Miriam E. Tucker

MONTREAL — The age-adjusted prevalence of visual impairment among people with diabetes in the United States underwent a relative decline of more than 20% between 1997 and 2008, despite a sharp rise in the number of people diagnosed with the disease during that time.

The findings, calculated from National Health Interview Survey data, were presented in a poster by Dr. Nilka Rios Burrows at the World Diabetes Congress.

The number of adults aged 18 and older with both diabetes and visual impairment increased from 2.6 million in 1997 to 3.6 million in 2008. The prevalence of visual impairment was greater with increasing age, and was higher for women than men, said Dr. Burrows of the Centers for Disease Control and Prevention, Atlanta.

The prevalence of visual impairment declined steadily and significantly during the study period. The overall prevalence declined from 26% in 1997 to 22% in 2008, while the age-adjusted prevalence dropped from 24% to 19%, with an average annual relative decline of 2.7%.

The decline in visual impairment may be due in part to a improved detection and treatment of eye problems or better health in the diabetes population overall. However, the increase in the number of new diabetes cases since the 1990s may have led to a large number of people who have not had diabetes long enough to develop visual impairment, Dr. Burrows and her associates noted in the poster.

On a less positive note, only half of those surveyed reported having seen an eye doctor in 2008.

Dr. Burrows declared that she had no conflicts of interest.

MONTREAL — The age-adjusted prevalence of visual impairment among people with diabetes in the United States underwent a relative decline of more than 20% between 1997 and 2008, despite a sharp rise in the number of people diagnosed with the disease during that time.

The findings, calculated from National Health Interview Survey data, were presented in a poster by Dr. Nilka Rios Burrows at the World Diabetes Congress.

The number of adults aged 18 and older with both diabetes and visual impairment increased from 2.6 million in 1997 to 3.6 million in 2008. The prevalence of visual impairment was greater with increasing age, and was higher for women than men, said Dr. Burrows of the Centers for Disease Control and Prevention, Atlanta.

The prevalence of visual impairment declined steadily and significantly during the study period. The overall prevalence declined from 26% in 1997 to 22% in 2008, while the age-adjusted prevalence dropped from 24% to 19%, with an average annual relative decline of 2.7%.

The decline in visual impairment may be due in part to a improved detection and treatment of eye problems or better health in the diabetes population overall. However, the increase in the number of new diabetes cases since the 1990s may have led to a large number of people who have not had diabetes long enough to develop visual impairment, Dr. Burrows and her associates noted in the poster.

On a less positive note, only half of those surveyed reported having seen an eye doctor in 2008.

Dr. Burrows declared that she had no conflicts of interest.

MONTREAL — The age-adjusted prevalence of visual impairment among people with diabetes in the United States underwent a relative decline of more than 20% between 1997 and 2008, despite a sharp rise in the number of people diagnosed with the disease during that time.

The findings, calculated from National Health Interview Survey data, were presented in a poster by Dr. Nilka Rios Burrows at the World Diabetes Congress.

The number of adults aged 18 and older with both diabetes and visual impairment increased from 2.6 million in 1997 to 3.6 million in 2008. The prevalence of visual impairment was greater with increasing age, and was higher for women than men, said Dr. Burrows of the Centers for Disease Control and Prevention, Atlanta.

The prevalence of visual impairment declined steadily and significantly during the study period. The overall prevalence declined from 26% in 1997 to 22% in 2008, while the age-adjusted prevalence dropped from 24% to 19%, with an average annual relative decline of 2.7%.

The decline in visual impairment may be due in part to a improved detection and treatment of eye problems or better health in the diabetes population overall. However, the increase in the number of new diabetes cases since the 1990s may have led to a large number of people who have not had diabetes long enough to develop visual impairment, Dr. Burrows and her associates noted in the poster.

On a less positive note, only half of those surveyed reported having seen an eye doctor in 2008.

Dr. Burrows declared that she had no conflicts of interest.

VIENNA — Glycemic control was maintained over 5 years using metformin, sulfonylureas, and insulin almost exclusively in a longitudinal study of cholesterol lowering in 4,900 patients with type 2 diabetes.

The findings call into question the need for new diabetes drugs, especially now that increased emphasis is being placed on the safety of these agents, Dr. James Best said at the annual meeting of the European Association for the Study of Diabetes.

The finding comes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, which investigated whether fenofibrate could reduce the risk of cardiovascular disease in patients with type 2 diabetes in Finland, Australia, and New Zealand (Lancet 2005;366:1849-61). FIELD failed in its primary end point, but because its design did not involve modifying any aspect of glycemic management, it offered a real-world opportunity to see what happened over time with standard care for diabetes, mainly in primary care settings.

The results suggest that diabetes control can be effectively maintained using the three oldest and least expensive classes of diabetes drugs, and challenges the prevailing belief that new types of glucose-lowering drugs are needed. “There's this background subtext that diabetes control inexorably deteriorates despite optimal therapy and therefore we need to find new drugs to treat this disease. My message is that we don't,” Dr. Best, professor of medicine and head of the school of medicine at the University of Melbourne, said in an interview.

At baseline, the study population had a mean age of 62 years and diabetes duration of 5 years. Just over a third were women. They were reasonably well controlled at baseline, with a median hemoglobin A_1c of 6.9%, even though 26% were on no diabetes medications, 60% were on oral agents only, and just 14% were using insulin. Median body weight was 86.3 kg.

Over the subsequent 5 years, the median HbA_1c rose slightly (0.22 percentage points), to just over 7.0%, while body weight fell slightly, to 85.0 kg. Oral hypoglycemic medication—nearly all metformin, sulfonylureas, or both—was initiated in 56% of the 1,287 who had been taking no medications at baseline, and insulin was started in 25% of the 2,917 who had not been taking it at baseline. Thus, at 5 years, 77% of patients were on oral agents and 28% were on insulin, but only 4% were on oral agents other than sulfonylureas or metformin, Dr. Best reported.

The 0.22 percentage-point increase in HbA_1c seen in FIELD is in contrast to the 1.0 percentage-point rise that occurred in the landmark U.K. Prospective Diabetes Study (UKPDS), which is often cited as evidence for the inevitable decline in glucose control in patients with type 2 diabetes (Lancet 1998;352:837-53).

The findings support the new emphasis on cardiovascular safety that regulatory bodies are now imposing on all glucose-lowering drugs, following reports of adverse cardiovascular outcomes with the thiazolidinedione (TZD) rosiglitazone, Dr. Best said.

“I see much less urgency for new therapies. We need safety outcomes for new treatments, rather than just efficacy. The TZDs are a good example. They got to market before there was really safety data, on the grounds that glycemic control deteriorates with standard treatment and therefore we needed them. Now that we've seen the safety outcomes, their use should be much more limited than was thought initially.”

Dr. Best stated that he did not have any relevant financial disclosures.

VIENNA — Glycemic control was maintained over 5 years using metformin, sulfonylureas, and insulin almost exclusively in a longitudinal study of cholesterol lowering in 4,900 patients with type 2 diabetes.

The findings call into question the need for new diabetes drugs, especially now that increased emphasis is being placed on the safety of these agents, Dr. James Best said at the annual meeting of the European Association for the Study of Diabetes.

The finding comes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, which investigated whether fenofibrate could reduce the risk of cardiovascular disease in patients with type 2 diabetes in Finland, Australia, and New Zealand (Lancet 2005;366:1849-61). FIELD failed in its primary end point, but because its design did not involve modifying any aspect of glycemic management, it offered a real-world opportunity to see what happened over time with standard care for diabetes, mainly in primary care settings.

The results suggest that diabetes control can be effectively maintained using the three oldest and least expensive classes of diabetes drugs, and challenges the prevailing belief that new types of glucose-lowering drugs are needed. “There's this background subtext that diabetes control inexorably deteriorates despite optimal therapy and therefore we need to find new drugs to treat this disease. My message is that we don't,” Dr. Best, professor of medicine and head of the school of medicine at the University of Melbourne, said in an interview.

At baseline, the study population had a mean age of 62 years and diabetes duration of 5 years. Just over a third were women. They were reasonably well controlled at baseline, with a median hemoglobin A_1c of 6.9%, even though 26% were on no diabetes medications, 60% were on oral agents only, and just 14% were using insulin. Median body weight was 86.3 kg.

Over the subsequent 5 years, the median HbA_1c rose slightly (0.22 percentage points), to just over 7.0%, while body weight fell slightly, to 85.0 kg. Oral hypoglycemic medication—nearly all metformin, sulfonylureas, or both—was initiated in 56% of the 1,287 who had been taking no medications at baseline, and insulin was started in 25% of the 2,917 who had not been taking it at baseline. Thus, at 5 years, 77% of patients were on oral agents and 28% were on insulin, but only 4% were on oral agents other than sulfonylureas or metformin, Dr. Best reported.

The 0.22 percentage-point increase in HbA_1c seen in FIELD is in contrast to the 1.0 percentage-point rise that occurred in the landmark U.K. Prospective Diabetes Study (UKPDS), which is often cited as evidence for the inevitable decline in glucose control in patients with type 2 diabetes (Lancet 1998;352:837-53).

The findings support the new emphasis on cardiovascular safety that regulatory bodies are now imposing on all glucose-lowering drugs, following reports of adverse cardiovascular outcomes with the thiazolidinedione (TZD) rosiglitazone, Dr. Best said.

“I see much less urgency for new therapies. We need safety outcomes for new treatments, rather than just efficacy. The TZDs are a good example. They got to market before there was really safety data, on the grounds that glycemic control deteriorates with standard treatment and therefore we needed them. Now that we've seen the safety outcomes, their use should be much more limited than was thought initially.”

Dr. Best stated that he did not have any relevant financial disclosures.

VIENNA — Glycemic control was maintained over 5 years using metformin, sulfonylureas, and insulin almost exclusively in a longitudinal study of cholesterol lowering in 4,900 patients with type 2 diabetes.

The findings call into question the need for new diabetes drugs, especially now that increased emphasis is being placed on the safety of these agents, Dr. James Best said at the annual meeting of the European Association for the Study of Diabetes.

