Miriam E. Tucker

COLUMBUS, OHIO — Real-time continuous glucose monitoring is likely to become the standard of care for the treatment of type 1 diabetes within the next 5–10 years, but for now it's best to reserve the technology for selected patients, Dr. Irl B. Hirsch said at a meeting on diabetes sponsored by Ohio State University.

Real-time continuous glucose monitors (RT-CGMs) have been on the market only since 2006 and are not yet indicated to replace fingerstick glucose testing. Currently, the main benefits of RT-CGMs are their capability for detecting glucose trends throughout the day and night, and their ability to alert the patient when glucose levels become too high or too low.

The potential for decreasing glucose variability—both the danger of severe hypoglycemia and the damaging oxidative stress that accompanies postprandial glucose surges—is what makes the technology so promising for the future and also valuable for some patients even now in its very early stages, said Dr. Hirsch, professor of medicine and medical director of the diabetes care center at the University of Washington, Seattle.

Still, until the technology and experience with RT-CGMs improve—along with the insurance coverage—they are not for everyone, according to Dr. Hirsch. This was demonstrated in the STAR I (Successful Teens Achieving Readiness for Independence I) study, in which 138 adolescents and adults with poorly controlled type 1 diabetes (hemoglobin A_1c of 7.5% or greater) despite 6 months or more of insulin pump therapy were randomized to one of two groups: One group wore the combined pump/RT-CGM device (the MiniMed Paradigm 722 system) and performed self-monitoring of blood glucose (SMBG) four or more times per day, and the other group performed SMBG while wearing the pump by itself.

At 13 weeks, mean HbA_1c levels had dropped significantly and to a nearly identical degree in both groups, from 8.4% to 7.8% in the controls and from 8.5% to 7.7% in the RT-CGM group. There were no further significant drops in either group, and by week 26, both groups had a mean HbA_1c of 7.8%, Dr. Hirsch first reported last summer at the American Diabetes Association's annual scientific sessions (FAMILY PRACTICE NEWS, Sept. 1, 2007, p. 15).

Although the findings might seem negative, further analysis revealed that compliance strongly predicted the results among the RT-CGM patients. With “compliance” defined as wearing the sensor 6 days per week (meaning it was possible to be more than 100% compliant) HbA_1c levels among the patients with 100% compliance or greater dropped from 8.6% at baseline to 7.7% at 26 weeks. Those with 80%–100% compliance dropped similarly (from 8.4% to 7.7%), as did those with 60%–80% compliance (from 8.2% to 7.5%).

All of those reductions were significant. However, when compliance dropped below 60%, mean HbA_1c actually rose slightly, but not significantly (from 9.5% to 9.6%).

“I think we have oversold this technology, which is really in its first generation,” Dr. Hirsch commented at the OSU meeting. “Patients and providers have to know how to use the technology appropriately, including putting it on the right patient.”

For example, it's unlikely that patients with very poor glucose control who are not committed to treatment goals and aren't already performing frequent fingerstick glucose testing will benefit from an RT-CGM.

“If the hemoglobin A_1c is high at baseline, the patient may not be using current tools adequately. My personal opinion is that RT-CGM is a better technology for the patient who is closer to target, in order to prevent hypoglycemia. Someone with an A_1c above 9%–10% probably doesn't need CGM,” he said.

Based on his experience using both the Medtronic and the DexCom Inc. RT-CGM products, Dr. Hirsch offered the following clinical “pearls” for patients' use:

▸ The more you look, the better you do. Patients who wear the sensor but don't look at it often do no better than those who don't wear it at all. “No matter which sensor you're using, you have to look at it over and over to see the trend,” he said.

▸ Trend trumps “insulin on board.” This is controversial. Insulin pumps that automatically perform bolus calculations will instruct the patient not to take any more insulin if there is already a large amount “on board.” However, if the glucose is rapidly rising for longer than 1 hour, Dr. Hirsch recommends that adult patients take at least a small bolus. “If the glucose is going up, you need insulin,” he said. For children, however, pediatric endocrinologist Dr. William Tamborlane of Yale University, New Haven, Conn., recommends waiting at least 2 hours before overriding the bolus calculator.

▸ For an upward trend, delay eating or at least reduce carbs. This is especially true if the glucose is rising faster than 1 mg/dL per minute. And remember Pearl #2: For a correction dose with an upward trend before a meal, more insulin is needed.

▸ For a downward trend, fingerstick glucose measurements are critical. That's because of the lag time with the interstitial fluid that the RT-CGM is sampling. Relying solely on the RT-CGM reading is especially dangerous with significant insulin on board. If the glucose is dropping rapidly, you want to take less insulin or decrease the time between the insulin and the food. Consider a snack at the low end of the target range if the downward trend is at 1–2 mg/dL per minute, and at the high end of the target range if the trend is at or above 2 mg/dL per minute.

“With RT-CGM, we're starting to talk about the velocity of glucose changes. Velocity is a concept we've never talked about before,” Dr. Hirsch noted.

▸ We have much yet to learn from this new technology. “What is the potential for use in the hospital? In pregnant patients? Insulin-requiring patients with type 2 diabetes? We're just at the beginning, but one thing is certain right now: If the technology allows some of our patients to live happier lives without hypoglycemia, there's something to be said for that, even if the reimbursers don't agree.”

Dr. Hirsch said he has received grants and research support from Medtronic, but has no financial relationship with DexCom.

COLUMBUS, OHIO — Real-time continuous glucose monitoring is likely to become the standard of care for the treatment of type 1 diabetes within the next 5–10 years, but for now it's best to reserve the technology for selected patients, Dr. Irl B. Hirsch said at a meeting on diabetes sponsored by Ohio State University.

Real-time continuous glucose monitors (RT-CGMs) have been on the market only since 2006 and are not yet indicated to replace fingerstick glucose testing. Currently, the main benefits of RT-CGMs are their capability for detecting glucose trends throughout the day and night, and their ability to alert the patient when glucose levels become too high or too low.

The potential for decreasing glucose variability—both the danger of severe hypoglycemia and the damaging oxidative stress that accompanies postprandial glucose surges—is what makes the technology so promising for the future and also valuable for some patients even now in its very early stages, said Dr. Hirsch, professor of medicine and medical director of the diabetes care center at the University of Washington, Seattle.

Still, until the technology and experience with RT-CGMs improve—along with the insurance coverage—they are not for everyone, according to Dr. Hirsch. This was demonstrated in the STAR I (Successful Teens Achieving Readiness for Independence I) study, in which 138 adolescents and adults with poorly controlled type 1 diabetes (hemoglobin A_1c of 7.5% or greater) despite 6 months or more of insulin pump therapy were randomized to one of two groups: One group wore the combined pump/RT-CGM device (the MiniMed Paradigm 722 system) and performed self-monitoring of blood glucose (SMBG) four or more times per day, and the other group performed SMBG while wearing the pump by itself.

At 13 weeks, mean HbA_1c levels had dropped significantly and to a nearly identical degree in both groups, from 8.4% to 7.8% in the controls and from 8.5% to 7.7% in the RT-CGM group. There were no further significant drops in either group, and by week 26, both groups had a mean HbA_1c of 7.8%, Dr. Hirsch first reported last summer at the American Diabetes Association's annual scientific sessions (FAMILY PRACTICE NEWS, Sept. 1, 2007, p. 15).

Although the findings might seem negative, further analysis revealed that compliance strongly predicted the results among the RT-CGM patients. With “compliance” defined as wearing the sensor 6 days per week (meaning it was possible to be more than 100% compliant) HbA_1c levels among the patients with 100% compliance or greater dropped from 8.6% at baseline to 7.7% at 26 weeks. Those with 80%–100% compliance dropped similarly (from 8.4% to 7.7%), as did those with 60%–80% compliance (from 8.2% to 7.5%).

All of those reductions were significant. However, when compliance dropped below 60%, mean HbA_1c actually rose slightly, but not significantly (from 9.5% to 9.6%).

“I think we have oversold this technology, which is really in its first generation,” Dr. Hirsch commented at the OSU meeting. “Patients and providers have to know how to use the technology appropriately, including putting it on the right patient.”

For example, it's unlikely that patients with very poor glucose control who are not committed to treatment goals and aren't already performing frequent fingerstick glucose testing will benefit from an RT-CGM.

“If the hemoglobin A_1c is high at baseline, the patient may not be using current tools adequately. My personal opinion is that RT-CGM is a better technology for the patient who is closer to target, in order to prevent hypoglycemia. Someone with an A_1c above 9%–10% probably doesn't need CGM,” he said.

Based on his experience using both the Medtronic and the DexCom Inc. RT-CGM products, Dr. Hirsch offered the following clinical “pearls” for patients' use:

▸ The more you look, the better you do. Patients who wear the sensor but don't look at it often do no better than those who don't wear it at all. “No matter which sensor you're using, you have to look at it over and over to see the trend,” he said.

▸ Trend trumps “insulin on board.” This is controversial. Insulin pumps that automatically perform bolus calculations will instruct the patient not to take any more insulin if there is already a large amount “on board.” However, if the glucose is rapidly rising for longer than 1 hour, Dr. Hirsch recommends that adult patients take at least a small bolus. “If the glucose is going up, you need insulin,” he said. For children, however, pediatric endocrinologist Dr. William Tamborlane of Yale University, New Haven, Conn., recommends waiting at least 2 hours before overriding the bolus calculator.

▸ For an upward trend, delay eating or at least reduce carbs. This is especially true if the glucose is rising faster than 1 mg/dL per minute. And remember Pearl #2: For a correction dose with an upward trend before a meal, more insulin is needed.

▸ For a downward trend, fingerstick glucose measurements are critical. That's because of the lag time with the interstitial fluid that the RT-CGM is sampling. Relying solely on the RT-CGM reading is especially dangerous with significant insulin on board. If the glucose is dropping rapidly, you want to take less insulin or decrease the time between the insulin and the food. Consider a snack at the low end of the target range if the downward trend is at 1–2 mg/dL per minute, and at the high end of the target range if the trend is at or above 2 mg/dL per minute.

“With RT-CGM, we're starting to talk about the velocity of glucose changes. Velocity is a concept we've never talked about before,” Dr. Hirsch noted.

▸ We have much yet to learn from this new technology. “What is the potential for use in the hospital? In pregnant patients? Insulin-requiring patients with type 2 diabetes? We're just at the beginning, but one thing is certain right now: If the technology allows some of our patients to live happier lives without hypoglycemia, there's something to be said for that, even if the reimbursers don't agree.”

Dr. Hirsch said he has received grants and research support from Medtronic, but has no financial relationship with DexCom.

COLUMBUS, OHIO — Real-time continuous glucose monitoring is likely to become the standard of care for the treatment of type 1 diabetes within the next 5–10 years, but for now it's best to reserve the technology for selected patients, Dr. Irl B. Hirsch said at a meeting on diabetes sponsored by Ohio State University.

Real-time continuous glucose monitors (RT-CGMs) have been on the market only since 2006 and are not yet indicated to replace fingerstick glucose testing. Currently, the main benefits of RT-CGMs are their capability for detecting glucose trends throughout the day and night, and their ability to alert the patient when glucose levels become too high or too low.

The potential for decreasing glucose variability—both the danger of severe hypoglycemia and the damaging oxidative stress that accompanies postprandial glucose surges—is what makes the technology so promising for the future and also valuable for some patients even now in its very early stages, said Dr. Hirsch, professor of medicine and medical director of the diabetes care center at the University of Washington, Seattle.

Still, until the technology and experience with RT-CGMs improve—along with the insurance coverage—they are not for everyone, according to Dr. Hirsch. This was demonstrated in the STAR I (Successful Teens Achieving Readiness for Independence I) study, in which 138 adolescents and adults with poorly controlled type 1 diabetes (hemoglobin A_1c of 7.5% or greater) despite 6 months or more of insulin pump therapy were randomized to one of two groups: One group wore the combined pump/RT-CGM device (the MiniMed Paradigm 722 system) and performed self-monitoring of blood glucose (SMBG) four or more times per day, and the other group performed SMBG while wearing the pump by itself.

At 13 weeks, mean HbA_1c levels had dropped significantly and to a nearly identical degree in both groups, from 8.4% to 7.8% in the controls and from 8.5% to 7.7% in the RT-CGM group. There were no further significant drops in either group, and by week 26, both groups had a mean HbA_1c of 7.8%, Dr. Hirsch first reported last summer at the American Diabetes Association's annual scientific sessions (FAMILY PRACTICE NEWS, Sept. 1, 2007, p. 15).

Although the findings might seem negative, further analysis revealed that compliance strongly predicted the results among the RT-CGM patients. With “compliance” defined as wearing the sensor 6 days per week (meaning it was possible to be more than 100% compliant) HbA_1c levels among the patients with 100% compliance or greater dropped from 8.6% at baseline to 7.7% at 26 weeks. Those with 80%–100% compliance dropped similarly (from 8.4% to 7.7%), as did those with 60%–80% compliance (from 8.2% to 7.5%).

All of those reductions were significant. However, when compliance dropped below 60%, mean HbA_1c actually rose slightly, but not significantly (from 9.5% to 9.6%).

“I think we have oversold this technology, which is really in its first generation,” Dr. Hirsch commented at the OSU meeting. “Patients and providers have to know how to use the technology appropriately, including putting it on the right patient.”

For example, it's unlikely that patients with very poor glucose control who are not committed to treatment goals and aren't already performing frequent fingerstick glucose testing will benefit from an RT-CGM.

“If the hemoglobin A_1c is high at baseline, the patient may not be using current tools adequately. My personal opinion is that RT-CGM is a better technology for the patient who is closer to target, in order to prevent hypoglycemia. Someone with an A_1c above 9%–10% probably doesn't need CGM,” he said.

Based on his experience using both the Medtronic and the DexCom Inc. RT-CGM products, Dr. Hirsch offered the following clinical “pearls” for patients' use:

▸ The more you look, the better you do. Patients who wear the sensor but don't look at it often do no better than those who don't wear it at all. “No matter which sensor you're using, you have to look at it over and over to see the trend,” he said.

▸ Trend trumps “insulin on board.” This is controversial. Insulin pumps that automatically perform bolus calculations will instruct the patient not to take any more insulin if there is already a large amount “on board.” However, if the glucose is rapidly rising for longer than 1 hour, Dr. Hirsch recommends that adult patients take at least a small bolus. “If the glucose is going up, you need insulin,” he said. For children, however, pediatric endocrinologist Dr. William Tamborlane of Yale University, New Haven, Conn., recommends waiting at least 2 hours before overriding the bolus calculator.

▸ For an upward trend, delay eating or at least reduce carbs. This is especially true if the glucose is rising faster than 1 mg/dL per minute. And remember Pearl #2: For a correction dose with an upward trend before a meal, more insulin is needed.

