Sherry Boschert

SAN FRANCISCO — The use of a hemoglobin A_1c level of 6.5% or higher to diagnose type 2 diabetes is now mainstream, with formal endorsements from three major U.S. medical associations in 2010 supporting an International Expert Committee's 2009 consensus recommendations.

The World Health Organization and other groups are likely to follow suit, though with greater emphasis on this as an alternative to conventional means of diagnosing diabetes in regions that don't have easy access to standardized assays for HbA_1c, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association

He welcomed the change, and the rationale for using HbA_1c to diagnose diabetes. “Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?” asked Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center, Saint Louis Park, Minn.

The International Expert Committee, with members appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation, got the ball rolling by publishing a consensus opinion in July 2009 to make HbA_1c the preferred test for diagnosing type 2 diabetes (Diabetes Care 2009;32:1327-34).

The ADA translated the international consensus into clinical practice recommendations that were published in its annual update on standards of care in January 2010 (Diabetes Care 2010;33:S11-61). The ADA backed away from calling HbA_1c the preferred test, instead saying it's one of four options, but acknowledged that it may become the most popular diagnostic test for type 2 diabetes.

The other, conventional diagnostic criteria are a fasting plasma glucose level of at least 126 mg/dL, an oral glucose tolerance test result of 200 mg/dL or higher, or classic symptoms of hyperglycemia plus a randomly obtained glucose level of at least 200 mg/dL.

The Endocrine Society endorsed the ADA clinical practice recommendations in a separate statement that was issued Jan. 20, 2010. The American Association of Clinical Endocrinologists followed with its own supportive statement on Feb. 1, 2010.

Inevitably, clinicians will have patients whose HbA_1c and glucose results conflict, Dr. Bergenstal noted. If one is abnormal and the other is not, repeat the abnormal test, the ADA recommendations say. “If that is still abnormal, you've made the diagnosis,” he said. If, instead, you perform a third test method for confirmation and the result meets diagnostic criteria, diabetes is confirmed, he added.

Results are less clear when a patient has one normal and one abnormal test result, and repeating the abnormal test produces a normal result. “Then you have someone who is obviously on the edge” and who should be retested again in 3-6 months, he said.

Another gray area is the use of HbA_1c to define prediabetes (patients at high risk for developing diabetes or cardiovascular disease). The statements from the various groups differ somewhat in how they address this. “I think everyone agrees that for at-risk patients, that's a little bit more of a judgment call,” Dr. Bergenstal said.

The International Expert Committee suggested avoiding the concept of prediabetes because the risk is a continuum with a fairly steady rise in risk as HbA_1c levels increase. They identified HbA_1c levels of 6.0%–6.4% as “very high risk” while noting that people with lower HbA_1c levels also may have increased risk for diabetes if other risk factors are present.

The ADA's 2010 clinical practice recommendations declare HbA_1c levels of 5.7%–6.4% to be indicative of high risk, and state that patients with these levels may be referred to as having prediabetes, Dr. Bergenstal said. “At 5.7% we thought the risk was really quite high, and that people deserved to have some kind of program” to prevent diabetes.

The American Association of Clinical Endocrinologists suggested that an HbA_1c level of 5.5%–6.4% may be a better cut-off to identify higher-risk patients.

Unlike the glucose tests, HbA_1c testing does not require patients to fast before testing and carries several other advantages. Each of the statements supporting HbA_1c testing for diabetes diagnosis acknowledged a number of caveats, however, such as recognition that marginally elevated HbA_1c values in certain ethnic groups do not necessarily indicate diabetes. HbA_1c testing should not be used for diabetes diagnosis in patients with conditions that impair the correlation between HbA_1c and average blood glucose, such as iron deficiency or renal disease.

Only standardized, validated laboratory assays for HbA_1c were endorsed. Some of the newer point-of-care tests may be sufficiently accurate, but others are not, and more testing is needed before these can be endorsed for diabetes diagnosis, he said.

Disclosures: Dr. Bergenstal has held stock in Merck & Co. and participated in research or consulted for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly & Co., Intuity Medical, Lifescan (Johnson & Johnson), Mannkind, Medtronic, Merck, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

'Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?'

Source DR. BERGENSTAL

SAN FRANCISCO — The use of a hemoglobin A_1c level of 6.5% or higher to diagnose type 2 diabetes is now mainstream, with formal endorsements from three major U.S. medical associations in 2010 supporting an International Expert Committee's 2009 consensus recommendations.

The World Health Organization and other groups are likely to follow suit, though with greater emphasis on this as an alternative to conventional means of diagnosing diabetes in regions that don't have easy access to standardized assays for HbA_1c, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association

He welcomed the change, and the rationale for using HbA_1c to diagnose diabetes. “Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?” asked Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center, Saint Louis Park, Minn.

The International Expert Committee, with members appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation, got the ball rolling by publishing a consensus opinion in July 2009 to make HbA_1c the preferred test for diagnosing type 2 diabetes (Diabetes Care 2009;32:1327-34).

The ADA translated the international consensus into clinical practice recommendations that were published in its annual update on standards of care in January 2010 (Diabetes Care 2010;33:S11-61). The ADA backed away from calling HbA_1c the preferred test, instead saying it's one of four options, but acknowledged that it may become the most popular diagnostic test for type 2 diabetes.