The finding comes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, which investigated whether fenofibrate could reduce the risk of cardiovascular disease in patients with type 2 diabetes in Finland, Australia, and New Zealand (Lancet 2005;366:1849-61). FIELD failed in its primary end point, but because its design did not involve modifying any aspect of glycemic management, it offered a real-world opportunity to see what happened over time with standard care for diabetes, mainly in primary care settings.

The results suggest that diabetes control can be effectively maintained using the three oldest and least expensive classes of diabetes drugs, and challenges the prevailing belief that new types of glucose-lowering drugs are needed. “There's this background subtext that diabetes control inexorably deteriorates despite optimal therapy and therefore we need to find new drugs to treat this disease. My message is that we don't,” Dr. Best, professor of medicine and head of the school of medicine at the University of Melbourne, said in an interview.

At baseline, the study population had a mean age of 62 years and diabetes duration of 5 years. Just over a third were women. They were reasonably well controlled at baseline, with a median hemoglobin A_1c of 6.9%, even though 26% were on no diabetes medications, 60% were on oral agents only, and just 14% were using insulin. Median body weight was 86.3 kg.

Over the subsequent 5 years, the median HbA_1c rose slightly (0.22 percentage points), to just over 7.0%, while body weight fell slightly, to 85.0 kg. Oral hypoglycemic medication—nearly all metformin, sulfonylureas, or both—was initiated in 56% of the 1,287 who had been taking no medications at baseline, and insulin was started in 25% of the 2,917 who had not been taking it at baseline. Thus, at 5 years, 77% of patients were on oral agents and 28% were on insulin, but only 4% were on oral agents other than sulfonylureas or metformin, Dr. Best reported.

The 0.22 percentage-point increase in HbA_1c seen in FIELD is in contrast to the 1.0 percentage-point rise that occurred in the landmark U.K. Prospective Diabetes Study (UKPDS), which is often cited as evidence for the inevitable decline in glucose control in patients with type 2 diabetes (Lancet 1998;352:837-53).

The findings support the new emphasis on cardiovascular safety that regulatory bodies are now imposing on all glucose-lowering drugs, following reports of adverse cardiovascular outcomes with the thiazolidinedione (TZD) rosiglitazone, Dr. Best said.

“I see much less urgency for new therapies. We need safety outcomes for new treatments, rather than just efficacy. The TZDs are a good example. They got to market before there was really safety data, on the grounds that glycemic control deteriorates with standard treatment and therefore we needed them. Now that we've seen the safety outcomes, their use should be much more limited than was thought initially.”

Dr. Best stated that he did not have any relevant financial disclosures.

A new one-page treatment algorithm for type 2 diabetes from the American Association of Clinical Endocrinologists is aimed at assisting physicians in choosing appropriate therapy from among all the approved classes of glucose-lowering medications.

The algorithm stratifies treatment based on hemoglobin A_1c values, with separate treatment pathways for patients with levels of 6.5%-7.5%, 7.6%-9.0%, and greater than 9.0% (Endocrine Practice 2009;15:541-59).

In general, patients with HbA_1c values of 7.5% or lower can start with monotherapy, with metformin considered the “cornerstone” but with three other drug classes included as alternatives. Patients with values of 7.6%-9.0% typically require dual therapy. The algorithm advises insulin for patients with values higher than 9% who already are receiving other treatments or who are drug-naive and symptomatic. For patients with levels higher than 9% who are drug-naive but asymptomatic, dual or triple combination therapies can be used.

“This is an authoritative, up-to-date, practical, and simple algorithm which should provide meaningful guidance to physicians as they make their therapeutic decisions,” said Dr. Helena W. Rodbard, cochair of the consensus panel that developed the algorithm, which is officially a publication of both AACE and its educational branch, the American College of Endocrinology (ACE).

“It's an easily readable clinical point-of-care tool designed to assist endocrinologists, primary care physicians, and others involved in the care of patients with type 2 diabetes,” said Dr. Paul S. Jellinger, panel cochair who, like Dr. Rodbard, is a former president of both AACE and ACE.

Both Dr. Jellinger and Dr. Rodbard emphasized that the algorithm—written by a panel of 14 practicing endocrinologists—accurately represents the way a majority of experienced endocrinologists approach the treatment of type 2 diabetes.

In contrast to a recently revised algorithm from the American Diabetes Association and the European Association for the Study of Diabetes (Diabetes Care 2009;32:193-203), the AACE/ACE algorithm fully incorporates all classes of drugs approved to treat type 2 diabetes and places less emphasis on the drug costs.

“Most previous algorithms placed an undue emphasis on the cost of medications. Drugs can be expensive, but the cost of medications is only about 11% of the total cost of care of the population with diabetes. We need to consider the total cost of care, which is overwhelmingly driven by the cost of complications,” said Dr. Rodbard, an endocrinologist in Rockville, Md.

Dr. Jellinger, who practices endocrinology in Hollywood, Fla., added: “We placed a big emphasis on safety, particularly in terms of hypoglycemia. We included GLP-1 mimetics, DPP4 inhibitors and TZDs, along with metformin, since those classes have no potential for hypoglycemia. At the same time, we have downgraded the use of sulfonylureas due to their increased risk for hypoglycemia. By avoiding hypoglycemia, you avoid hospitalizations, which are far more expensive than the medicine.”

But Dr. David M. Nathan, chair of the ADA/EASD consensus panel, said he doesn't believe it makes sense to include the additional agents as alternatives to metformin for first-line therapy or to list so many drug classes at every level. “The ADA/EASD guidelines were specifically formulated to help busy nonspecialists make informed choices from the large number of treatments that have become available in the last decade. With that in mind, the ADA/EASD consensus committee tried to narrow the choices based on effectiveness, safety, tolerability, acceptability, and cost.”

In contrast, “AACE has taken a different tack and included all approved medications. Their more complex algorithm offers more choices but, in our opinion, doesn't help the busy clinician make the best choices,” said Dr. Nathan, professor of medicine at Harvard University and director of the diabetes center at Massachusetts General Hospital, Boston.

“The TZD, DPP-4, and AGI they recommend are manyfold more expensive than metformin, have far less clinical experience than with metformin, are no safer—and probably less safe for TZD—and have the same frequency or far more side effects,” he added.

Accompanying the AACE algorithm is a text document that explains the rationale for each treatment option and other issues, which include the following:

▸ Lifestyle (diet and exercise) modifications are essential for all patients with diabetes, but delaying pharmacotherapy to allow for lifestyle modifications to take effect is likely to be inadequate. Counseling regarding lifestyle changes should be initiated along with diabetes self-management education and medications.

▸ Achieving an HbA_1c of 6.5% is the primary goal, but this goal must be individualized based on factors such as comorbid conditions, hypoglycemia history, and life expectancy.

▸ Effectiveness of therapy must be evaluated frequently, typically every 2-3 months.

▸ Safety and efficacy should be given greater priority than cost of medications because the cost of drugs is only a small part of the total cost of diabetes care.

▸ Rapid-acting insulin analogs are a better alternative to “regular human insulin.” Similarly, long-acting synthetic analogs glargine and insulin detemir yield better reproducibility and consistency as basal insulins than does NPH, which is not recommended.

Also included is a one-page summary of the major risks and benefits of each of the classes of drugs, described further in an appendix.

Dr. Rodbard has received consultant honoraria, speakers honoraria, and research grant support from several pharmaceutical companies. Dr. Jellinger has received consultant and speaker honoraria from several pharmaceutical companies. Dr. Nathan has received a research grant and support for educational programs from two pharmaceutical companies.

The diabetes care algorithm can be accessed at www.aace.com/pub/pdf/GlycemicControlAlgorithmPPT.pdf

'This is an authoritative, up-to-date, practical, and simple algorithm.'

Source DR. RODBARD

'Their more complex algorithm … doesn't help the busy clinician make the best choices.'

Source DR. NATHAN

A new one-page treatment algorithm for type 2 diabetes from the American Association of Clinical Endocrinologists is aimed at assisting physicians in choosing appropriate therapy from among all the approved classes of glucose-lowering medications.

The algorithm stratifies treatment based on hemoglobin A_1c values, with separate treatment pathways for patients with levels of 6.5%-7.5%, 7.6%-9.0%, and greater than 9.0% (Endocrine Practice 2009;15:541-59).

In general, patients with HbA_1c values of 7.5% or lower can start with monotherapy, with metformin considered the “cornerstone” but with three other drug classes included as alternatives. Patients with values of 7.6%-9.0% typically require dual therapy. The algorithm advises insulin for patients with values higher than 9% who already are receiving other treatments or who are drug-naive and symptomatic. For patients with levels higher than 9% who are drug-naive but asymptomatic, dual or triple combination therapies can be used.

“This is an authoritative, up-to-date, practical, and simple algorithm which should provide meaningful guidance to physicians as they make their therapeutic decisions,” said Dr. Helena W. Rodbard, cochair of the consensus panel that developed the algorithm, which is officially a publication of both AACE and its educational branch, the American College of Endocrinology (ACE).

“It's an easily readable clinical point-of-care tool designed to assist endocrinologists, primary care physicians, and others involved in the care of patients with type 2 diabetes,” said Dr. Paul S. Jellinger, panel cochair who, like Dr. Rodbard, is a former president of both AACE and ACE.

Both Dr. Jellinger and Dr. Rodbard emphasized that the algorithm—written by a panel of 14 practicing endocrinologists—accurately represents the way a majority of experienced endocrinologists approach the treatment of type 2 diabetes.

In contrast to a recently revised algorithm from the American Diabetes Association and the European Association for the Study of Diabetes (Diabetes Care 2009;32:193-203), the AACE/ACE algorithm fully incorporates all classes of drugs approved to treat type 2 diabetes and places less emphasis on the drug costs.

“Most previous algorithms placed an undue emphasis on the cost of medications. Drugs can be expensive, but the cost of medications is only about 11% of the total cost of care of the population with diabetes. We need to consider the total cost of care, which is overwhelmingly driven by the cost of complications,” said Dr. Rodbard, an endocrinologist in Rockville, Md.