▸ For a downward trend, fingerstick glucose measurements are critical. That's because of the lag time with the interstitial fluid that the RT-CGM is sampling. Relying solely on the RT-CGM reading is especially dangerous with significant insulin on board. If the glucose is dropping rapidly, you want to take less insulin or decrease the time between the insulin and the food. Consider a snack at the low end of the target range if the downward trend is at 1–2 mg/dL per minute, and at the high end of the target range if the trend is at or above 2 mg/dL per minute.

“With RT-CGM, we're starting to talk about the velocity of glucose changes. Velocity is a concept we've never talked about before,” Dr. Hirsch noted.

▸ We have much yet to learn from this new technology. “What is the potential for use in the hospital? In pregnant patients? Insulin-requiring patients with type 2 diabetes? We're just at the beginning, but one thing is certain right now: If the technology allows some of our patients to live happier lives without hypoglycemia, there's something to be said for that, even if the reimbursers don't agree.”

Dr. Hirsch said he has received grants and research support from Medtronic, but has no financial relationship with DexCom.

New guidance from the American Diabetes Association gives a green light to the use of low-carbohydrate diets as a weight-control measure for patients with diabetes.

The updated guidelines for 2008 also revise recommendations on prediabetes testing, metformin use, and hypoglycemia prevention, among other topics.

The organization still does not endorse low-carbohydrate diets for weight loss or diabetes management, but it has updated the section of its guidelines that covers nutrition recommendations and interventions for diabetes to remove a specific recommendation against diets that restrict carbohydrates to less than 130 g/day. Now, for weight loss, the ADA says that either low-carbohydrate or low-fat calorie-restricted diets might be effective in the short term (up to 1 year). Previous language that recommended against low-carb diets was also removed from the 2008 update.

For patients who are on low-carbohydrate diets, the ADA now advises monitoring of lipid profiles, renal function, and protein intake (in patients with nephropathy), as well as adjustment of glucose-lowering therapy as needed (Diabetes Care 2008;30[suppl. 1]:S61-78).

“The evidence is clear that both low-carbohydrate and low-fat calorie-restricted diets result in similar weight loss at 1 year. We're not endorsing either of these weight-loss plans over any other method of losing weight. It's important for patients to choose a plan that works for them, and that the health care team support their patients' weight loss efforts and provide appropriate monitoring of patients' health,” guideline panel member and registered dietician Ann Albright, Ph.D., ADA President of Health Care and Education, said in a statement.

New data cited in the 2008 document are from the A to Z Weight Loss Study, a randomized trial that compared the Atkins, Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitude, Relationships, and Nutrition) diets in a total of 311 overweight premenopausal women. At 1 year, those who followed the Atkins diet showed significantly more weight loss (-4.7 kg) than did the other three diet groups (-1.6 kg with Zone, -2.6 kg with LEARN, and -2.2 kg with Ornish). Secondary outcomes, including lipid profile, percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure, were comparable or better with Atkins versus the other diet groups (JAMA 2007;297:969-77).

However, the ADA reiterated a point it had made in 2007: The recommended daily allowance for digestible carbohydrate is 130 g/day, based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.

“Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very low-carbohydrate diets are unclear, and such diets eliminate foods that are important sources of energy, fiber, vitamins, and minerals that are important in dietary palatability,” according to the 11-member writing panel, which was cochaired by Dr. John P. Bantle of the University of Minnesota, Minneapolis, and Judith Wylie-Rosett, Ed.D., a registered dietician, who is with Albert Einstein College of Medicine, New York.

Dr. Neil J. Stone, professor of clinical medicine at Northwestern University, Chicago, is similarly cautious. “The new guideline acknowledges that based on available data, there are choices when it comes to choosing a weight loss regimen for the short term. This is not an endorsement of lifelong marked carbohydrate restriction, and the general public as well as diabetics need to consider reasonable carbohydrate intake for nutritional balance, as [carbohydrates] can provide important sources of energy, fiber, vitamins, and minerals,” he said in an interview.

But Dr. Eric C. Westman, director of the Lifestyle Medicine Clinic at Duke University, Durham, N.C., believes that low-carb diets can play an important role in diabetes management. “Carbohydrates, especially sugar and starch, are the main factors in the diet that raise blood glucose. Carbohydrate-restricted diets are as effective, and sometimes even more effective, than medication therapy for type 2 diabetes.

“[With obesity], carbohydrate-restricted diets have the advantage over medication because most people then lose weight, which then improves insulin resistance. Those with type 2 diabetes who are taking medications should consult a physician trained in using the carbohydrate-restricted approach, to ensure a safe reduction and possibly elimination of medication,” he said in an interview.

Other guideline revisions include:

▸ The addition of new tables that list screening recommendations and diagnostic cutpoints for gestational diabetes, summarize interventions and results of diabetes prevention trials, and summarize evidence for statin therapy in diabetics.

▸ A more explicit recommendation to consider testing for prediabetes in asymptomatic patients of any age who are overweight and have additional risk factors for diabetes.

▸ Metformin, in addition to lifestyle counseling, as an option in those at high risk and who are obese and aged under 60 years.

▸ Continuous glucose monitoring might be a supplemental tool to self-monitoring of blood glucose for selected patients with type 1 diabetes, especially those with hypoglycemic unawareness.

▸ More information in the hypoglycemia section about prevention and hypoglycemia unawareness, with the recommendation that patients who have hypoglycemic unawareness or episodes of severe hypoglycemia raise their glycemic targets to strictly avoid hypoglycemia for at least several weeks, with the aim of partially reversing the unawareness and reducing the risk of further episodes.

▸ The reduction of the number of treatment recommendations for hypertension and blood pressure control to emphasize use of ACE inhibitors or angiotensin receptor blockers.

▸ Fewer recommendations in the dyslipidemia/lipid management section to emphasize the use of statins for most patients, along with new language stating that if patients don't reach specified targets on maximal tolerated statin therapy, an LDL cholesterol reduction of about 40% from baseline is an alternative goal. Triglyceride levels of less than 150 mg/dL and HDL cholesterol levels greater than 40 mg/dL in men and more than 50 mg/dL in women are desirable, though “cholesterol-targeted statin therapy remains the preferred strategy.”

'This is notan endorsementof lifelongmarked carbohydrate restriction.' DR. STONE

New guidance from the American Diabetes Association gives a green light to the use of low-carbohydrate diets as a weight-control measure for patients with diabetes.

The updated guidelines for 2008 also revise recommendations on prediabetes testing, metformin use, and hypoglycemia prevention, among other topics.

The organization still does not endorse low-carbohydrate diets for weight loss or diabetes management, but it has updated the section of its guidelines that covers nutrition recommendations and interventions for diabetes to remove a specific recommendation against diets that restrict carbohydrates to less than 130 g/day. Now, for weight loss, the ADA says that either low-carbohydrate or low-fat calorie-restricted diets might be effective in the short term (up to 1 year). Previous language that recommended against low-carb diets was also removed from the 2008 update.

For patients who are on low-carbohydrate diets, the ADA now advises monitoring of lipid profiles, renal function, and protein intake (in patients with nephropathy), as well as adjustment of glucose-lowering therapy as needed (Diabetes Care 2008;30[suppl. 1]:S61-78).

“The evidence is clear that both low-carbohydrate and low-fat calorie-restricted diets result in similar weight loss at 1 year. We're not endorsing either of these weight-loss plans over any other method of losing weight. It's important for patients to choose a plan that works for them, and that the health care team support their patients' weight loss efforts and provide appropriate monitoring of patients' health,” guideline panel member and registered dietician Ann Albright, Ph.D., ADA President of Health Care and Education, said in a statement.

New data cited in the 2008 document are from the A to Z Weight Loss Study, a randomized trial that compared the Atkins, Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitude, Relationships, and Nutrition) diets in a total of 311 overweight premenopausal women. At 1 year, those who followed the Atkins diet showed significantly more weight loss (-4.7 kg) than did the other three diet groups (-1.6 kg with Zone, -2.6 kg with LEARN, and -2.2 kg with Ornish). Secondary outcomes, including lipid profile, percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure, were comparable or better with Atkins versus the other diet groups (JAMA 2007;297:969-77).

However, the ADA reiterated a point it had made in 2007: The recommended daily allowance for digestible carbohydrate is 130 g/day, based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.

“Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very low-carbohydrate diets are unclear, and such diets eliminate foods that are important sources of energy, fiber, vitamins, and minerals that are important in dietary palatability,” according to the 11-member writing panel, which was cochaired by Dr. John P. Bantle of the University of Minnesota, Minneapolis, and Judith Wylie-Rosett, Ed.D., a registered dietician, who is with Albert Einstein College of Medicine, New York.

Dr. Neil J. Stone, professor of clinical medicine at Northwestern University, Chicago, is similarly cautious. “The new guideline acknowledges that based on available data, there are choices when it comes to choosing a weight loss regimen for the short term. This is not an endorsement of lifelong marked carbohydrate restriction, and the general public as well as diabetics need to consider reasonable carbohydrate intake for nutritional balance, as [carbohydrates] can provide important sources of energy, fiber, vitamins, and minerals,” he said in an interview.

But Dr. Eric C. Westman, director of the Lifestyle Medicine Clinic at Duke University, Durham, N.C., believes that low-carb diets can play an important role in diabetes management. “Carbohydrates, especially sugar and starch, are the main factors in the diet that raise blood glucose. Carbohydrate-restricted diets are as effective, and sometimes even more effective, than medication therapy for type 2 diabetes.

“[With obesity], carbohydrate-restricted diets have the advantage over medication because most people then lose weight, which then improves insulin resistance. Those with type 2 diabetes who are taking medications should consult a physician trained in using the carbohydrate-restricted approach, to ensure a safe reduction and possibly elimination of medication,” he said in an interview.

Other guideline revisions include:

▸ The addition of new tables that list screening recommendations and diagnostic cutpoints for gestational diabetes, summarize interventions and results of diabetes prevention trials, and summarize evidence for statin therapy in diabetics.

▸ A more explicit recommendation to consider testing for prediabetes in asymptomatic patients of any age who are overweight and have additional risk factors for diabetes.

▸ Metformin, in addition to lifestyle counseling, as an option in those at high risk and who are obese and aged under 60 years.

▸ Continuous glucose monitoring might be a supplemental tool to self-monitoring of blood glucose for selected patients with type 1 diabetes, especially those with hypoglycemic unawareness.

▸ More information in the hypoglycemia section about prevention and hypoglycemia unawareness, with the recommendation that patients who have hypoglycemic unawareness or episodes of severe hypoglycemia raise their glycemic targets to strictly avoid hypoglycemia for at least several weeks, with the aim of partially reversing the unawareness and reducing the risk of further episodes.

▸ The reduction of the number of treatment recommendations for hypertension and blood pressure control to emphasize use of ACE inhibitors or angiotensin receptor blockers.

▸ Fewer recommendations in the dyslipidemia/lipid management section to emphasize the use of statins for most patients, along with new language stating that if patients don't reach specified targets on maximal tolerated statin therapy, an LDL cholesterol reduction of about 40% from baseline is an alternative goal. Triglyceride levels of less than 150 mg/dL and HDL cholesterol levels greater than 40 mg/dL in men and more than 50 mg/dL in women are desirable, though “cholesterol-targeted statin therapy remains the preferred strategy.”

'This is notan endorsementof lifelongmarked carbohydrate restriction.' DR. STONE

New guidance from the American Diabetes Association gives a green light to the use of low-carbohydrate diets as a weight-control measure for patients with diabetes.

The updated guidelines for 2008 also revise recommendations on prediabetes testing, metformin use, and hypoglycemia prevention, among other topics.

The organization still does not endorse low-carbohydrate diets for weight loss or diabetes management, but it has updated the section of its guidelines that covers nutrition recommendations and interventions for diabetes to remove a specific recommendation against diets that restrict carbohydrates to less than 130 g/day. Now, for weight loss, the ADA says that either low-carbohydrate or low-fat calorie-restricted diets might be effective in the short term (up to 1 year). Previous language that recommended against low-carb diets was also removed from the 2008 update.

For patients who are on low-carbohydrate diets, the ADA now advises monitoring of lipid profiles, renal function, and protein intake (in patients with nephropathy), as well as adjustment of glucose-lowering therapy as needed (Diabetes Care 2008;30[suppl. 1]:S61-78).

“The evidence is clear that both low-carbohydrate and low-fat calorie-restricted diets result in similar weight loss at 1 year. We're not endorsing either of these weight-loss plans over any other method of losing weight. It's important for patients to choose a plan that works for them, and that the health care team support their patients' weight loss efforts and provide appropriate monitoring of patients' health,” guideline panel member and registered dietician Ann Albright, Ph.D., ADA President of Health Care and Education, said in a statement.

New data cited in the 2008 document are from the A to Z Weight Loss Study, a randomized trial that compared the Atkins, Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitude, Relationships, and Nutrition) diets in a total of 311 overweight premenopausal women. At 1 year, those who followed the Atkins diet showed significantly more weight loss (-4.7 kg) than did the other three diet groups (-1.6 kg with Zone, -2.6 kg with LEARN, and -2.2 kg with Ornish). Secondary outcomes, including lipid profile, percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure, were comparable or better with Atkins versus the other diet groups (JAMA 2007;297:969-77).

However, the ADA reiterated a point it had made in 2007: The recommended daily allowance for digestible carbohydrate is 130 g/day, based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.

“Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very low-carbohydrate diets are unclear, and such diets eliminate foods that are important sources of energy, fiber, vitamins, and minerals that are important in dietary palatability,” according to the 11-member writing panel, which was cochaired by Dr. John P. Bantle of the University of Minnesota, Minneapolis, and Judith Wylie-Rosett, Ed.D., a registered dietician, who is with Albert Einstein College of Medicine, New York.

Dr. Neil J. Stone, professor of clinical medicine at Northwestern University, Chicago, is similarly cautious. “The new guideline acknowledges that based on available data, there are choices when it comes to choosing a weight loss regimen for the short term. This is not an endorsement of lifelong marked carbohydrate restriction, and the general public as well as diabetics need to consider reasonable carbohydrate intake for nutritional balance, as [carbohydrates] can provide important sources of energy, fiber, vitamins, and minerals,” he said in an interview.

But Dr. Eric C. Westman, director of the Lifestyle Medicine Clinic at Duke University, Durham, N.C., believes that low-carb diets can play an important role in diabetes management. “Carbohydrates, especially sugar and starch, are the main factors in the diet that raise blood glucose. Carbohydrate-restricted diets are as effective, and sometimes even more effective, than medication therapy for type 2 diabetes.

“[With obesity], carbohydrate-restricted diets have the advantage over medication because most people then lose weight, which then improves insulin resistance. Those with type 2 diabetes who are taking medications should consult a physician trained in using the carbohydrate-restricted approach, to ensure a safe reduction and possibly elimination of medication,” he said in an interview.

Other guideline revisions include:

▸ The addition of new tables that list screening recommendations and diagnostic cutpoints for gestational diabetes, summarize interventions and results of diabetes prevention trials, and summarize evidence for statin therapy in diabetics.

