Christine Kilgore

WASHINGTON — A significant number of patients with diabetes say they need help coping with the disease, but too few have such psychological needs addressed during initial diabetes education sessions, Mark Peyrot, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

“Most of patients' basic care needs are addressed [in diabetes self-management training],” said Dr. Peyrot of the department of medicine at Johns Hopkins University, Baltimore. “But very little of their psychosocial needs are being addressed.”

Dr. Peyrot reported that 44% percent of 178 patients in this study, which was based at the University of Pittsburgh Medical Center, chose “healthy coping” as one of the areas in which they wanted help.

The patients were asked to review the American Association of Diabetes Educators' seven “self-care behaviors”—used in AADE's patient assessment and outcomes evaluation tools—and choose areas in which they wanted to set goals and learn skills. Patients could choose as many behaviors as they wished. The interest in “healthy coping” was unexpectedly similar to the interest expressed in “reducing risks” (49%), “being active” (46%), and “problem-solving” (41%).

Dr. Peyrot said that he expected interest in coping would be more modest. On the other hand, some areas—such as “monitoring” (chosen by 39%) and “taking medications” (chosen by 34%)—were rated “lower than what we'd expect,” he said.

Diabetes educators' responses to patients' needs varied widely. In 94% of initial visits, educators addressed monitoring issues, for instance, and in 88% and 87% of initial visits they addressed exercise and eating, respectively. Medications were addressed in 75% of visits, problem-solving in 44%, and risk reduction in 56%, said Dr. Peyrot, who is also director of the center for social and community research at Loyola College, Baltimore.

Although almost half of patients expressed psychological needs, coping was addressed in only 18% of patients' initial visits, he said. “To a large extent, there was a standardized package being delivered to patients.”

Patients in the study were seen at four University of Pittsburgh Medical Center diabetes self-management training programs.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A significant number of patients with diabetes say they need help coping with the disease, but too few have such psychological needs addressed during initial diabetes education sessions, Mark Peyrot, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

“Most of patients' basic care needs are addressed [in diabetes self-management training],” said Dr. Peyrot of the department of medicine at Johns Hopkins University, Baltimore. “But very little of their psychosocial needs are being addressed.”

Dr. Peyrot reported that 44% percent of 178 patients in this study, which was based at the University of Pittsburgh Medical Center, chose “healthy coping” as one of the areas in which they wanted help.

The patients were asked to review the American Association of Diabetes Educators' seven “self-care behaviors”—used in AADE's patient assessment and outcomes evaluation tools—and choose areas in which they wanted to set goals and learn skills. Patients could choose as many behaviors as they wished. The interest in “healthy coping” was unexpectedly similar to the interest expressed in “reducing risks” (49%), “being active” (46%), and “problem-solving” (41%).

Dr. Peyrot said that he expected interest in coping would be more modest. On the other hand, some areas—such as “monitoring” (chosen by 39%) and “taking medications” (chosen by 34%)—were rated “lower than what we'd expect,” he said.

Diabetes educators' responses to patients' needs varied widely. In 94% of initial visits, educators addressed monitoring issues, for instance, and in 88% and 87% of initial visits they addressed exercise and eating, respectively. Medications were addressed in 75% of visits, problem-solving in 44%, and risk reduction in 56%, said Dr. Peyrot, who is also director of the center for social and community research at Loyola College, Baltimore.

Although almost half of patients expressed psychological needs, coping was addressed in only 18% of patients' initial visits, he said. “To a large extent, there was a standardized package being delivered to patients.”

Patients in the study were seen at four University of Pittsburgh Medical Center diabetes self-management training programs.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A significant number of patients with diabetes say they need help coping with the disease, but too few have such psychological needs addressed during initial diabetes education sessions, Mark Peyrot, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

“Most of patients' basic care needs are addressed [in diabetes self-management training],” said Dr. Peyrot of the department of medicine at Johns Hopkins University, Baltimore. “But very little of their psychosocial needs are being addressed.”

Dr. Peyrot reported that 44% percent of 178 patients in this study, which was based at the University of Pittsburgh Medical Center, chose “healthy coping” as one of the areas in which they wanted help.

The patients were asked to review the American Association of Diabetes Educators' seven “self-care behaviors”—used in AADE's patient assessment and outcomes evaluation tools—and choose areas in which they wanted to set goals and learn skills. Patients could choose as many behaviors as they wished. The interest in “healthy coping” was unexpectedly similar to the interest expressed in “reducing risks” (49%), “being active” (46%), and “problem-solving” (41%).

Dr. Peyrot said that he expected interest in coping would be more modest. On the other hand, some areas—such as “monitoring” (chosen by 39%) and “taking medications” (chosen by 34%)—were rated “lower than what we'd expect,” he said.

Diabetes educators' responses to patients' needs varied widely. In 94% of initial visits, educators addressed monitoring issues, for instance, and in 88% and 87% of initial visits they addressed exercise and eating, respectively. Medications were addressed in 75% of visits, problem-solving in 44%, and risk reduction in 56%, said Dr. Peyrot, who is also director of the center for social and community research at Loyola College, Baltimore.

Although almost half of patients expressed psychological needs, coping was addressed in only 18% of patients' initial visits, he said. “To a large extent, there was a standardized package being delivered to patients.”

Patients in the study were seen at four University of Pittsburgh Medical Center diabetes self-management training programs.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON – A significant number of patients with diabetes say they need help coping with the disease, but too few have such psychological needs addressed during initial diabetes education sessions, Mark Peyrot, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

“Most of patients' basic care needs are addressed” in diabetes self-management training, said Dr. Peyrot of the department of medicine at Johns Hopkins University, Baltimore. “But very little of their psychosocial needs are being addressed.”

Dr. Peyrot reported that 44% percent of 178 patients in this study, which was based at the University of Pittsburgh Medical Center, chose “healthy coping” as one of the areas in which they wanted help.

Patients were asked to review the American Association of Diabetes Educators' seven “self-care behaviors”–which it uses in its patient assessment instrument and in its system for evaluating outcomes in diabetes education–and choose areas in which they wanted to set goals and learn skills. Patients could choose as many behaviors as they wished.

The interest in “healthy coping” was unexpectedly similar to the interest in “reducing risks” (49%), “being active” (46%), and “problem-solving” (41%).

Dr. Peyrot said that he expected interest in coping would be more modest. On the other hand, some areas–such as “monitoring” (chosen by 39%) and “taking medications” (chosen by 34%)–were rated “lower than what we'd expect,” he said.

Diabetes educators' responses to patients' needs varied widely. In 94% of initial visits, educators addressed monitoring issues, for instance, and in 88% and 87% of initial visits they addressed exercise and eating, respectively. Medications were addressed in 75% of visits, problem-solving in 44%, and risk reduction in 56%, said Dr. Peyrot, who is also director of the center for social and community research at Loyola College, Baltimore.

Although almost half of patients expressed psychological needs, coping was addressed in only 18% of patients' initial visits, he said.

“To a large extent, there was a standardized package being delivered to patients,” he noted.

They were seen at four of the University of Pittsburgh Medical Center's diabetes self-management training programs, each of which uses the AADE's National Diabetes Education Outcomes System to track and assess diabetes education.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON – A significant number of patients with diabetes say they need help coping with the disease, but too few have such psychological needs addressed during initial diabetes education sessions, Mark Peyrot, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

“Most of patients' basic care needs are addressed” in diabetes self-management training, said Dr. Peyrot of the department of medicine at Johns Hopkins University, Baltimore. “But very little of their psychosocial needs are being addressed.”

Dr. Peyrot reported that 44% percent of 178 patients in this study, which was based at the University of Pittsburgh Medical Center, chose “healthy coping” as one of the areas in which they wanted help.

Patients were asked to review the American Association of Diabetes Educators' seven “self-care behaviors”–which it uses in its patient assessment instrument and in its system for evaluating outcomes in diabetes education–and choose areas in which they wanted to set goals and learn skills. Patients could choose as many behaviors as they wished.

The interest in “healthy coping” was unexpectedly similar to the interest in “reducing risks” (49%), “being active” (46%), and “problem-solving” (41%).

Dr. Peyrot said that he expected interest in coping would be more modest. On the other hand, some areas–such as “monitoring” (chosen by 39%) and “taking medications” (chosen by 34%)–were rated “lower than what we'd expect,” he said.

Diabetes educators' responses to patients' needs varied widely. In 94% of initial visits, educators addressed monitoring issues, for instance, and in 88% and 87% of initial visits they addressed exercise and eating, respectively. Medications were addressed in 75% of visits, problem-solving in 44%, and risk reduction in 56%, said Dr. Peyrot, who is also director of the center for social and community research at Loyola College, Baltimore.

Although almost half of patients expressed psychological needs, coping was addressed in only 18% of patients' initial visits, he said.

“To a large extent, there was a standardized package being delivered to patients,” he noted.

They were seen at four of the University of Pittsburgh Medical Center's diabetes self-management training programs, each of which uses the AADE's National Diabetes Education Outcomes System to track and assess diabetes education.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON – A significant number of patients with diabetes say they need help coping with the disease, but too few have such psychological needs addressed during initial diabetes education sessions, Mark Peyrot, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

“Most of patients' basic care needs are addressed” in diabetes self-management training, said Dr. Peyrot of the department of medicine at Johns Hopkins University, Baltimore. “But very little of their psychosocial needs are being addressed.”

Dr. Peyrot reported that 44% percent of 178 patients in this study, which was based at the University of Pittsburgh Medical Center, chose “healthy coping” as one of the areas in which they wanted help.

Patients were asked to review the American Association of Diabetes Educators' seven “self-care behaviors”–which it uses in its patient assessment instrument and in its system for evaluating outcomes in diabetes education–and choose areas in which they wanted to set goals and learn skills. Patients could choose as many behaviors as they wished.

The interest in “healthy coping” was unexpectedly similar to the interest in “reducing risks” (49%), “being active” (46%), and “problem-solving” (41%).

Dr. Peyrot said that he expected interest in coping would be more modest. On the other hand, some areas–such as “monitoring” (chosen by 39%) and “taking medications” (chosen by 34%)–were rated “lower than what we'd expect,” he said.

Diabetes educators' responses to patients' needs varied widely. In 94% of initial visits, educators addressed monitoring issues, for instance, and in 88% and 87% of initial visits they addressed exercise and eating, respectively. Medications were addressed in 75% of visits, problem-solving in 44%, and risk reduction in 56%, said Dr. Peyrot, who is also director of the center for social and community research at Loyola College, Baltimore.

Although almost half of patients expressed psychological needs, coping was addressed in only 18% of patients' initial visits, he said.

“To a large extent, there was a standardized package being delivered to patients,” he noted.

They were seen at four of the University of Pittsburgh Medical Center's diabetes self-management training programs, each of which uses the AADE's National Diabetes Education Outcomes System to track and assess diabetes education.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Early experience suggests that the health benefits of bariatric surgery offset the risks for severely obese adolescents, based on the results of small studies reported at the annual scientific sessions of the American Diabetes Association.

Significant metabolic improvements and near-complete resolution of type 2 diabetes and obstructive sleep apnea were among the 1-year outcomes of Roux-en-Y gastric bypass surgery performed in 36 morbidly obese adolescents, aged 13–21, at three pediatric surgical centers participating in the Pediatric Bariatric Study Group.

Severely obese adolescents are developing serious adultlike comorbidities at an unexpectedly high frequency. Limited success with behavioral and lifestyle interventions has left physicians considering more aggressive interventions. “Children who are obese become obese adults,” said Dr. Carroll M. Harmon, of the Children's Hospital of Alabama, Birmingham.

Teens were eligible for the surgery at Children's Hospital and the other institutions in the Pediatric Bariatric Study Group (the University of Florida in Gainesville and the Cincinnati Children's Hospital Medical Center) if they had a body mass index (BMI) of at least 40 kg/m

The teens in the multicenter cohort had a mean BMI preoperatively of approximately 57. Postoperatively, the mean BMI fell to 36, a 37% reduction.

None of the patients included in the weight loss analysis (9 of the 36 teens in the cohort were excluded because they did not comply with follow-up requirements) attained normal weight in the year of follow-up; BMI values, in fact, still ranged from overweight to severe obesity.

Still, the postoperative weight loss was significant and consistent with outcomes in adults who undergo bariatric surgery, said Dr. Harmon, professor of surgery in the University of Alabama division of pediatric surgery.

Metabolic measures improved as a result of significant decreases in triglycerides (−65 mg/dL), total cholesterol (−30 mg/dL), fasting blood glucose (−12 g/dL), and fasting insulin (−21.3 μU/mL). Changes in HDL and LDL cholesterol values were not statistically significant.

Mean hemoglobin A_1c decreased from 7.3% to 5.6% in the 10 patients diagnosed with type 2 diabetes. At 1 year after surgery, 1 of 10 patients remained on diabetic medications; 9 of 10 were on diabetic medications preoperatively, Dr. Harmon reported.

The adolescents also scored significantly higher postoperatively on various quality-of-life measures than they did preoperatively, he added.