Dr. Jellinger, who practices endocrinology in Hollywood, Fla., added: “We placed a big emphasis on safety, particularly in terms of hypoglycemia. We included GLP-1 mimetics, DPP4 inhibitors and TZDs, along with metformin, since those classes have no potential for hypoglycemia. At the same time, we have downgraded the use of sulfonylureas due to their increased risk for hypoglycemia. By avoiding hypoglycemia, you avoid hospitalizations, which are far more expensive than the medicine.”

But Dr. David M. Nathan, chair of the ADA/EASD consensus panel, said he doesn't believe it makes sense to include the additional agents as alternatives to metformin for first-line therapy or to list so many drug classes at every level. “The ADA/EASD guidelines were specifically formulated to help busy nonspecialists make informed choices from the large number of treatments that have become available in the last decade. With that in mind, the ADA/EASD consensus committee tried to narrow the choices based on effectiveness, safety, tolerability, acceptability, and cost.”

In contrast, “AACE has taken a different tack and included all approved medications. Their more complex algorithm offers more choices but, in our opinion, doesn't help the busy clinician make the best choices,” said Dr. Nathan, professor of medicine at Harvard University and director of the diabetes center at Massachusetts General Hospital, Boston.

“The TZD, DPP-4, and AGI they recommend are manyfold more expensive than metformin, have far less clinical experience than with metformin, are no safer—and probably less safe for TZD—and have the same frequency or far more side effects,” he added.

Accompanying the AACE algorithm is a text document that explains the rationale for each treatment option and other issues, which include the following:

▸ Lifestyle (diet and exercise) modifications are essential for all patients with diabetes, but delaying pharmacotherapy to allow for lifestyle modifications to take effect is likely to be inadequate. Counseling regarding lifestyle changes should be initiated along with diabetes self-management education and medications.

▸ Achieving an HbA_1c of 6.5% is the primary goal, but this goal must be individualized based on factors such as comorbid conditions, hypoglycemia history, and life expectancy.

▸ Effectiveness of therapy must be evaluated frequently, typically every 2-3 months.

▸ Safety and efficacy should be given greater priority than cost of medications because the cost of drugs is only a small part of the total cost of diabetes care.

▸ Rapid-acting insulin analogs are a better alternative to “regular human insulin.” Similarly, long-acting synthetic analogs glargine and insulin detemir yield better reproducibility and consistency as basal insulins than does NPH, which is not recommended.

Also included is a one-page summary of the major risks and benefits of each of the classes of drugs, described further in an appendix.

Dr. Rodbard has received consultant honoraria, speakers honoraria, and research grant support from several pharmaceutical companies. Dr. Jellinger has received consultant and speaker honoraria from several pharmaceutical companies. Dr. Nathan has received a research grant and support for educational programs from two pharmaceutical companies.

The diabetes care algorithm can be accessed at www.aace.com/pub/pdf/GlycemicControlAlgorithmPPT.pdf

'This is an authoritative, up-to-date, practical, and simple algorithm.'

Source DR. RODBARD

'Their more complex algorithm … doesn't help the busy clinician make the best choices.'

Source DR. NATHAN

A new one-page treatment algorithm for type 2 diabetes from the American Association of Clinical Endocrinologists is aimed at assisting physicians in choosing appropriate therapy from among all the approved classes of glucose-lowering medications.

The algorithm stratifies treatment based on hemoglobin A_1c values, with separate treatment pathways for patients with levels of 6.5%-7.5%, 7.6%-9.0%, and greater than 9.0% (Endocrine Practice 2009;15:541-59).

In general, patients with HbA_1c values of 7.5% or lower can start with monotherapy, with metformin considered the “cornerstone” but with three other drug classes included as alternatives. Patients with values of 7.6%-9.0% typically require dual therapy. The algorithm advises insulin for patients with values higher than 9% who already are receiving other treatments or who are drug-naive and symptomatic. For patients with levels higher than 9% who are drug-naive but asymptomatic, dual or triple combination therapies can be used.

“This is an authoritative, up-to-date, practical, and simple algorithm which should provide meaningful guidance to physicians as they make their therapeutic decisions,” said Dr. Helena W. Rodbard, cochair of the consensus panel that developed the algorithm, which is officially a publication of both AACE and its educational branch, the American College of Endocrinology (ACE).

“It's an easily readable clinical point-of-care tool designed to assist endocrinologists, primary care physicians, and others involved in the care of patients with type 2 diabetes,” said Dr. Paul S. Jellinger, panel cochair who, like Dr. Rodbard, is a former president of both AACE and ACE.

Both Dr. Jellinger and Dr. Rodbard emphasized that the algorithm—written by a panel of 14 practicing endocrinologists—accurately represents the way a majority of experienced endocrinologists approach the treatment of type 2 diabetes.

In contrast to a recently revised algorithm from the American Diabetes Association and the European Association for the Study of Diabetes (Diabetes Care 2009;32:193-203), the AACE/ACE algorithm fully incorporates all classes of drugs approved to treat type 2 diabetes and places less emphasis on the drug costs.

“Most previous algorithms placed an undue emphasis on the cost of medications. Drugs can be expensive, but the cost of medications is only about 11% of the total cost of care of the population with diabetes. We need to consider the total cost of care, which is overwhelmingly driven by the cost of complications,” said Dr. Rodbard, an endocrinologist in Rockville, Md.

Dr. Jellinger, who practices endocrinology in Hollywood, Fla., added: “We placed a big emphasis on safety, particularly in terms of hypoglycemia. We included GLP-1 mimetics, DPP4 inhibitors and TZDs, along with metformin, since those classes have no potential for hypoglycemia. At the same time, we have downgraded the use of sulfonylureas due to their increased risk for hypoglycemia. By avoiding hypoglycemia, you avoid hospitalizations, which are far more expensive than the medicine.”

But Dr. David M. Nathan, chair of the ADA/EASD consensus panel, said he doesn't believe it makes sense to include the additional agents as alternatives to metformin for first-line therapy or to list so many drug classes at every level. “The ADA/EASD guidelines were specifically formulated to help busy nonspecialists make informed choices from the large number of treatments that have become available in the last decade. With that in mind, the ADA/EASD consensus committee tried to narrow the choices based on effectiveness, safety, tolerability, acceptability, and cost.”

In contrast, “AACE has taken a different tack and included all approved medications. Their more complex algorithm offers more choices but, in our opinion, doesn't help the busy clinician make the best choices,” said Dr. Nathan, professor of medicine at Harvard University and director of the diabetes center at Massachusetts General Hospital, Boston.

“The TZD, DPP-4, and AGI they recommend are manyfold more expensive than metformin, have far less clinical experience than with metformin, are no safer—and probably less safe for TZD—and have the same frequency or far more side effects,” he added.

Accompanying the AACE algorithm is a text document that explains the rationale for each treatment option and other issues, which include the following:

▸ Lifestyle (diet and exercise) modifications are essential for all patients with diabetes, but delaying pharmacotherapy to allow for lifestyle modifications to take effect is likely to be inadequate. Counseling regarding lifestyle changes should be initiated along with diabetes self-management education and medications.

▸ Achieving an HbA_1c of 6.5% is the primary goal, but this goal must be individualized based on factors such as comorbid conditions, hypoglycemia history, and life expectancy.

▸ Effectiveness of therapy must be evaluated frequently, typically every 2-3 months.

▸ Safety and efficacy should be given greater priority than cost of medications because the cost of drugs is only a small part of the total cost of diabetes care.

▸ Rapid-acting insulin analogs are a better alternative to “regular human insulin.” Similarly, long-acting synthetic analogs glargine and insulin detemir yield better reproducibility and consistency as basal insulins than does NPH, which is not recommended.

Also included is a one-page summary of the major risks and benefits of each of the classes of drugs, described further in an appendix.

Dr. Rodbard has received consultant honoraria, speakers honoraria, and research grant support from several pharmaceutical companies. Dr. Jellinger has received consultant and speaker honoraria from several pharmaceutical companies. Dr. Nathan has received a research grant and support for educational programs from two pharmaceutical companies.

The diabetes care algorithm can be accessed at www.aace.com/pub/pdf/GlycemicControlAlgorithmPPT.pdf

'This is an authoritative, up-to-date, practical, and simple algorithm.'

Source DR. RODBARD

'Their more complex algorithm … doesn't help the busy clinician make the best choices.'

Source DR. NATHAN

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

While magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose polycystic ovary syndrome (PCOS), Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology-internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years, a mean body mass index of 31.5 kg/m

They underwent TAUS that was read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (body mass index greater than 30), 12 overweight (BMI of 25–29.9), and 9 lean (less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, vs. 66 nmol/L in the lean group). They also had greater insulin resistance, as measured by the homeostasis assessment model (5.1 and 3.3, vs. 2.0 in the lean group).

Total testosterone levels were not statistically different between the three BMI groups. Everyone in the lean group had at least one enlarged ovary, as did slightly over half of the overweight and obese groups. Bilateral ovarian enlargement was present in 33%–44% of the girls in each group.

In an interview, Dr. Flannery said that most of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance. Examination of ovarian morphology provides another tool for diagnosis, she said.

Dr. Flannery stated that neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

While magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose polycystic ovary syndrome (PCOS), Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology-internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years, a mean body mass index of 31.5 kg/m

They underwent TAUS that was read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (body mass index greater than 30), 12 overweight (BMI of 25–29.9), and 9 lean (less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, vs. 66 nmol/L in the lean group). They also had greater insulin resistance, as measured by the homeostasis assessment model (5.1 and 3.3, vs. 2.0 in the lean group).

Total testosterone levels were not statistically different between the three BMI groups. Everyone in the lean group had at least one enlarged ovary, as did slightly over half of the overweight and obese groups. Bilateral ovarian enlargement was present in 33%–44% of the girls in each group.

In an interview, Dr. Flannery said that most of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance. Examination of ovarian morphology provides another tool for diagnosis, she said.