▸ A more explicit recommendation to consider testing for prediabetes in asymptomatic patients of any age who are overweight and have additional risk factors for diabetes.

▸ Metformin, in addition to lifestyle counseling, as an option in those at high risk and who are obese and aged under 60 years.

▸ Continuous glucose monitoring might be a supplemental tool to self-monitoring of blood glucose for selected patients with type 1 diabetes, especially those with hypoglycemic unawareness.

▸ More information in the hypoglycemia section about prevention and hypoglycemia unawareness, with the recommendation that patients who have hypoglycemic unawareness or episodes of severe hypoglycemia raise their glycemic targets to strictly avoid hypoglycemia for at least several weeks, with the aim of partially reversing the unawareness and reducing the risk of further episodes.

▸ The reduction of the number of treatment recommendations for hypertension and blood pressure control to emphasize use of ACE inhibitors or angiotensin receptor blockers.

▸ Fewer recommendations in the dyslipidemia/lipid management section to emphasize the use of statins for most patients, along with new language stating that if patients don't reach specified targets on maximal tolerated statin therapy, an LDL cholesterol reduction of about 40% from baseline is an alternative goal. Triglyceride levels of less than 150 mg/dL and HDL cholesterol levels greater than 40 mg/dL in men and more than 50 mg/dL in women are desirable, though “cholesterol-targeted statin therapy remains the preferred strategy.”

'This is notan endorsementof lifelongmarked carbohydrate restriction.' DR. STONE

COLUMBUS, OHIO — For patients with metabolic syndrome, the focus should be on the two “L” words: lifestyle and LDL.

That was the message from a talk given by former American Heart Association president Robert H. Eckel at a meeting on diabetes sponsored by Ohio State University. The term “metabolic syndrome” has become controversial since the September 2005 publication of a joint statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes that called into question whether classifying the entity as a “syndrome” adds any clinical utility beyond its individual components (Diabetes Care 2005:28:2289–304).

With that debate still ongoing, Dr. Eckel was the lead author of a “call to action” from the ADA and the American Heart Association (AHA) in which both organizations expressed their strong commitment to prevention of cardiovascular disease and type 2 diabetes, and urged all health care providers to assess patients—especially those who are overweight or obese—for their CVD risk factors (Diabetes Care 2006;29:1697–9).

“The metabolic syndrome wasn't meant to be a global risk predictor for heart disease. It was meant to identify a cluster of risk factors that can be best modified initially by lifestyle,” said Dr. Eckel, professor of medicine and the Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado, Denver.

Although data conflict somewhat as to whether metabolic syndrome does in fact increase the risk for CVD and death, a recent meta-analysis of 43 cohorts in 37 longitudinal studies comprising 172,573 patients found that metabolic syndrome conferred an independent relative risk of 1.54 after adjusting for all known cardiovascular risk factors (J. Am. Coll. Cardiol. 2007;49:403–14).

In contrast to the disagreement on cardiovascular disease (CVD) risk, the data agree overwhelmingly on the benefits of lifestyle modification in patients with metabolic syndrome. Interventions that improve the quality of the diet, increase physical activity, and reduce weight often lead to improvements in a long list of cardiovascular risk factors, including reductions in waist circumference (a surrogate for visceral fat deposition), triglycerides, blood pressure, glucose, and inflammatory markers, along with increases in HDL cholesterol. “Seems like the perfect therapy to me,” Dr. Eckel remarked.

Still, diet specifics remain controversial. Although the key to weight reduction is clearly to expend more energy than is consumed, the importance of the carbohydrate/protein/fat ratio to the equation is still debated. Many people believe that low-carbohydrate plans such as the Atkins diet produce superior weight loss, but Atkins fared no better at 1 year than did the low-fat, high-fiber Ornish regimen or other popular diets such as the Zone diet and Weight Watchers when compared in a head-to-head study (JAMA 2005;293:43–53).

Data supporting the medical benefits of lifestyle modification include an analysis of the landmark Diabetes Prevention Program. That study found that weight loss via lifestyle modification was the predominant predictor of reduced diabetes incidence in 1,079 program participants aged 25–84 years (Diabetes Care 2006;29:2102–7). And in the first year of the Look AHEAD (Action for Health in Diabetes), intensive lifestyle modification resulted in an average 8.6% weight loss in 5,145 patients with type 2 diabetes, which was associated with a reduction in CVD risk factors and a reduced need for medication (Diabetes Care 2007;30:1374–83).

Yet, despite such strong evidence, an AHA survey of physicians found that fewer than 10% of cardiologists and fewer than 15% of family physicians even ask patients about their current diet and physical activity levels, let alone spend much time encouraging improvement in them. “As physicians we have to be engaged, informed, and passionate about lifestyle and how important it really is,” Dr. Eckel said.

Beyond lifestyle, medications that address the various components of metabolic syndrome can affect other components as well. The weight-loss drugs orlistat and sibutramine both also reduce waist circumference, glucose, triglycerides, and C-reactive protein. Statins, besides lowering LDL cholesterol, also raise HDL cholesterol.

Although data strongly support blood pressure and glucose as primary targets of therapy beyond lifestyle in people with metabolic syndrome, the strongest data are those that support LDL lowering in patients with and without diabetes. “Let's not lose the importance of focusing on LDL lowering in patients with metabolic syndrome, even though it's not a part of the clustering of components,” Dr. Eckel remarked.

'We have to be engaged, informed, and passionate about lifestyle and how important it really is.' DR. ECKEL

COLUMBUS, OHIO — For patients with metabolic syndrome, the focus should be on the two “L” words: lifestyle and LDL.

That was the message from a talk given by former American Heart Association president Robert H. Eckel at a meeting on diabetes sponsored by Ohio State University. The term “metabolic syndrome” has become controversial since the September 2005 publication of a joint statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes that called into question whether classifying the entity as a “syndrome” adds any clinical utility beyond its individual components (Diabetes Care 2005:28:2289–304).

With that debate still ongoing, Dr. Eckel was the lead author of a “call to action” from the ADA and the American Heart Association (AHA) in which both organizations expressed their strong commitment to prevention of cardiovascular disease and type 2 diabetes, and urged all health care providers to assess patients—especially those who are overweight or obese—for their CVD risk factors (Diabetes Care 2006;29:1697–9).

“The metabolic syndrome wasn't meant to be a global risk predictor for heart disease. It was meant to identify a cluster of risk factors that can be best modified initially by lifestyle,” said Dr. Eckel, professor of medicine and the Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado, Denver.

Although data conflict somewhat as to whether metabolic syndrome does in fact increase the risk for CVD and death, a recent meta-analysis of 43 cohorts in 37 longitudinal studies comprising 172,573 patients found that metabolic syndrome conferred an independent relative risk of 1.54 after adjusting for all known cardiovascular risk factors (J. Am. Coll. Cardiol. 2007;49:403–14).

In contrast to the disagreement on cardiovascular disease (CVD) risk, the data agree overwhelmingly on the benefits of lifestyle modification in patients with metabolic syndrome. Interventions that improve the quality of the diet, increase physical activity, and reduce weight often lead to improvements in a long list of cardiovascular risk factors, including reductions in waist circumference (a surrogate for visceral fat deposition), triglycerides, blood pressure, glucose, and inflammatory markers, along with increases in HDL cholesterol. “Seems like the perfect therapy to me,” Dr. Eckel remarked.

Still, diet specifics remain controversial. Although the key to weight reduction is clearly to expend more energy than is consumed, the importance of the carbohydrate/protein/fat ratio to the equation is still debated. Many people believe that low-carbohydrate plans such as the Atkins diet produce superior weight loss, but Atkins fared no better at 1 year than did the low-fat, high-fiber Ornish regimen or other popular diets such as the Zone diet and Weight Watchers when compared in a head-to-head study (JAMA 2005;293:43–53).

Data supporting the medical benefits of lifestyle modification include an analysis of the landmark Diabetes Prevention Program. That study found that weight loss via lifestyle modification was the predominant predictor of reduced diabetes incidence in 1,079 program participants aged 25–84 years (Diabetes Care 2006;29:2102–7). And in the first year of the Look AHEAD (Action for Health in Diabetes), intensive lifestyle modification resulted in an average 8.6% weight loss in 5,145 patients with type 2 diabetes, which was associated with a reduction in CVD risk factors and a reduced need for medication (Diabetes Care 2007;30:1374–83).

Yet, despite such strong evidence, an AHA survey of physicians found that fewer than 10% of cardiologists and fewer than 15% of family physicians even ask patients about their current diet and physical activity levels, let alone spend much time encouraging improvement in them. “As physicians we have to be engaged, informed, and passionate about lifestyle and how important it really is,” Dr. Eckel said.

Beyond lifestyle, medications that address the various components of metabolic syndrome can affect other components as well. The weight-loss drugs orlistat and sibutramine both also reduce waist circumference, glucose, triglycerides, and C-reactive protein. Statins, besides lowering LDL cholesterol, also raise HDL cholesterol.

Although data strongly support blood pressure and glucose as primary targets of therapy beyond lifestyle in people with metabolic syndrome, the strongest data are those that support LDL lowering in patients with and without diabetes. “Let's not lose the importance of focusing on LDL lowering in patients with metabolic syndrome, even though it's not a part of the clustering of components,” Dr. Eckel remarked.

'We have to be engaged, informed, and passionate about lifestyle and how important it really is.' DR. ECKEL

COLUMBUS, OHIO — For patients with metabolic syndrome, the focus should be on the two “L” words: lifestyle and LDL.

That was the message from a talk given by former American Heart Association president Robert H. Eckel at a meeting on diabetes sponsored by Ohio State University. The term “metabolic syndrome” has become controversial since the September 2005 publication of a joint statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes that called into question whether classifying the entity as a “syndrome” adds any clinical utility beyond its individual components (Diabetes Care 2005:28:2289–304).

With that debate still ongoing, Dr. Eckel was the lead author of a “call to action” from the ADA and the American Heart Association (AHA) in which both organizations expressed their strong commitment to prevention of cardiovascular disease and type 2 diabetes, and urged all health care providers to assess patients—especially those who are overweight or obese—for their CVD risk factors (Diabetes Care 2006;29:1697–9).

“The metabolic syndrome wasn't meant to be a global risk predictor for heart disease. It was meant to identify a cluster of risk factors that can be best modified initially by lifestyle,” said Dr. Eckel, professor of medicine and the Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado, Denver.

Although data conflict somewhat as to whether metabolic syndrome does in fact increase the risk for CVD and death, a recent meta-analysis of 43 cohorts in 37 longitudinal studies comprising 172,573 patients found that metabolic syndrome conferred an independent relative risk of 1.54 after adjusting for all known cardiovascular risk factors (J. Am. Coll. Cardiol. 2007;49:403–14).

In contrast to the disagreement on cardiovascular disease (CVD) risk, the data agree overwhelmingly on the benefits of lifestyle modification in patients with metabolic syndrome. Interventions that improve the quality of the diet, increase physical activity, and reduce weight often lead to improvements in a long list of cardiovascular risk factors, including reductions in waist circumference (a surrogate for visceral fat deposition), triglycerides, blood pressure, glucose, and inflammatory markers, along with increases in HDL cholesterol. “Seems like the perfect therapy to me,” Dr. Eckel remarked.

Still, diet specifics remain controversial. Although the key to weight reduction is clearly to expend more energy than is consumed, the importance of the carbohydrate/protein/fat ratio to the equation is still debated. Many people believe that low-carbohydrate plans such as the Atkins diet produce superior weight loss, but Atkins fared no better at 1 year than did the low-fat, high-fiber Ornish regimen or other popular diets such as the Zone diet and Weight Watchers when compared in a head-to-head study (JAMA 2005;293:43–53).

Data supporting the medical benefits of lifestyle modification include an analysis of the landmark Diabetes Prevention Program. That study found that weight loss via lifestyle modification was the predominant predictor of reduced diabetes incidence in 1,079 program participants aged 25–84 years (Diabetes Care 2006;29:2102–7). And in the first year of the Look AHEAD (Action for Health in Diabetes), intensive lifestyle modification resulted in an average 8.6% weight loss in 5,145 patients with type 2 diabetes, which was associated with a reduction in CVD risk factors and a reduced need for medication (Diabetes Care 2007;30:1374–83).

Yet, despite such strong evidence, an AHA survey of physicians found that fewer than 10% of cardiologists and fewer than 15% of family physicians even ask patients about their current diet and physical activity levels, let alone spend much time encouraging improvement in them. “As physicians we have to be engaged, informed, and passionate about lifestyle and how important it really is,” Dr. Eckel said.

Beyond lifestyle, medications that address the various components of metabolic syndrome can affect other components as well. The weight-loss drugs orlistat and sibutramine both also reduce waist circumference, glucose, triglycerides, and C-reactive protein. Statins, besides lowering LDL cholesterol, also raise HDL cholesterol.

Although data strongly support blood pressure and glucose as primary targets of therapy beyond lifestyle in people with metabolic syndrome, the strongest data are those that support LDL lowering in patients with and without diabetes. “Let's not lose the importance of focusing on LDL lowering in patients with metabolic syndrome, even though it's not a part of the clustering of components,” Dr. Eckel remarked.

'We have to be engaged, informed, and passionate about lifestyle and how important it really is.' DR. ECKEL

New guidance from the American Diabetes Association gives a green light to the use of low-carbohydrate diets as a weight-control measure for patients with diabetes.

As part of the ADA's annual update of its clinical practice recommendations, the organization has dropped its formerly restrictive stance on low-carbohydrate diets.

The updated guidelines for 2008 also revise recommendations on prediabetes testing, metformin use, and hypoglycemia prevention, among other topics.

Although the ADA still does not endorse low-carbohydrate diets for weight loss or diabetes management, the association has updated the section of its guidelines that covers nutrition recommendations and interventions for diabetes to remove a specific recommendation against diets that restrict carbohydrates to less than 130 g/day. Now, for weight loss, the ADA says that either low-carbohydrate or low-fat calorie-restricted diets might be effective in the short term (up to 1 year). Previous language that recommended against low-carb diets was also removed from the 2008 section on nutrition recommendations for managing diabetes (secondary prevention).

For patients who are on low-carbohydrate diets, the ADA now advises monitoring of lipid profiles, renal function, and protein intake (in patients with nephropathy), as well as adjustment of glucose-lowering therapy as needed (Diabetes Care 2008;30[suppl. 1]:S61–78).

“The evidence is clear that both low-carbohydrate and low-fat calorie-restricted diets result in similar weight loss at 1 year. We're not endorsing either of these weight-loss plans over any other method of losing weight. … It's important for patients to choose a plan that works for them, and that the health care team support their patients' weight loss efforts,” guideline panel member and registered dietician Ann Albright, Ph.D., ADA President of Health Care and Education, said in a statement.