In a separate poster presentation, Dr. Marc P. Michalsky and Dr. Dara Schuster of Ohio State University, Columbus, reported on what they said are similarly good outcomes in five morbidly obese adolescents (BMI of at least 57) who underwent Roux-en-Y gastric bypass surgery at Columbus Children's Hospital.

Serum hemoglobin A_1c reached normal values within 20 weeks of surgery in each of the four adolescents with type 2 diabetes. Blood pressures reached normal values within 20 weeks in each of four hypertensive patients, and obstructive sleep apnea resolved after surgery in two of three affected patients. Insulin resistance (as determined by calculating the homeostasis model assessment of insulin resistance) also was reduced by a mean of 66% at 12 weeks post surgery.

“These are superobese kids,” and they have the same morbidities as obese adults who qualify for gastric bypass surgery, Dr. Schuster said in an interview. “The question we need to answer is: Do we do them a favor by operating early?”

Long-term follow-up, each of the physicians emphasized, will be necessary to determine both the durability of the patients' improvements and the safety of the surgery. Whether the patients will experience nutritional malabsorption is a question, they noted.

None of the five adolescents treated in Columbus experienced complications during the 20-week follow-up period, but there were complications among the 36 who were followed for a year.

Nine of the 36 patients had “minor” complications with no long-term sequelae (nausea, wound infection, and food obstruction), and 4 had at least one “moderate” complication (persistent iron-deficiency anemia or the need for reoperation).

Two patients, Dr. Harmon reported, had severe complications: One developed severe thiamine deficiency with significant sequelae, and the other, who initially presented with a BMI of 80 and a weight of 630 pounds, died 9 months after surgery due to infectious colitis contracted while undergoing inpatient rehabilitation for osteoarthritis.

The complication profile thus far is similar to that seen in superobese adults who undergo the surgery, Dr. Harmon said. Among adults, 0.2%–2% die from the surgery and more than 15% experience complications.

“The risks are still considerable, but so far in adolescents, just as in adults, these risks seem to be offset by the benefits,” said Dr. Harmon. “It's encouraging.”

The adjustable gastric banding procedure, which does not involve an intestinal bypass, is getting more attention as a possible “best” operation for adolescents—even though long-term results in adults have not been compared with those of gastric bypass surgery—because it eliminates concerns about nutritional and mineral malabsorption, Dr. Harmon said.

Insurance coverage is variable nationwide and difficult to secure in some locales. “In Ohio, Medicaid has been favorable toward covering these kids so far,” Dr. Michalsky said. “We have a high rate of obesity, so the state may be especially attuned [to the problem].”

Comorbidities Are Missed in Teens

Dr. Schuster said the “most striking thing” about seeing adolescents referred to her hospital's bariatric surgery clinic is how “many of them didn't have their comorbid conditions diagnosed” before their surgical evaluations.

Hypertension, sleep apnea, diabetes, and other obesity-related comorbid conditions “are underdiagnosed and undermanaged” in obese adolescents, Dr. Schuster and her colleagues said in a poster presented at the annual scientific sessions of the American Diabetes Association.

Of 46 patients who were seen at the Columbus Children's Hospital Adolescent Bariatric Surgery Clinic in 2004 and 2005, 42% received a “new diagnosis” of obstructive sleep apnea and 33% learned they were hypothyroid.

During their initial presurgical evaluation, 25% were first told they had type 2 diabetes, 13% learned they had gastroesophageal reflux disease, and 10% received a new diagnosis of hypertension. Not surprisingly, since insulin resistance is hard to diagnose in most clinical settings, 54% learned for the first time that they were insulin resistant.

The prevalence of comorbidities was similar to, or higher than, the rates recorded among morbidly obese adults presenting at other clinics at Ohio State University in Columbus, reported Dr. Schuster and her associates.

WASHINGTON — Early experience suggests that the health benefits of bariatric surgery offset the risks for severely obese adolescents, based on the results of small studies reported at the annual scientific sessions of the American Diabetes Association.

Significant metabolic improvements and near-complete resolution of type 2 diabetes and obstructive sleep apnea were among the 1-year outcomes of Roux-en-Y gastric bypass surgery performed in 36 morbidly obese adolescents, aged 13–21, at three pediatric surgical centers participating in the Pediatric Bariatric Study Group.

Severely obese adolescents are developing serious adultlike comorbidities at an unexpectedly high frequency. Limited success with behavioral and lifestyle interventions has left physicians considering more aggressive interventions. “Children who are obese become obese adults,” said Dr. Carroll M. Harmon, of the Children's Hospital of Alabama, Birmingham.

Teens were eligible for the surgery at Children's Hospital and the other institutions in the Pediatric Bariatric Study Group (the University of Florida in Gainesville and the Cincinnati Children's Hospital Medical Center) if they had a body mass index (BMI) of at least 40 kg/m

The teens in the multicenter cohort had a mean BMI preoperatively of approximately 57. Postoperatively, the mean BMI fell to 36, a 37% reduction.

None of the patients included in the weight loss analysis (9 of the 36 teens in the cohort were excluded because they did not comply with follow-up requirements) attained normal weight in the year of follow-up; BMI values, in fact, still ranged from overweight to severe obesity.

Still, the postoperative weight loss was significant and consistent with outcomes in adults who undergo bariatric surgery, said Dr. Harmon, professor of surgery in the University of Alabama division of pediatric surgery.

Metabolic measures improved as a result of significant decreases in triglycerides (−65 mg/dL), total cholesterol (−30 mg/dL), fasting blood glucose (−12 g/dL), and fasting insulin (−21.3 μU/mL). Changes in HDL and LDL cholesterol values were not statistically significant.

Mean hemoglobin A_1c decreased from 7.3% to 5.6% in the 10 patients diagnosed with type 2 diabetes. At 1 year after surgery, 1 of 10 patients remained on diabetic medications; 9 of 10 were on diabetic medications preoperatively, Dr. Harmon reported.

The adolescents also scored significantly higher postoperatively on various quality-of-life measures than they did preoperatively, he added.

In a separate poster presentation, Dr. Marc P. Michalsky and Dr. Dara Schuster of Ohio State University, Columbus, reported on what they said are similarly good outcomes in five morbidly obese adolescents (BMI of at least 57) who underwent Roux-en-Y gastric bypass surgery at Columbus Children's Hospital.

Serum hemoglobin A_1c reached normal values within 20 weeks of surgery in each of the four adolescents with type 2 diabetes. Blood pressures reached normal values within 20 weeks in each of four hypertensive patients, and obstructive sleep apnea resolved after surgery in two of three affected patients. Insulin resistance (as determined by calculating the homeostasis model assessment of insulin resistance) also was reduced by a mean of 66% at 12 weeks post surgery.

“These are superobese kids,” and they have the same morbidities as obese adults who qualify for gastric bypass surgery, Dr. Schuster said in an interview. “The question we need to answer is: Do we do them a favor by operating early?”

Long-term follow-up, each of the physicians emphasized, will be necessary to determine both the durability of the patients' improvements and the safety of the surgery. Whether the patients will experience nutritional malabsorption is a question, they noted.

None of the five adolescents treated in Columbus experienced complications during the 20-week follow-up period, but there were complications among the 36 who were followed for a year.

Nine of the 36 patients had “minor” complications with no long-term sequelae (nausea, wound infection, and food obstruction), and 4 had at least one “moderate” complication (persistent iron-deficiency anemia or the need for reoperation).

Two patients, Dr. Harmon reported, had severe complications: One developed severe thiamine deficiency with significant sequelae, and the other, who initially presented with a BMI of 80 and a weight of 630 pounds, died 9 months after surgery due to infectious colitis contracted while undergoing inpatient rehabilitation for osteoarthritis.

The complication profile thus far is similar to that seen in superobese adults who undergo the surgery, Dr. Harmon said. Among adults, 0.2%–2% die from the surgery and more than 15% experience complications.

“The risks are still considerable, but so far in adolescents, just as in adults, these risks seem to be offset by the benefits,” said Dr. Harmon. “It's encouraging.”

The adjustable gastric banding procedure, which does not involve an intestinal bypass, is getting more attention as a possible “best” operation for adolescents—even though long-term results in adults have not been compared with those of gastric bypass surgery—because it eliminates concerns about nutritional and mineral malabsorption, Dr. Harmon said.

Insurance coverage is variable nationwide and difficult to secure in some locales. “In Ohio, Medicaid has been favorable toward covering these kids so far,” Dr. Michalsky said. “We have a high rate of obesity, so the state may be especially attuned [to the problem].”

Comorbidities Are Missed in Teens

Dr. Schuster said the “most striking thing” about seeing adolescents referred to her hospital's bariatric surgery clinic is how “many of them didn't have their comorbid conditions diagnosed” before their surgical evaluations.

Hypertension, sleep apnea, diabetes, and other obesity-related comorbid conditions “are underdiagnosed and undermanaged” in obese adolescents, Dr. Schuster and her colleagues said in a poster presented at the annual scientific sessions of the American Diabetes Association.

Of 46 patients who were seen at the Columbus Children's Hospital Adolescent Bariatric Surgery Clinic in 2004 and 2005, 42% received a “new diagnosis” of obstructive sleep apnea and 33% learned they were hypothyroid.

During their initial presurgical evaluation, 25% were first told they had type 2 diabetes, 13% learned they had gastroesophageal reflux disease, and 10% received a new diagnosis of hypertension. Not surprisingly, since insulin resistance is hard to diagnose in most clinical settings, 54% learned for the first time that they were insulin resistant.

The prevalence of comorbidities was similar to, or higher than, the rates recorded among morbidly obese adults presenting at other clinics at Ohio State University in Columbus, reported Dr. Schuster and her associates.

WASHINGTON — Early experience suggests that the health benefits of bariatric surgery offset the risks for severely obese adolescents, based on the results of small studies reported at the annual scientific sessions of the American Diabetes Association.

Significant metabolic improvements and near-complete resolution of type 2 diabetes and obstructive sleep apnea were among the 1-year outcomes of Roux-en-Y gastric bypass surgery performed in 36 morbidly obese adolescents, aged 13–21, at three pediatric surgical centers participating in the Pediatric Bariatric Study Group.

Severely obese adolescents are developing serious adultlike comorbidities at an unexpectedly high frequency. Limited success with behavioral and lifestyle interventions has left physicians considering more aggressive interventions. “Children who are obese become obese adults,” said Dr. Carroll M. Harmon, of the Children's Hospital of Alabama, Birmingham.

Teens were eligible for the surgery at Children's Hospital and the other institutions in the Pediatric Bariatric Study Group (the University of Florida in Gainesville and the Cincinnati Children's Hospital Medical Center) if they had a body mass index (BMI) of at least 40 kg/m

The teens in the multicenter cohort had a mean BMI preoperatively of approximately 57. Postoperatively, the mean BMI fell to 36, a 37% reduction.

None of the patients included in the weight loss analysis (9 of the 36 teens in the cohort were excluded because they did not comply with follow-up requirements) attained normal weight in the year of follow-up; BMI values, in fact, still ranged from overweight to severe obesity.

Still, the postoperative weight loss was significant and consistent with outcomes in adults who undergo bariatric surgery, said Dr. Harmon, professor of surgery in the University of Alabama division of pediatric surgery.

Metabolic measures improved as a result of significant decreases in triglycerides (−65 mg/dL), total cholesterol (−30 mg/dL), fasting blood glucose (−12 g/dL), and fasting insulin (−21.3 μU/mL). Changes in HDL and LDL cholesterol values were not statistically significant.

Mean hemoglobin A_1c decreased from 7.3% to 5.6% in the 10 patients diagnosed with type 2 diabetes. At 1 year after surgery, 1 of 10 patients remained on diabetic medications; 9 of 10 were on diabetic medications preoperatively, Dr. Harmon reported.

The adolescents also scored significantly higher postoperatively on various quality-of-life measures than they did preoperatively, he added.

In a separate poster presentation, Dr. Marc P. Michalsky and Dr. Dara Schuster of Ohio State University, Columbus, reported on what they said are similarly good outcomes in five morbidly obese adolescents (BMI of at least 57) who underwent Roux-en-Y gastric bypass surgery at Columbus Children's Hospital.

Serum hemoglobin A_1c reached normal values within 20 weeks of surgery in each of the four adolescents with type 2 diabetes. Blood pressures reached normal values within 20 weeks in each of four hypertensive patients, and obstructive sleep apnea resolved after surgery in two of three affected patients. Insulin resistance (as determined by calculating the homeostasis model assessment of insulin resistance) also was reduced by a mean of 66% at 12 weeks post surgery.

“These are superobese kids,” and they have the same morbidities as obese adults who qualify for gastric bypass surgery, Dr. Schuster said in an interview. “The question we need to answer is: Do we do them a favor by operating early?”

Long-term follow-up, each of the physicians emphasized, will be necessary to determine both the durability of the patients' improvements and the safety of the surgery. Whether the patients will experience nutritional malabsorption is a question, they noted.