Dr. Flannery stated that neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

While magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose polycystic ovary syndrome (PCOS), Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology-internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years, a mean body mass index of 31.5 kg/m

They underwent TAUS that was read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (body mass index greater than 30), 12 overweight (BMI of 25–29.9), and 9 lean (less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, vs. 66 nmol/L in the lean group). They also had greater insulin resistance, as measured by the homeostasis assessment model (5.1 and 3.3, vs. 2.0 in the lean group).

Total testosterone levels were not statistically different between the three BMI groups. Everyone in the lean group had at least one enlarged ovary, as did slightly over half of the overweight and obese groups. Bilateral ovarian enlargement was present in 33%–44% of the girls in each group.

In an interview, Dr. Flannery said that most of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance. Examination of ovarian morphology provides another tool for diagnosis, she said.

Dr. Flannery stated that neither she nor Dr. Burgert had any financial disclosures.

VIENNA — Ranibizumab treatment was associated with continuous improvement in best-corrected visual acuity and central retinal thickness over 12 months in a randomized, placebo-controlled study of 151 patients with diabetic macular edema.

The multicenter RESOLVE (Safety and Efficacy of Ranibizumab in Diabetic Macular Edema With Center Involvement) study randomized 51 patients to 6 mg/mL and 51 patients to 10 mg/mL of ranibizumab per intravitreal injection, and 49 patients to sham injections, Dr. Katrin Engelmann said at the annual meeting of the European Association for the Study of Diabetes.

Patients were given three initial monthly injections followed by retreatment based on predefined success or safety criteria. After the first month, the injection volume was doubled if central retinal thickness was greater than 300 mcm or was greater than 225 mcm and the reduction in edema from the previous treatment was less than 50 mcm. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) were assessed monthly.

Injection volume was doubled in 65% of the ranibizumab patients (both dose groups combined), compared with 92% of the sham injection group. Rescue laser photocoagulation treatment was required in 9% of the ranibizumab group, compared with 33% of the sham treatment group.

The proportion of patients who gained visual acuity from baseline to month 12 was 90% with ranibizumab, compared with 55% who received sham injections.

The mean BCVA increased and mean OCT decreased continuously over time in the ranibizumab patients. From baseline to month 12 there was a mean gain of 11.8 letters in the 6-mg/mL ranibizumab group, and 8.8 letters with the 10-mg/mL group (a pooled mean gain of 10.3 letters), compared with a loss of 1.4 letters in the sham treatment group, said Dr. Engelmann, of Klinikum Chemnitz GmbH, Saxony, Germany.

The most frequent ocular adverse events were conjunctival hemorrhage (14% sham, 23% ranibizumab) and eye pain (20% and 18%). Serious ocular adverse events occurred in one sham patient and in four ranibizumab patients. Nonocular arterial thromboembolic events occurred in two sham and three ranibizumab (10 mg/mL) patients.

Overall, the profile of ranibizumab in diabetic macular edema as seen in this study was similar to that found in previous randomized controlled studies trials of patients with neovascular age-related macular degeneration, she noted.

Ranibizumab (Lucentis) is marketed in Europe by Novartis and in the United States by Genentech for the treatment of patients with wet age-related macular degeneration. Novartis funded the RESOLVE study.

VIENNA — Ranibizumab treatment was associated with continuous improvement in best-corrected visual acuity and central retinal thickness over 12 months in a randomized, placebo-controlled study of 151 patients with diabetic macular edema.

The multicenter RESOLVE (Safety and Efficacy of Ranibizumab in Diabetic Macular Edema With Center Involvement) study randomized 51 patients to 6 mg/mL and 51 patients to 10 mg/mL of ranibizumab per intravitreal injection, and 49 patients to sham injections, Dr. Katrin Engelmann said at the annual meeting of the European Association for the Study of Diabetes.

Patients were given three initial monthly injections followed by retreatment based on predefined success or safety criteria. After the first month, the injection volume was doubled if central retinal thickness was greater than 300 mcm or was greater than 225 mcm and the reduction in edema from the previous treatment was less than 50 mcm. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) were assessed monthly.

Injection volume was doubled in 65% of the ranibizumab patients (both dose groups combined), compared with 92% of the sham injection group. Rescue laser photocoagulation treatment was required in 9% of the ranibizumab group, compared with 33% of the sham treatment group.

The proportion of patients who gained visual acuity from baseline to month 12 was 90% with ranibizumab, compared with 55% who received sham injections.

The mean BCVA increased and mean OCT decreased continuously over time in the ranibizumab patients. From baseline to month 12 there was a mean gain of 11.8 letters in the 6-mg/mL ranibizumab group, and 8.8 letters with the 10-mg/mL group (a pooled mean gain of 10.3 letters), compared with a loss of 1.4 letters in the sham treatment group, said Dr. Engelmann, of Klinikum Chemnitz GmbH, Saxony, Germany.

The most frequent ocular adverse events were conjunctival hemorrhage (14% sham, 23% ranibizumab) and eye pain (20% and 18%). Serious ocular adverse events occurred in one sham patient and in four ranibizumab patients. Nonocular arterial thromboembolic events occurred in two sham and three ranibizumab (10 mg/mL) patients.

Overall, the profile of ranibizumab in diabetic macular edema as seen in this study was similar to that found in previous randomized controlled studies trials of patients with neovascular age-related macular degeneration, she noted.

Ranibizumab (Lucentis) is marketed in Europe by Novartis and in the United States by Genentech for the treatment of patients with wet age-related macular degeneration. Novartis funded the RESOLVE study.

VIENNA — Ranibizumab treatment was associated with continuous improvement in best-corrected visual acuity and central retinal thickness over 12 months in a randomized, placebo-controlled study of 151 patients with diabetic macular edema.

The multicenter RESOLVE (Safety and Efficacy of Ranibizumab in Diabetic Macular Edema With Center Involvement) study randomized 51 patients to 6 mg/mL and 51 patients to 10 mg/mL of ranibizumab per intravitreal injection, and 49 patients to sham injections, Dr. Katrin Engelmann said at the annual meeting of the European Association for the Study of Diabetes.

Patients were given three initial monthly injections followed by retreatment based on predefined success or safety criteria. After the first month, the injection volume was doubled if central retinal thickness was greater than 300 mcm or was greater than 225 mcm and the reduction in edema from the previous treatment was less than 50 mcm. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) were assessed monthly.

Injection volume was doubled in 65% of the ranibizumab patients (both dose groups combined), compared with 92% of the sham injection group. Rescue laser photocoagulation treatment was required in 9% of the ranibizumab group, compared with 33% of the sham treatment group.

The proportion of patients who gained visual acuity from baseline to month 12 was 90% with ranibizumab, compared with 55% who received sham injections.

The mean BCVA increased and mean OCT decreased continuously over time in the ranibizumab patients. From baseline to month 12 there was a mean gain of 11.8 letters in the 6-mg/mL ranibizumab group, and 8.8 letters with the 10-mg/mL group (a pooled mean gain of 10.3 letters), compared with a loss of 1.4 letters in the sham treatment group, said Dr. Engelmann, of Klinikum Chemnitz GmbH, Saxony, Germany.

The most frequent ocular adverse events were conjunctival hemorrhage (14% sham, 23% ranibizumab) and eye pain (20% and 18%). Serious ocular adverse events occurred in one sham patient and in four ranibizumab patients. Nonocular arterial thromboembolic events occurred in two sham and three ranibizumab (10 mg/mL) patients.

Overall, the profile of ranibizumab in diabetic macular edema as seen in this study was similar to that found in previous randomized controlled studies trials of patients with neovascular age-related macular degeneration, she noted.

Ranibizumab (Lucentis) is marketed in Europe by Novartis and in the United States by Genentech for the treatment of patients with wet age-related macular degeneration. Novartis funded the RESOLVE study.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

Although magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose PCOS, Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS, but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology–internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years and a mean body mass index of 31.5 kg/m

They underwent TAUS scans that were read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (BMI greater than 30), 12 overweight (BMI of 25–29.9), and 9 lean (BMI less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, compared with 66 nmol/L in the lean group). They also had greater insulin resistance.

Total testosterone levels were not statistically different among the three BMI groups, although they trended higher in the obese group (mean total testosterone 56 mg/dL).

In an interview, Dr. Flannery said that the majority of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty, namely irregular periods and acne. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance, she said.

Dr. Flannery said neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

Although magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose PCOS, Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS, but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology–internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years and a mean body mass index of 31.5 kg/m

They underwent TAUS scans that were read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (BMI greater than 30), 12 overweight (BMI of 25–29.9), and 9 lean (BMI less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, compared with 66 nmol/L in the lean group). They also had greater insulin resistance.

Total testosterone levels were not statistically different among the three BMI groups, although they trended higher in the obese group (mean total testosterone 56 mg/dL).

In an interview, Dr. Flannery said that the majority of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty, namely irregular periods and acne. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance, she said.

Dr. Flannery said neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Ovarian volume assessed by transabdominal ultrasound correlated strongly with serum testosterone levels in a study of 39 adolescent girls undergoing evaluation for polycystic ovary syndrome.

Although magnetic resonance imaging and transrectal or transvaginal ultrasound (TVUS) may better visualize ovarian follicles, transabdominal ultrasound (TAUS) is a less invasive, cheaper, and more readily available imaging modality to diagnose PCOS, Dr. Clare A. Flannery said in a poster presented at a joint meeting of the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology.

With TAUS, the ovarian volume—the sum of the stromal volume and multiple follicles—can be easily calculated from the three dimensions of the ovary. Elevation of serum testosterone, a well-validated diagnostic criterion for PCOS, has been shown to correlate with typical PCOS using TVUS, but little is known about how accurately it relates to increased ovarian volume in TAUS, said Dr. Flannery of the department of endocrinology–internal medicine at Yale University, New Haven, Conn.

The 39 adolescents had a mean age of 15.3 years and a mean body mass index of 31.5 kg/m

They underwent TAUS scans that were read by a radiologist blinded to all clinical information. Ovarian volume was calculated with three diameter measurements, and total ovarian volume was obtained by adding the volume of both ovaries. They had a mean total ovarian volume of 23.2 cm

Total testosterone levels correlated with both single largest ovary volume and total ovarian volume, as did free testosterone. When ovarian volume was analyzed on a continuum, adolescents whose ovaries were less than 10 cm

Differences were seen between the 18 obese (BMI greater than 30), 12 overweight (BMI of 25–29.9), and 9 lean (BMI less than 25) patients. The overweight and obese groups had lower sex hormone–binding globulin than did the lean group (37 nmol/L and 27 nmol/L, respectively, compared with 66 nmol/L in the lean group). They also had greater insulin resistance.

