dr. Ryan reported serving as a scientific advisor to Vivus but holds no equity interest in the company.

HOUSTON – Nearly one-third of obese patients who had type 2 diabetes and were randomized to an extended-release formulation of phentermine plus topiramate for 1 year achieved a rigorous composite diabetes management end point comprising greater-than-10% weight loss, an HbA_1c level lower than 6.5%, and systolic blood pressure lower than 130 mm Hg.

Moreover, almost 40% of patients who were randomized to the full dose of the drug combo achieved a less-rigorous trifecta consisting of the same blood pressure and HbA1c targets, plus a greater-than-5% weight loss, Dr. Donna H. Ryan reported at the annual meeting of the Endocrine Society.

On the basis of favorable feedback from the Food and Drug Administration, she expects the combination drug (brand name, Qnexa) will receive marketing approval before year’s end and perhaps as early as mid-July.

In late February, the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa. The FDA is expected to issue its decision by July 17.

The approved indication will be for medical weight loss in the treatment of obesity in patients with either a body mass index of at least 30 kg/m², or a BMI of 27 plus a comorbid condition, such as type 2 diabetes, according to Dr. Ryan of the Pennington Biomedical Research Center in Baton Rouge, La.

If approved, Qnexa would join lorcaserin (Belviq), which was approved by the FDA in late June and which also is indicated for patients with either a BMI of at least 30, or a BMI of at least 27 plus weight-related comorbidities.

More than 25 million Americans have type 2 diabetes, and most of them are obese.

Because both the FDA and Vivus Inc. (Qnexa’s developer) want to avoid the widespread abuse that often has been a problem with diet medications, the drug will be subject to a risk-management program. It will be available only through certified mail-order pharmacies that will collect patient data.

"This won’t be something you can get over the Internet. Patients won’t be able to go to a doc-in-a-box and say, ‘I want a diet drug; give me a prescription for this drug I read about in the newspaper.’ It won’t be like that," she said.

Dr. Ryan presented a secondary analysis from the randomized, double-blind, phase III CONQUER trial that involved roughly 2,500 obese patients (Lancet 2011;377:1341-52).

Her new substudy focused on the 388 CONQUER participants with type 2 diabetes. Like all participants in CONQUER, the diabetic patients were placed on a well-known, structured, lifestyle/behavioral modification program known as the LEARN (lifestyle, exercise, attitudes, relationships, nutrition) program for weight management. In addition, they were randomized to phentermine 7.5 mg/topiramate 46 mg, to phentermine 15 mg/topiramate 92 mg, or to placebo once daily. The subjects had relatively well-controlled diabetes and were on metformin as their sole antidiabetic medication at baseline.

At 56 weeks, the composite goal of a greater-than-5% weight loss from baseline, an HbA_1c level lower than 6.5%, and a systolic blood pressure lower than 130 mm Hg was met by 12% of patients on lifestyle modification plus placebo, by 27% of those on the lifestyle program and the lower dose, and by 39% of those on the full dose. The tougher goal, which involved a greater-than-10% weight loss, was achieved in 4% of controls, 14% on the lower dose, and 31% on the full dose, which suggests that the drug plus lifestyle modification was roughly eightfold more effective than lifestyle modification alone.

The mean weight loss from baseline was 2% in controls, 7% in patients on the lower dose, and 9% in those on full-dose therapy.

To reach the composite goals, 12% of control subjects required a net increase in antidiabetic medications, as did 2% of those on the low dose and 0.6% of those on the full dose.

Both phentermine and topiramate have been on the market as individual drugs for many years, and their side effects in the CONQUER diabetic subgroup were the familiar ones associated with those agents. Dry mouth and paresthesia each occurred in about 8% of patients on the lower dose, and constipation occurred in 15%. Because the side effects are dose related, it’s quite likely that phentermine 7.5 mg/topiramate 46 mg will be the recommended starting dose, according to Dr. Ryan.

Topiramate is a known teratogen with a risk of four or five cases of cleft palate per 1,000 exposures during pregnancy. For this reason, the combination drug will be a category X drug.

In an interview, Dr. Ryan said that she could see physicians setting up contracts with their patients to take the drug for at least a year, then stopping it in order to see if lifestyle modification efforts enable them to avoid weight regain. If the pounds start piling up, they’ll restart the drug.

Dr. Ryan reported serving as a scientific advisor to Vivus but holds no equity interest in the company.