None of the five adolescents treated in Columbus experienced complications during the 20-week follow-up period, but there were complications among the 36 who were followed for a year.

Nine of the 36 patients had “minor” complications with no long-term sequelae (nausea, wound infection, and food obstruction), and 4 had at least one “moderate” complication (persistent iron-deficiency anemia or the need for reoperation).

Two patients, Dr. Harmon reported, had severe complications: One developed severe thiamine deficiency with significant sequelae, and the other, who initially presented with a BMI of 80 and a weight of 630 pounds, died 9 months after surgery due to infectious colitis contracted while undergoing inpatient rehabilitation for osteoarthritis.

The complication profile thus far is similar to that seen in superobese adults who undergo the surgery, Dr. Harmon said. Among adults, 0.2%–2% die from the surgery and more than 15% experience complications.

“The risks are still considerable, but so far in adolescents, just as in adults, these risks seem to be offset by the benefits,” said Dr. Harmon. “It's encouraging.”

The adjustable gastric banding procedure, which does not involve an intestinal bypass, is getting more attention as a possible “best” operation for adolescents—even though long-term results in adults have not been compared with those of gastric bypass surgery—because it eliminates concerns about nutritional and mineral malabsorption, Dr. Harmon said.

Insurance coverage is variable nationwide and difficult to secure in some locales. “In Ohio, Medicaid has been favorable toward covering these kids so far,” Dr. Michalsky said. “We have a high rate of obesity, so the state may be especially attuned [to the problem].”

Comorbidities Are Missed in Teens

Dr. Schuster said the “most striking thing” about seeing adolescents referred to her hospital's bariatric surgery clinic is how “many of them didn't have their comorbid conditions diagnosed” before their surgical evaluations.

Hypertension, sleep apnea, diabetes, and other obesity-related comorbid conditions “are underdiagnosed and undermanaged” in obese adolescents, Dr. Schuster and her colleagues said in a poster presented at the annual scientific sessions of the American Diabetes Association.

Of 46 patients who were seen at the Columbus Children's Hospital Adolescent Bariatric Surgery Clinic in 2004 and 2005, 42% received a “new diagnosis” of obstructive sleep apnea and 33% learned they were hypothyroid.

During their initial presurgical evaluation, 25% were first told they had type 2 diabetes, 13% learned they had gastroesophageal reflux disease, and 10% received a new diagnosis of hypertension. Not surprisingly, since insulin resistance is hard to diagnose in most clinical settings, 54% learned for the first time that they were insulin resistant.

The prevalence of comorbidities was similar to, or higher than, the rates recorded among morbidly obese adults presenting at other clinics at Ohio State University in Columbus, reported Dr. Schuster and her associates.

WASHINGTON — Women with a history of preeclampsia have a twofold greater risk of developing subsequent type 2 diabetes—even in the absence of gestational diabetes—than do women without a history of the complication, said Dr. Darcy B. Carr in a report on a retrospective cohort study at the annual scientific sessions of the American Diabetes Association.

Dr. Carr, of the division of maternal-fetal medicine at the University of Washington, Seattle, and her colleagues looked at more than 25,000 women who delivered at the GHC between 1985 and 2002 after having been enrolled in the consumer-owned nonprofit health care system for at least a year. They followed the women, each of whom remained in GHC, for a mean of 8 years.

The women did not have known diabetes before pregnancy or subsequent type 1 diabetes. Subsequent type 2 diabetes was determined through 2005 based on inpatient and outpatient ICD-9 codes, pharmacy data, or lab data showing two elevated plasma glucose levels.

The two groups—about 2,100 women with preeclampsia and almost 25,000 without—had a similar mean age at the time of delivery, but those women who had preeclampsia were more likely to be multiparous and have gestational diabetes or preexisting chronic hypertension.

Subsequent type 2 diabetes was significantly more common in women who had preeclampsia (1.9% vs. 0.96%). A similar twofold increased risk remained after adjustment for age, multiparity, gestational diabetes, and chronic hypertension—and after women with gestational diabetes were excluded from the analysis, said Dr. Carr.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Women with a history of preeclampsia have a twofold greater risk of developing subsequent type 2 diabetes—even in the absence of gestational diabetes—than do women without a history of the complication, said Dr. Darcy B. Carr in a report on a retrospective cohort study at the annual scientific sessions of the American Diabetes Association.

Dr. Carr, of the division of maternal-fetal medicine at the University of Washington, Seattle, and her colleagues looked at more than 25,000 women who delivered at the GHC between 1985 and 2002 after having been enrolled in the consumer-owned nonprofit health care system for at least a year. They followed the women, each of whom remained in GHC, for a mean of 8 years.

The women did not have known diabetes before pregnancy or subsequent type 1 diabetes. Subsequent type 2 diabetes was determined through 2005 based on inpatient and outpatient ICD-9 codes, pharmacy data, or lab data showing two elevated plasma glucose levels.

The two groups—about 2,100 women with preeclampsia and almost 25,000 without—had a similar mean age at the time of delivery, but those women who had preeclampsia were more likely to be multiparous and have gestational diabetes or preexisting chronic hypertension.

Subsequent type 2 diabetes was significantly more common in women who had preeclampsia (1.9% vs. 0.96%). A similar twofold increased risk remained after adjustment for age, multiparity, gestational diabetes, and chronic hypertension—and after women with gestational diabetes were excluded from the analysis, said Dr. Carr.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Women with a history of preeclampsia have a twofold greater risk of developing subsequent type 2 diabetes—even in the absence of gestational diabetes—than do women without a history of the complication, said Dr. Darcy B. Carr in a report on a retrospective cohort study at the annual scientific sessions of the American Diabetes Association.

Dr. Carr, of the division of maternal-fetal medicine at the University of Washington, Seattle, and her colleagues looked at more than 25,000 women who delivered at the GHC between 1985 and 2002 after having been enrolled in the consumer-owned nonprofit health care system for at least a year. They followed the women, each of whom remained in GHC, for a mean of 8 years.

The women did not have known diabetes before pregnancy or subsequent type 1 diabetes. Subsequent type 2 diabetes was determined through 2005 based on inpatient and outpatient ICD-9 codes, pharmacy data, or lab data showing two elevated plasma glucose levels.

The two groups—about 2,100 women with preeclampsia and almost 25,000 without—had a similar mean age at the time of delivery, but those women who had preeclampsia were more likely to be multiparous and have gestational diabetes or preexisting chronic hypertension.

Subsequent type 2 diabetes was significantly more common in women who had preeclampsia (1.9% vs. 0.96%). A similar twofold increased risk remained after adjustment for age, multiparity, gestational diabetes, and chronic hypertension—and after women with gestational diabetes were excluded from the analysis, said Dr. Carr.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Insulin resistance is such an integral and dangerous feature of polycystic ovary syndrome that metformin should be favored over oral contraceptive pills for treatment of the syndrome, said physicians in annual scientific sessions of the American Diabetes Association meeting.

While there is a paucity of “good, prospective outcomes data” on cardiovascular disease in PCOS patients—as well as the existence of only limited data on the effect of oral contraceptives (OCs) on insulin resistance—the speakers warned against waiting for definitive data to appear. Current knowledge of the risks of insulin resistance and the potential disadvantages of OCs is too convincing, they said.

“Given everything [we know now], I believe we now must have the goals of preventing glucose intolerance and diabetes, and preventing atherosclerosis and acute coronary events” in addition to addressing the immediate symptoms of PCOS, said Dr. John Nestler, professor of medicine, ob.gyn., pharmacology, and toxicology at the Virginia Commonwealth University, Richmond.

“I will be provocative, because there aren't a lot of studies, but I'm going to argue that there may be disadvantages to using OCs,” said Dr. Nestler, who also chairs the division of endocrinology and metabolism.

OCs may be better for treating symptoms such as acne and hirsutism (studies of metformin have not addressed these problems as primary end points), but studies indicate that OCs worsen insulin resistance and glucose intolerance and that they may increase triglycerides, worsening the risk of diabetes and cardiovascular disease, he said.

Metformin, on the other hand, targets insulin resistance, “what may well be the initiating abnormality in PCOS, and has been shown to normalize or improve the biochemical, clinical, and reproductive abnormalities of PCOS,” said pediatric endocrinologist Dr. Tessa Lebinger.

The drug is effective whether or not insulin resistance can be documented, she said.

In most cases, Dr. Nestler agreed, it won't be documented because insulin resistance is too difficult to accurately measure in a clinical setting. “Most women with PCOS are insulin resistant … so an empiric trial of metformin in any woman with PCOS is reasonable as long as you monitor her and make sure that her menses are improving,” he said.

Dr. Burton Sobel, who directs the Cardiovascular Research Institute at the University of Vermont, said during a symposium on PCOS that from his perspective as a cardiologist, “PCOS is a cardiovascular disease.”

“We know, from so many perspectives, that impaired sensitivity to insulin is a forerunner, and probably a determinant, of premature coronary disease,” Dr. Sobel said. “It may be years before we have prospective data and legitimacy for using insulin sensitizers [in PCOS patients], but if I had a daughter with PCOS, I'd use an insulin sensitizer beginning with my recognition of the problem regardless of whether she had abnormal glucose tolerance. … I wouldn't wait—to me this is a smoking gun.”

The relationship between hyperinsulinemia and hyperandrogenism—in particular, the question of which causes which—is still discussed, but these physicians said they're convinced from available data that insulin resistance leads to hyperandrogenism and is likely a primary cause of PCOS.

Studies have shown that 30%–35% of women with PCOS have impaired glucose tolerance, and that 8%–10% have type 2 diabetes.

On the whole, Dr. Nestler said, 30%–50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by age 30. Lean women with PCOS, on the other hand, are just as insulin resistant—if not more so—than obese women without PCOS, several speakers said.

Dr. Nestler said that he and his colleagues found in a chart review of 50 consecutive PCOS patients treated with metformin that the incidence of impaired glucose tolerance was “dramatically” reduced.

At baseline, 78% of the 50 patients had normal glucose tolerance (NGT), and 22% had impaired glucose tolerance (IGT). At follow-up (a mean of 43 months for NGT patients, and 29 months for IGT patients), 55% of the IGT patients had converted to normal, with 45% continuing to have IGT. Of the NGT patients, 95% continued to have NGT, and 5% converted to IGT.

“It needs to be verified in a prospective study, but our annual conversion rate to IGT of 1.4% with metformin treatment is a dramatic reduction from the 16%–19% annual conversion rates” reported in women with PCOS who are not treated with metformin, he said.

He and other physicians at the meeting pointed to the Nurses' Health Study as the best of few studies that provides a look at the cardiovascular “outcomes” of PCOS.

In its tracking of over 80,000 women for 14 years, the study found that women with abnormal menstrual cyclicity had a relative risk for cardiovascular disease of 1.5 and a relative risk of fatal MI of 1.9, compared with women with normal menses. (The NHS also found a twofold increased risk, independent of weight, of type 2 diabetes in women with oligomenorrhea.)

Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs. The risk may be higher in women with PCOS, since they likely start at a higher baseline risk and take OCs for long periods of time, she said.

Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”

And the “question is, whether she'll take a pill for the next 30 years that doesn't make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.

Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”

Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y. Her adolescent patients on metformin also have improvements in their acne and frequently lose weight.

“We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said. Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.

Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and is a stock/shareholder of the Bristol-Myers Squibb Co. and Pfizer Inc.

Metformin OK for Infertile Patients

If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.

“If a woman comes to me with PCOS who wants to get pregnant, I usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. This way we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If at the end of 6 months she doesn't become pregnant, I send her to the endocrinologist.”

The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.

In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.

Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.

WASHINGTON — Insulin resistance is such an integral and dangerous feature of polycystic ovary syndrome that metformin should be favored over oral contraceptive pills for treatment of the syndrome, said physicians in annual scientific sessions of the American Diabetes Association meeting.

While there is a paucity of “good, prospective outcomes data” on cardiovascular disease in PCOS patients—as well as the existence of only limited data on the effect of oral contraceptives (OCs) on insulin resistance—the speakers warned against waiting for definitive data to appear. Current knowledge of the risks of insulin resistance and the potential disadvantages of OCs is too convincing, they said.

“Given everything [we know now], I believe we now must have the goals of preventing glucose intolerance and diabetes, and preventing atherosclerosis and acute coronary events” in addition to addressing the immediate symptoms of PCOS, said Dr. John Nestler, professor of medicine, ob.gyn., pharmacology, and toxicology at the Virginia Commonwealth University, Richmond.

“I will be provocative, because there aren't a lot of studies, but I'm going to argue that there may be disadvantages to using OCs,” said Dr. Nestler, who also chairs the division of endocrinology and metabolism.

OCs may be better for treating symptoms such as acne and hirsutism (studies of metformin have not addressed these problems as primary end points), but studies indicate that OCs worsen insulin resistance and glucose intolerance and that they may increase triglycerides, worsening the risk of diabetes and cardiovascular disease, he said.