Total testosterone levels were not statistically different among the three BMI groups, although they trended higher in the obese group (mean total testosterone 56 mg/dL).

In an interview, Dr. Flannery said that the majority of the adolescent girls referred to their specialty clinic are obese with symptoms that may be consistent with signs of puberty, namely irregular periods and acne. It is a challenge to differentiate between girls with early or established PCOS versus girls with just obesity and insulin resistance, she said.

Dr. Flannery said neither she nor Dr. Burgert had any financial disclosures.

NEW YORK — Partial anomalous pulmonary venous return was detected by cardiac magnetic resonance imaging in 7 of 39 adolescent and young adult women with Turner's syndrome whose charts were retrospectively evaluated.

The finding suggests that screening for the partial anomalous pulmonary venous return (PAPVR) heart defect is indicated in Turner's syndrome patients, along with appropriate cardiac referral and management, Dr. Iris Gutmark-Little said at the joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

The results also suggest that cardiac magnetic resonance (CMR) imaging is more sensitive than echocardiography for the detection of PAPVR in Turner's patients, said Dr. Gutmark-Little of Cincinnati Children's Hospital Medical Center.

The 39 patients were the first to be screened with CMR after Cincinnati Children's began using the modality routinely in all Turner's patients during their early teen years. The patients also underwent echocardiographic evaluation.

Seven patients (18%) were found to have PAPVR by cardiac magnetic resonance imaging, six of them following a normal echocardiogram. Aberrant drainage of the right upper pulmonary veins was seen in five patients, three of whom had involvement of at least a portion of the right middle lobe vein. The other two had the defect in the left upper pulmonary vein.

The 18% PAPVR prevalence seen here is similar to the 13% found in a previous study of adult Turner's patients (Circulation 2004;110:1694–700).

In one patient, PAPVR was associated with clinically significant enlargement of the right ventricle, with a pulmonary-to-systemic blood flow ratio (Qp:Qs) of 1.9:1. She required surgical repair. The other six patients had Qp:Qs ratios ranging from 1.24:1 to 1.62:1 and did not require intervention.

There were no differences in age, height, karyotype, or right ventricular ejection fraction between the 7 patients with PAPVR and the 32 without, nor did the two groups differ in peripheral lymphedema, neck webbing, renal malformations, coarctation, or bicuspid aortic valve. This finding differs from previous studies that have linked some of these features to PAPVR in Turner's patients, said Dr. Gutmark-Little, who stated that she had no financial disclosures.

A four-chamber MRI view shows a dilated right ventricle resulting from a right-sided PAPVR lesion in a Turner's patient.

Three-dimensional MRI of a right-sided PAPVR lesion shows anomalous pulmonary veins draining into the superior vena cava.

Source Images Courtesy Cincinnati Children's Hospital

NEW YORK — Partial anomalous pulmonary venous return was detected by cardiac magnetic resonance imaging in 7 of 39 adolescent and young adult women with Turner's syndrome whose charts were retrospectively evaluated.

The finding suggests that screening for the partial anomalous pulmonary venous return (PAPVR) heart defect is indicated in Turner's syndrome patients, along with appropriate cardiac referral and management, Dr. Iris Gutmark-Little said at the joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

The results also suggest that cardiac magnetic resonance (CMR) imaging is more sensitive than echocardiography for the detection of PAPVR in Turner's patients, said Dr. Gutmark-Little of Cincinnati Children's Hospital Medical Center.

The 39 patients were the first to be screened with CMR after Cincinnati Children's began using the modality routinely in all Turner's patients during their early teen years. The patients also underwent echocardiographic evaluation.

Seven patients (18%) were found to have PAPVR by cardiac magnetic resonance imaging, six of them following a normal echocardiogram. Aberrant drainage of the right upper pulmonary veins was seen in five patients, three of whom had involvement of at least a portion of the right middle lobe vein. The other two had the defect in the left upper pulmonary vein.

The 18% PAPVR prevalence seen here is similar to the 13% found in a previous study of adult Turner's patients (Circulation 2004;110:1694–700).

In one patient, PAPVR was associated with clinically significant enlargement of the right ventricle, with a pulmonary-to-systemic blood flow ratio (Qp:Qs) of 1.9:1. She required surgical repair. The other six patients had Qp:Qs ratios ranging from 1.24:1 to 1.62:1 and did not require intervention.

There were no differences in age, height, karyotype, or right ventricular ejection fraction between the 7 patients with PAPVR and the 32 without, nor did the two groups differ in peripheral lymphedema, neck webbing, renal malformations, coarctation, or bicuspid aortic valve. This finding differs from previous studies that have linked some of these features to PAPVR in Turner's patients, said Dr. Gutmark-Little, who stated that she had no financial disclosures.

A four-chamber MRI view shows a dilated right ventricle resulting from a right-sided PAPVR lesion in a Turner's patient.

Three-dimensional MRI of a right-sided PAPVR lesion shows anomalous pulmonary veins draining into the superior vena cava.

Source Images Courtesy Cincinnati Children's Hospital

NEW YORK — Partial anomalous pulmonary venous return was detected by cardiac magnetic resonance imaging in 7 of 39 adolescent and young adult women with Turner's syndrome whose charts were retrospectively evaluated.

The finding suggests that screening for the partial anomalous pulmonary venous return (PAPVR) heart defect is indicated in Turner's syndrome patients, along with appropriate cardiac referral and management, Dr. Iris Gutmark-Little said at the joint meeting of the Lawson Wilkins Pediatric Endocrine Society/European Society for Pediatric Endocrinology.

The results also suggest that cardiac magnetic resonance (CMR) imaging is more sensitive than echocardiography for the detection of PAPVR in Turner's patients, said Dr. Gutmark-Little of Cincinnati Children's Hospital Medical Center.

The 39 patients were the first to be screened with CMR after Cincinnati Children's began using the modality routinely in all Turner's patients during their early teen years. The patients also underwent echocardiographic evaluation.

Seven patients (18%) were found to have PAPVR by cardiac magnetic resonance imaging, six of them following a normal echocardiogram. Aberrant drainage of the right upper pulmonary veins was seen in five patients, three of whom had involvement of at least a portion of the right middle lobe vein. The other two had the defect in the left upper pulmonary vein.

The 18% PAPVR prevalence seen here is similar to the 13% found in a previous study of adult Turner's patients (Circulation 2004;110:1694–700).

In one patient, PAPVR was associated with clinically significant enlargement of the right ventricle, with a pulmonary-to-systemic blood flow ratio (Qp:Qs) of 1.9:1. She required surgical repair. The other six patients had Qp:Qs ratios ranging from 1.24:1 to 1.62:1 and did not require intervention.

There were no differences in age, height, karyotype, or right ventricular ejection fraction between the 7 patients with PAPVR and the 32 without, nor did the two groups differ in peripheral lymphedema, neck webbing, renal malformations, coarctation, or bicuspid aortic valve. This finding differs from previous studies that have linked some of these features to PAPVR in Turner's patients, said Dr. Gutmark-Little, who stated that she had no financial disclosures.

A four-chamber MRI view shows a dilated right ventricle resulting from a right-sided PAPVR lesion in a Turner's patient.

Three-dimensional MRI of a right-sided PAPVR lesion shows anomalous pulmonary veins draining into the superior vena cava.

Source Images Courtesy Cincinnati Children's Hospital

VIENNA — A new joint position statement from three European medical organizations is aimed at reducing cardiovascular risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population, statement co-author Dr. Richard Holt said at the briefing.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt of the department of endocrinology and metabolism at the University of Southampton, England.

Because of reduced access to physical health care services, the rate of screening for diabetes and cardiovascular disease (CVD) is significantly lower than in the general population. About 20% of diabetes in the general population is undiagnosed; that rate is about 70% among people with mental illness, he noted.

“In putting together this statement, the three organizations have developed pragmatic guidelines,” Dr. Holt said. Clearly, this is a collaborative effort.”

The document urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in patients who are overweight or obese.

In the United States, a similar set of recommendations from the National Association of State Mental Health Program Directors (NASMHPD) was issued in 2006 and 2008. In addition to clinical recommendations, the NASMHPD guidelines focus on the establishment of systems of care for people with SMI at both the national and state levels.

In an interview, Dr. Joe Parks, the lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director of the Missouri Department of Mental Health, Jefferson City.

“Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking,” he said.

VIENNA — A new joint position statement from three European medical organizations is aimed at reducing cardiovascular risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population, statement co-author Dr. Richard Holt said at the briefing.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt of the department of endocrinology and metabolism at the University of Southampton, England.

Because of reduced access to physical health care services, the rate of screening for diabetes and cardiovascular disease (CVD) is significantly lower than in the general population. About 20% of diabetes in the general population is undiagnosed; that rate is about 70% among people with mental illness, he noted.

“In putting together this statement, the three organizations have developed pragmatic guidelines,” Dr. Holt said. Clearly, this is a collaborative effort.”

The document urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in patients who are overweight or obese.

In the United States, a similar set of recommendations from the National Association of State Mental Health Program Directors (NASMHPD) was issued in 2006 and 2008. In addition to clinical recommendations, the NASMHPD guidelines focus on the establishment of systems of care for people with SMI at both the national and state levels.

In an interview, Dr. Joe Parks, the lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director of the Missouri Department of Mental Health, Jefferson City.

“Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking,” he said.

VIENNA — A new joint position statement from three European medical organizations is aimed at reducing cardiovascular risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population, statement co-author Dr. Richard Holt said at the briefing.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt of the department of endocrinology and metabolism at the University of Southampton, England.

Because of reduced access to physical health care services, the rate of screening for diabetes and cardiovascular disease (CVD) is significantly lower than in the general population. About 20% of diabetes in the general population is undiagnosed; that rate is about 70% among people with mental illness, he noted.