HOUSTON – Nearly one-third of obese patients who had type 2 diabetes and were randomized to an extended-release formulation of phentermine plus topiramate for 1 year achieved a rigorous composite diabetes management end point comprising greater-than-10% weight loss, an HbA_1c level lower than 6.5%, and systolic blood pressure lower than 130 mm Hg.

Moreover, almost 40% of patients who were randomized to the full dose of the drug combo achieved a less-rigorous trifecta consisting of the same blood pressure and HbA1c targets, plus a greater-than-5% weight loss, Dr. Donna H. Ryan reported at the annual meeting of the Endocrine Society.

On the basis of favorable feedback from the Food and Drug Administration, she expects the combination drug (brand name, Qnexa) will receive marketing approval before year’s end and perhaps as early as mid-July.

In late February, the Endocrinologic and Metabolic Drugs Advisory Committee voted 20-2 for approval of Qnexa. The FDA is expected to issue its decision by July 17.

The approved indication will be for medical weight loss in the treatment of obesity in patients with either a body mass index of at least 30 kg/m², or a BMI of 27 plus a comorbid condition, such as type 2 diabetes, according to Dr. Ryan of the Pennington Biomedical Research Center in Baton Rouge, La.

If approved, Qnexa would join lorcaserin (Belviq), which was approved by the FDA in late June and which also is indicated for patients with either a BMI of at least 30, or a BMI of at least 27 plus weight-related comorbidities.

More than 25 million Americans have type 2 diabetes, and most of them are obese.

Because both the FDA and Vivus Inc. (Qnexa’s developer) want to avoid the widespread abuse that often has been a problem with diet medications, the drug will be subject to a risk-management program. It will be available only through certified mail-order pharmacies that will collect patient data.

"This won’t be something you can get over the Internet. Patients won’t be able to go to a doc-in-a-box and say, ‘I want a diet drug; give me a prescription for this drug I read about in the newspaper.’ It won’t be like that," she said.

Dr. Ryan presented a secondary analysis from the randomized, double-blind, phase III CONQUER trial that involved roughly 2,500 obese patients (Lancet 2011;377:1341-52).

Her new substudy focused on the 388 CONQUER participants with type 2 diabetes. Like all participants in CONQUER, the diabetic patients were placed on a well-known, structured, lifestyle/behavioral modification program known as the LEARN (lifestyle, exercise, attitudes, relationships, nutrition) program for weight management. In addition, they were randomized to phentermine 7.5 mg/topiramate 46 mg, to phentermine 15 mg/topiramate 92 mg, or to placebo once daily. The subjects had relatively well-controlled diabetes and were on metformin as their sole antidiabetic medication at baseline.

At 56 weeks, the composite goal of a greater-than-5% weight loss from baseline, an HbA_1c level lower than 6.5%, and a systolic blood pressure lower than 130 mm Hg was met by 12% of patients on lifestyle modification plus placebo, by 27% of those on the lifestyle program and the lower dose, and by 39% of those on the full dose. The tougher goal, which involved a greater-than-10% weight loss, was achieved in 4% of controls, 14% on the lower dose, and 31% on the full dose, which suggests that the drug plus lifestyle modification was roughly eightfold more effective than lifestyle modification alone.

The mean weight loss from baseline was 2% in controls, 7% in patients on the lower dose, and 9% in those on full-dose therapy.

To reach the composite goals, 12% of control subjects required a net increase in antidiabetic medications, as did 2% of those on the low dose and 0.6% of those on the full dose.

Both phentermine and topiramate have been on the market as individual drugs for many years, and their side effects in the CONQUER diabetic subgroup were the familiar ones associated with those agents. Dry mouth and paresthesia each occurred in about 8% of patients on the lower dose, and constipation occurred in 15%. Because the side effects are dose related, it’s quite likely that phentermine 7.5 mg/topiramate 46 mg will be the recommended starting dose, according to Dr. Ryan.

Topiramate is a known teratogen with a risk of four or five cases of cleft palate per 1,000 exposures during pregnancy. For this reason, the combination drug will be a category X drug.

In an interview, Dr. Ryan said that she could see physicians setting up contracts with their patients to take the drug for at least a year, then stopping it in order to see if lifestyle modification efforts enable them to avoid weight regain. If the pounds start piling up, they’ll restart the drug.

Dr. Ryan reported serving as a scientific advisor to Vivus but holds no equity interest in the company.