Metformin, on the other hand, targets insulin resistance, “what may well be the initiating abnormality in PCOS, and has been shown to normalize or improve the biochemical, clinical, and reproductive abnormalities of PCOS,” said pediatric endocrinologist Dr. Tessa Lebinger.

The drug is effective whether or not insulin resistance can be documented, she said.

In most cases, Dr. Nestler agreed, it won't be documented because insulin resistance is too difficult to accurately measure in a clinical setting. “Most women with PCOS are insulin resistant … so an empiric trial of metformin in any woman with PCOS is reasonable as long as you monitor her and make sure that her menses are improving,” he said.

Dr. Burton Sobel, who directs the Cardiovascular Research Institute at the University of Vermont, said during a symposium on PCOS that from his perspective as a cardiologist, “PCOS is a cardiovascular disease.”

“We know, from so many perspectives, that impaired sensitivity to insulin is a forerunner, and probably a determinant, of premature coronary disease,” Dr. Sobel said. “It may be years before we have prospective data and legitimacy for using insulin sensitizers [in PCOS patients], but if I had a daughter with PCOS, I'd use an insulin sensitizer beginning with my recognition of the problem regardless of whether she had abnormal glucose tolerance. … I wouldn't wait—to me this is a smoking gun.”

The relationship between hyperinsulinemia and hyperandrogenism—in particular, the question of which causes which—is still discussed, but these physicians said they're convinced from available data that insulin resistance leads to hyperandrogenism and is likely a primary cause of PCOS.

Studies have shown that 30%–35% of women with PCOS have impaired glucose tolerance, and that 8%–10% have type 2 diabetes.

On the whole, Dr. Nestler said, 30%–50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by age 30. Lean women with PCOS, on the other hand, are just as insulin resistant—if not more so—than obese women without PCOS, several speakers said.

Dr. Nestler said that he and his colleagues found in a chart review of 50 consecutive PCOS patients treated with metformin that the incidence of impaired glucose tolerance was “dramatically” reduced.

At baseline, 78% of the 50 patients had normal glucose tolerance (NGT), and 22% had impaired glucose tolerance (IGT). At follow-up (a mean of 43 months for NGT patients, and 29 months for IGT patients), 55% of the IGT patients had converted to normal, with 45% continuing to have IGT. Of the NGT patients, 95% continued to have NGT, and 5% converted to IGT.

“It needs to be verified in a prospective study, but our annual conversion rate to IGT of 1.4% with metformin treatment is a dramatic reduction from the 16%–19% annual conversion rates” reported in women with PCOS who are not treated with metformin, he said.

He and other physicians at the meeting pointed to the Nurses' Health Study as the best of few studies that provides a look at the cardiovascular “outcomes” of PCOS.

In its tracking of over 80,000 women for 14 years, the study found that women with abnormal menstrual cyclicity had a relative risk for cardiovascular disease of 1.5 and a relative risk of fatal MI of 1.9, compared with women with normal menses. (The NHS also found a twofold increased risk, independent of weight, of type 2 diabetes in women with oligomenorrhea.)

Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs. The risk may be higher in women with PCOS, since they likely start at a higher baseline risk and take OCs for long periods of time, she said.

Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”

And the “question is, whether she'll take a pill for the next 30 years that doesn't make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.

Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”

Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y. Her adolescent patients on metformin also have improvements in their acne and frequently lose weight.

“We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said. Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.

Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and is a stock/shareholder of the Bristol-Myers Squibb Co. and Pfizer Inc.

Metformin OK for Infertile Patients

If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.

“If a woman comes to me with PCOS who wants to get pregnant, I usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. This way we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If at the end of 6 months she doesn't become pregnant, I send her to the endocrinologist.”

The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.

In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.

Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.

WASHINGTON — Insulin resistance is such an integral and dangerous feature of polycystic ovary syndrome that metformin should be favored over oral contraceptive pills for treatment of the syndrome, said physicians in annual scientific sessions of the American Diabetes Association meeting.

While there is a paucity of “good, prospective outcomes data” on cardiovascular disease in PCOS patients—as well as the existence of only limited data on the effect of oral contraceptives (OCs) on insulin resistance—the speakers warned against waiting for definitive data to appear. Current knowledge of the risks of insulin resistance and the potential disadvantages of OCs is too convincing, they said.

“Given everything [we know now], I believe we now must have the goals of preventing glucose intolerance and diabetes, and preventing atherosclerosis and acute coronary events” in addition to addressing the immediate symptoms of PCOS, said Dr. John Nestler, professor of medicine, ob.gyn., pharmacology, and toxicology at the Virginia Commonwealth University, Richmond.

“I will be provocative, because there aren't a lot of studies, but I'm going to argue that there may be disadvantages to using OCs,” said Dr. Nestler, who also chairs the division of endocrinology and metabolism.

OCs may be better for treating symptoms such as acne and hirsutism (studies of metformin have not addressed these problems as primary end points), but studies indicate that OCs worsen insulin resistance and glucose intolerance and that they may increase triglycerides, worsening the risk of diabetes and cardiovascular disease, he said.

Metformin, on the other hand, targets insulin resistance, “what may well be the initiating abnormality in PCOS, and has been shown to normalize or improve the biochemical, clinical, and reproductive abnormalities of PCOS,” said pediatric endocrinologist Dr. Tessa Lebinger.

The drug is effective whether or not insulin resistance can be documented, she said.

In most cases, Dr. Nestler agreed, it won't be documented because insulin resistance is too difficult to accurately measure in a clinical setting. “Most women with PCOS are insulin resistant … so an empiric trial of metformin in any woman with PCOS is reasonable as long as you monitor her and make sure that her menses are improving,” he said.

Dr. Burton Sobel, who directs the Cardiovascular Research Institute at the University of Vermont, said during a symposium on PCOS that from his perspective as a cardiologist, “PCOS is a cardiovascular disease.”

“We know, from so many perspectives, that impaired sensitivity to insulin is a forerunner, and probably a determinant, of premature coronary disease,” Dr. Sobel said. “It may be years before we have prospective data and legitimacy for using insulin sensitizers [in PCOS patients], but if I had a daughter with PCOS, I'd use an insulin sensitizer beginning with my recognition of the problem regardless of whether she had abnormal glucose tolerance. … I wouldn't wait—to me this is a smoking gun.”

The relationship between hyperinsulinemia and hyperandrogenism—in particular, the question of which causes which—is still discussed, but these physicians said they're convinced from available data that insulin resistance leads to hyperandrogenism and is likely a primary cause of PCOS.

Studies have shown that 30%–35% of women with PCOS have impaired glucose tolerance, and that 8%–10% have type 2 diabetes.

On the whole, Dr. Nestler said, 30%–50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by age 30. Lean women with PCOS, on the other hand, are just as insulin resistant—if not more so—than obese women without PCOS, several speakers said.

Dr. Nestler said that he and his colleagues found in a chart review of 50 consecutive PCOS patients treated with metformin that the incidence of impaired glucose tolerance was “dramatically” reduced.

At baseline, 78% of the 50 patients had normal glucose tolerance (NGT), and 22% had impaired glucose tolerance (IGT). At follow-up (a mean of 43 months for NGT patients, and 29 months for IGT patients), 55% of the IGT patients had converted to normal, with 45% continuing to have IGT. Of the NGT patients, 95% continued to have NGT, and 5% converted to IGT.

“It needs to be verified in a prospective study, but our annual conversion rate to IGT of 1.4% with metformin treatment is a dramatic reduction from the 16%–19% annual conversion rates” reported in women with PCOS who are not treated with metformin, he said.

He and other physicians at the meeting pointed to the Nurses' Health Study as the best of few studies that provides a look at the cardiovascular “outcomes” of PCOS.

In its tracking of over 80,000 women for 14 years, the study found that women with abnormal menstrual cyclicity had a relative risk for cardiovascular disease of 1.5 and a relative risk of fatal MI of 1.9, compared with women with normal menses. (The NHS also found a twofold increased risk, independent of weight, of type 2 diabetes in women with oligomenorrhea.)

Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs. The risk may be higher in women with PCOS, since they likely start at a higher baseline risk and take OCs for long periods of time, she said.

Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”

And the “question is, whether she'll take a pill for the next 30 years that doesn't make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.

Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”

Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y. Her adolescent patients on metformin also have improvements in their acne and frequently lose weight.

“We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said. Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.

Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and is a stock/shareholder of the Bristol-Myers Squibb Co. and Pfizer Inc.

Metformin OK for Infertile Patients

If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.

“If a woman comes to me with PCOS who wants to get pregnant, I usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. This way we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If at the end of 6 months she doesn't become pregnant, I send her to the endocrinologist.”

The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.

In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.

Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.

WASHINGTON — Patients who regularly skip breakfast have as high a risk of obesity as patients who have a family history of type 2 diabetes, a cross-sectional study of adolescents has shown.

Regularly skipping breakfast has been linked to obesity before, but Alison Okada Wollitzer, Ph.D., who reported the study at the annual scientific sessions of the American Diabetes Association, said she and her colleagues at the Sansum Diabetes Research Institute in Santa Barbara, Calif, wondered about the importance of the link and the reasons for it.

They studied 2,700 high school students in Santa Barbara and found that skipping breakfast doubles the risk of obesity—just as a family history of diabetes does.

Those with both risk factors—breakfast-skipping and a family history—had double the risk of obesity as did adolescents with only one of the risk factors, Dr. Wollitzer reported in a poster presentation at the meeting.

Adolescents at two public high schools who did not have a known diagnosis of diabetes (1,060 males and 1,640 females) participated in a brief physical exam and lifestyle questionnaire, which asked if breakfast was eaten on school days. Only those answering yes or no were included in the analysis.

Obesity was defined as having a body mass index at or above the 95th percentile; diabetes in any first-degree relative constituted a positive family history. About 34% of the students were white and 57% were Hispanic.

Of those who skipped breakfast but had no family history of diabetes, 16% were obese, compared with almost 18% of those who ate breakfast but had a positive family history.

Only 8% of the adolescents with neither risk factor were obese. Of those who skipped breakfast and had a positive family history, 32% were obese, Dr. Wollitzer reported.

Students who ate breakfast regularly were less likely to eat junk food at lunch, more likely to eat fruits and vegetables, and more likely to exercise regularly, she reported.

WASHINGTON — Patients who regularly skip breakfast have as high a risk of obesity as patients who have a family history of type 2 diabetes, a cross-sectional study of adolescents has shown.

Regularly skipping breakfast has been linked to obesity before, but Alison Okada Wollitzer, Ph.D., who reported the study at the annual scientific sessions of the American Diabetes Association, said she and her colleagues at the Sansum Diabetes Research Institute in Santa Barbara, Calif, wondered about the importance of the link and the reasons for it.

They studied 2,700 high school students in Santa Barbara and found that skipping breakfast doubles the risk of obesity—just as a family history of diabetes does.

Those with both risk factors—breakfast-skipping and a family history—had double the risk of obesity as did adolescents with only one of the risk factors, Dr. Wollitzer reported in a poster presentation at the meeting.

Adolescents at two public high schools who did not have a known diagnosis of diabetes (1,060 males and 1,640 females) participated in a brief physical exam and lifestyle questionnaire, which asked if breakfast was eaten on school days. Only those answering yes or no were included in the analysis.

Obesity was defined as having a body mass index at or above the 95th percentile; diabetes in any first-degree relative constituted a positive family history. About 34% of the students were white and 57% were Hispanic.

Of those who skipped breakfast but had no family history of diabetes, 16% were obese, compared with almost 18% of those who ate breakfast but had a positive family history.

Only 8% of the adolescents with neither risk factor were obese. Of those who skipped breakfast and had a positive family history, 32% were obese, Dr. Wollitzer reported.

Students who ate breakfast regularly were less likely to eat junk food at lunch, more likely to eat fruits and vegetables, and more likely to exercise regularly, she reported.

WASHINGTON — Patients who regularly skip breakfast have as high a risk of obesity as patients who have a family history of type 2 diabetes, a cross-sectional study of adolescents has shown.

Regularly skipping breakfast has been linked to obesity before, but Alison Okada Wollitzer, Ph.D., who reported the study at the annual scientific sessions of the American Diabetes Association, said she and her colleagues at the Sansum Diabetes Research Institute in Santa Barbara, Calif, wondered about the importance of the link and the reasons for it.

They studied 2,700 high school students in Santa Barbara and found that skipping breakfast doubles the risk of obesity—just as a family history of diabetes does.

Those with both risk factors—breakfast-skipping and a family history—had double the risk of obesity as did adolescents with only one of the risk factors, Dr. Wollitzer reported in a poster presentation at the meeting.

Adolescents at two public high schools who did not have a known diagnosis of diabetes (1,060 males and 1,640 females) participated in a brief physical exam and lifestyle questionnaire, which asked if breakfast was eaten on school days. Only those answering yes or no were included in the analysis.

Obesity was defined as having a body mass index at or above the 95th percentile; diabetes in any first-degree relative constituted a positive family history. About 34% of the students were white and 57% were Hispanic.

Of those who skipped breakfast but had no family history of diabetes, 16% were obese, compared with almost 18% of those who ate breakfast but had a positive family history.