“In putting together this statement, the three organizations have developed pragmatic guidelines,” Dr. Holt said. Clearly, this is a collaborative effort.”

The document urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in patients who are overweight or obese.

In the United States, a similar set of recommendations from the National Association of State Mental Health Program Directors (NASMHPD) was issued in 2006 and 2008. In addition to clinical recommendations, the NASMHPD guidelines focus on the establishment of systems of care for people with SMI at both the national and state levels.

In an interview, Dr. Joe Parks, the lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director of the Missouri Department of Mental Health, Jefferson City.

“Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking,” he said.

VIENNA — Both diabetes itself and insulin therapy are associated with an increased risk for cancer, but the question of whether insulin glargine—or insulin analogues in general—are associated with a further increased risk remains open.

Those were among the conclusions from five speakers at a special symposium, “Diabetes Therapy and Cancer,” held during the annual meeting of the European Association for the Study of Diabetes.

Although there has been a steady progression of research papers over the past decade on the relationship between diabetes and cancer, the topic was suddenly thrust into the spotlight in June with the release of a series of studies in EASD's journal Diabetologia, suggesting that the insulin analogue glargine may be associated with an increased risk for cancer (www.diabetologia-journal.org/cancer.html

Since then, researchers have been refocusing efforts to shed further light on the complicated relationship between the two conditions. “What has emerged in the past few months is a whole new area of investigation,” said Dr. Edwin A. M. Gale, Diabetologia editor-in-chief, who moderated the symposium that attracted a large proportion of the meeting's 18,000 attendees.

“We're talking about what I think is one of the most interesting, challenging, and important issues to confront us since I came into the field of diabetes: the relationship between diabetes and cancer. Two areas of expertise have suddenly come together,” said Dr. Gale of the University of Bristol, England.

Dr. Jeffrey A. Johnson, who is professor at the School of Public Health, Health Policy and Management, University of Alberta in Edmonton, said that strong associations have been found between diabetes and obesity and a variety of cancers (relative risk 1.52 for all cancers in one large study), with a likely role for insulin resistance and hyperinsulinemia.

Evidence also suggests that glucose-lowering medications that modulate these factors—including the thiazolidinediones and sulfonylureas as well as insulin—could therefore also have positive or negative modifying effects with regard to cancer, he said.

Craig J. Currie, Ph.D., of Cardiff (Wales) University, presented new data from a retrospective cohort study of a U.K. general practice population. In this extension study of the one published online in July (Diabetologia 2009:52;1766-77) they examined 31,421 type 2 diabetes patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only.

There was a strong dose-response relationship between insulin exposure and first diagnosis of a solid cancer tumor. Compared with the crude rate of 10 cancers per 1,000 person-years for those who were taking metformin alone, the rates for those on insulin plus metformin increased from 9 for those using fewer than 7 insulin prescriptions per year to 11-12 for those using 8-14 prescriptions per year to 34 for those using more than 15 prescriptions per year, Dr. Currie reported.

Patients on insulin monotherapy showed an even greater dose-response: Those using fewer than 7 prescriptions per year had a rate of 15 per 1,000 person-years, those with 7-15 prescriptions had 19, and those with more than 15 prescriptions had three times that rate, at 60 cancers per 1,000 person-years.

After adjustment for age, sex, and smoking status, hazard ratios in the insulin plus metformin groups were 0.87 per 1,000 person-years for metformin alone, 1.0 for 8-14 prescriptions a year, and 3.2 for those with more than 15 prescriptions a year. For those on insulin alone, hazard ratios were 1.05 for metformin alone, up to 5.73 for those with more than 15 prescriptions per year. The same pattern of association persisted after adjustment for other covariates such as weight, insulin exposure, and hemoglobin A_1c, he said.

Some of the risk is attenuated in those using metformin with insulin, because metformin appears to have a protective effect, he noted.

Dr. Ulf Smith, president of the EASD, clarified a point that has caused confusion: Insulin is not oncogenic, but rather it may promote the growth of cells that have already undergone oncogenic transformation. “I don't think anyone has suggested that insulin causes cancer, but it is a growth-promoting hormone. This has been known for some time.”

The mechanism is likely to relate to insulin's binding of insulin-like growth factor receptors on tumors, noted Dr. Smith of the Salgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

The two final speakers presented information from the two relevant manufacturers: Dr. Jay Skyler of the University of Miami spoke on behalf of glargine (Lantus) manufacturer Sanofi-Aventis. He noted that, even in the original four Diabetologia studies, only one—the original German database analysis—showed that there was any statistically significant increase in cancer risk with glargine, and that was only after adjustment for insulin dose, a method that has been called invalid by many experts.

The other three studies show no statistically significant overall increased risk for glargine, nor did a subsequent analysis conducted by Sanofi-Aventis of its data from 31 clinical trials involving a combined population of 10,880 people with 5,657 on glargine. For all cancers, the rates were no different than in the general population. A further analysis from 26 uncontrolled trials also showed no indication of increased risk, said Dr. Skyler.

And one more source of data, the ongoing ORIGIN (Outcome Reduction With an Initial Glargine Intervention) study of more than 12,612 randomized subjects has also found no increased cancer risk in more than 50,000 patient-years of exposure, he added.

“The totality of the available evidence suggests that the headlines which suggested that 'Glargine Causes Cancer' are unsubstantiated, unwarranted, and unproven,” Dr. Skyler commented.

Dr. David Russell-Jones gave an overview of a new meta-analysis of safety data conducted by Novo-Nordisk for its long-acting insulin analogue, detemir. In studies lasting about 24 weeks, the risk for cancers of all types among 3,983 patients with either type 1 or type 2 diabetes on detemir was 0.36 per 1,000 person-years of exposure, compared with 0.92 for 2,661 similar patients using NPH insulin.

Those rates yielded an identical odds ratio of 2.53 using two different methods of statistical calculation, said Dr. Russell-Jones of the University of Surrey, England.

Dr. Gale, in his closing remarks, referred to Diabetologia as the “epicenter of the storm.” As a result, “many members of the medical community and the public have been confused, and in some cases angry. I think this has been one of the most difficult, confusing, emotive and controversial issues I have ever had to deal with.”

And while acknowledging that he had received some criticism for publishing the articles in the first place—given that they raised more questions about the glargine/cancer issue than they answered—Dr. Gale said he has no regrets or apologies, noting, “The answer to the question may well be negative, but the question has to be asked.”

Dr. Johnson declared he had participated as a speaker for Eli Lilly & Co. Dr. Gale, Dr. Smith, and Dr. Currie stated they had no conflicts of interest. Both Dr. Skyler and Dr. Russell-Jones declared financial relationships with other diabetes-related companies in addition to the ones they were representing at the symposium.

In September, Sanofi-Aventis announced the launch of a research program to investigate whether there is a relationship between cancer and insulin use, including the analogues.

'The answer to the question may well be negative, but the question has to be asked.'

Source DR. GALE

Some of the cancer risk was attenuated in those using metformin with insulin.

Source DR. CURRIE

VIENNA — Both diabetes itself and insulin therapy are associated with an increased risk for cancer, but the question of whether insulin glargine—or insulin analogues in general—are associated with a further increased risk remains open.

Those were among the conclusions from five speakers at a special symposium, “Diabetes Therapy and Cancer,” held during the annual meeting of the European Association for the Study of Diabetes.

Although there has been a steady progression of research papers over the past decade on the relationship between diabetes and cancer, the topic was suddenly thrust into the spotlight in June with the release of a series of studies in EASD's journal Diabetologia, suggesting that the insulin analogue glargine may be associated with an increased risk for cancer (www.diabetologia-journal.org/cancer.html

Since then, researchers have been refocusing efforts to shed further light on the complicated relationship between the two conditions. “What has emerged in the past few months is a whole new area of investigation,” said Dr. Edwin A. M. Gale, Diabetologia editor-in-chief, who moderated the symposium that attracted a large proportion of the meeting's 18,000 attendees.

“We're talking about what I think is one of the most interesting, challenging, and important issues to confront us since I came into the field of diabetes: the relationship between diabetes and cancer. Two areas of expertise have suddenly come together,” said Dr. Gale of the University of Bristol, England.

Dr. Jeffrey A. Johnson, who is professor at the School of Public Health, Health Policy and Management, University of Alberta in Edmonton, said that strong associations have been found between diabetes and obesity and a variety of cancers (relative risk 1.52 for all cancers in one large study), with a likely role for insulin resistance and hyperinsulinemia.

Evidence also suggests that glucose-lowering medications that modulate these factors—including the thiazolidinediones and sulfonylureas as well as insulin—could therefore also have positive or negative modifying effects with regard to cancer, he said.

Craig J. Currie, Ph.D., of Cardiff (Wales) University, presented new data from a retrospective cohort study of a U.K. general practice population. In this extension study of the one published online in July (Diabetologia 2009:52;1766-77) they examined 31,421 type 2 diabetes patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only.

There was a strong dose-response relationship between insulin exposure and first diagnosis of a solid cancer tumor. Compared with the crude rate of 10 cancers per 1,000 person-years for those who were taking metformin alone, the rates for those on insulin plus metformin increased from 9 for those using fewer than 7 insulin prescriptions per year to 11-12 for those using 8-14 prescriptions per year to 34 for those using more than 15 prescriptions per year, Dr. Currie reported.

Patients on insulin monotherapy showed an even greater dose-response: Those using fewer than 7 prescriptions per year had a rate of 15 per 1,000 person-years, those with 7-15 prescriptions had 19, and those with more than 15 prescriptions had three times that rate, at 60 cancers per 1,000 person-years.

After adjustment for age, sex, and smoking status, hazard ratios in the insulin plus metformin groups were 0.87 per 1,000 person-years for metformin alone, 1.0 for 8-14 prescriptions a year, and 3.2 for those with more than 15 prescriptions a year. For those on insulin alone, hazard ratios were 1.05 for metformin alone, up to 5.73 for those with more than 15 prescriptions per year. The same pattern of association persisted after adjustment for other covariates such as weight, insulin exposure, and hemoglobin A_1c, he said.