HOUSTON – One in five patients whose type 2 diabetes went into remission following gastric bypass surgery experienced disease re-emergence within 5 years postoperatively.

The likelihood of diabetes recurrence in this retrospective single-center study wasn’t affected by preoperative body mass index or the amount of weight regained postsurgically.

Indeed, the only significant risk factor for diabetes reemergence was a longer duration of type 2 diabetes preoperatively. Patients with a greater than 5-year preoperative history of the disease were 3.8-fold more likely to experience disease recurrence, according to Dr. Yessica Ramos of the Mayo Clinic Arizona, Scottsdale.

The clinical implication: "Early surgical intervention in the type 2 diabetic obese population may improve the durability of remission of type 2 diabetes," she said.

Dr. Ramos reported on 72 obese patients with type 2 diabetes who underwent Roux-en-Y gastric bypass at the Mayo Clinic Arizona during 2000-2007 for whom 5-year follow-up data were available. The patients’ mean preoperative body mass index was 45 kg/m², with an average age of 49.5 years.

Sixty-six of the 72 patients (92%) experienced remission of their diabetes as defined by a hemoglobin A_1c below 6.5% while off all antidiabetic medications. The other six patients had persistent type 2 diabetes throughout follow-up.

A total of 14 of 66 patients, or 21%, whose type 2 diabetes went into remission subsequently saw their disease return as defined by an HbA_1c of 6.5% or more, a fasting blood glucose greater than 7 mmol/L, or use of antidiabetic drugs.

Diabetes returned as early as 2 years post surgery in five patients.

The explanation for the high rate of diabetes reemergence remains unclear. Retrospective studies of bariatric surgery patients are notoriously difficult because the surgery is often life changing and patients are frequently lost to follow-up.

Dr. Ramos’s working hypothesis is that patients with longer duration of type 2 diabetes are at a higher risk of recurrence because they have more compromised beta cell function. But definitive answers must await further reports from prospective randomized trials of surgery vs. medication as a treatment for type 2 diabetes in obese patients, such as the one reported from the Cleveland Clinic (N. Engl. J. Med. 2012;366:1567-76), or analysis of data from the large multicenter bariatric surgery registries.

Dr. Ramos reported having no financial conflicts.

HOUSTON – One in five patients whose type 2 diabetes went into remission following gastric bypass surgery experienced disease re-emergence within 5 years postoperatively.

The likelihood of diabetes recurrence in this retrospective single-center study wasn’t affected by preoperative body mass index or the amount of weight regained postsurgically.

Indeed, the only significant risk factor for diabetes reemergence was a longer duration of type 2 diabetes preoperatively. Patients with a greater than 5-year preoperative history of the disease were 3.8-fold more likely to experience disease recurrence, according to Dr. Yessica Ramos of the Mayo Clinic Arizona, Scottsdale.

The clinical implication: "Early surgical intervention in the type 2 diabetic obese population may improve the durability of remission of type 2 diabetes," she said.

Dr. Ramos reported on 72 obese patients with type 2 diabetes who underwent Roux-en-Y gastric bypass at the Mayo Clinic Arizona during 2000-2007 for whom 5-year follow-up data were available. The patients’ mean preoperative body mass index was 45 kg/m², with an average age of 49.5 years.

Sixty-six of the 72 patients (92%) experienced remission of their diabetes as defined by a hemoglobin A_1c below 6.5% while off all antidiabetic medications. The other six patients had persistent type 2 diabetes throughout follow-up.

A total of 14 of 66 patients, or 21%, whose type 2 diabetes went into remission subsequently saw their disease return as defined by an HbA_1c of 6.5% or more, a fasting blood glucose greater than 7 mmol/L, or use of antidiabetic drugs.

Diabetes returned as early as 2 years post surgery in five patients.

The explanation for the high rate of diabetes reemergence remains unclear. Retrospective studies of bariatric surgery patients are notoriously difficult because the surgery is often life changing and patients are frequently lost to follow-up.

Dr. Ramos’s working hypothesis is that patients with longer duration of type 2 diabetes are at a higher risk of recurrence because they have more compromised beta cell function. But definitive answers must await further reports from prospective randomized trials of surgery vs. medication as a treatment for type 2 diabetes in obese patients, such as the one reported from the Cleveland Clinic (N. Engl. J. Med. 2012;366:1567-76), or analysis of data from the large multicenter bariatric surgery registries.

Dr. Ramos reported having no financial conflicts.