Only 8% of the adolescents with neither risk factor were obese. Of those who skipped breakfast and had a positive family history, 32% were obese, Dr. Wollitzer reported.

Students who ate breakfast regularly were less likely to eat junk food at lunch, more likely to eat fruits and vegetables, and more likely to exercise regularly, she reported.

WASHINGTON — A preliminary look at the children referred for participation in a large treatment trial of type 2 diabetes in overweight and obese youth shows that the children not only have a high prevalence of hypertension and dyslipidemia, but a high incidence of autoantibody positivity as well, investigators reported at the annual scientific sessions of the American Diabetes Association.

The findings add to those of other studies suggesting that a significant number of children with apparent type 2 diabetes mellitus also may have diabetes autoimmunity consistent with type 1 diabetes, reported Dr. Georgeanna J. Klingensmith, director of pediatric clinics at the Barbara Davis Center for Childhood Diabetes in Aurora, Colo.

Approximately 18% of the 535 children screened for inclusion thus far in the 15-center, National Institutes of Health-sponsored Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study were found to be positive for diabetes autoimmunity. The children, who were racially and ethnically diverse, were considered by their pediatric endocrinologists to have type 2 diabetes.

The number of youth with diabetes autoimmunity in conjunction with characteristics of type 2 diabetes is likely much higher, however, because some potential study participants were locally prescreened for autoantibodies and were not even sent to the TODAY study investigators. The presence of islet cell autoimmunity is an exclusion criterion for the study, Dr. Klingensmith said.

Indeed, other studies have reported higher rates of what some physicians and investigators are now calling “double,” “hybrid,” or “type 3” diabetes.

Investigators of a large British study, for instance, reported almost 10 years ago that 33% of 157 young adults with type 2 diabetes were found to be positive for diabetes-associated antibodies. And, just this year, investigators of a German study reported that 36% of 128 children thought to have type 2 diabetes also had diabetes-associated antibodies, Dr. Klingensmith said.

Dr. Ingrid M. Libman of the Children's Hospital in Pittsburgh said in another presentation that the “spectrum” of diabetes now presenting in youth presents treatment dilemmas.

“If insulin therapy preserves B-cell function, should all patients that phenotypically look like type 2 but have antibodies be treated with insulin?” she asked. “And should patients [with type 1 and obesity] be treated with insulin sensitizers?”

There have been few studies on treatment for “double” diabetes, she continued. Children who are registered in the Allegheny County Registry for diabetes and the Children's Hospital Registry who have characteristics of both type 1 (antibodies and/or ketones and diabetic ketoacidosis, for instance) and type 2 (obesity and/or acanthosis nigricans) are being treated in their communities with either insulin alone or with insulin and an oral agent, mainly metformin, she said.

It is possible that obesity and insulin resistance may accelerate the presentation of type 1 diabetes in patients with type 2, said Dr. Libman.

The children being enrolled in the TODAY study, in addition to having an absence of islet cell autoimmunity, must have had diabetes for 2 years or less, be 10–17 years of age, and have a fasting C-peptide greater than 0.6 ng/mL and a body mass index at the 85th percentile or above. Participants will be randomized to receive metformin alone, metformin and rosiglitazone, or metformin and intensive lifestyle therapy.

Of the 535 children who were screened for inclusion in the TODAY study, approximately 5% had only glutamic acid decarboxylase (GAD) autoantibodies and 6% had only IA-2 autoantibodies. Approximately 7% had both GAD and IA-2 autoantibodies. All told, 18% were positive for one or both of the antibodies measured.

Dr. Klingensmith and her coinvestigators also looked at the number of children who had very high titer antibody levels. They found that 12% of the children screened—and 65% of all antibody-positive children—were either positive for both autoantibodies or had antibody titers that were more than 300% above normal (above the cut-off point for positivity).

They found that there were no differences between the groups in age, gender, or duration of diabetes. Children with both antibodies, however, had lower C-peptide levels, BMI and triglyceride levels, as well as higher HDL cholesterol and HbA_1c levels, and greater insulin use than did children with no antibodies, Dr. Klingensmith said.

According to Dr. Neil H. White, director of the division of pediatric endocrinology and metabolism at St. Louis University who is also a TODAY study investigator, approximately 12% of the children were receiving insulin alone at the time of screening for the study, and almost 50% were receiving metformin only. Approximately 25% were receiving both. The remaining children were receiving other medications or no treatment at all.

In terms of comorbidities, he reported, 26% had hypertension and almost 60% had dyslipidemia.

It remains to be seen whether diabetes autoimmunity will alter the clinical course of the disorder in youth with the clinical features of type 2 diabetes, Dr. Klingensmith said.

When it comes to the risk of conditions and complications traditionally associated with type 1 diabetes, it very well may, Dr. Libman warned.

Current guidelines, for instance, recommend screening for autoimmune thyroid disease in children with type 1 diabetes who, in contrast to those with type 2 diabetes, are known to have an increased frequency of thyroid antibodies and thyroid dysfunction. But a look at a sample of children in the Pittsburgh registries shows that children with “double” diabetes may have the same prevalence of thyroid antibodies as do those with type 1 diabetes.

Twenty percent of 24 children with double diabetes (defined here as obese with diabetes antibodies) were positive for thyroid antibodies, as were 21% of 117 children with type 1 diabetes (lean with diabetes antibodies). The two groups had a similar incidence of hypothyroidism. A sample of 21 children with type 2 diabetes (obese with no diabetes antibodies) had neither problem, Dr. Libman reported.

WASHINGTON — A preliminary look at the children referred for participation in a large treatment trial of type 2 diabetes in overweight and obese youth shows that the children not only have a high prevalence of hypertension and dyslipidemia, but a high incidence of autoantibody positivity as well, investigators reported at the annual scientific sessions of the American Diabetes Association.

The findings add to those of other studies suggesting that a significant number of children with apparent type 2 diabetes mellitus also may have diabetes autoimmunity consistent with type 1 diabetes, reported Dr. Georgeanna J. Klingensmith, director of pediatric clinics at the Barbara Davis Center for Childhood Diabetes in Aurora, Colo.

Approximately 18% of the 535 children screened for inclusion thus far in the 15-center, National Institutes of Health-sponsored Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study were found to be positive for diabetes autoimmunity. The children, who were racially and ethnically diverse, were considered by their pediatric endocrinologists to have type 2 diabetes.

The number of youth with diabetes autoimmunity in conjunction with characteristics of type 2 diabetes is likely much higher, however, because some potential study participants were locally prescreened for autoantibodies and were not even sent to the TODAY study investigators. The presence of islet cell autoimmunity is an exclusion criterion for the study, Dr. Klingensmith said.

Indeed, other studies have reported higher rates of what some physicians and investigators are now calling “double,” “hybrid,” or “type 3” diabetes.

Investigators of a large British study, for instance, reported almost 10 years ago that 33% of 157 young adults with type 2 diabetes were found to be positive for diabetes-associated antibodies. And, just this year, investigators of a German study reported that 36% of 128 children thought to have type 2 diabetes also had diabetes-associated antibodies, Dr. Klingensmith said.

Dr. Ingrid M. Libman of the Children's Hospital in Pittsburgh said in another presentation that the “spectrum” of diabetes now presenting in youth presents treatment dilemmas.

“If insulin therapy preserves B-cell function, should all patients that phenotypically look like type 2 but have antibodies be treated with insulin?” she asked. “And should patients [with type 1 and obesity] be treated with insulin sensitizers?”

There have been few studies on treatment for “double” diabetes, she continued. Children who are registered in the Allegheny County Registry for diabetes and the Children's Hospital Registry who have characteristics of both type 1 (antibodies and/or ketones and diabetic ketoacidosis, for instance) and type 2 (obesity and/or acanthosis nigricans) are being treated in their communities with either insulin alone or with insulin and an oral agent, mainly metformin, she said.

It is possible that obesity and insulin resistance may accelerate the presentation of type 1 diabetes in patients with type 2, said Dr. Libman.

The children being enrolled in the TODAY study, in addition to having an absence of islet cell autoimmunity, must have had diabetes for 2 years or less, be 10–17 years of age, and have a fasting C-peptide greater than 0.6 ng/mL and a body mass index at the 85th percentile or above. Participants will be randomized to receive metformin alone, metformin and rosiglitazone, or metformin and intensive lifestyle therapy.

Of the 535 children who were screened for inclusion in the TODAY study, approximately 5% had only glutamic acid decarboxylase (GAD) autoantibodies and 6% had only IA-2 autoantibodies. Approximately 7% had both GAD and IA-2 autoantibodies. All told, 18% were positive for one or both of the antibodies measured.

Dr. Klingensmith and her coinvestigators also looked at the number of children who had very high titer antibody levels. They found that 12% of the children screened—and 65% of all antibody-positive children—were either positive for both autoantibodies or had antibody titers that were more than 300% above normal (above the cut-off point for positivity).

They found that there were no differences between the groups in age, gender, or duration of diabetes. Children with both antibodies, however, had lower C-peptide levels, BMI and triglyceride levels, as well as higher HDL cholesterol and HbA_1c levels, and greater insulin use than did children with no antibodies, Dr. Klingensmith said.

According to Dr. Neil H. White, director of the division of pediatric endocrinology and metabolism at St. Louis University who is also a TODAY study investigator, approximately 12% of the children were receiving insulin alone at the time of screening for the study, and almost 50% were receiving metformin only. Approximately 25% were receiving both. The remaining children were receiving other medications or no treatment at all.

In terms of comorbidities, he reported, 26% had hypertension and almost 60% had dyslipidemia.

It remains to be seen whether diabetes autoimmunity will alter the clinical course of the disorder in youth with the clinical features of type 2 diabetes, Dr. Klingensmith said.

When it comes to the risk of conditions and complications traditionally associated with type 1 diabetes, it very well may, Dr. Libman warned.

Current guidelines, for instance, recommend screening for autoimmune thyroid disease in children with type 1 diabetes who, in contrast to those with type 2 diabetes, are known to have an increased frequency of thyroid antibodies and thyroid dysfunction. But a look at a sample of children in the Pittsburgh registries shows that children with “double” diabetes may have the same prevalence of thyroid antibodies as do those with type 1 diabetes.

Twenty percent of 24 children with double diabetes (defined here as obese with diabetes antibodies) were positive for thyroid antibodies, as were 21% of 117 children with type 1 diabetes (lean with diabetes antibodies). The two groups had a similar incidence of hypothyroidism. A sample of 21 children with type 2 diabetes (obese with no diabetes antibodies) had neither problem, Dr. Libman reported.

WASHINGTON — A preliminary look at the children referred for participation in a large treatment trial of type 2 diabetes in overweight and obese youth shows that the children not only have a high prevalence of hypertension and dyslipidemia, but a high incidence of autoantibody positivity as well, investigators reported at the annual scientific sessions of the American Diabetes Association.

The findings add to those of other studies suggesting that a significant number of children with apparent type 2 diabetes mellitus also may have diabetes autoimmunity consistent with type 1 diabetes, reported Dr. Georgeanna J. Klingensmith, director of pediatric clinics at the Barbara Davis Center for Childhood Diabetes in Aurora, Colo.

Approximately 18% of the 535 children screened for inclusion thus far in the 15-center, National Institutes of Health-sponsored Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study were found to be positive for diabetes autoimmunity. The children, who were racially and ethnically diverse, were considered by their pediatric endocrinologists to have type 2 diabetes.

The number of youth with diabetes autoimmunity in conjunction with characteristics of type 2 diabetes is likely much higher, however, because some potential study participants were locally prescreened for autoantibodies and were not even sent to the TODAY study investigators. The presence of islet cell autoimmunity is an exclusion criterion for the study, Dr. Klingensmith said.

Indeed, other studies have reported higher rates of what some physicians and investigators are now calling “double,” “hybrid,” or “type 3” diabetes.

Investigators of a large British study, for instance, reported almost 10 years ago that 33% of 157 young adults with type 2 diabetes were found to be positive for diabetes-associated antibodies. And, just this year, investigators of a German study reported that 36% of 128 children thought to have type 2 diabetes also had diabetes-associated antibodies, Dr. Klingensmith said.

Dr. Ingrid M. Libman of the Children's Hospital in Pittsburgh said in another presentation that the “spectrum” of diabetes now presenting in youth presents treatment dilemmas.

“If insulin therapy preserves B-cell function, should all patients that phenotypically look like type 2 but have antibodies be treated with insulin?” she asked. “And should patients [with type 1 and obesity] be treated with insulin sensitizers?”

There have been few studies on treatment for “double” diabetes, she continued. Children who are registered in the Allegheny County Registry for diabetes and the Children's Hospital Registry who have characteristics of both type 1 (antibodies and/or ketones and diabetic ketoacidosis, for instance) and type 2 (obesity and/or acanthosis nigricans) are being treated in their communities with either insulin alone or with insulin and an oral agent, mainly metformin, she said.

It is possible that obesity and insulin resistance may accelerate the presentation of type 1 diabetes in patients with type 2, said Dr. Libman.