New data cited in the 2008 document are from the A to Z Weight Loss Study, a randomized trial that compared the Atkins, Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitude, Relationships, and Nutrition) diets in a total of 311 overweight premenopausal women. At 1 year, those who followed the Atkins diet showed significantly more weight loss (−4.7 kg) than did the other three diet groups (−1.6 kg with Zone, −2.6 kg with LEARN, and −2.2 kg with Ornish). Secondary outcomes, including lipid profile, percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure, were comparable or better with Atkins versus the other diet groups (JAMA 2007;297:969–77).

However, the ADA repeated a point it had made in 2007: The recommended daily allowance for digestible carbohydrate is 130 g/day, based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.

“Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very low-carbohydrate diets are unclear, and such diets eliminate foods that are important sources of energy, fiber, vitamins, and minerals that are important in dietary palatability,” according to the 11-member writing panel, which was cochaired by Dr. John P. Bantle of the University of Minnesota, Minneapolis, and Judith Wylie-Rosett, Ed.D., a registered dietician, who is with Albert Einstein College of Medicine, New York.

Dr. Neil J. Stone, professor of clinical medicine at Northwestern University, Chicago, is similarly cautious. “The new guideline acknowledges that based on available data, there are choices when it comes to choosing a weight loss regimen for the short term. This is not an endorsement of lifelong marked carbohydrate restriction, and the general public as well as diabetics need to consider reasonable carbohydrate intake for nutritional balance, as [carbohydrates] can provide important sources of energy, fiber, vitamins, and minerals,” he said in an interview.

But Dr. Eric C. Westman, director of the Lifestyle Medicine Clinic at Duke University, Durham, N.C., believes that low-carb diets can play an important role in diabetes management. “Carbohydrates, especially sugar and starch, are the main factors in the diet that raise blood glucose. Carbohydrate-restricted diets are as effective, and sometimes even more effective, than medication therapy for type 2 diabetes.

“When obesity is present, carbohydrate-restricted diets have the advantage over medication because most people then lose weight, which then improves insulin resistance,” Dr. Westman said in an interview.

Other revisions in the 2008 guidelines—some of which were previously published during 2007—include the following:

▸ New tables have been added that list screening recommendations and diagnostic cutpoints for gestational diabetes, summarize interventions and results of diabetes prevention trials, and summarize the evidence for statin therapy in people with diabetes.

▸ There is now a more explicit recommendation to consider testing for prediabetes (previously just for diabetes) in asymptomatic patients of any age who are overweight and have additional risk factors for diabetes.

▸ In addition to lifestyle counseling, metformin might now be an option in people considered to be at high risk (combined impaired fasting glucose and impaired glucose tolerance plus other risk factors) and who are obese and under 60 years of age.

▸ Continuous glucose monitoring might be a supplemental tool to self-monitoring of blood glucose for selected patients with type 1 diabetes, especially those with hypoglycemic unawareness.

Dr. Phillip Levy, a Phoenix endocrinologist, said the recommendations sounded pretty reasonable. “I don't think it matters what kind of diet patients use as long as they lose the weight,” he said. Although increased cholesterol may occur with a low-carb diet, “I don't see that causing any permanent problems, because people don't stay on the diets” forever; instead they go off them once they lose the weight.

New guidance from the American Diabetes Association gives a green light to the use of low-carbohydrate diets as a weight-control measure for patients with diabetes.

As part of the ADA's annual update of its clinical practice recommendations, the organization has dropped its formerly restrictive stance on low-carbohydrate diets.

The updated guidelines for 2008 also revise recommendations on prediabetes testing, metformin use, and hypoglycemia prevention, among other topics.

Although the ADA still does not endorse low-carbohydrate diets for weight loss or diabetes management, the association has updated the section of its guidelines that covers nutrition recommendations and interventions for diabetes to remove a specific recommendation against diets that restrict carbohydrates to less than 130 g/day. Now, for weight loss, the ADA says that either low-carbohydrate or low-fat calorie-restricted diets might be effective in the short term (up to 1 year). Previous language that recommended against low-carb diets was also removed from the 2008 section on nutrition recommendations for managing diabetes (secondary prevention).

For patients who are on low-carbohydrate diets, the ADA now advises monitoring of lipid profiles, renal function, and protein intake (in patients with nephropathy), as well as adjustment of glucose-lowering therapy as needed (Diabetes Care 2008;30[suppl. 1]:S61–78).

“The evidence is clear that both low-carbohydrate and low-fat calorie-restricted diets result in similar weight loss at 1 year. We're not endorsing either of these weight-loss plans over any other method of losing weight. … It's important for patients to choose a plan that works for them, and that the health care team support their patients' weight loss efforts,” guideline panel member and registered dietician Ann Albright, Ph.D., ADA President of Health Care and Education, said in a statement.

New data cited in the 2008 document are from the A to Z Weight Loss Study, a randomized trial that compared the Atkins, Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitude, Relationships, and Nutrition) diets in a total of 311 overweight premenopausal women. At 1 year, those who followed the Atkins diet showed significantly more weight loss (−4.7 kg) than did the other three diet groups (−1.6 kg with Zone, −2.6 kg with LEARN, and −2.2 kg with Ornish). Secondary outcomes, including lipid profile, percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure, were comparable or better with Atkins versus the other diet groups (JAMA 2007;297:969–77).

However, the ADA repeated a point it had made in 2007: The recommended daily allowance for digestible carbohydrate is 130 g/day, based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.

“Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very low-carbohydrate diets are unclear, and such diets eliminate foods that are important sources of energy, fiber, vitamins, and minerals that are important in dietary palatability,” according to the 11-member writing panel, which was cochaired by Dr. John P. Bantle of the University of Minnesota, Minneapolis, and Judith Wylie-Rosett, Ed.D., a registered dietician, who is with Albert Einstein College of Medicine, New York.

Dr. Neil J. Stone, professor of clinical medicine at Northwestern University, Chicago, is similarly cautious. “The new guideline acknowledges that based on available data, there are choices when it comes to choosing a weight loss regimen for the short term. This is not an endorsement of lifelong marked carbohydrate restriction, and the general public as well as diabetics need to consider reasonable carbohydrate intake for nutritional balance, as [carbohydrates] can provide important sources of energy, fiber, vitamins, and minerals,” he said in an interview.

But Dr. Eric C. Westman, director of the Lifestyle Medicine Clinic at Duke University, Durham, N.C., believes that low-carb diets can play an important role in diabetes management. “Carbohydrates, especially sugar and starch, are the main factors in the diet that raise blood glucose. Carbohydrate-restricted diets are as effective, and sometimes even more effective, than medication therapy for type 2 diabetes.

“When obesity is present, carbohydrate-restricted diets have the advantage over medication because most people then lose weight, which then improves insulin resistance,” Dr. Westman said in an interview.

Other revisions in the 2008 guidelines—some of which were previously published during 2007—include the following:

▸ New tables have been added that list screening recommendations and diagnostic cutpoints for gestational diabetes, summarize interventions and results of diabetes prevention trials, and summarize the evidence for statin therapy in people with diabetes.

▸ There is now a more explicit recommendation to consider testing for prediabetes (previously just for diabetes) in asymptomatic patients of any age who are overweight and have additional risk factors for diabetes.

▸ In addition to lifestyle counseling, metformin might now be an option in people considered to be at high risk (combined impaired fasting glucose and impaired glucose tolerance plus other risk factors) and who are obese and under 60 years of age.

▸ Continuous glucose monitoring might be a supplemental tool to self-monitoring of blood glucose for selected patients with type 1 diabetes, especially those with hypoglycemic unawareness.

Dr. Phillip Levy, a Phoenix endocrinologist, said the recommendations sounded pretty reasonable. “I don't think it matters what kind of diet patients use as long as they lose the weight,” he said. Although increased cholesterol may occur with a low-carb diet, “I don't see that causing any permanent problems, because people don't stay on the diets” forever; instead they go off them once they lose the weight.

New guidance from the American Diabetes Association gives a green light to the use of low-carbohydrate diets as a weight-control measure for patients with diabetes.

As part of the ADA's annual update of its clinical practice recommendations, the organization has dropped its formerly restrictive stance on low-carbohydrate diets.

The updated guidelines for 2008 also revise recommendations on prediabetes testing, metformin use, and hypoglycemia prevention, among other topics.

Although the ADA still does not endorse low-carbohydrate diets for weight loss or diabetes management, the association has updated the section of its guidelines that covers nutrition recommendations and interventions for diabetes to remove a specific recommendation against diets that restrict carbohydrates to less than 130 g/day. Now, for weight loss, the ADA says that either low-carbohydrate or low-fat calorie-restricted diets might be effective in the short term (up to 1 year). Previous language that recommended against low-carb diets was also removed from the 2008 section on nutrition recommendations for managing diabetes (secondary prevention).

For patients who are on low-carbohydrate diets, the ADA now advises monitoring of lipid profiles, renal function, and protein intake (in patients with nephropathy), as well as adjustment of glucose-lowering therapy as needed (Diabetes Care 2008;30[suppl. 1]:S61–78).

“The evidence is clear that both low-carbohydrate and low-fat calorie-restricted diets result in similar weight loss at 1 year. We're not endorsing either of these weight-loss plans over any other method of losing weight. … It's important for patients to choose a plan that works for them, and that the health care team support their patients' weight loss efforts,” guideline panel member and registered dietician Ann Albright, Ph.D., ADA President of Health Care and Education, said in a statement.

New data cited in the 2008 document are from the A to Z Weight Loss Study, a randomized trial that compared the Atkins, Zone, Ornish, and LEARN (Lifestyle, Exercise, Attitude, Relationships, and Nutrition) diets in a total of 311 overweight premenopausal women. At 1 year, those who followed the Atkins diet showed significantly more weight loss (−4.7 kg) than did the other three diet groups (−1.6 kg with Zone, −2.6 kg with LEARN, and −2.2 kg with Ornish). Secondary outcomes, including lipid profile, percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure, were comparable or better with Atkins versus the other diet groups (JAMA 2007;297:969–77).

However, the ADA repeated a point it had made in 2007: The recommended daily allowance for digestible carbohydrate is 130 g/day, based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.

“Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very low-carbohydrate diets are unclear, and such diets eliminate foods that are important sources of energy, fiber, vitamins, and minerals that are important in dietary palatability,” according to the 11-member writing panel, which was cochaired by Dr. John P. Bantle of the University of Minnesota, Minneapolis, and Judith Wylie-Rosett, Ed.D., a registered dietician, who is with Albert Einstein College of Medicine, New York.

Dr. Neil J. Stone, professor of clinical medicine at Northwestern University, Chicago, is similarly cautious. “The new guideline acknowledges that based on available data, there are choices when it comes to choosing a weight loss regimen for the short term. This is not an endorsement of lifelong marked carbohydrate restriction, and the general public as well as diabetics need to consider reasonable carbohydrate intake for nutritional balance, as [carbohydrates] can provide important sources of energy, fiber, vitamins, and minerals,” he said in an interview.

But Dr. Eric C. Westman, director of the Lifestyle Medicine Clinic at Duke University, Durham, N.C., believes that low-carb diets can play an important role in diabetes management. “Carbohydrates, especially sugar and starch, are the main factors in the diet that raise blood glucose. Carbohydrate-restricted diets are as effective, and sometimes even more effective, than medication therapy for type 2 diabetes.

“When obesity is present, carbohydrate-restricted diets have the advantage over medication because most people then lose weight, which then improves insulin resistance,” Dr. Westman said in an interview.

Other revisions in the 2008 guidelines—some of which were previously published during 2007—include the following:

▸ New tables have been added that list screening recommendations and diagnostic cutpoints for gestational diabetes, summarize interventions and results of diabetes prevention trials, and summarize the evidence for statin therapy in people with diabetes.

▸ There is now a more explicit recommendation to consider testing for prediabetes (previously just for diabetes) in asymptomatic patients of any age who are overweight and have additional risk factors for diabetes.

▸ In addition to lifestyle counseling, metformin might now be an option in people considered to be at high risk (combined impaired fasting glucose and impaired glucose tolerance plus other risk factors) and who are obese and under 60 years of age.

▸ Continuous glucose monitoring might be a supplemental tool to self-monitoring of blood glucose for selected patients with type 1 diabetes, especially those with hypoglycemic unawareness.

Dr. Phillip Levy, a Phoenix endocrinologist, said the recommendations sounded pretty reasonable. “I don't think it matters what kind of diet patients use as long as they lose the weight,” he said. Although increased cholesterol may occur with a low-carb diet, “I don't see that causing any permanent problems, because people don't stay on the diets” forever; instead they go off them once they lose the weight.

WASHINGTON — A biodegradable, polymer-based, rapamycin-eluting stent developed by a group in Germany is at least as effective as the Cypher stent, Dr. Julinda Mehilli reported at a conference on transcatheter cardiovascular therapeutics, sponsored by the Cardiovascular Research Foundation.

Although the use of polymers in drug-eluting stents (DES) may provide better release kinetics of the drug, their permanent presence in the vessel is believed to have a negative impact on the long-term outcome. Polymer-free and biodegradable polymer-based DES are two potential approaches to eliminate the presence of permanent polymers, said Dr. Mehilli, of the Technical University, Munich.

In this study, called ISAR-TEST 3, the investigators compared both the polymer-free (PF) rapamycin-eluting stent and a rapamycin-eluting stent that uses a mixture of biodegradable polymer (BP) and natural resin with the permanent polymer rapamycin-eluting stent Cypher in a randomized trial involving 605 patients with coronary artery disease: 202 were randomized to BP DES, 202 to Cypher, and 201 to PF DES. About a third of all three groups had unstable angina and a history of myocardial infarction, with no significant differences in baseline angiographic characteristics. A majority of the patients (79%–83%) had multivessel disease, and about three-fourths had complex lesions.

The primary end point, in-stent late lumen loss at 1 year, was 0.17 mm for BP DES, 0.23 mm for Cypher, and 0.47 mm for PF DES. Compared with the Cypher, the results demonstrated noninferiority for the BP DES but not for the PF DES, Dr. Mehilli reported.

Rates of angiographic restenosis were 9.0% for the BP DES, 10.8% for the Cypher, and 16.9% for PF DES. Clinical restenosis (target lesion revascularization) rates were 5.9%, 7.9%, and 12.9%, respectively, all nonsignificant differences, compared with Cypher. Death or myocardial infarction occurred in 2.5% with BP DES, 3.5% with Cypher, and 4.0% with PF DES, while death rates were identical (2.5%) in each of the groups.

Definite/probable/possible stent thrombosis (Academic Research Consortium definition) occurred in 1.0% of the BP DES group, 2.0% with Cypher, and 1.5% of the PF DES recipients, also not significantly different. The three types of DES did not differ in terms of their safety profile at 1 year, Dr. Mehilli reported.