HOUSTON – One in five patients whose type 2 diabetes went into remission following gastric bypass surgery experienced disease re-emergence within 5 years postoperatively.

The likelihood of diabetes recurrence in this retrospective single-center study wasn’t affected by preoperative body mass index or the amount of weight regained postsurgically.

Indeed, the only significant risk factor for diabetes reemergence was a longer duration of type 2 diabetes preoperatively. Patients with a greater than 5-year preoperative history of the disease were 3.8-fold more likely to experience disease recurrence, according to Dr. Yessica Ramos of the Mayo Clinic Arizona, Scottsdale.

The clinical implication: "Early surgical intervention in the type 2 diabetic obese population may improve the durability of remission of type 2 diabetes," she said.

Dr. Ramos reported on 72 obese patients with type 2 diabetes who underwent Roux-en-Y gastric bypass at the Mayo Clinic Arizona during 2000-2007 for whom 5-year follow-up data were available. The patients’ mean preoperative body mass index was 45 kg/m², with an average age of 49.5 years.

Sixty-six of the 72 patients (92%) experienced remission of their diabetes as defined by a hemoglobin A_1c below 6.5% while off all antidiabetic medications. The other six patients had persistent type 2 diabetes throughout follow-up.

A total of 14 of 66 patients, or 21%, whose type 2 diabetes went into remission subsequently saw their disease return as defined by an HbA_1c of 6.5% or more, a fasting blood glucose greater than 7 mmol/L, or use of antidiabetic drugs.

Diabetes returned as early as 2 years post surgery in five patients.

The explanation for the high rate of diabetes reemergence remains unclear. Retrospective studies of bariatric surgery patients are notoriously difficult because the surgery is often life changing and patients are frequently lost to follow-up.

Dr. Ramos’s working hypothesis is that patients with longer duration of type 2 diabetes are at a higher risk of recurrence because they have more compromised beta cell function. But definitive answers must await further reports from prospective randomized trials of surgery vs. medication as a treatment for type 2 diabetes in obese patients, such as the one reported from the Cleveland Clinic (N. Engl. J. Med. 2012;366:1567-76), or analysis of data from the large multicenter bariatric surgery registries.

Dr. Ramos reported having no financial conflicts.

HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.

The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.

"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.

Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.

"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.

ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.

Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.

At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.

Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.

In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.

Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.

One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.

Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.

He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.

HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.

The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.

"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.

Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.

"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.

ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.

Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.

At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.

Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.

In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.

Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.

One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.

Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.

He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.

HOUSTON – One year of denosumab for treatment of men with low bone mineral density resulted in significant increases in bone density at the lumbar spine and all other measured skeletal sites in the phase III ADAMO trial.

The drug’s effects on BMD were similar regardless of patient age, baseline testosterone level, initial BMD, and estimated 10-year osteoporotic fracture risk, according to Dr. Ugis Gruntmanis of the Dallas Veterans Affairs Medical Center and the University of Texas Southwestern Medical Center.

"The increases in bone mineral density in this population were similar to those observed in earlier trials in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy," he reported at the annual meeting of the Endocrine Society.

Moreover, the adverse event profile for denosumab (Prolia) in ADAMO was indistinguishable from that with placebo.

"There was no osteonecrosis of the jaw or atypical femur fractures in this study. You really wouldn’t expect to see that in a study of this size," the endocrinologist added.

ADAMO is a multicenter, double-blind, randomized, phase III clinical trial in which 242 men with low BMD were randomized to 60 mg of denosumab or to placebo given subcutaneously every 6 months for 1 year. The primary end point in ADAMO was change in BMD at the lumbar spine from baseline through 12 months. At the 12-month mark, all patients were placed on open-label denosumab for another year; the 24-month secondary outcomes are not in yet.

Participants had to have a BMD T-score of -2.0 or less and -3.5 or greater at the lumbar spine or femoral neck, or a prior major osteoporotic fracture along with a T-score of -1.0 or less and -3.5 at the lumbar spine or femoral neck. The men’s average age was 65 years, 94% were white, and one-quarter had a history of a major osteoporotic fracture. All subjects received daily calcium and vitamin D supplements.

At the 6-month mark, lumbar spine BMD had improved by 4.3% over baseline in the denosumab group compared with 0.9% in controls. At 1 year, the denosumab group averaged a 5.7% increase over baseline while the placebo group remained flat at a 0.9% gain.