The children being enrolled in the TODAY study, in addition to having an absence of islet cell autoimmunity, must have had diabetes for 2 years or less, be 10–17 years of age, and have a fasting C-peptide greater than 0.6 ng/mL and a body mass index at the 85th percentile or above. Participants will be randomized to receive metformin alone, metformin and rosiglitazone, or metformin and intensive lifestyle therapy.

Of the 535 children who were screened for inclusion in the TODAY study, approximately 5% had only glutamic acid decarboxylase (GAD) autoantibodies and 6% had only IA-2 autoantibodies. Approximately 7% had both GAD and IA-2 autoantibodies. All told, 18% were positive for one or both of the antibodies measured.

Dr. Klingensmith and her coinvestigators also looked at the number of children who had very high titer antibody levels. They found that 12% of the children screened—and 65% of all antibody-positive children—were either positive for both autoantibodies or had antibody titers that were more than 300% above normal (above the cut-off point for positivity).

They found that there were no differences between the groups in age, gender, or duration of diabetes. Children with both antibodies, however, had lower C-peptide levels, BMI and triglyceride levels, as well as higher HDL cholesterol and HbA_1c levels, and greater insulin use than did children with no antibodies, Dr. Klingensmith said.

According to Dr. Neil H. White, director of the division of pediatric endocrinology and metabolism at St. Louis University who is also a TODAY study investigator, approximately 12% of the children were receiving insulin alone at the time of screening for the study, and almost 50% were receiving metformin only. Approximately 25% were receiving both. The remaining children were receiving other medications or no treatment at all.

In terms of comorbidities, he reported, 26% had hypertension and almost 60% had dyslipidemia.

It remains to be seen whether diabetes autoimmunity will alter the clinical course of the disorder in youth with the clinical features of type 2 diabetes, Dr. Klingensmith said.

When it comes to the risk of conditions and complications traditionally associated with type 1 diabetes, it very well may, Dr. Libman warned.

Current guidelines, for instance, recommend screening for autoimmune thyroid disease in children with type 1 diabetes who, in contrast to those with type 2 diabetes, are known to have an increased frequency of thyroid antibodies and thyroid dysfunction. But a look at a sample of children in the Pittsburgh registries shows that children with “double” diabetes may have the same prevalence of thyroid antibodies as do those with type 1 diabetes.

Twenty percent of 24 children with double diabetes (defined here as obese with diabetes antibodies) were positive for thyroid antibodies, as were 21% of 117 children with type 1 diabetes (lean with diabetes antibodies). The two groups had a similar incidence of hypothyroidism. A sample of 21 children with type 2 diabetes (obese with no diabetes antibodies) had neither problem, Dr. Libman reported.

WASHINGTON — Early evidence suggests that the health benefits of bariatric surgery offset the risks for severely obese adolescents, according to the results of small studies reported at the annual scientific sessions of the American Diabetes Association.

Significant metabolic improvements and near-complete resolution of type 2 diabetes and obstructive sleep apnea were among the 1-year outcomes of Roux-en-Y gastric bypass surgery performed in 36 morbidly obese adolescents, aged 13–21 years, at three pediatric surgical centers participating in the Pediatric Bariatric Study Group.

Severely obese adolescents are developing serious adultlike comorbidities at an unexpectedly high frequency. Limited success with behavioral and lifestyle interventions has left physicians considering more aggressive interventions. “Children who are obese become obese adults,” said Dr. Carroll M. Harmon, of the Children's Hospital of Alabama, Birmingham.

Teens were eligible for the surgery at Children's Hospital and the other institutions in the Pediatric Bariatric Study Group (the University of Florida in Gainesville and the Cincinnati Children's Hospital Medical Center) if they had a body mass index (BMI) of at least 40 kg/m

The teens in the multicenter cohort had a mean BMI preoperatively of approximately 57. Postoperatively, the mean BMI fell to 36, a 37% reduction.

None of the patients included in the weight loss analysis (9 of the 36 teens in the cohort were excluded because they did not comply with follow-up requirements) attained normal weight in the year of follow-up; BMI values, in fact, still ranged from overweight to severe obesity.

Still, the postoperative weight loss was significant and consistent with outcomes in adults who undergo bariatric surgery, said Dr. Harmon, professor of surgery in the University of Alabama division of pediatric surgery.

Metabolic measures improved as a result of significant changes in triglycerides (−65 mg/dL), total cholesterol (−30 mg/dL), fasting blood glucose (−12 g/dL), and fasting insulin (−21.3 μU/mL). Changes in HDL and LDL cholesterol values were not statistically significant.

Mean hemoglobin A_1c decreased from 7.3% to 5.6% in the 10 patients diagnosed with type 2 diabetes. At 1 year after surgery, 1 of 10 patients remained on diabetic medications; 9 of 10 were on diabetic medications preoperatively, Dr. Harmon reported, adding that the adolescents also scored significantly higher postoperatively on various quality-of-life measures than they did preoperatively.

In a separate poster presentation, Dr. Marc P. Michalsky and Dr. Dara Schuster of Ohio State University, Columbus, reported on what they said are similarly good outcomes in five morbidly obese adolescents (BMI of at least 57) who underwent Roux-en-Y gastric bypass surgery at Columbus Children's Hospital.

Serum hemoglobin A_1c reached normal values within 20 weeks of surgery in each of the four adolescents with type 2 diabetes. Blood pressures reached normal values within 20 weeks in each of four hypertensive patients, and obstructive sleep apnea resolved after surgery in two of three affected patients. Insulin resistance (as determined by calculating the homeostasis model assessment of insulin resistance) also was reduced by a mean of 66% at 12 weeks post surgery.

“These are superobese kids,” and they have the same morbidities as obese adults who qualify for gastric bypass surgery, Dr. Schuster said in an interview. “The question we need to answer is: Do we do them a favor by operating early?”

Long-term follow-up will be necessary to determine the durability of the patients' improvements and the safety of the surger, the physicians said. It remains to be seen whether the patients will experience nutritional malabsorption, they noted.

None of the 5 adolescents treated in Columbus experienced complications during the 20-week follow-up period, but there were complications among the 36 who were followed for a year.

Nine of the 36 patients had minor complications with no long-term sequelae (nausea, wound infection, and food obstruction), and 4 had at least one moderate complication (persistent iron-deficiency anemia or the need for reoperation).

Two patients had severe complications, said Dr. Harmon. One developed severe thiamine deficiency with significant sequelae, and the other, who initially presented with a BMI of 80 and a weight of 630 pounds, died 9 months after surgery due to infectious colitis contracted while undergoing inpatient rehabilitation for osteoarthritis.

The complication profile thus far is similar to that seen in superobese adults who undergo the surgery. “But so far, in adolescents, just as in adults, these risks seem to be offset by the benefits,” he said.

The adjustable gastric banding procedure, which does not involve an intestinal bypass, is getting more attention as a possible “best” operation for adolescents—even though long-term results in adults have not been compared with those of gastric bypass surgery—because it eliminates concerns about nutritional and mineral malabsorption, Dr. Harmon said.

Insurance coverage varies nationwide and is difficult to secure in some locales. “In Ohio, Medicaid has been favorable toward covering these kids so far,” Dr. Michalsky said. “We have a high rate of obesity, so the state may be attuned [to the problem].”

Comorbid Conditions Often Missed

Dr. Schuster said the “most striking thing” about seeing adolescents referred to her hospital's bariatric surgery clinic is how “many of them didn't have their comorbid conditions diagnosed” before their surgical evaluations.

Hypertension, sleep apnea, diabetes, and other obesity-related comorbid conditions “are underdiagnosed and undermanaged” in obese adolescents, Dr. Schuster and her colleagues said in a poster presented at the annual scientific sessions of the American Diabetes Association.

Of 46 patients who were seen at the Columbus Children's Hospital Adolescent Bariatric Surgery Clinic in 2004 and 2005, 42% received a “new diagnosis” of obstructive sleep apnea and 33% learned they were hypothyroid.

During their initial presurgical evaluation, 25% were first told they had type 2 diabetes, 13% learned they had gastroesophageal reflux disease, and 10% received a new diagnosis of hypertension. Not surprisingly, since insulin resistance is hard to diagnose in most clinical settings, 54% learned for the first time that they were insulin resistant.

The prevalence of comorbidities was similar to, or higher than, the rates recorded among morbidly obese adults presenting at other clinics at Ohio State University in Columbus, reported Dr. Schuster and her associates.

WASHINGTON — Early evidence suggests that the health benefits of bariatric surgery offset the risks for severely obese adolescents, according to the results of small studies reported at the annual scientific sessions of the American Diabetes Association.

Significant metabolic improvements and near-complete resolution of type 2 diabetes and obstructive sleep apnea were among the 1-year outcomes of Roux-en-Y gastric bypass surgery performed in 36 morbidly obese adolescents, aged 13–21 years, at three pediatric surgical centers participating in the Pediatric Bariatric Study Group.

Severely obese adolescents are developing serious adultlike comorbidities at an unexpectedly high frequency. Limited success with behavioral and lifestyle interventions has left physicians considering more aggressive interventions. “Children who are obese become obese adults,” said Dr. Carroll M. Harmon, of the Children's Hospital of Alabama, Birmingham.

Teens were eligible for the surgery at Children's Hospital and the other institutions in the Pediatric Bariatric Study Group (the University of Florida in Gainesville and the Cincinnati Children's Hospital Medical Center) if they had a body mass index (BMI) of at least 40 kg/m

The teens in the multicenter cohort had a mean BMI preoperatively of approximately 57. Postoperatively, the mean BMI fell to 36, a 37% reduction.

None of the patients included in the weight loss analysis (9 of the 36 teens in the cohort were excluded because they did not comply with follow-up requirements) attained normal weight in the year of follow-up; BMI values, in fact, still ranged from overweight to severe obesity.

Still, the postoperative weight loss was significant and consistent with outcomes in adults who undergo bariatric surgery, said Dr. Harmon, professor of surgery in the University of Alabama division of pediatric surgery.

Metabolic measures improved as a result of significant changes in triglycerides (−65 mg/dL), total cholesterol (−30 mg/dL), fasting blood glucose (−12 g/dL), and fasting insulin (−21.3 μU/mL). Changes in HDL and LDL cholesterol values were not statistically significant.

Mean hemoglobin A_1c decreased from 7.3% to 5.6% in the 10 patients diagnosed with type 2 diabetes. At 1 year after surgery, 1 of 10 patients remained on diabetic medications; 9 of 10 were on diabetic medications preoperatively, Dr. Harmon reported, adding that the adolescents also scored significantly higher postoperatively on various quality-of-life measures than they did preoperatively.

In a separate poster presentation, Dr. Marc P. Michalsky and Dr. Dara Schuster of Ohio State University, Columbus, reported on what they said are similarly good outcomes in five morbidly obese adolescents (BMI of at least 57) who underwent Roux-en-Y gastric bypass surgery at Columbus Children's Hospital.

Serum hemoglobin A_1c reached normal values within 20 weeks of surgery in each of the four adolescents with type 2 diabetes. Blood pressures reached normal values within 20 weeks in each of four hypertensive patients, and obstructive sleep apnea resolved after surgery in two of three affected patients. Insulin resistance (as determined by calculating the homeostasis model assessment of insulin resistance) also was reduced by a mean of 66% at 12 weeks post surgery.

“These are superobese kids,” and they have the same morbidities as obese adults who qualify for gastric bypass surgery, Dr. Schuster said in an interview. “The question we need to answer is: Do we do them a favor by operating early?”

Long-term follow-up will be necessary to determine the durability of the patients' improvements and the safety of the surger, the physicians said. It remains to be seen whether the patients will experience nutritional malabsorption, they noted.

None of the 5 adolescents treated in Columbus experienced complications during the 20-week follow-up period, but there were complications among the 36 who were followed for a year.

Nine of the 36 patients had minor complications with no long-term sequelae (nausea, wound infection, and food obstruction), and 4 had at least one moderate complication (persistent iron-deficiency anemia or the need for reoperation).

Two patients had severe complications, said Dr. Harmon. One developed severe thiamine deficiency with significant sequelae, and the other, who initially presented with a BMI of 80 and a weight of 630 pounds, died 9 months after surgery due to infectious colitis contracted while undergoing inpatient rehabilitation for osteoarthritis.

The complication profile thus far is similar to that seen in superobese adults who undergo the surgery. “But so far, in adolescents, just as in adults, these risks seem to be offset by the benefits,” he said.

The adjustable gastric banding procedure, which does not involve an intestinal bypass, is getting more attention as a possible “best” operation for adolescents—even though long-term results in adults have not been compared with those of gastric bypass surgery—because it eliminates concerns about nutritional and mineral malabsorption, Dr. Harmon said.

Insurance coverage varies nationwide and is difficult to secure in some locales. “In Ohio, Medicaid has been favorable toward covering these kids so far,” Dr. Michalsky said. “We have a high rate of obesity, so the state may be attuned [to the problem].”