In a critical appraisal of ISAR-TEST 3, Dr. Jeffrey J. Popma called it “an important study” because “Reduction in intimal hyperplasia will not simply be enough as we move forward with our [DES] programs. We're looking for new stents that have rapid endothelialization, less inflammation, and a reduction in the requirement for antiplatelet therapy, and these two agents may do that.”

The bioresorbable polymer might result in less very late stent thrombosis, while the microporous surface would possibly produce more rapid endothelialization, noted Dr. Popma, director of invasive cardiovascular services at Caritas Christi Health Care System, St. Elizabeth Research Center, Harvard Medical School, Boston.

However, he questioned whether “in-stent” late loss was the right primary study end point. While it is the best measure for the degree of intimal hyperplasia within the stent, it has no implications for endothelialization and healing. In-segment follow-up percent diameter stenosis would be a better predictor of clinical events, he said.

WASHINGTON — A biodegradable, polymer-based, rapamycin-eluting stent developed by a group in Germany is at least as effective as the Cypher stent, Dr. Julinda Mehilli reported at a conference on transcatheter cardiovascular therapeutics, sponsored by the Cardiovascular Research Foundation.

Although the use of polymers in drug-eluting stents (DES) may provide better release kinetics of the drug, their permanent presence in the vessel is believed to have a negative impact on the long-term outcome. Polymer-free and biodegradable polymer-based DES are two potential approaches to eliminate the presence of permanent polymers, said Dr. Mehilli, of the Technical University, Munich.

In this study, called ISAR-TEST 3, the investigators compared both the polymer-free (PF) rapamycin-eluting stent and a rapamycin-eluting stent that uses a mixture of biodegradable polymer (BP) and natural resin with the permanent polymer rapamycin-eluting stent Cypher in a randomized trial involving 605 patients with coronary artery disease: 202 were randomized to BP DES, 202 to Cypher, and 201 to PF DES. About a third of all three groups had unstable angina and a history of myocardial infarction, with no significant differences in baseline angiographic characteristics. A majority of the patients (79%–83%) had multivessel disease, and about three-fourths had complex lesions.

The primary end point, in-stent late lumen loss at 1 year, was 0.17 mm for BP DES, 0.23 mm for Cypher, and 0.47 mm for PF DES. Compared with the Cypher, the results demonstrated noninferiority for the BP DES but not for the PF DES, Dr. Mehilli reported.

Rates of angiographic restenosis were 9.0% for the BP DES, 10.8% for the Cypher, and 16.9% for PF DES. Clinical restenosis (target lesion revascularization) rates were 5.9%, 7.9%, and 12.9%, respectively, all nonsignificant differences, compared with Cypher. Death or myocardial infarction occurred in 2.5% with BP DES, 3.5% with Cypher, and 4.0% with PF DES, while death rates were identical (2.5%) in each of the groups.

Definite/probable/possible stent thrombosis (Academic Research Consortium definition) occurred in 1.0% of the BP DES group, 2.0% with Cypher, and 1.5% of the PF DES recipients, also not significantly different. The three types of DES did not differ in terms of their safety profile at 1 year, Dr. Mehilli reported.

In a critical appraisal of ISAR-TEST 3, Dr. Jeffrey J. Popma called it “an important study” because “Reduction in intimal hyperplasia will not simply be enough as we move forward with our [DES] programs. We're looking for new stents that have rapid endothelialization, less inflammation, and a reduction in the requirement for antiplatelet therapy, and these two agents may do that.”

The bioresorbable polymer might result in less very late stent thrombosis, while the microporous surface would possibly produce more rapid endothelialization, noted Dr. Popma, director of invasive cardiovascular services at Caritas Christi Health Care System, St. Elizabeth Research Center, Harvard Medical School, Boston.

However, he questioned whether “in-stent” late loss was the right primary study end point. While it is the best measure for the degree of intimal hyperplasia within the stent, it has no implications for endothelialization and healing. In-segment follow-up percent diameter stenosis would be a better predictor of clinical events, he said.

WASHINGTON — A biodegradable, polymer-based, rapamycin-eluting stent developed by a group in Germany is at least as effective as the Cypher stent, Dr. Julinda Mehilli reported at a conference on transcatheter cardiovascular therapeutics, sponsored by the Cardiovascular Research Foundation.

Although the use of polymers in drug-eluting stents (DES) may provide better release kinetics of the drug, their permanent presence in the vessel is believed to have a negative impact on the long-term outcome. Polymer-free and biodegradable polymer-based DES are two potential approaches to eliminate the presence of permanent polymers, said Dr. Mehilli, of the Technical University, Munich.

In this study, called ISAR-TEST 3, the investigators compared both the polymer-free (PF) rapamycin-eluting stent and a rapamycin-eluting stent that uses a mixture of biodegradable polymer (BP) and natural resin with the permanent polymer rapamycin-eluting stent Cypher in a randomized trial involving 605 patients with coronary artery disease: 202 were randomized to BP DES, 202 to Cypher, and 201 to PF DES. About a third of all three groups had unstable angina and a history of myocardial infarction, with no significant differences in baseline angiographic characteristics. A majority of the patients (79%–83%) had multivessel disease, and about three-fourths had complex lesions.

The primary end point, in-stent late lumen loss at 1 year, was 0.17 mm for BP DES, 0.23 mm for Cypher, and 0.47 mm for PF DES. Compared with the Cypher, the results demonstrated noninferiority for the BP DES but not for the PF DES, Dr. Mehilli reported.

Rates of angiographic restenosis were 9.0% for the BP DES, 10.8% for the Cypher, and 16.9% for PF DES. Clinical restenosis (target lesion revascularization) rates were 5.9%, 7.9%, and 12.9%, respectively, all nonsignificant differences, compared with Cypher. Death or myocardial infarction occurred in 2.5% with BP DES, 3.5% with Cypher, and 4.0% with PF DES, while death rates were identical (2.5%) in each of the groups.

Definite/probable/possible stent thrombosis (Academic Research Consortium definition) occurred in 1.0% of the BP DES group, 2.0% with Cypher, and 1.5% of the PF DES recipients, also not significantly different. The three types of DES did not differ in terms of their safety profile at 1 year, Dr. Mehilli reported.

In a critical appraisal of ISAR-TEST 3, Dr. Jeffrey J. Popma called it “an important study” because “Reduction in intimal hyperplasia will not simply be enough as we move forward with our [DES] programs. We're looking for new stents that have rapid endothelialization, less inflammation, and a reduction in the requirement for antiplatelet therapy, and these two agents may do that.”

The bioresorbable polymer might result in less very late stent thrombosis, while the microporous surface would possibly produce more rapid endothelialization, noted Dr. Popma, director of invasive cardiovascular services at Caritas Christi Health Care System, St. Elizabeth Research Center, Harvard Medical School, Boston.

However, he questioned whether “in-stent” late loss was the right primary study end point. While it is the best measure for the degree of intimal hyperplasia within the stent, it has no implications for endothelialization and healing. In-segment follow-up percent diameter stenosis would be a better predictor of clinical events, he said.

WASHINGTON — The constellation of symptoms characterizing endometriosis may be more specific than currently thought, Karen D. Ballard, Ph.D., said at the annual meeting of the AAGL.

There is often a long delay in the diagnosis of endometriosis, in large part because the symptoms—primarily pelvic pain and dysmenorrhea—are nonspecific and can overlap with other conditions. But now, a case-control study from a primary care database in the United Kingdom suggests that women with a combination of gynecologic, urologic, and bowel symptoms are likely to have the condition.

“Specific, unremitting symptoms should raise a high suspicion of endometriosis,” said Dr. Ballard of the University of Surrey, Guildford, England.

Data were collected from the General Practice Research Database, the largest computerized database in the world containing longitudinal medical records from primary care. It currently comprises more than 3 million active patients from about 450 primary care practices, the setting in which all nonemergency patients in the United Kingdom are first seen.

During 1992–2002, 5,540 cases of endometriosis were identified from a total of 1,276,100 women aged 15–55 years. The average age at diagnosis was 35 years. The incidence of diagnosed endometriosis was 0.97 per 1,000 women-years, and the prevalence—calculated from the incidence rate and the average disease duration—was 1.5%. This proportion is lower than what has been reported in the literature, probably because it comes from general medical practice rather than a gynecology-based setting, Dr. Ballard noted.

There were 21,239 matched controls. The women with endometriosis were significantly thinner, with 49.3% having a body mass index less than 25 kg/m

As expected, the women with endometriosis had high rates of pelvic pain (15.6%) and dysmenorrhea (24.6%). But somewhat surprising was how low those rates were in the controls—1.5% and 3.4%, respectively—suggesting that “these symptoms are actually more specific than previously acknowledged,” Dr. Ballard said.

Other menstrual/pain symptoms reported significantly more often by the endometriosis patients than the controls were dyspareunia (9% vs. 1%, respectively), abdominal pain (45% vs. 13%), menorrhagia (23% vs. 6%) and menstrual problems (27% vs. 13%).

Gastrointestinal symptoms were also more common in the endometriosis group than in the control group, including constipation (9.2% vs. 4.4%) and rectal bleeding (2.0% vs. 1.1%), as were the urologic symptoms cystitis (8.8% vs. 5.3%) and dysuria (6.1% vs. 2.7%). Postcoital bleeding was reported by 2.9% vs. 0.7% and backache by 16.4% vs. 11.0%. All of these differences were statistically significant.

Women with endometriosis were also significantly more likely than were controls to have been diagnosed with subfertility (9.6% vs. 1.8%). But less expected was an association with the diagnosis of irritable bowel syndrome: 10.6% vs. 3.3%. Other diagnoses reported significantly more often among the women with endometriosis were urinary tract infection (18.5% vs. 9.8%), pelvic inflammatory disease (10.3% vs. 1.8%), and ovarian cysts (6.8% vs. 0.6%).

Stepwise regression analysis showed that the five “key symptoms” most strongly associated with endometriosis were infertility or subfertility (adjusted odds ratio 8.2), dysmenorrhea (8.1), symptoms associated with sexual intercourse (6.8), abdomino- pelvic pain (5.2), and menorrhagia (4.0).

In all, 84% of those with endometriosis had at least one of those symptoms, compared with 23% of those without, Dr. Ballard said.

The data also suggest there is opportunity for intervention: Nearly all (98%) of the women who were ultimately diagnosed with endometriosis had made at least one visit to a physician in the year before the diagnosis, compared with 81% of the controls. In fact, 62% had visited the physician at least six times in that year, compared with 27% of those not diagnosed with endometriosis, she reported.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The constellation of symptoms characterizing endometriosis may be more specific than currently thought, Karen D. Ballard, Ph.D., said at the annual meeting of the AAGL.

There is often a long delay in the diagnosis of endometriosis, in large part because the symptoms—primarily pelvic pain and dysmenorrhea—are nonspecific and can overlap with other conditions. But now, a case-control study from a primary care database in the United Kingdom suggests that women with a combination of gynecologic, urologic, and bowel symptoms are likely to have the condition.

“Specific, unremitting symptoms should raise a high suspicion of endometriosis,” said Dr. Ballard of the University of Surrey, Guildford, England.

Data were collected from the General Practice Research Database, the largest computerized database in the world containing longitudinal medical records from primary care. It currently comprises more than 3 million active patients from about 450 primary care practices, the setting in which all nonemergency patients in the United Kingdom are first seen.

During 1992–2002, 5,540 cases of endometriosis were identified from a total of 1,276,100 women aged 15–55 years. The average age at diagnosis was 35 years. The incidence of diagnosed endometriosis was 0.97 per 1,000 women-years, and the prevalence—calculated from the incidence rate and the average disease duration—was 1.5%. This proportion is lower than what has been reported in the literature, probably because it comes from general medical practice rather than a gynecology-based setting, Dr. Ballard noted.

There were 21,239 matched controls. The women with endometriosis were significantly thinner, with 49.3% having a body mass index less than 25 kg/m

As expected, the women with endometriosis had high rates of pelvic pain (15.6%) and dysmenorrhea (24.6%). But somewhat surprising was how low those rates were in the controls—1.5% and 3.4%, respectively—suggesting that “these symptoms are actually more specific than previously acknowledged,” Dr. Ballard said.

Other menstrual/pain symptoms reported significantly more often by the endometriosis patients than the controls were dyspareunia (9% vs. 1%, respectively), abdominal pain (45% vs. 13%), menorrhagia (23% vs. 6%) and menstrual problems (27% vs. 13%).

Gastrointestinal symptoms were also more common in the endometriosis group than in the control group, including constipation (9.2% vs. 4.4%) and rectal bleeding (2.0% vs. 1.1%), as were the urologic symptoms cystitis (8.8% vs. 5.3%) and dysuria (6.1% vs. 2.7%). Postcoital bleeding was reported by 2.9% vs. 0.7% and backache by 16.4% vs. 11.0%. All of these differences were statistically significant.

Women with endometriosis were also significantly more likely than were controls to have been diagnosed with subfertility (9.6% vs. 1.8%). But less expected was an association with the diagnosis of irritable bowel syndrome: 10.6% vs. 3.3%. Other diagnoses reported significantly more often among the women with endometriosis were urinary tract infection (18.5% vs. 9.8%), pelvic inflammatory disease (10.3% vs. 1.8%), and ovarian cysts (6.8% vs. 0.6%).

Stepwise regression analysis showed that the five “key symptoms” most strongly associated with endometriosis were infertility or subfertility (adjusted odds ratio 8.2), dysmenorrhea (8.1), symptoms associated with sexual intercourse (6.8), abdomino- pelvic pain (5.2), and menorrhagia (4.0).

In all, 84% of those with endometriosis had at least one of those symptoms, compared with 23% of those without, Dr. Ballard said.

The data also suggest there is opportunity for intervention: Nearly all (98%) of the women who were ultimately diagnosed with endometriosis had made at least one visit to a physician in the year before the diagnosis, compared with 81% of the controls. In fact, 62% had visited the physician at least six times in that year, compared with 27% of those not diagnosed with endometriosis, she reported.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The constellation of symptoms characterizing endometriosis may be more specific than currently thought, Karen D. Ballard, Ph.D., said at the annual meeting of the AAGL.

There is often a long delay in the diagnosis of endometriosis, in large part because the symptoms—primarily pelvic pain and dysmenorrhea—are nonspecific and can overlap with other conditions. But now, a case-control study from a primary care database in the United Kingdom suggests that women with a combination of gynecologic, urologic, and bowel symptoms are likely to have the condition.

“Specific, unremitting symptoms should raise a high suspicion of endometriosis,” said Dr. Ballard of the University of Surrey, Guildford, England.

Data were collected from the General Practice Research Database, the largest computerized database in the world containing longitudinal medical records from primary care. It currently comprises more than 3 million active patients from about 450 primary care practices, the setting in which all nonemergency patients in the United Kingdom are first seen.