Total hip BMD improved by 2.4% at 12 months in the denosumab group compared with 0.3% in controls, and by 0.6% at the distal one-third of the radius compared with a 0.3% loss with placebo; both of those differences favoring denosumab were statistically significant. So were the denosumab-induced BMD gains at the femoral neck and trochanter.

In subgroup analyses, the 15% of men with a baseline serum testosterone below 250 ng/dL had a 4.4% greater gain in lumbar spine BMD than with placebo, while those with a testosterone of 250 ng/dL or above had a similar 4.8% net gain.

Men with a baseline FRAX score placing them in the lowest tertile for 10-year major osteoporotic fracture risk, at less than 6.4%, had an absolute 5.1% greater gain in lumbar spine BMD than with placebo, while those with a 10-year risk of 6.4%-11.2% had a net 5.3% gain in lumbar spine BMD and men with a greater than 11.2% fracture risk had a net placebo-subtracted 4.0% gain; the denosumab-driven BMD gains in these three fracture risk groups were statistically similar, according to Dr. Gruntmanis.

One of the secondary end points in ADAMO was the change in the bone resorption biomarker CTX-1 between baseline and day 15 of the study. The CTX-1 level plunged by 81% in the denosumab group by day 15, with 60% suppression at 12 months.

Osteoporosis and fractures remain widely underrecognized and undertreated in men, Dr. Gruntmanis said. An estimated 2 million American men have osteoporosis. Worldwide, 39% of all osteoporotic fractures occur in men above age 50.

He reported receiving research grants from Amgen, Novartis, GlaxoSmithKline, and Procter & Gamble.

HOUSTON – Second-trimester maternal obesity was associated with lower scores in offspring on neurocognitive tests in early childhood.

This observation initially came as an unexpected finding, a byproduct of a case-control study set up for another purpose. But the disturbing finding, particularly in light of the ongoing obesity epidemic, led researchers to take a second look at the issue using an entirely separate data set. Those findings were confirmatory, Wendy Y. Craig, Ph.D., of the Foundation for Blood Research in Scarborough, Maine, reported at the annual meeting of the Endocrine Society.

The initial study involved a cohort of 101 children who underwent neurocognitive testing at age 2 years using the Bayley Scales of Infant Development, Third Edition (BSID-III). Their mothers, who were pregnant during 2004-2006, had a 30% prevalence of second trimester obesity.

The mean BSID-III cognitive and motor scores didn’t differ significantly between offspring of mothers who were normal-weight, overweight, or obese in pregnancy. However, mean BSID-III language scores averaged 110.6 in the children of normal-weight mothers, 107.2 in those whose mothers were overweight, and 98.0 in children born to women with second trimester obesity; that difference was highly statistically significant (P = .009).

Moreover, after adjustment for potential confounders in a multivariate regression analysis, it was apparent that the proportion of children with a BSID-III composite score below 85 rose with increasing maternal weight in pregnancy. The rate was 3.1% in the offspring of normal weight mothers, 7.7% in kids whose mothers were overweight, and 33.3% in those whose mothers were obese.

The second study included 118 children tested at age 8 years using the Wechsler Intelligence Scale for Children (WISC-III). Their mothers had been pregnant during 1987-1990, or 15 years earlier than in the first study population, and their prevalence of second-trimester obesity in that earlier, leaner era was a mere 10%.

The mean unadjusted WISC-III performance IQ score for children whose mothers were obese in pregnancy was 10.7 points lower than children of normal-weight mothers. Similarly, the full scale IQ and verbal subscale scores were lower by an average of 9.2 and 6.4 points, respectively.

"Although we cannot rule out the possibility that other covariates not measured in this study were responsible for the observed relationships, an independent effect of maternal obesity on the child’s early neurocognitive development deserves further investigation," Dr. Craig concluded.

All participants in both studies were recruited from the Maine statewide pregnancy project. The studies were supported by the National Institute of Child Health and Human Development, the Thrasher Fund, and Knoll Pharmaceuticals. Dr. Craig reported having no financial conflicts.

HOUSTON – Second-trimester maternal obesity was associated with lower scores in offspring on neurocognitive tests in early childhood.

This observation initially came as an unexpected finding, a byproduct of a case-control study set up for another purpose. But the disturbing finding, particularly in light of the ongoing obesity epidemic, led researchers to take a second look at the issue using an entirely separate data set. Those findings were confirmatory, Wendy Y. Craig, Ph.D., of the Foundation for Blood Research in Scarborough, Maine, reported at the annual meeting of the Endocrine Society.