Some of the risk is attenuated in those using metformin with insulin, because metformin appears to have a protective effect, he noted.

Dr. Ulf Smith, president of the EASD, clarified a point that has caused confusion: Insulin is not oncogenic, but rather it may promote the growth of cells that have already undergone oncogenic transformation. “I don't think anyone has suggested that insulin causes cancer, but it is a growth-promoting hormone. This has been known for some time.”

The mechanism is likely to relate to insulin's binding of insulin-like growth factor receptors on tumors, noted Dr. Smith of the Salgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

The two final speakers presented information from the two relevant manufacturers: Dr. Jay Skyler of the University of Miami spoke on behalf of glargine (Lantus) manufacturer Sanofi-Aventis. He noted that, even in the original four Diabetologia studies, only one—the original German database analysis—showed that there was any statistically significant increase in cancer risk with glargine, and that was only after adjustment for insulin dose, a method that has been called invalid by many experts.

The other three studies show no statistically significant overall increased risk for glargine, nor did a subsequent analysis conducted by Sanofi-Aventis of its data from 31 clinical trials involving a combined population of 10,880 people with 5,657 on glargine. For all cancers, the rates were no different than in the general population. A further analysis from 26 uncontrolled trials also showed no indication of increased risk, said Dr. Skyler.

And one more source of data, the ongoing ORIGIN (Outcome Reduction With an Initial Glargine Intervention) study of more than 12,612 randomized subjects has also found no increased cancer risk in more than 50,000 patient-years of exposure, he added.

“The totality of the available evidence suggests that the headlines which suggested that 'Glargine Causes Cancer' are unsubstantiated, unwarranted, and unproven,” Dr. Skyler commented.

Dr. David Russell-Jones gave an overview of a new meta-analysis of safety data conducted by Novo-Nordisk for its long-acting insulin analogue, detemir. In studies lasting about 24 weeks, the risk for cancers of all types among 3,983 patients with either type 1 or type 2 diabetes on detemir was 0.36 per 1,000 person-years of exposure, compared with 0.92 for 2,661 similar patients using NPH insulin.

Those rates yielded an identical odds ratio of 2.53 using two different methods of statistical calculation, said Dr. Russell-Jones of the University of Surrey, England.

Dr. Gale, in his closing remarks, referred to Diabetologia as the “epicenter of the storm.” As a result, “many members of the medical community and the public have been confused, and in some cases angry. I think this has been one of the most difficult, confusing, emotive and controversial issues I have ever had to deal with.”

And while acknowledging that he had received some criticism for publishing the articles in the first place—given that they raised more questions about the glargine/cancer issue than they answered—Dr. Gale said he has no regrets or apologies, noting, “The answer to the question may well be negative, but the question has to be asked.”

Dr. Johnson declared he had participated as a speaker for Eli Lilly & Co. Dr. Gale, Dr. Smith, and Dr. Currie stated they had no conflicts of interest. Both Dr. Skyler and Dr. Russell-Jones declared financial relationships with other diabetes-related companies in addition to the ones they were representing at the symposium.

In September, Sanofi-Aventis announced the launch of a research program to investigate whether there is a relationship between cancer and insulin use, including the analogues.

'The answer to the question may well be negative, but the question has to be asked.'

Source DR. GALE

Some of the cancer risk was attenuated in those using metformin with insulin.

Source DR. CURRIE

VIENNA — Both diabetes itself and insulin therapy are associated with an increased risk for cancer, but the question of whether insulin glargine—or insulin analogues in general—are associated with a further increased risk remains open.

Those were among the conclusions from five speakers at a special symposium, “Diabetes Therapy and Cancer,” held during the annual meeting of the European Association for the Study of Diabetes.

Although there has been a steady progression of research papers over the past decade on the relationship between diabetes and cancer, the topic was suddenly thrust into the spotlight in June with the release of a series of studies in EASD's journal Diabetologia, suggesting that the insulin analogue glargine may be associated with an increased risk for cancer (www.diabetologia-journal.org/cancer.html

Since then, researchers have been refocusing efforts to shed further light on the complicated relationship between the two conditions. “What has emerged in the past few months is a whole new area of investigation,” said Dr. Edwin A. M. Gale, Diabetologia editor-in-chief, who moderated the symposium that attracted a large proportion of the meeting's 18,000 attendees.

“We're talking about what I think is one of the most interesting, challenging, and important issues to confront us since I came into the field of diabetes: the relationship between diabetes and cancer. Two areas of expertise have suddenly come together,” said Dr. Gale of the University of Bristol, England.

Dr. Jeffrey A. Johnson, who is professor at the School of Public Health, Health Policy and Management, University of Alberta in Edmonton, said that strong associations have been found between diabetes and obesity and a variety of cancers (relative risk 1.52 for all cancers in one large study), with a likely role for insulin resistance and hyperinsulinemia.

Evidence also suggests that glucose-lowering medications that modulate these factors—including the thiazolidinediones and sulfonylureas as well as insulin—could therefore also have positive or negative modifying effects with regard to cancer, he said.

Craig J. Currie, Ph.D., of Cardiff (Wales) University, presented new data from a retrospective cohort study of a U.K. general practice population. In this extension study of the one published online in July (Diabetologia 2009:52;1766-77) they examined 31,421 type 2 diabetes patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only.

There was a strong dose-response relationship between insulin exposure and first diagnosis of a solid cancer tumor. Compared with the crude rate of 10 cancers per 1,000 person-years for those who were taking metformin alone, the rates for those on insulin plus metformin increased from 9 for those using fewer than 7 insulin prescriptions per year to 11-12 for those using 8-14 prescriptions per year to 34 for those using more than 15 prescriptions per year, Dr. Currie reported.

Patients on insulin monotherapy showed an even greater dose-response: Those using fewer than 7 prescriptions per year had a rate of 15 per 1,000 person-years, those with 7-15 prescriptions had 19, and those with more than 15 prescriptions had three times that rate, at 60 cancers per 1,000 person-years.

After adjustment for age, sex, and smoking status, hazard ratios in the insulin plus metformin groups were 0.87 per 1,000 person-years for metformin alone, 1.0 for 8-14 prescriptions a year, and 3.2 for those with more than 15 prescriptions a year. For those on insulin alone, hazard ratios were 1.05 for metformin alone, up to 5.73 for those with more than 15 prescriptions per year. The same pattern of association persisted after adjustment for other covariates such as weight, insulin exposure, and hemoglobin A_1c, he said.

Some of the risk is attenuated in those using metformin with insulin, because metformin appears to have a protective effect, he noted.

Dr. Ulf Smith, president of the EASD, clarified a point that has caused confusion: Insulin is not oncogenic, but rather it may promote the growth of cells that have already undergone oncogenic transformation. “I don't think anyone has suggested that insulin causes cancer, but it is a growth-promoting hormone. This has been known for some time.”

The mechanism is likely to relate to insulin's binding of insulin-like growth factor receptors on tumors, noted Dr. Smith of the Salgrenska Center for Cardiovascular and Metabolic Research, Göteborg, Sweden.

The two final speakers presented information from the two relevant manufacturers: Dr. Jay Skyler of the University of Miami spoke on behalf of glargine (Lantus) manufacturer Sanofi-Aventis. He noted that, even in the original four Diabetologia studies, only one—the original German database analysis—showed that there was any statistically significant increase in cancer risk with glargine, and that was only after adjustment for insulin dose, a method that has been called invalid by many experts.

The other three studies show no statistically significant overall increased risk for glargine, nor did a subsequent analysis conducted by Sanofi-Aventis of its data from 31 clinical trials involving a combined population of 10,880 people with 5,657 on glargine. For all cancers, the rates were no different than in the general population. A further analysis from 26 uncontrolled trials also showed no indication of increased risk, said Dr. Skyler.

And one more source of data, the ongoing ORIGIN (Outcome Reduction With an Initial Glargine Intervention) study of more than 12,612 randomized subjects has also found no increased cancer risk in more than 50,000 patient-years of exposure, he added.

“The totality of the available evidence suggests that the headlines which suggested that 'Glargine Causes Cancer' are unsubstantiated, unwarranted, and unproven,” Dr. Skyler commented.

Dr. David Russell-Jones gave an overview of a new meta-analysis of safety data conducted by Novo-Nordisk for its long-acting insulin analogue, detemir. In studies lasting about 24 weeks, the risk for cancers of all types among 3,983 patients with either type 1 or type 2 diabetes on detemir was 0.36 per 1,000 person-years of exposure, compared with 0.92 for 2,661 similar patients using NPH insulin.

Those rates yielded an identical odds ratio of 2.53 using two different methods of statistical calculation, said Dr. Russell-Jones of the University of Surrey, England.

Dr. Gale, in his closing remarks, referred to Diabetologia as the “epicenter of the storm.” As a result, “many members of the medical community and the public have been confused, and in some cases angry. I think this has been one of the most difficult, confusing, emotive and controversial issues I have ever had to deal with.”

And while acknowledging that he had received some criticism for publishing the articles in the first place—given that they raised more questions about the glargine/cancer issue than they answered—Dr. Gale said he has no regrets or apologies, noting, “The answer to the question may well be negative, but the question has to be asked.”

Dr. Johnson declared he had participated as a speaker for Eli Lilly & Co. Dr. Gale, Dr. Smith, and Dr. Currie stated they had no conflicts of interest. Both Dr. Skyler and Dr. Russell-Jones declared financial relationships with other diabetes-related companies in addition to the ones they were representing at the symposium.

In September, Sanofi-Aventis announced the launch of a research program to investigate whether there is a relationship between cancer and insulin use, including the analogues.

'The answer to the question may well be negative, but the question has to be asked.'

Source DR. GALE

Some of the cancer risk was attenuated in those using metformin with insulin.

Source DR. CURRIE

VIENNA – A new joint position statement from three European medical organizations is aimed at reducing cardiovascular disease risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population. Data suggest that they die years prematurely. It's also much harder for these individuals to access health care services, statement co-author Dr. Richard Holt said at the briefing.