Comorbid Conditions Often Missed

Dr. Schuster said the “most striking thing” about seeing adolescents referred to her hospital's bariatric surgery clinic is how “many of them didn't have their comorbid conditions diagnosed” before their surgical evaluations.

Hypertension, sleep apnea, diabetes, and other obesity-related comorbid conditions “are underdiagnosed and undermanaged” in obese adolescents, Dr. Schuster and her colleagues said in a poster presented at the annual scientific sessions of the American Diabetes Association.

Of 46 patients who were seen at the Columbus Children's Hospital Adolescent Bariatric Surgery Clinic in 2004 and 2005, 42% received a “new diagnosis” of obstructive sleep apnea and 33% learned they were hypothyroid.

During their initial presurgical evaluation, 25% were first told they had type 2 diabetes, 13% learned they had gastroesophageal reflux disease, and 10% received a new diagnosis of hypertension. Not surprisingly, since insulin resistance is hard to diagnose in most clinical settings, 54% learned for the first time that they were insulin resistant.

The prevalence of comorbidities was similar to, or higher than, the rates recorded among morbidly obese adults presenting at other clinics at Ohio State University in Columbus, reported Dr. Schuster and her associates.

WASHINGTON — Early evidence suggests that the health benefits of bariatric surgery offset the risks for severely obese adolescents, according to the results of small studies reported at the annual scientific sessions of the American Diabetes Association.

Significant metabolic improvements and near-complete resolution of type 2 diabetes and obstructive sleep apnea were among the 1-year outcomes of Roux-en-Y gastric bypass surgery performed in 36 morbidly obese adolescents, aged 13–21 years, at three pediatric surgical centers participating in the Pediatric Bariatric Study Group.

Severely obese adolescents are developing serious adultlike comorbidities at an unexpectedly high frequency. Limited success with behavioral and lifestyle interventions has left physicians considering more aggressive interventions. “Children who are obese become obese adults,” said Dr. Carroll M. Harmon, of the Children's Hospital of Alabama, Birmingham.

Teens were eligible for the surgery at Children's Hospital and the other institutions in the Pediatric Bariatric Study Group (the University of Florida in Gainesville and the Cincinnati Children's Hospital Medical Center) if they had a body mass index (BMI) of at least 40 kg/m

The teens in the multicenter cohort had a mean BMI preoperatively of approximately 57. Postoperatively, the mean BMI fell to 36, a 37% reduction.

None of the patients included in the weight loss analysis (9 of the 36 teens in the cohort were excluded because they did not comply with follow-up requirements) attained normal weight in the year of follow-up; BMI values, in fact, still ranged from overweight to severe obesity.

Still, the postoperative weight loss was significant and consistent with outcomes in adults who undergo bariatric surgery, said Dr. Harmon, professor of surgery in the University of Alabama division of pediatric surgery.

Metabolic measures improved as a result of significant changes in triglycerides (−65 mg/dL), total cholesterol (−30 mg/dL), fasting blood glucose (−12 g/dL), and fasting insulin (−21.3 μU/mL). Changes in HDL and LDL cholesterol values were not statistically significant.

Mean hemoglobin A_1c decreased from 7.3% to 5.6% in the 10 patients diagnosed with type 2 diabetes. At 1 year after surgery, 1 of 10 patients remained on diabetic medications; 9 of 10 were on diabetic medications preoperatively, Dr. Harmon reported, adding that the adolescents also scored significantly higher postoperatively on various quality-of-life measures than they did preoperatively.

In a separate poster presentation, Dr. Marc P. Michalsky and Dr. Dara Schuster of Ohio State University, Columbus, reported on what they said are similarly good outcomes in five morbidly obese adolescents (BMI of at least 57) who underwent Roux-en-Y gastric bypass surgery at Columbus Children's Hospital.

Serum hemoglobin A_1c reached normal values within 20 weeks of surgery in each of the four adolescents with type 2 diabetes. Blood pressures reached normal values within 20 weeks in each of four hypertensive patients, and obstructive sleep apnea resolved after surgery in two of three affected patients. Insulin resistance (as determined by calculating the homeostasis model assessment of insulin resistance) also was reduced by a mean of 66% at 12 weeks post surgery.

“These are superobese kids,” and they have the same morbidities as obese adults who qualify for gastric bypass surgery, Dr. Schuster said in an interview. “The question we need to answer is: Do we do them a favor by operating early?”

Long-term follow-up will be necessary to determine the durability of the patients' improvements and the safety of the surger, the physicians said. It remains to be seen whether the patients will experience nutritional malabsorption, they noted.

None of the 5 adolescents treated in Columbus experienced complications during the 20-week follow-up period, but there were complications among the 36 who were followed for a year.

Nine of the 36 patients had minor complications with no long-term sequelae (nausea, wound infection, and food obstruction), and 4 had at least one moderate complication (persistent iron-deficiency anemia or the need for reoperation).

Two patients had severe complications, said Dr. Harmon. One developed severe thiamine deficiency with significant sequelae, and the other, who initially presented with a BMI of 80 and a weight of 630 pounds, died 9 months after surgery due to infectious colitis contracted while undergoing inpatient rehabilitation for osteoarthritis.

The complication profile thus far is similar to that seen in superobese adults who undergo the surgery. “But so far, in adolescents, just as in adults, these risks seem to be offset by the benefits,” he said.

The adjustable gastric banding procedure, which does not involve an intestinal bypass, is getting more attention as a possible “best” operation for adolescents—even though long-term results in adults have not been compared with those of gastric bypass surgery—because it eliminates concerns about nutritional and mineral malabsorption, Dr. Harmon said.

Insurance coverage varies nationwide and is difficult to secure in some locales. “In Ohio, Medicaid has been favorable toward covering these kids so far,” Dr. Michalsky said. “We have a high rate of obesity, so the state may be attuned [to the problem].”

Comorbid Conditions Often Missed

Dr. Schuster said the “most striking thing” about seeing adolescents referred to her hospital's bariatric surgery clinic is how “many of them didn't have their comorbid conditions diagnosed” before their surgical evaluations.

Hypertension, sleep apnea, diabetes, and other obesity-related comorbid conditions “are underdiagnosed and undermanaged” in obese adolescents, Dr. Schuster and her colleagues said in a poster presented at the annual scientific sessions of the American Diabetes Association.

Of 46 patients who were seen at the Columbus Children's Hospital Adolescent Bariatric Surgery Clinic in 2004 and 2005, 42% received a “new diagnosis” of obstructive sleep apnea and 33% learned they were hypothyroid.

During their initial presurgical evaluation, 25% were first told they had type 2 diabetes, 13% learned they had gastroesophageal reflux disease, and 10% received a new diagnosis of hypertension. Not surprisingly, since insulin resistance is hard to diagnose in most clinical settings, 54% learned for the first time that they were insulin resistant.

The prevalence of comorbidities was similar to, or higher than, the rates recorded among morbidly obese adults presenting at other clinics at Ohio State University in Columbus, reported Dr. Schuster and her associates.

WASHINGTON — Insulin resistance is such an integral and dangerous feature of polycystic ovary syndrome that metformin should be favored over oral contraceptive pills for treatment of the syndrome, said physicians in annual scientific sessions of the American Diabetes Association meeting.

Although there is a paucity of “good, prospective outcomes data” on cardiovascular disease in patients with polycystic ovary syndrome (PCOS)—as well as the existence of only limited data on oral contraceptives' (OCs) effect on insulin resistance—the speakers warned against waiting for definitive data to appear. Current knowledge of the risks of insulin resistance and the potential disadvantages of OCs is too convincing, they argued.

“Given everything [we know now], I believe we now must have the goals of preventing glucose intolerance and diabetes, and preventing atherosclerosis and acute coronary events” in addition to addressing the immediate symptoms of PCOS, said Dr. John Nestler, professor of medicine, ob.gyn., pharmacology, and toxicology at the Virginia Commonwealth University, Richmond.

“I will be provocative, because there aren't a lot of studies, but I'm going to argue that there may be disadvantages to using OCs,” said Dr. Nestler, who also chairs the division of endocrinology and metabolism.

OCs may be better for treating symptoms such as acne and hirsutism (studies of metformin have not addressed these problems as primary end points), but studies indicate that OCs worsen insulin resistance and glucose intolerance and that they may increase triglycerides, worsening the risk of diabetes and cardiovascular disease, he said.

Metformin, on the other hand, targets insulin resistance, “what may well be the initiating abnormality in PCOS, and has been shown to normalize or improve the biochemical, clinical, and reproductive abnormalities of PCOS,” said Dr. Tessa Lebinger, a pediatric endocrinologist. The drug is effective whether or not insulin resistance can be documented, she added.

In most cases, Dr. Nestler agreed, it won't be documented because insulin resistance is too difficult to accurately measure in a clinical setting. “Most women with PCOS are insulin resistant … so an empiric trial of metformin in any woman with PCOS is reasonable as you long as you monitor her and make sure that her menses are improving,” he said.

Dr. Burton Sobel, who directs the Cardiovascular Research Institute at the University of Vermont, said during a symposium on PCOS that from his perspective as a cardiologist, “PCOS is a cardiovascular disease.”

“We know, from so many perspectives, that impaired sensitivity to insulin is a forerunner, and probably a determinant, of premature coronary disease,” Dr. Sobel said. “It may be years before we have prospective data and legitimacy for using insulin sensitizers [in PCOS patients], but if I had a daughter with PCOS, I'd use an insulin sensitizer beginning with my recognition of the problem regardless of whether she had abnormal glucose tolerance. … I wouldn't wait—to me this is a smoking gun.”

The relationship between hyperinsulinemia and hyperandrogenism—in particular, the question of which causes which—is still discussed, but these physicians said they're convinced from available data that insulin resistance leads to hyperandrogenism and is likely a primary cause of PCOS.

Study results have shown that 30%–35% of women with PCOS have impaired glucose tolerance, and that 8%–10% have type 2 diabetes.

On the whole, Dr. Nestler said, 30%–50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by age 30. Lean women with PCOS, on the other hand, are just as insulin resistant—if not more so—than obese women without PCOS, several speakers said.

Dr. Nestler said he and his colleagues found in a chart review of 50 consecutive PCOS patients treated with metformin that the incidence of impaired glucose tolerance was “dramatically” reduced.

At baseline, 78% of the 50 patients had normal glucose tolerance (NGT), and 22% had impaired glucose tolerance (IGT). At follow-up (a mean of 43 months for NGT patients, and 29 months for IGT patients), 55% of the IGT patients had converted to normal, with 45% continuing to have IGT. Of the NGT patients, 95% continued to have NGT, and 5% converted to IGT.

“It needs to be verified in a prospective study, but our annual conversion rate to IGT of 1.4% with metformin treatment is a dramatic reduction from the 16%–19% annual conversion rates” reported in women with PCOS who are not treated with metformin, he said.

He and other physicians at the meeting pointed to the Nurses' Health Study as the best of few studies that provides a look at the cardiovascular “outcomes” of PCOS.

In its tracking of over 80,000 women for 14 years, the study found that women with abnormal menstrual cyclicity had a relative risk for cardiovascular disease of 1.5 and a relative risk of fatal MI of 1.9, compared with women with normal menses. (The NHS also found a twofold increased risk, independent of weight, of type 2 diabetes in women with oligomenorrhea.)

Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs.

The risk may be higher in women with PCOS, because they likely start at a higher baseline risk and take OCs for long periods of time, she said.

Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”

And the “question is, whether she'll take a pill for the next 30 years that does not make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.

Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”

Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y.

Her adolescent patients on metformin also have improvements in their acne and frequently lose weight. “We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said.

Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.

Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and that he is a stock/shareholder of the Bristol-Myers Squibb Co. and of Pfizer Inc.

Okay for Use in Infertile Patients

If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.

“If a woman comes to me with PCOS and wants to get pregnant, I will usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. In that way, we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If, at the end of 6 months, she doesn't become pregnant, I will send her to the endocrinologist.”

The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.

In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.

Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.

WASHINGTON — Insulin resistance is such an integral and dangerous feature of polycystic ovary syndrome that metformin should be favored over oral contraceptive pills for treatment of the syndrome, said physicians in annual scientific sessions of the American Diabetes Association meeting.

Although there is a paucity of “good, prospective outcomes data” on cardiovascular disease in patients with polycystic ovary syndrome (PCOS)—as well as the existence of only limited data on oral contraceptives' (OCs) effect on insulin resistance—the speakers warned against waiting for definitive data to appear. Current knowledge of the risks of insulin resistance and the potential disadvantages of OCs is too convincing, they argued.

“Given everything [we know now], I believe we now must have the goals of preventing glucose intolerance and diabetes, and preventing atherosclerosis and acute coronary events” in addition to addressing the immediate symptoms of PCOS, said Dr. John Nestler, professor of medicine, ob.gyn., pharmacology, and toxicology at the Virginia Commonwealth University, Richmond.

“I will be provocative, because there aren't a lot of studies, but I'm going to argue that there may be disadvantages to using OCs,” said Dr. Nestler, who also chairs the division of endocrinology and metabolism.