During 1992–2002, 5,540 cases of endometriosis were identified from a total of 1,276,100 women aged 15–55 years. The average age at diagnosis was 35 years. The incidence of diagnosed endometriosis was 0.97 per 1,000 women-years, and the prevalence—calculated from the incidence rate and the average disease duration—was 1.5%. This proportion is lower than what has been reported in the literature, probably because it comes from general medical practice rather than a gynecology-based setting, Dr. Ballard noted.

There were 21,239 matched controls. The women with endometriosis were significantly thinner, with 49.3% having a body mass index less than 25 kg/m

As expected, the women with endometriosis had high rates of pelvic pain (15.6%) and dysmenorrhea (24.6%). But somewhat surprising was how low those rates were in the controls—1.5% and 3.4%, respectively—suggesting that “these symptoms are actually more specific than previously acknowledged,” Dr. Ballard said.

Other menstrual/pain symptoms reported significantly more often by the endometriosis patients than the controls were dyspareunia (9% vs. 1%, respectively), abdominal pain (45% vs. 13%), menorrhagia (23% vs. 6%) and menstrual problems (27% vs. 13%).

Gastrointestinal symptoms were also more common in the endometriosis group than in the control group, including constipation (9.2% vs. 4.4%) and rectal bleeding (2.0% vs. 1.1%), as were the urologic symptoms cystitis (8.8% vs. 5.3%) and dysuria (6.1% vs. 2.7%). Postcoital bleeding was reported by 2.9% vs. 0.7% and backache by 16.4% vs. 11.0%. All of these differences were statistically significant.

Women with endometriosis were also significantly more likely than were controls to have been diagnosed with subfertility (9.6% vs. 1.8%). But less expected was an association with the diagnosis of irritable bowel syndrome: 10.6% vs. 3.3%. Other diagnoses reported significantly more often among the women with endometriosis were urinary tract infection (18.5% vs. 9.8%), pelvic inflammatory disease (10.3% vs. 1.8%), and ovarian cysts (6.8% vs. 0.6%).

Stepwise regression analysis showed that the five “key symptoms” most strongly associated with endometriosis were infertility or subfertility (adjusted odds ratio 8.2), dysmenorrhea (8.1), symptoms associated with sexual intercourse (6.8), abdomino- pelvic pain (5.2), and menorrhagia (4.0).

In all, 84% of those with endometriosis had at least one of those symptoms, compared with 23% of those without, Dr. Ballard said.

The data also suggest there is opportunity for intervention: Nearly all (98%) of the women who were ultimately diagnosed with endometriosis had made at least one visit to a physician in the year before the diagnosis, compared with 81% of the controls. In fact, 62% had visited the physician at least six times in that year, compared with 27% of those not diagnosed with endometriosis, she reported.

ELSEVIER GLOBAL MEDICAL NEWS

COLUMBUS, OHIO — For patients with metabolic syndrome, the focus should be on the two “L” words: lifestyle and LDL.

That was the message from a talk given by former American Heart Association president Dr. Robert H. Eckel at a meeting on diabetes sponsored by Ohio State University. The term “metabolic syndrome” has become controversial since the September 2005 publication of a joint statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes that called into question whether classifying the entity as a “syndrome” adds any clinical utility beyond its individual components (Diabetes Care 2005:28:2289–304).

With that debate still ongoing, Dr. Eckel authored a “call to action” from the ADA and the American Heart Association (AHA) in which both organizations expressed their strong commitment to prevention of cardiovascular disease and type 2 diabetes, and urged all health care providers to assess patients—especially those who are overweight or obese—for their CVD risk factors (Diabetes Care 2006;29:1697–9).

“The metabolic syndrome wasn't meant to be a global risk predictor for heart disease. It was meant to identify a cluster of risk factors that can be best modified initially by lifestyle,” said Dr. Eckel, professor of medicine and the Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado, Denver.

Although data conflict somewhat as to whether metabolic syndrome does in fact increase the risk for CVD and death, a recent meta-analysis of 43 cohorts in 37 longitudinal studies comprising 172,573 patients found that metabolic syndrome conferred an independent relative risk of 1.54 after adjusting for all known cardiovascular risk factors (J. Am. Coll. Cardiol. 2007;49:403–14).

The data overwhelmingly support the benefits of lifestyle modification in patients with metabolic syndrome. Interventions that improve the quality of the diet, increase physical activity, and reduce weight often lead to improvements in a long list of cardiovascular risk factors, including reductions in waist circumference (a surrogate for visceral fat deposition), triglycerides, blood pressure, glucose, and inflammatory markers, along with increases in HDL cholesterol.

Still, diet specifics remain controversial. While it is clear that the key to weight reduction is simply to expend more energy than is consumed, there is still debate as to the importance of the carbohydrate/protein/fat ratio to the equation. Many people believe that low-carbohydrate diets such as Atkins produce superior weight loss, but Atkins fared no better at 1 year than did the low-fat, high-fiber Ornish regimen or other popular diets such as the Zone diet and Weight Watchers when compared in a head-to-head study. All of the diets modestly reduced body weight and several cardiovascular risk factors, but adherence to all was low (JAMA 2005;293:43–53).

In a recent study that is not yet published, Dr. Eckel and his associates found that LDL cholesterol levels increase during active weight loss in people on the Atkins diet, probably related to the fact that free fatty acids stay elevated because of the diet's high saturated fat content and because its low carbohydrate intakes results in lower levels of insulin secretion. “The Atkins diet concerns me,” he remarked.

A much better bet is the American Heart Association's “No Fad Diet,” now in its second printing and available in hardcover or paperback at major book retailers. “This one is evidence-based. You can trust it,” he said.

Data supporting the medical benefits of lifestyle modification include an analysis of the landmark Diabetes Prevention Program. That study found that weight loss achieved via lifestyle modification was the predominant predictor of reduced diabetes incidence among 1,079 program participants aged 25–84 years. For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity (Diabetes Care 2006;29:2102–7). And in the first year of the Look AHEAD (Action for Health in Diabetes), intensive lifestyle modification resulted in an average 8.6% weight loss in 5,145 patients with type 2 diabetes, which was associated with a reduction in CVD risk factors and a reduced need for medication (Diabetes Care 2007;30:1374–83).

Yet, despite such evidence, an AHA survey of physicians found that fewer than 15% of family physicians even ask patients about their current diet and physical activity levels, let alone spend much time encouraging improvement in them.

The weight loss drugs orlistat and sibutramine also reduce waist circumference, glucose, triglycerides, and C-reactive protein. Statins lower LDL cholesterol and also reduce triglycerides and raise HDL cholesterol, and the glucose-lowering drug pioglitazone also has been associated with reductions in triglycerides and increased HDL.

While data strongly support blood pressure and glucose as primary targets of therapy beyond lifestyle in people with metabolic syndrome, the strongest data are those that support LDL lowering in patients with and without diabetes. In the Treating to New Targets study of over 10,000 patients with clinically evident coronary heart disease—including more than 5,000 patients with metabolic syndrome—major cardiovascular events were significantly reduced among those taking 80 mg vs. 20 mg/day of atorvastatin (13% vs. 9.5%) during a mean follow-up of almost 5 years (Lancet 2006;368:919–28).

“Let's not lose the importance of focusing on LDL lowering in patients with metabolic syndrome, even though it's not a part of the clustering of components,” he said.

COLUMBUS, OHIO — For patients with metabolic syndrome, the focus should be on the two “L” words: lifestyle and LDL.

That was the message from a talk given by former American Heart Association president Dr. Robert H. Eckel at a meeting on diabetes sponsored by Ohio State University. The term “metabolic syndrome” has become controversial since the September 2005 publication of a joint statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes that called into question whether classifying the entity as a “syndrome” adds any clinical utility beyond its individual components (Diabetes Care 2005:28:2289–304).

With that debate still ongoing, Dr. Eckel authored a “call to action” from the ADA and the American Heart Association (AHA) in which both organizations expressed their strong commitment to prevention of cardiovascular disease and type 2 diabetes, and urged all health care providers to assess patients—especially those who are overweight or obese—for their CVD risk factors (Diabetes Care 2006;29:1697–9).

“The metabolic syndrome wasn't meant to be a global risk predictor for heart disease. It was meant to identify a cluster of risk factors that can be best modified initially by lifestyle,” said Dr. Eckel, professor of medicine and the Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado, Denver.

Although data conflict somewhat as to whether metabolic syndrome does in fact increase the risk for CVD and death, a recent meta-analysis of 43 cohorts in 37 longitudinal studies comprising 172,573 patients found that metabolic syndrome conferred an independent relative risk of 1.54 after adjusting for all known cardiovascular risk factors (J. Am. Coll. Cardiol. 2007;49:403–14).

The data overwhelmingly support the benefits of lifestyle modification in patients with metabolic syndrome. Interventions that improve the quality of the diet, increase physical activity, and reduce weight often lead to improvements in a long list of cardiovascular risk factors, including reductions in waist circumference (a surrogate for visceral fat deposition), triglycerides, blood pressure, glucose, and inflammatory markers, along with increases in HDL cholesterol.

Still, diet specifics remain controversial. While it is clear that the key to weight reduction is simply to expend more energy than is consumed, there is still debate as to the importance of the carbohydrate/protein/fat ratio to the equation. Many people believe that low-carbohydrate diets such as Atkins produce superior weight loss, but Atkins fared no better at 1 year than did the low-fat, high-fiber Ornish regimen or other popular diets such as the Zone diet and Weight Watchers when compared in a head-to-head study. All of the diets modestly reduced body weight and several cardiovascular risk factors, but adherence to all was low (JAMA 2005;293:43–53).

In a recent study that is not yet published, Dr. Eckel and his associates found that LDL cholesterol levels increase during active weight loss in people on the Atkins diet, probably related to the fact that free fatty acids stay elevated because of the diet's high saturated fat content and because its low carbohydrate intakes results in lower levels of insulin secretion. “The Atkins diet concerns me,” he remarked.

A much better bet is the American Heart Association's “No Fad Diet,” now in its second printing and available in hardcover or paperback at major book retailers. “This one is evidence-based. You can trust it,” he said.

Data supporting the medical benefits of lifestyle modification include an analysis of the landmark Diabetes Prevention Program. That study found that weight loss achieved via lifestyle modification was the predominant predictor of reduced diabetes incidence among 1,079 program participants aged 25–84 years. For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity (Diabetes Care 2006;29:2102–7). And in the first year of the Look AHEAD (Action for Health in Diabetes), intensive lifestyle modification resulted in an average 8.6% weight loss in 5,145 patients with type 2 diabetes, which was associated with a reduction in CVD risk factors and a reduced need for medication (Diabetes Care 2007;30:1374–83).

Yet, despite such evidence, an AHA survey of physicians found that fewer than 15% of family physicians even ask patients about their current diet and physical activity levels, let alone spend much time encouraging improvement in them.

The weight loss drugs orlistat and sibutramine also reduce waist circumference, glucose, triglycerides, and C-reactive protein. Statins lower LDL cholesterol and also reduce triglycerides and raise HDL cholesterol, and the glucose-lowering drug pioglitazone also has been associated with reductions in triglycerides and increased HDL.

While data strongly support blood pressure and glucose as primary targets of therapy beyond lifestyle in people with metabolic syndrome, the strongest data are those that support LDL lowering in patients with and without diabetes. In the Treating to New Targets study of over 10,000 patients with clinically evident coronary heart disease—including more than 5,000 patients with metabolic syndrome—major cardiovascular events were significantly reduced among those taking 80 mg vs. 20 mg/day of atorvastatin (13% vs. 9.5%) during a mean follow-up of almost 5 years (Lancet 2006;368:919–28).

“Let's not lose the importance of focusing on LDL lowering in patients with metabolic syndrome, even though it's not a part of the clustering of components,” he said.

COLUMBUS, OHIO — For patients with metabolic syndrome, the focus should be on the two “L” words: lifestyle and LDL.

That was the message from a talk given by former American Heart Association president Dr. Robert H. Eckel at a meeting on diabetes sponsored by Ohio State University. The term “metabolic syndrome” has become controversial since the September 2005 publication of a joint statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes that called into question whether classifying the entity as a “syndrome” adds any clinical utility beyond its individual components (Diabetes Care 2005:28:2289–304).

With that debate still ongoing, Dr. Eckel authored a “call to action” from the ADA and the American Heart Association (AHA) in which both organizations expressed their strong commitment to prevention of cardiovascular disease and type 2 diabetes, and urged all health care providers to assess patients—especially those who are overweight or obese—for their CVD risk factors (Diabetes Care 2006;29:1697–9).

“The metabolic syndrome wasn't meant to be a global risk predictor for heart disease. It was meant to identify a cluster of risk factors that can be best modified initially by lifestyle,” said Dr. Eckel, professor of medicine and the Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado, Denver.

Although data conflict somewhat as to whether metabolic syndrome does in fact increase the risk for CVD and death, a recent meta-analysis of 43 cohorts in 37 longitudinal studies comprising 172,573 patients found that metabolic syndrome conferred an independent relative risk of 1.54 after adjusting for all known cardiovascular risk factors (J. Am. Coll. Cardiol. 2007;49:403–14).

The data overwhelmingly support the benefits of lifestyle modification in patients with metabolic syndrome. Interventions that improve the quality of the diet, increase physical activity, and reduce weight often lead to improvements in a long list of cardiovascular risk factors, including reductions in waist circumference (a surrogate for visceral fat deposition), triglycerides, blood pressure, glucose, and inflammatory markers, along with increases in HDL cholesterol.

Still, diet specifics remain controversial. While it is clear that the key to weight reduction is simply to expend more energy than is consumed, there is still debate as to the importance of the carbohydrate/protein/fat ratio to the equation. Many people believe that low-carbohydrate diets such as Atkins produce superior weight loss, but Atkins fared no better at 1 year than did the low-fat, high-fiber Ornish regimen or other popular diets such as the Zone diet and Weight Watchers when compared in a head-to-head study. All of the diets modestly reduced body weight and several cardiovascular risk factors, but adherence to all was low (JAMA 2005;293:43–53).

In a recent study that is not yet published, Dr. Eckel and his associates found that LDL cholesterol levels increase during active weight loss in people on the Atkins diet, probably related to the fact that free fatty acids stay elevated because of the diet's high saturated fat content and because its low carbohydrate intakes results in lower levels of insulin secretion. “The Atkins diet concerns me,” he remarked.

A much better bet is the American Heart Association's “No Fad Diet,” now in its second printing and available in hardcover or paperback at major book retailers. “This one is evidence-based. You can trust it,” he said.

Data supporting the medical benefits of lifestyle modification include an analysis of the landmark Diabetes Prevention Program. That study found that weight loss achieved via lifestyle modification was the predominant predictor of reduced diabetes incidence among 1,079 program participants aged 25–84 years. For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity (Diabetes Care 2006;29:2102–7). And in the first year of the Look AHEAD (Action for Health in Diabetes), intensive lifestyle modification resulted in an average 8.6% weight loss in 5,145 patients with type 2 diabetes, which was associated with a reduction in CVD risk factors and a reduced need for medication (Diabetes Care 2007;30:1374–83).