The initial study involved a cohort of 101 children who underwent neurocognitive testing at age 2 years using the Bayley Scales of Infant Development, Third Edition (BSID-III). Their mothers, who were pregnant during 2004-2006, had a 30% prevalence of second trimester obesity.

The mean BSID-III cognitive and motor scores didn’t differ significantly between offspring of mothers who were normal-weight, overweight, or obese in pregnancy. However, mean BSID-III language scores averaged 110.6 in the children of normal-weight mothers, 107.2 in those whose mothers were overweight, and 98.0 in children born to women with second trimester obesity; that difference was highly statistically significant (P = .009).

Moreover, after adjustment for potential confounders in a multivariate regression analysis, it was apparent that the proportion of children with a BSID-III composite score below 85 rose with increasing maternal weight in pregnancy. The rate was 3.1% in the offspring of normal weight mothers, 7.7% in kids whose mothers were overweight, and 33.3% in those whose mothers were obese.

The second study included 118 children tested at age 8 years using the Wechsler Intelligence Scale for Children (WISC-III). Their mothers had been pregnant during 1987-1990, or 15 years earlier than in the first study population, and their prevalence of second-trimester obesity in that earlier, leaner era was a mere 10%.

The mean unadjusted WISC-III performance IQ score for children whose mothers were obese in pregnancy was 10.7 points lower than children of normal-weight mothers. Similarly, the full scale IQ and verbal subscale scores were lower by an average of 9.2 and 6.4 points, respectively.

"Although we cannot rule out the possibility that other covariates not measured in this study were responsible for the observed relationships, an independent effect of maternal obesity on the child’s early neurocognitive development deserves further investigation," Dr. Craig concluded.

All participants in both studies were recruited from the Maine statewide pregnancy project. The studies were supported by the National Institute of Child Health and Human Development, the Thrasher Fund, and Knoll Pharmaceuticals. Dr. Craig reported having no financial conflicts.

HOUSTON – Second-trimester maternal obesity was associated with lower scores in offspring on neurocognitive tests in early childhood.

This observation initially came as an unexpected finding, a byproduct of a case-control study set up for another purpose. But the disturbing finding, particularly in light of the ongoing obesity epidemic, led researchers to take a second look at the issue using an entirely separate data set. Those findings were confirmatory, Wendy Y. Craig, Ph.D., of the Foundation for Blood Research in Scarborough, Maine, reported at the annual meeting of the Endocrine Society.

The initial study involved a cohort of 101 children who underwent neurocognitive testing at age 2 years using the Bayley Scales of Infant Development, Third Edition (BSID-III). Their mothers, who were pregnant during 2004-2006, had a 30% prevalence of second trimester obesity.

The mean BSID-III cognitive and motor scores didn’t differ significantly between offspring of mothers who were normal-weight, overweight, or obese in pregnancy. However, mean BSID-III language scores averaged 110.6 in the children of normal-weight mothers, 107.2 in those whose mothers were overweight, and 98.0 in children born to women with second trimester obesity; that difference was highly statistically significant (P = .009).

Moreover, after adjustment for potential confounders in a multivariate regression analysis, it was apparent that the proportion of children with a BSID-III composite score below 85 rose with increasing maternal weight in pregnancy. The rate was 3.1% in the offspring of normal weight mothers, 7.7% in kids whose mothers were overweight, and 33.3% in those whose mothers were obese.

The second study included 118 children tested at age 8 years using the Wechsler Intelligence Scale for Children (WISC-III). Their mothers had been pregnant during 1987-1990, or 15 years earlier than in the first study population, and their prevalence of second-trimester obesity in that earlier, leaner era was a mere 10%.

The mean unadjusted WISC-III performance IQ score for children whose mothers were obese in pregnancy was 10.7 points lower than children of normal-weight mothers. Similarly, the full scale IQ and verbal subscale scores were lower by an average of 9.2 and 6.4 points, respectively.

"Although we cannot rule out the possibility that other covariates not measured in this study were responsible for the observed relationships, an independent effect of maternal obesity on the child’s early neurocognitive development deserves further investigation," Dr. Craig concluded.

All participants in both studies were recruited from the Maine statewide pregnancy project. The studies were supported by the National Institute of Child Health and Human Development, the Thrasher Fund, and Knoll Pharmaceuticals. Dr. Craig reported having no financial conflicts.