OCs may be better for treating symptoms such as acne and hirsutism (studies of metformin have not addressed these problems as primary end points), but studies indicate that OCs worsen insulin resistance and glucose intolerance and that they may increase triglycerides, worsening the risk of diabetes and cardiovascular disease, he said.

Metformin, on the other hand, targets insulin resistance, “what may well be the initiating abnormality in PCOS, and has been shown to normalize or improve the biochemical, clinical, and reproductive abnormalities of PCOS,” said Dr. Tessa Lebinger, a pediatric endocrinologist. The drug is effective whether or not insulin resistance can be documented, she added.

In most cases, Dr. Nestler agreed, it won't be documented because insulin resistance is too difficult to accurately measure in a clinical setting. “Most women with PCOS are insulin resistant … so an empiric trial of metformin in any woman with PCOS is reasonable as you long as you monitor her and make sure that her menses are improving,” he said.

Dr. Burton Sobel, who directs the Cardiovascular Research Institute at the University of Vermont, said during a symposium on PCOS that from his perspective as a cardiologist, “PCOS is a cardiovascular disease.”

“We know, from so many perspectives, that impaired sensitivity to insulin is a forerunner, and probably a determinant, of premature coronary disease,” Dr. Sobel said. “It may be years before we have prospective data and legitimacy for using insulin sensitizers [in PCOS patients], but if I had a daughter with PCOS, I'd use an insulin sensitizer beginning with my recognition of the problem regardless of whether she had abnormal glucose tolerance. … I wouldn't wait—to me this is a smoking gun.”

The relationship between hyperinsulinemia and hyperandrogenism—in particular, the question of which causes which—is still discussed, but these physicians said they're convinced from available data that insulin resistance leads to hyperandrogenism and is likely a primary cause of PCOS.

Study results have shown that 30%–35% of women with PCOS have impaired glucose tolerance, and that 8%–10% have type 2 diabetes.

On the whole, Dr. Nestler said, 30%–50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by age 30. Lean women with PCOS, on the other hand, are just as insulin resistant—if not more so—than obese women without PCOS, several speakers said.

Dr. Nestler said he and his colleagues found in a chart review of 50 consecutive PCOS patients treated with metformin that the incidence of impaired glucose tolerance was “dramatically” reduced.

At baseline, 78% of the 50 patients had normal glucose tolerance (NGT), and 22% had impaired glucose tolerance (IGT). At follow-up (a mean of 43 months for NGT patients, and 29 months for IGT patients), 55% of the IGT patients had converted to normal, with 45% continuing to have IGT. Of the NGT patients, 95% continued to have NGT, and 5% converted to IGT.

“It needs to be verified in a prospective study, but our annual conversion rate to IGT of 1.4% with metformin treatment is a dramatic reduction from the 16%–19% annual conversion rates” reported in women with PCOS who are not treated with metformin, he said.

He and other physicians at the meeting pointed to the Nurses' Health Study as the best of few studies that provides a look at the cardiovascular “outcomes” of PCOS.

In its tracking of over 80,000 women for 14 years, the study found that women with abnormal menstrual cyclicity had a relative risk for cardiovascular disease of 1.5 and a relative risk of fatal MI of 1.9, compared with women with normal menses. (The NHS also found a twofold increased risk, independent of weight, of type 2 diabetes in women with oligomenorrhea.)

Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs.

The risk may be higher in women with PCOS, because they likely start at a higher baseline risk and take OCs for long periods of time, she said.

Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”

And the “question is, whether she'll take a pill for the next 30 years that does not make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.

Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”

Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y.

Her adolescent patients on metformin also have improvements in their acne and frequently lose weight. “We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said.

Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.

Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and that he is a stock/shareholder of the Bristol-Myers Squibb Co. and of Pfizer Inc.

Okay for Use in Infertile Patients

If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.

“If a woman comes to me with PCOS and wants to get pregnant, I will usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. In that way, we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If, at the end of 6 months, she doesn't become pregnant, I will send her to the endocrinologist.”

The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.

In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.

Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.

WASHINGTON — Insulin resistance is such an integral and dangerous feature of polycystic ovary syndrome that metformin should be favored over oral contraceptive pills for treatment of the syndrome, said physicians in annual scientific sessions of the American Diabetes Association meeting.

Although there is a paucity of “good, prospective outcomes data” on cardiovascular disease in patients with polycystic ovary syndrome (PCOS)—as well as the existence of only limited data on oral contraceptives' (OCs) effect on insulin resistance—the speakers warned against waiting for definitive data to appear. Current knowledge of the risks of insulin resistance and the potential disadvantages of OCs is too convincing, they argued.

“Given everything [we know now], I believe we now must have the goals of preventing glucose intolerance and diabetes, and preventing atherosclerosis and acute coronary events” in addition to addressing the immediate symptoms of PCOS, said Dr. John Nestler, professor of medicine, ob.gyn., pharmacology, and toxicology at the Virginia Commonwealth University, Richmond.

“I will be provocative, because there aren't a lot of studies, but I'm going to argue that there may be disadvantages to using OCs,” said Dr. Nestler, who also chairs the division of endocrinology and metabolism.

OCs may be better for treating symptoms such as acne and hirsutism (studies of metformin have not addressed these problems as primary end points), but studies indicate that OCs worsen insulin resistance and glucose intolerance and that they may increase triglycerides, worsening the risk of diabetes and cardiovascular disease, he said.

Metformin, on the other hand, targets insulin resistance, “what may well be the initiating abnormality in PCOS, and has been shown to normalize or improve the biochemical, clinical, and reproductive abnormalities of PCOS,” said Dr. Tessa Lebinger, a pediatric endocrinologist. The drug is effective whether or not insulin resistance can be documented, she added.

In most cases, Dr. Nestler agreed, it won't be documented because insulin resistance is too difficult to accurately measure in a clinical setting. “Most women with PCOS are insulin resistant … so an empiric trial of metformin in any woman with PCOS is reasonable as you long as you monitor her and make sure that her menses are improving,” he said.

Dr. Burton Sobel, who directs the Cardiovascular Research Institute at the University of Vermont, said during a symposium on PCOS that from his perspective as a cardiologist, “PCOS is a cardiovascular disease.”

“We know, from so many perspectives, that impaired sensitivity to insulin is a forerunner, and probably a determinant, of premature coronary disease,” Dr. Sobel said. “It may be years before we have prospective data and legitimacy for using insulin sensitizers [in PCOS patients], but if I had a daughter with PCOS, I'd use an insulin sensitizer beginning with my recognition of the problem regardless of whether she had abnormal glucose tolerance. … I wouldn't wait—to me this is a smoking gun.”

The relationship between hyperinsulinemia and hyperandrogenism—in particular, the question of which causes which—is still discussed, but these physicians said they're convinced from available data that insulin resistance leads to hyperandrogenism and is likely a primary cause of PCOS.

Study results have shown that 30%–35% of women with PCOS have impaired glucose tolerance, and that 8%–10% have type 2 diabetes.

On the whole, Dr. Nestler said, 30%–50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by age 30. Lean women with PCOS, on the other hand, are just as insulin resistant—if not more so—than obese women without PCOS, several speakers said.

Dr. Nestler said he and his colleagues found in a chart review of 50 consecutive PCOS patients treated with metformin that the incidence of impaired glucose tolerance was “dramatically” reduced.

At baseline, 78% of the 50 patients had normal glucose tolerance (NGT), and 22% had impaired glucose tolerance (IGT). At follow-up (a mean of 43 months for NGT patients, and 29 months for IGT patients), 55% of the IGT patients had converted to normal, with 45% continuing to have IGT. Of the NGT patients, 95% continued to have NGT, and 5% converted to IGT.

“It needs to be verified in a prospective study, but our annual conversion rate to IGT of 1.4% with metformin treatment is a dramatic reduction from the 16%–19% annual conversion rates” reported in women with PCOS who are not treated with metformin, he said.

He and other physicians at the meeting pointed to the Nurses' Health Study as the best of few studies that provides a look at the cardiovascular “outcomes” of PCOS.

In its tracking of over 80,000 women for 14 years, the study found that women with abnormal menstrual cyclicity had a relative risk for cardiovascular disease of 1.5 and a relative risk of fatal MI of 1.9, compared with women with normal menses. (The NHS also found a twofold increased risk, independent of weight, of type 2 diabetes in women with oligomenorrhea.)

Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs.

The risk may be higher in women with PCOS, because they likely start at a higher baseline risk and take OCs for long periods of time, she said.

Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”

And the “question is, whether she'll take a pill for the next 30 years that does not make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.

Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”

Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y.

Her adolescent patients on metformin also have improvements in their acne and frequently lose weight. “We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said.

Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.

Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and that he is a stock/shareholder of the Bristol-Myers Squibb Co. and of Pfizer Inc.

Okay for Use in Infertile Patients

If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.

“If a woman comes to me with PCOS and wants to get pregnant, I will usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. In that way, we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If, at the end of 6 months, she doesn't become pregnant, I will send her to the endocrinologist.”

The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.

In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.

Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.

Patients with early-stage rheumatoid arthritis who are treated with methotrexate plus infliximab are more likely to remain employed or able to work than are patients treated with methotrexate alone, according to findings from another new analysis of the ASPIRE trial data.

Physical function deteriorates so rapidly in rheumatoid arthritis (RA) that 20% of employed patients have to quit their jobs within 2 years of disease onset, and approximately half of RA patients face work disability within 10 years, reported Dr. Josef S. Smolen of the Medical University of Vienna, and his colleagues in Europe and the United States (Arthritis Rheum. 2006;54:716–22).

Patients in the ASPIRE (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset) trial—which compared methotrexate alone with methotrexate plus infliximab—were asked at each visit whether they were currently employed and if not, whether they felt well enough to work if a job were available.

The new analysis, which covered approximately 850 patients aged 65 years or younger, found that rapid disease control in early-stage RA reduced patients work disability and improved their employability, reported Dr. Smolen and colleagues.

While the actual employment rate did not differ significantly between the two treatment groups, the patients treated with both drugs were more likely to maintain their employability or to feel able to work throughout the 54-week study.

The proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the methotrexate-plus-infliximab group than in the methotrexate-only group (8% vs. 14%, respectively). Similarly, the proportion of employed patients who lost more than 10 workdays was smaller in the combination group, when compared with the methotrexate-only group (10% vs. 17%, respectively), the investigators reported.

Patients with early-stage rheumatoid arthritis who are treated with methotrexate plus infliximab are more likely to remain employed or able to work than are patients treated with methotrexate alone, according to findings from another new analysis of the ASPIRE trial data.

Physical function deteriorates so rapidly in rheumatoid arthritis (RA) that 20% of employed patients have to quit their jobs within 2 years of disease onset, and approximately half of RA patients face work disability within 10 years, reported Dr. Josef S. Smolen of the Medical University of Vienna, and his colleagues in Europe and the United States (Arthritis Rheum. 2006;54:716–22).

Patients in the ASPIRE (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset) trial—which compared methotrexate alone with methotrexate plus infliximab—were asked at each visit whether they were currently employed and if not, whether they felt well enough to work if a job were available.

The new analysis, which covered approximately 850 patients aged 65 years or younger, found that rapid disease control in early-stage RA reduced patients work disability and improved their employability, reported Dr. Smolen and colleagues.

While the actual employment rate did not differ significantly between the two treatment groups, the patients treated with both drugs were more likely to maintain their employability or to feel able to work throughout the 54-week study.

The proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the methotrexate-plus-infliximab group than in the methotrexate-only group (8% vs. 14%, respectively). Similarly, the proportion of employed patients who lost more than 10 workdays was smaller in the combination group, when compared with the methotrexate-only group (10% vs. 17%, respectively), the investigators reported.

Patients with early-stage rheumatoid arthritis who are treated with methotrexate plus infliximab are more likely to remain employed or able to work than are patients treated with methotrexate alone, according to findings from another new analysis of the ASPIRE trial data.

Physical function deteriorates so rapidly in rheumatoid arthritis (RA) that 20% of employed patients have to quit their jobs within 2 years of disease onset, and approximately half of RA patients face work disability within 10 years, reported Dr. Josef S. Smolen of the Medical University of Vienna, and his colleagues in Europe and the United States (Arthritis Rheum. 2006;54:716–22).

Patients in the ASPIRE (Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset) trial—which compared methotrexate alone with methotrexate plus infliximab—were asked at each visit whether they were currently employed and if not, whether they felt well enough to work if a job were available.

The new analysis, which covered approximately 850 patients aged 65 years or younger, found that rapid disease control in early-stage RA reduced patients work disability and improved their employability, reported Dr. Smolen and colleagues.

While the actual employment rate did not differ significantly between the two treatment groups, the patients treated with both drugs were more likely to maintain their employability or to feel able to work throughout the 54-week study.

The proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the methotrexate-plus-infliximab group than in the methotrexate-only group (8% vs. 14%, respectively). Similarly, the proportion of employed patients who lost more than 10 workdays was smaller in the combination group, when compared with the methotrexate-only group (10% vs. 17%, respectively), the investigators reported.