Yet, despite such evidence, an AHA survey of physicians found that fewer than 15% of family physicians even ask patients about their current diet and physical activity levels, let alone spend much time encouraging improvement in them.

The weight loss drugs orlistat and sibutramine also reduce waist circumference, glucose, triglycerides, and C-reactive protein. Statins lower LDL cholesterol and also reduce triglycerides and raise HDL cholesterol, and the glucose-lowering drug pioglitazone also has been associated with reductions in triglycerides and increased HDL.

While data strongly support blood pressure and glucose as primary targets of therapy beyond lifestyle in people with metabolic syndrome, the strongest data are those that support LDL lowering in patients with and without diabetes. In the Treating to New Targets study of over 10,000 patients with clinically evident coronary heart disease—including more than 5,000 patients with metabolic syndrome—major cardiovascular events were significantly reduced among those taking 80 mg vs. 20 mg/day of atorvastatin (13% vs. 9.5%) during a mean follow-up of almost 5 years (Lancet 2006;368:919–28).

“Let's not lose the importance of focusing on LDL lowering in patients with metabolic syndrome, even though it's not a part of the clustering of components,” he said.

WASHINGTON — Women with premenstrual syndrome are at increased risk for pelvic floor disorders, according to results from a study of twin sisters.

In addition, women who do not have PMS but who have a first-degree relative with PMS may also be at increased risk for pelvic floor disorders, Dr. Sarit O. Aschkenazi said at the annual meeting of the AAGL.

The findings come from a cross-sectional survey of 362 premenopausal identical twin sisters who were recruited at the 2005–2006 Twins Day Annual Festival in Twinsburg, Ohio.

The women filled out two validated questionnaires. One, the 14-item Premenstrual Symptoms Screening Tool (PSST), identifies individuals with PMS and premenstrual dysphoric disorder (PMDD), and grades severity. The other, the short form of the Pelvic Floor Disorder Inventory (PFDI-20), comprises subscales for distress related to urinary, pelvic organ prolapse, and colorectal/anal symptoms.

Each subscale is scored from 0 (least distress) to 100 (greatest distress), yielding a 0–300 range of total score.

A total of 12% of the women met criteria for moderate to severe PMS/PMDD.

The patients had a mean age of 26 years and a mean body mass index of 23.4 kg/m

Ninety percent were white; 3%, black; 3%, Hispanic; and 4%, other ethnicities, noted Dr. Aschkenazi, a urogynecologist at Evanston (Ill.) Northwestern Hospital.

Compared with the 318 women who had no or mild PMS/PMDD, the 44 who had severe PMS or PMDD scored significantly higher on all three of the PFDI-20 distress subscales: 12.4 vs. 4.8 for pelvic organ prolapse, 10.2 vs. 2.9 for co-lorectal/anal, and 18.6 vs. 6.7 for urinary symptoms.

Scores for symptoms of pelvic pressure and dullness, incomplete bowel emptying, fecal urgency, and frequent urination/leakage were each significantly worse in the women with severe PMS/PMDD, compared with those without, she reported.

The mean total PDFI-20 scores were higher among the 28 women without severe PMS/PMDD whose twin did have PMS than they were among the 262 women whose twin did not have severe PMS/PMDD, reaching significance for the urinary symptom component (12.8 vs. 6.0).

This finding suggests that the PMS-free women whose twin sisters have PMS might be at increased risk for pelvic floor disorders because of genetic factors, she commented.

WASHINGTON — Women with premenstrual syndrome are at increased risk for pelvic floor disorders, according to results from a study of twin sisters.

In addition, women who do not have PMS but who have a first-degree relative with PMS may also be at increased risk for pelvic floor disorders, Dr. Sarit O. Aschkenazi said at the annual meeting of the AAGL.

The findings come from a cross-sectional survey of 362 premenopausal identical twin sisters who were recruited at the 2005–2006 Twins Day Annual Festival in Twinsburg, Ohio.

The women filled out two validated questionnaires. One, the 14-item Premenstrual Symptoms Screening Tool (PSST), identifies individuals with PMS and premenstrual dysphoric disorder (PMDD), and grades severity. The other, the short form of the Pelvic Floor Disorder Inventory (PFDI-20), comprises subscales for distress related to urinary, pelvic organ prolapse, and colorectal/anal symptoms.

Each subscale is scored from 0 (least distress) to 100 (greatest distress), yielding a 0–300 range of total score.

A total of 12% of the women met criteria for moderate to severe PMS/PMDD.

The patients had a mean age of 26 years and a mean body mass index of 23.4 kg/m

Ninety percent were white; 3%, black; 3%, Hispanic; and 4%, other ethnicities, noted Dr. Aschkenazi, a urogynecologist at Evanston (Ill.) Northwestern Hospital.

Compared with the 318 women who had no or mild PMS/PMDD, the 44 who had severe PMS or PMDD scored significantly higher on all three of the PFDI-20 distress subscales: 12.4 vs. 4.8 for pelvic organ prolapse, 10.2 vs. 2.9 for co-lorectal/anal, and 18.6 vs. 6.7 for urinary symptoms.

Scores for symptoms of pelvic pressure and dullness, incomplete bowel emptying, fecal urgency, and frequent urination/leakage were each significantly worse in the women with severe PMS/PMDD, compared with those without, she reported.

The mean total PDFI-20 scores were higher among the 28 women without severe PMS/PMDD whose twin did have PMS than they were among the 262 women whose twin did not have severe PMS/PMDD, reaching significance for the urinary symptom component (12.8 vs. 6.0).

This finding suggests that the PMS-free women whose twin sisters have PMS might be at increased risk for pelvic floor disorders because of genetic factors, she commented.

WASHINGTON — Women with premenstrual syndrome are at increased risk for pelvic floor disorders, according to results from a study of twin sisters.

In addition, women who do not have PMS but who have a first-degree relative with PMS may also be at increased risk for pelvic floor disorders, Dr. Sarit O. Aschkenazi said at the annual meeting of the AAGL.

The findings come from a cross-sectional survey of 362 premenopausal identical twin sisters who were recruited at the 2005–2006 Twins Day Annual Festival in Twinsburg, Ohio.

The women filled out two validated questionnaires. One, the 14-item Premenstrual Symptoms Screening Tool (PSST), identifies individuals with PMS and premenstrual dysphoric disorder (PMDD), and grades severity. The other, the short form of the Pelvic Floor Disorder Inventory (PFDI-20), comprises subscales for distress related to urinary, pelvic organ prolapse, and colorectal/anal symptoms.

Each subscale is scored from 0 (least distress) to 100 (greatest distress), yielding a 0–300 range of total score.

A total of 12% of the women met criteria for moderate to severe PMS/PMDD.

The patients had a mean age of 26 years and a mean body mass index of 23.4 kg/m

Ninety percent were white; 3%, black; 3%, Hispanic; and 4%, other ethnicities, noted Dr. Aschkenazi, a urogynecologist at Evanston (Ill.) Northwestern Hospital.

Compared with the 318 women who had no or mild PMS/PMDD, the 44 who had severe PMS or PMDD scored significantly higher on all three of the PFDI-20 distress subscales: 12.4 vs. 4.8 for pelvic organ prolapse, 10.2 vs. 2.9 for co-lorectal/anal, and 18.6 vs. 6.7 for urinary symptoms.

Scores for symptoms of pelvic pressure and dullness, incomplete bowel emptying, fecal urgency, and frequent urination/leakage were each significantly worse in the women with severe PMS/PMDD, compared with those without, she reported.

The mean total PDFI-20 scores were higher among the 28 women without severe PMS/PMDD whose twin did have PMS than they were among the 262 women whose twin did not have severe PMS/PMDD, reaching significance for the urinary symptom component (12.8 vs. 6.0).

This finding suggests that the PMS-free women whose twin sisters have PMS might be at increased risk for pelvic floor disorders because of genetic factors, she commented.

WASHINGTON — The constellation of symptoms characterizing endometriosis may be more specific than currently thought, Karen D. Ballard, Ph.D., said at the annual meeting of the AAGL.

There is often a long delay in the diagnosis of endometriosis, in large part because the symptoms—primarily pelvic pain and dysmenorrhea—are nonspecific and can overlap with other conditions. But now, a case-control study from a primary care database in the United Kingdom suggests that women with a combination of gynecologic, urologic, and bowel symptoms are likely to have the condition.

“Specific, unremitting symptoms should raise a high suspicion of endometriosis,” said Dr. Ballard of the University of Surrey, Guildford, England.

Data were collected from the General Practice Research Database, the largest computerized database in the world containing longitudinal medical records from primary care. It currently comprises more than 3 million active patients from about 450 primary care practices, the setting in which all nonemergency patients in the United Kingdom are first seen.

During 1992–2002, 5,540 cases of endometriosis were identified from a total of 1,276,100 women aged 15–55 years. The average age at diagnosis was 35 years. The incidence of diagnosed endometriosis was 0.97 per 1,000 women-years, and the prevalence—calculated from the incidence rate and the average disease duration—was 1.5%. This proportion is lower than what has been reported in the literature, probably because it comes from general medical practice rather than a gynecology-based setting, Dr. Ballard noted.

There were 21,239 matched controls. The women with endometriosis were significantly thinner, with 49.3% having a body mass index less than 25 kg/m

As expected, the women with endometriosis had high rates of pelvic pain (15.6%) and dysmenorrhea (24.6%). But somewhat surprising was how low those rates were in the controls—1.5% and 3.4%, respectively—suggesting that “these symptoms are actually more specific than previously acknowledged,” Dr. Ballard said.

Other menstrual/pain symptoms reported significantly more often by the endometriosis patients than the controls were dyspareunia (9% vs. 1%, respectively), abdominal pain (45% vs. 13%), menorrhagia (23% vs. 6%), and menstrual problems (27% vs. 13%).

Gastrointestinal symptoms were also more common in the endometriosis group than in the control group, including constipation (9.2% vs. 4.4%) and rectal bleeding (2.0% vs. 1.1%), as were the urologic symptoms cystitis (8.8% vs. 5.3%) and dysuria (6.1% vs. 2.7%). Postcoital bleeding was reported by 2.9% vs. 0.7% and backache by 16.4% vs. 11.0%. All of these differences were statistically significant.

Women with endometriosis were also significantly more likely than were controls to have been diagnosed with subfertility (9.6% vs. 1.8%). But less expected was an association with the diagnosis of irritable bowel syndrome: 10.6% vs. 3.3%. Other diagnoses reported significantly more often among the women with endometriosis were urinary tract infection (18.5% vs. 9.8%), pelvic inflammatory disease (10.3% vs. 1.8%), and ovarian cysts (6.8% vs. 0.6%).

Stepwise regression analysis showed that the five “key symptoms” most strongly associated with endometriosis were infertility or subfertility (adjusted odds ratio 8.2), dysmenorrhea (8.1), symptoms associated with sexual intercourse (6.8), abdominopelvic pain (5.2), and menorrhagia (4.0).

In all, 84% of those with endometriosis had at least one of those symptoms, compared with 23% of those without, Dr. Ballard said.

The data also suggest there is opportunity for intervention: Nearly all (98%) of the women who were ultimately diagnosed with endometriosis had made at least one visit to a physician in the year before the diagnosis, compared with 81% of the controls.

In fact, 62% had visited the physician at least six times in that year, compared with 27% of those not diagnosed with endometriosis, she reported.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The constellation of symptoms characterizing endometriosis may be more specific than currently thought, Karen D. Ballard, Ph.D., said at the annual meeting of the AAGL.

There is often a long delay in the diagnosis of endometriosis, in large part because the symptoms—primarily pelvic pain and dysmenorrhea—are nonspecific and can overlap with other conditions. But now, a case-control study from a primary care database in the United Kingdom suggests that women with a combination of gynecologic, urologic, and bowel symptoms are likely to have the condition.

“Specific, unremitting symptoms should raise a high suspicion of endometriosis,” said Dr. Ballard of the University of Surrey, Guildford, England.

Data were collected from the General Practice Research Database, the largest computerized database in the world containing longitudinal medical records from primary care. It currently comprises more than 3 million active patients from about 450 primary care practices, the setting in which all nonemergency patients in the United Kingdom are first seen.

During 1992–2002, 5,540 cases of endometriosis were identified from a total of 1,276,100 women aged 15–55 years. The average age at diagnosis was 35 years. The incidence of diagnosed endometriosis was 0.97 per 1,000 women-years, and the prevalence—calculated from the incidence rate and the average disease duration—was 1.5%. This proportion is lower than what has been reported in the literature, probably because it comes from general medical practice rather than a gynecology-based setting, Dr. Ballard noted.

There were 21,239 matched controls. The women with endometriosis were significantly thinner, with 49.3% having a body mass index less than 25 kg/m

As expected, the women with endometriosis had high rates of pelvic pain (15.6%) and dysmenorrhea (24.6%). But somewhat surprising was how low those rates were in the controls—1.5% and 3.4%, respectively—suggesting that “these symptoms are actually more specific than previously acknowledged,” Dr. Ballard said.

Other menstrual/pain symptoms reported significantly more often by the endometriosis patients than the controls were dyspareunia (9% vs. 1%, respectively), abdominal pain (45% vs. 13%), menorrhagia (23% vs. 6%), and menstrual problems (27% vs. 13%).

Gastrointestinal symptoms were also more common in the endometriosis group than in the control group, including constipation (9.2% vs. 4.4%) and rectal bleeding (2.0% vs. 1.1%), as were the urologic symptoms cystitis (8.8% vs. 5.3%) and dysuria (6.1% vs. 2.7%). Postcoital bleeding was reported by 2.9% vs. 0.7% and backache by 16.4% vs. 11.0%. All of these differences were statistically significant.

Women with endometriosis were also significantly more likely than were controls to have been diagnosed with subfertility (9.6% vs. 1.8%). But less expected was an association with the diagnosis of irritable bowel syndrome: 10.6% vs. 3.3%. Other diagnoses reported significantly more often among the women with endometriosis were urinary tract infection (18.5% vs. 9.8%), pelvic inflammatory disease (10.3% vs. 1.8%), and ovarian cysts (6.8% vs. 0.6%).

Stepwise regression analysis showed that the five “key symptoms” most strongly associated with endometriosis were infertility or subfertility (adjusted odds ratio 8.2), dysmenorrhea (8.1), symptoms associated with sexual intercourse (6.8), abdominopelvic pain (5.2), and menorrhagia (4.0).

In all, 84% of those with endometriosis had at least one of those symptoms, compared with 23% of those without, Dr. Ballard said.

The data also suggest there is opportunity for intervention: Nearly all (98%) of the women who were ultimately diagnosed with endometriosis had made at least one visit to a physician in the year before the diagnosis, compared with 81% of the controls.