People with SMI are more likely to be overweight, to smoke, and to have diabetes, hypertension, and dyslipidemia. Antipsychotics also can induce weight gain and worsen other metabolic cardiovascular disease (CVD) risk factors.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt, of the department of endocrinology and metabolism at the University of Southampton (England) Because of the reduced access to physical health care services, the rate of screening for diabetes and CVD is significantly lower than that in the general population. In fact, while about 20% of diabetes in the general population is undiagnosed, that rate is about 70% among people with mental illness. People with mental illness also have high rates of untreated dyslipidemia and hypertension, he noted.

With this new statement, “We have an opportunity here of bringing together psychiatry and physical health services–in both primary care and secondary care–to try to address this problem, to increase the amount of screening for CV risk factors, to identify individuals at high risk, and to then come together with a strategy to treat them.”

“In putting together this statement, the three organizations have developed pragmatic guidelines,” he said. “Clearly, this is a collaborative effort.”

The document, for which the lead author was Dr. Marc De Hert of University Psychiatric Centre, Catholic University, Leuven Campus Kortenberg, Belgium, urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in overweight or obese patients. A dilemma may arise with clozapine, which is recommended by many guidelines as the antipsychotic of choice for patients with refractory schizophrenia, but it is also associated with the highest risk of weight gain and related CVD risk factors, the document says.

In the United States, a similar set of recommendations from the American Psychiatric Association, the American Diabetes Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity was issued in 2004 (Diabetes Care 2004;27:596-61). In addition, the National Association of State Mental Health Program Directors (NASMHPD) issued similiar recommendations in 2006 and 2008 that are available at www.nasmhpd.org

In an interview, Dr. Joe Parks, lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director for the Missouri Department of Mental Health, Jefferson City.

Some U.S. states have made progress. The New York State Department of Mental Health, for example, has implemented tracking of obesity and blood pressure in its state-operated hospitals and clinics. In Missouri, the Department of Mental Health has just begun to require and fund annual screening and some interventions for obesity, blood pressure, diabetes, high cholesterol, and dyslipidemia in its programs serving people with mental illness for both Medicaid covered individuals and the uninsured.

Several private insurers encourage and attempt to incentivize clinics and individual providers to follow these recommendations, but Dr. Parks said he is unaware of any that actually require compliance.

“I don't know of any health care entity anywhere that delivers on all of either the American or European recommendations,” Dr. Parks said. “If we want to see widespread adoption of these kind of evidence-based standards of care, then the payers need to require it in their contracts, pay more when evidence-based standards of care are followed, and pay less when they are not. Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking.”

The three organizations have developed pragmatic guidelines. This is a collaborative effort.

Source Dr. Holt

VIENNA – A new joint position statement from three European medical organizations is aimed at reducing cardiovascular disease risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population. Data suggest that they die years prematurely. It's also much harder for these individuals to access health care services, statement co-author Dr. Richard Holt said at the briefing.

People with SMI are more likely to be overweight, to smoke, and to have diabetes, hypertension, and dyslipidemia. Antipsychotics also can induce weight gain and worsen other metabolic cardiovascular disease (CVD) risk factors.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt, of the department of endocrinology and metabolism at the University of Southampton (England) Because of the reduced access to physical health care services, the rate of screening for diabetes and CVD is significantly lower than that in the general population. In fact, while about 20% of diabetes in the general population is undiagnosed, that rate is about 70% among people with mental illness. People with mental illness also have high rates of untreated dyslipidemia and hypertension, he noted.

With this new statement, “We have an opportunity here of bringing together psychiatry and physical health services–in both primary care and secondary care–to try to address this problem, to increase the amount of screening for CV risk factors, to identify individuals at high risk, and to then come together with a strategy to treat them.”

“In putting together this statement, the three organizations have developed pragmatic guidelines,” he said. “Clearly, this is a collaborative effort.”

The document, for which the lead author was Dr. Marc De Hert of University Psychiatric Centre, Catholic University, Leuven Campus Kortenberg, Belgium, urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in overweight or obese patients. A dilemma may arise with clozapine, which is recommended by many guidelines as the antipsychotic of choice for patients with refractory schizophrenia, but it is also associated with the highest risk of weight gain and related CVD risk factors, the document says.

In the United States, a similar set of recommendations from the American Psychiatric Association, the American Diabetes Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity was issued in 2004 (Diabetes Care 2004;27:596-61). In addition, the National Association of State Mental Health Program Directors (NASMHPD) issued similiar recommendations in 2006 and 2008 that are available at www.nasmhpd.org

In an interview, Dr. Joe Parks, lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director for the Missouri Department of Mental Health, Jefferson City.

Some U.S. states have made progress. The New York State Department of Mental Health, for example, has implemented tracking of obesity and blood pressure in its state-operated hospitals and clinics. In Missouri, the Department of Mental Health has just begun to require and fund annual screening and some interventions for obesity, blood pressure, diabetes, high cholesterol, and dyslipidemia in its programs serving people with mental illness for both Medicaid covered individuals and the uninsured.

Several private insurers encourage and attempt to incentivize clinics and individual providers to follow these recommendations, but Dr. Parks said he is unaware of any that actually require compliance.

“I don't know of any health care entity anywhere that delivers on all of either the American or European recommendations,” Dr. Parks said. “If we want to see widespread adoption of these kind of evidence-based standards of care, then the payers need to require it in their contracts, pay more when evidence-based standards of care are followed, and pay less when they are not. Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking.”

The three organizations have developed pragmatic guidelines. This is a collaborative effort.

Source Dr. Holt

VIENNA – A new joint position statement from three European medical organizations is aimed at reducing cardiovascular disease risk and improving diabetes care in people with severe mental illness, as well as improving their overall health and well-being.

The statement is from the European Psychiatric Association and supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (www.em-consulte.com/article/223719

People with severe mental illnesses (SMI), including schizophrenia, depression, and bipolar disorder, have worse physical health and reduced life expectancy compared with the general population. Data suggest that they die years prematurely. It's also much harder for these individuals to access health care services, statement co-author Dr. Richard Holt said at the briefing.

People with SMI are more likely to be overweight, to smoke, and to have diabetes, hypertension, and dyslipidemia. Antipsychotics also can induce weight gain and worsen other metabolic cardiovascular disease (CVD) risk factors.

“The problem is that as well as the devastating effects of SMI, people with bipolar disorder and schizophrenia die on average 10-20 years earlier than the general population,” said Dr. Holt, of the department of endocrinology and metabolism at the University of Southampton (England) Because of the reduced access to physical health care services, the rate of screening for diabetes and CVD is significantly lower than that in the general population. In fact, while about 20% of diabetes in the general population is undiagnosed, that rate is about 70% among people with mental illness. People with mental illness also have high rates of untreated dyslipidemia and hypertension, he noted.

With this new statement, “We have an opportunity here of bringing together psychiatry and physical health services–in both primary care and secondary care–to try to address this problem, to increase the amount of screening for CV risk factors, to identify individuals at high risk, and to then come together with a strategy to treat them.”

“In putting together this statement, the three organizations have developed pragmatic guidelines,” he said. “Clearly, this is a collaborative effort.”

The document, for which the lead author was Dr. Marc De Hert of University Psychiatric Centre, Catholic University, Leuven Campus Kortenberg, Belgium, urges coordinated CVD risk assessment and management for this population, and names psychiatrists as often being the best placed to lead the health care team that ideally includes shared care arrangements between general and specialist health care services.

Establishing baseline CVD risk at initial presentation is advised, and recommendations are given for assessment of medical history and examination of all CVD risk factors, including lipids, glucose, smoking habit, and blood pressure. Electrocardiogram also is recommended. Monitoring should be carried out at regular intervals, depending on the patient's individual risk level. Weight should be closely monitored in patients taking psychotropic medications, the document advises.

Psychiatric centers and diabetes centers should cooperate in the care of patients with SMI and diabetes. A diabetes nurse-educator also should be involved in the care of those on insulin. The document also outlines management of blood lipids and blood pressure, along with smoking cessation counseling.

The choice of psychotropic medications should take into account the potential effects of the agent on CVD risk factors, particularly in overweight or obese patients. A dilemma may arise with clozapine, which is recommended by many guidelines as the antipsychotic of choice for patients with refractory schizophrenia, but it is also associated with the highest risk of weight gain and related CVD risk factors, the document says.

In the United States, a similar set of recommendations from the American Psychiatric Association, the American Diabetes Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity was issued in 2004 (Diabetes Care 2004;27:596-61). In addition, the National Association of State Mental Health Program Directors (NASMHPD) issued similiar recommendations in 2006 and 2008 that are available at www.nasmhpd.org

In an interview, Dr. Joe Parks, lead author of the NASMHPD papers, said the problem in the United States is that it's often not clear who is responsible for ensuring that evidence-based standards of care are provided.

“Are the recommendations the responsibility of the individual health care provider? Or the local health care organizations such as hospitals and clinics? Or the payers such as private insurers and Medicaid? Because of this lack of accountability, implementation has been fragmented and spotty,” said Dr. Parks, medical director for the Missouri Department of Mental Health, Jefferson City.

Some U.S. states have made progress. The New York State Department of Mental Health, for example, has implemented tracking of obesity and blood pressure in its state-operated hospitals and clinics. In Missouri, the Department of Mental Health has just begun to require and fund annual screening and some interventions for obesity, blood pressure, diabetes, high cholesterol, and dyslipidemia in its programs serving people with mental illness for both Medicaid covered individuals and the uninsured.

Several private insurers encourage and attempt to incentivize clinics and individual providers to follow these recommendations, but Dr. Parks said he is unaware of any that actually require compliance.

“I don't know of any health care entity anywhere that delivers on all of either the American or European recommendations,” Dr. Parks said. “If we want to see widespread adoption of these kind of evidence-based standards of care, then the payers need to require it in their contracts, pay more when evidence-based standards of care are followed, and pay less when they are not. Within our current system if you really want something to happen routinely and systematically throughout the health care delivery system, there must be either a legal requirement or financial incentives. Everything else is just wishful thinking.”

The three organizations have developed pragmatic guidelines. This is a collaborative effort.

Source Dr. Holt