In fact, 62% had visited the physician at least six times in that year, compared with 27% of those not diagnosed with endometriosis, she reported.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The constellation of symptoms characterizing endometriosis may be more specific than currently thought, Karen D. Ballard, Ph.D., said at the annual meeting of the AAGL.

There is often a long delay in the diagnosis of endometriosis, in large part because the symptoms—primarily pelvic pain and dysmenorrhea—are nonspecific and can overlap with other conditions. But now, a case-control study from a primary care database in the United Kingdom suggests that women with a combination of gynecologic, urologic, and bowel symptoms are likely to have the condition.

“Specific, unremitting symptoms should raise a high suspicion of endometriosis,” said Dr. Ballard of the University of Surrey, Guildford, England.

Data were collected from the General Practice Research Database, the largest computerized database in the world containing longitudinal medical records from primary care. It currently comprises more than 3 million active patients from about 450 primary care practices, the setting in which all nonemergency patients in the United Kingdom are first seen.

During 1992–2002, 5,540 cases of endometriosis were identified from a total of 1,276,100 women aged 15–55 years. The average age at diagnosis was 35 years. The incidence of diagnosed endometriosis was 0.97 per 1,000 women-years, and the prevalence—calculated from the incidence rate and the average disease duration—was 1.5%. This proportion is lower than what has been reported in the literature, probably because it comes from general medical practice rather than a gynecology-based setting, Dr. Ballard noted.

There were 21,239 matched controls. The women with endometriosis were significantly thinner, with 49.3% having a body mass index less than 25 kg/m

As expected, the women with endometriosis had high rates of pelvic pain (15.6%) and dysmenorrhea (24.6%). But somewhat surprising was how low those rates were in the controls—1.5% and 3.4%, respectively—suggesting that “these symptoms are actually more specific than previously acknowledged,” Dr. Ballard said.

Other menstrual/pain symptoms reported significantly more often by the endometriosis patients than the controls were dyspareunia (9% vs. 1%, respectively), abdominal pain (45% vs. 13%), menorrhagia (23% vs. 6%), and menstrual problems (27% vs. 13%).

Gastrointestinal symptoms were also more common in the endometriosis group than in the control group, including constipation (9.2% vs. 4.4%) and rectal bleeding (2.0% vs. 1.1%), as were the urologic symptoms cystitis (8.8% vs. 5.3%) and dysuria (6.1% vs. 2.7%). Postcoital bleeding was reported by 2.9% vs. 0.7% and backache by 16.4% vs. 11.0%. All of these differences were statistically significant.

Women with endometriosis were also significantly more likely than were controls to have been diagnosed with subfertility (9.6% vs. 1.8%). But less expected was an association with the diagnosis of irritable bowel syndrome: 10.6% vs. 3.3%. Other diagnoses reported significantly more often among the women with endometriosis were urinary tract infection (18.5% vs. 9.8%), pelvic inflammatory disease (10.3% vs. 1.8%), and ovarian cysts (6.8% vs. 0.6%).

Stepwise regression analysis showed that the five “key symptoms” most strongly associated with endometriosis were infertility or subfertility (adjusted odds ratio 8.2), dysmenorrhea (8.1), symptoms associated with sexual intercourse (6.8), abdominopelvic pain (5.2), and menorrhagia (4.0).

In all, 84% of those with endometriosis had at least one of those symptoms, compared with 23% of those without, Dr. Ballard said.

The data also suggest there is opportunity for intervention: Nearly all (98%) of the women who were ultimately diagnosed with endometriosis had made at least one visit to a physician in the year before the diagnosis, compared with 81% of the controls.

In fact, 62% had visited the physician at least six times in that year, compared with 27% of those not diagnosed with endometriosis, she reported.

ELSEVIER GLOBAL MEDICAL NEWS

Multiple lines of research are aimed at halting the immunologic cascade that leads to the development of type 1 diabetes.

In a press briefing with the 9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium, four speakers discussed ongoing research around the world involving the identification of individuals, primarily children, at risk for type 1 diabetes and efforts to halt the advance of autoimmune ?-cell destruction.

The briefing was sponsored by Type 1 Diabetes TrialNet, a group of studies looking at the development, prevention, and early treatment of type 1 diabetes, and jointly funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association.

TrialNet chairman Dr. Jay S. Skyler gave an overview of efforts to block type 1 diabetes.

Studies targeting individuals found to be at increased genetic risk for type 1 diabetes include the Trial to Reduce Insulin-Dependent Diabetes in the Genetically at Risk (TRIGR), comparing the role of hydrolyzed infant formula versus cow's milk-based formula in the development of the disease; the Nutritional Intervention to Prevent Diabetes (NIP) study, which looks at the role of omega-3 fatty acids; and the BABYDIET study investigating whether the delay of gluten introduction into the diet might prevent type 1 diabetes in high-risk infants.

At the stage of multiple antibody positivity, studies are looking at the potential impact of intervention with oral insulin, aerosolized intranasal insulin, and of a glutamic acid decarboxylase-aluminum vaccine. And at the time of new-onset diabetes, administration of mycophenolate mofetil, anti-CD20, thymoglobulin, and interleukin-2 plus sirolimus are among the compounds being looked at, said Dr. Skyler, professor of medicine, pediatrics, and psychology in the University of Miami's division of endocrinology, diabetes, and metabolism.

Dr. Olli Simell, a TrialNet principal investigator, described his work in Finland, where 1 in every 120 children develops type 1 diabetes, compared with 1 in 300 in the United States. Since 1994, the Diabetes Prediction and Prevention (DIPP) project has screened more than 100,000 newborns for type 1 diabetes susceptibility genes and identified more than 10,000 at-risk children. As of October 2007, 328 have been found to have at least two types of autoantibodies in at least two consecutive samples, and 181 of them have developed diabetes.

Thus far, DIPP has shown that although the age of diagnosis of diabetes is fairly evenly distributed throughout childhood, autoantibodies emerge before age 3 years in more than 90% of children who develop the disease. The study has also identified new serum markers that differentiate future progressors from nonprogressors by 1 year of age, said Dr. Simell, professor and chairman of pediatrics at the University of Turku (Finland), and chief physician in the department of pediatrics at Turku University Hospital.

Dr. Massimo Trucco, also a TrialNet principal investigator, outlined an ongoing randomized phase I study evaluating the safety of a diabetes-suppressive cell vaccine consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleo- tides targeting the primary transcripts of the CD40, CD80, and CD86 costimulatory molecules. Seven volunteers with type 1 diabetes are receiving autologous control dendritic cells; eight receive the immuno-regulatory dendritic cells. If all goes well in the safety trial, efficacy trials in new-onset type 1 patients could begin in the spring of 2008, said Dr. Trucco, director of the division of Immunogenetics at Children's Hospital of Pittsburgh and the Hillman Professor of Pediatric Immunology and professor of pediatrics at the University of Pittsburgh.

A third TrialNet principal investigator, Dr. Michael Haller, spoke of autologous stem cell transfusion as a possible means of reversing type 1 diabetes by restoring immune tolerance. In a pilot study of 21 children with type 1 diabetes (mean age 4.5 years), 8 who received cord blood had significantly lower insulin requirements (0.45 vs. 0.69 units/kg a day) and hemoglobin A_1c values (7.0% vs. 8.04%) than did 13 controls, with little or no decline in insulin production over 6 months. An increase in the number of regulatory T cells in the blood samples of subjects 6 months after the infusion may explain some of the benefits, said Dr. Haller, of the department of pediatrics at the University of Florida, Gainsville.

Multiple lines of research are aimed at halting the immunologic cascade that leads to the development of type 1 diabetes.

In a press briefing with the 9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium, four speakers discussed ongoing research around the world involving the identification of individuals, primarily children, at risk for type 1 diabetes and efforts to halt the advance of autoimmune ?-cell destruction.

The briefing was sponsored by Type 1 Diabetes TrialNet, a group of studies looking at the development, prevention, and early treatment of type 1 diabetes, and jointly funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association.

TrialNet chairman Dr. Jay S. Skyler gave an overview of efforts to block type 1 diabetes.

Studies targeting individuals found to be at increased genetic risk for type 1 diabetes include the Trial to Reduce Insulin-Dependent Diabetes in the Genetically at Risk (TRIGR), comparing the role of hydrolyzed infant formula versus cow's milk-based formula in the development of the disease; the Nutritional Intervention to Prevent Diabetes (NIP) study, which looks at the role of omega-3 fatty acids; and the BABYDIET study investigating whether the delay of gluten introduction into the diet might prevent type 1 diabetes in high-risk infants.

At the stage of multiple antibody positivity, studies are looking at the potential impact of intervention with oral insulin, aerosolized intranasal insulin, and of a glutamic acid decarboxylase-aluminum vaccine. And at the time of new-onset diabetes, administration of mycophenolate mofetil, anti-CD20, thymoglobulin, and interleukin-2 plus sirolimus are among the compounds being looked at, said Dr. Skyler, professor of medicine, pediatrics, and psychology in the University of Miami's division of endocrinology, diabetes, and metabolism.

Dr. Olli Simell, a TrialNet principal investigator, described his work in Finland, where 1 in every 120 children develops type 1 diabetes, compared with 1 in 300 in the United States. Since 1994, the Diabetes Prediction and Prevention (DIPP) project has screened more than 100,000 newborns for type 1 diabetes susceptibility genes and identified more than 10,000 at-risk children. As of October 2007, 328 have been found to have at least two types of autoantibodies in at least two consecutive samples, and 181 of them have developed diabetes.

Thus far, DIPP has shown that although the age of diagnosis of diabetes is fairly evenly distributed throughout childhood, autoantibodies emerge before age 3 years in more than 90% of children who develop the disease. The study has also identified new serum markers that differentiate future progressors from nonprogressors by 1 year of age, said Dr. Simell, professor and chairman of pediatrics at the University of Turku (Finland), and chief physician in the department of pediatrics at Turku University Hospital.

Dr. Massimo Trucco, also a TrialNet principal investigator, outlined an ongoing randomized phase I study evaluating the safety of a diabetes-suppressive cell vaccine consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleo- tides targeting the primary transcripts of the CD40, CD80, and CD86 costimulatory molecules. Seven volunteers with type 1 diabetes are receiving autologous control dendritic cells; eight receive the immuno-regulatory dendritic cells. If all goes well in the safety trial, efficacy trials in new-onset type 1 patients could begin in the spring of 2008, said Dr. Trucco, director of the division of Immunogenetics at Children's Hospital of Pittsburgh and the Hillman Professor of Pediatric Immunology and professor of pediatrics at the University of Pittsburgh.

A third TrialNet principal investigator, Dr. Michael Haller, spoke of autologous stem cell transfusion as a possible means of reversing type 1 diabetes by restoring immune tolerance. In a pilot study of 21 children with type 1 diabetes (mean age 4.5 years), 8 who received cord blood had significantly lower insulin requirements (0.45 vs. 0.69 units/kg a day) and hemoglobin A_1c values (7.0% vs. 8.04%) than did 13 controls, with little or no decline in insulin production over 6 months. An increase in the number of regulatory T cells in the blood samples of subjects 6 months after the infusion may explain some of the benefits, said Dr. Haller, of the department of pediatrics at the University of Florida, Gainsville.

Multiple lines of research are aimed at halting the immunologic cascade that leads to the development of type 1 diabetes.

In a press briefing with the 9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium, four speakers discussed ongoing research around the world involving the identification of individuals, primarily children, at risk for type 1 diabetes and efforts to halt the advance of autoimmune ?-cell destruction.

The briefing was sponsored by Type 1 Diabetes TrialNet, a group of studies looking at the development, prevention, and early treatment of type 1 diabetes, and jointly funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association.

TrialNet chairman Dr. Jay S. Skyler gave an overview of efforts to block type 1 diabetes.

Studies targeting individuals found to be at increased genetic risk for type 1 diabetes include the Trial to Reduce Insulin-Dependent Diabetes in the Genetically at Risk (TRIGR), comparing the role of hydrolyzed infant formula versus cow's milk-based formula in the development of the disease; the Nutritional Intervention to Prevent Diabetes (NIP) study, which looks at the role of omega-3 fatty acids; and the BABYDIET study investigating whether the delay of gluten introduction into the diet might prevent type 1 diabetes in high-risk infants.

At the stage of multiple antibody positivity, studies are looking at the potential impact of intervention with oral insulin, aerosolized intranasal insulin, and of a glutamic acid decarboxylase-aluminum vaccine. And at the time of new-onset diabetes, administration of mycophenolate mofetil, anti-CD20, thymoglobulin, and interleukin-2 plus sirolimus are among the compounds being looked at, said Dr. Skyler, professor of medicine, pediatrics, and psychology in the University of Miami's division of endocrinology, diabetes, and metabolism.

Dr. Olli Simell, a TrialNet principal investigator, described his work in Finland, where 1 in every 120 children develops type 1 diabetes, compared with 1 in 300 in the United States. Since 1994, the Diabetes Prediction and Prevention (DIPP) project has screened more than 100,000 newborns for type 1 diabetes susceptibility genes and identified more than 10,000 at-risk children. As of October 2007, 328 have been found to have at least two types of autoantibodies in at least two consecutive samples, and 181 of them have developed diabetes.

Thus far, DIPP has shown that although the age of diagnosis of diabetes is fairly evenly distributed throughout childhood, autoantibodies emerge before age 3 years in more than 90% of children who develop the disease. The study has also identified new serum markers that differentiate future progressors from nonprogressors by 1 year of age, said Dr. Simell, professor and chairman of pediatrics at the University of Turku (Finland), and chief physician in the department of pediatrics at Turku University Hospital.

Dr. Massimo Trucco, also a TrialNet principal investigator, outlined an ongoing randomized phase I study evaluating the safety of a diabetes-suppressive cell vaccine consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleo- tides targeting the primary transcripts of the CD40, CD80, and CD86 costimulatory molecules. Seven volunteers with type 1 diabetes are receiving autologous control dendritic cells; eight receive the immuno-regulatory dendritic cells. If all goes well in the safety trial, efficacy trials in new-onset type 1 patients could begin in the spring of 2008, said Dr. Trucco, director of the division of Immunogenetics at Children's Hospital of Pittsburgh and the Hillman Professor of Pediatric Immunology and professor of pediatrics at the University of Pittsburgh.

A third TrialNet principal investigator, Dr. Michael Haller, spoke of autologous stem cell transfusion as a possible means of reversing type 1 diabetes by restoring immune tolerance. In a pilot study of 21 children with type 1 diabetes (mean age 4.5 years), 8 who received cord blood had significantly lower insulin requirements (0.45 vs. 0.69 units/kg a day) and hemoglobin A_1c values (7.0% vs. 8.04%) than did 13 controls, with little or no decline in insulin production over 6 months. An increase in the number of regulatory T cells in the blood samples of subjects 6 months after the infusion may explain some of the benefits, said Dr. Haller, of the department of pediatrics at the University of Florida, Gainsville.