The other, conventional diagnostic criteria are a fasting plasma glucose level of at least 126 mg/dL, an oral glucose tolerance test result of 200 mg/dL or higher, or classic symptoms of hyperglycemia plus a randomly obtained glucose level of at least 200 mg/dL.

The Endocrine Society endorsed the ADA clinical practice recommendations in a separate statement that was issued Jan. 20, 2010. The American Association of Clinical Endocrinologists followed with its own supportive statement on Feb. 1, 2010.

Inevitably, clinicians will have patients whose HbA_1c and glucose results conflict, Dr. Bergenstal noted. If one is abnormal and the other is not, repeat the abnormal test, the ADA recommendations say. “If that is still abnormal, you've made the diagnosis,” he said. If, instead, you perform a third test method for confirmation and the result meets diagnostic criteria, diabetes is confirmed, he added.

Results are less clear when a patient has one normal and one abnormal test result, and repeating the abnormal test produces a normal result. “Then you have someone who is obviously on the edge” and who should be retested again in 3-6 months, he said.

Another gray area is the use of HbA_1c to define prediabetes (patients at high risk for developing diabetes or cardiovascular disease). The statements from the various groups differ somewhat in how they address this. “I think everyone agrees that for at-risk patients, that's a little bit more of a judgment call,” Dr. Bergenstal said.

The International Expert Committee suggested avoiding the concept of prediabetes because the risk is a continuum with a fairly steady rise in risk as HbA_1c levels increase. They identified HbA_1c levels of 6.0%–6.4% as “very high risk” while noting that people with lower HbA_1c levels also may have increased risk for diabetes if other risk factors are present.

The ADA's 2010 clinical practice recommendations declare HbA_1c levels of 5.7%–6.4% to be indicative of high risk, and state that patients with these levels may be referred to as having prediabetes, Dr. Bergenstal said. “At 5.7% we thought the risk was really quite high, and that people deserved to have some kind of program” to prevent diabetes.

The American Association of Clinical Endocrinologists suggested that an HbA_1c level of 5.5%–6.4% may be a better cut-off to identify higher-risk patients.

Unlike the glucose tests, HbA_1c testing does not require patients to fast before testing and carries several other advantages. Each of the statements supporting HbA_1c testing for diabetes diagnosis acknowledged a number of caveats, however, such as recognition that marginally elevated HbA_1c values in certain ethnic groups do not necessarily indicate diabetes. HbA_1c testing should not be used for diabetes diagnosis in patients with conditions that impair the correlation between HbA_1c and average blood glucose, such as iron deficiency or renal disease.

Only standardized, validated laboratory assays for HbA_1c were endorsed. Some of the newer point-of-care tests may be sufficiently accurate, but others are not, and more testing is needed before these can be endorsed for diabetes diagnosis, he said.

Disclosures: Dr. Bergenstal has held stock in Merck & Co. and participated in research or consulted for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly & Co., Intuity Medical, Lifescan (Johnson & Johnson), Mannkind, Medtronic, Merck, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

'Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?'

Source DR. BERGENSTAL

SAN FRANCISCO — The use of a hemoglobin A_1c level of 6.5% or higher to diagnose type 2 diabetes is now mainstream, with formal endorsements from three major U.S. medical associations in 2010 supporting an International Expert Committee's 2009 consensus recommendations.

The World Health Organization and other groups are likely to follow suit, though with greater emphasis on this as an alternative to conventional means of diagnosing diabetes in regions that don't have easy access to standardized assays for HbA_1c, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association

He welcomed the change, and the rationale for using HbA_1c to diagnose diabetes. “Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?” asked Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center, Saint Louis Park, Minn.

The International Expert Committee, with members appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation, got the ball rolling by publishing a consensus opinion in July 2009 to make HbA_1c the preferred test for diagnosing type 2 diabetes (Diabetes Care 2009;32:1327-34).

The ADA translated the international consensus into clinical practice recommendations that were published in its annual update on standards of care in January 2010 (Diabetes Care 2010;33:S11-61). The ADA backed away from calling HbA_1c the preferred test, instead saying it's one of four options, but acknowledged that it may become the most popular diagnostic test for type 2 diabetes.

The other, conventional diagnostic criteria are a fasting plasma glucose level of at least 126 mg/dL, an oral glucose tolerance test result of 200 mg/dL or higher, or classic symptoms of hyperglycemia plus a randomly obtained glucose level of at least 200 mg/dL.

The Endocrine Society endorsed the ADA clinical practice recommendations in a separate statement that was issued Jan. 20, 2010. The American Association of Clinical Endocrinologists followed with its own supportive statement on Feb. 1, 2010.

Inevitably, clinicians will have patients whose HbA_1c and glucose results conflict, Dr. Bergenstal noted. If one is abnormal and the other is not, repeat the abnormal test, the ADA recommendations say. “If that is still abnormal, you've made the diagnosis,” he said. If, instead, you perform a third test method for confirmation and the result meets diagnostic criteria, diabetes is confirmed, he added.

Results are less clear when a patient has one normal and one abnormal test result, and repeating the abnormal test produces a normal result. “Then you have someone who is obviously on the edge” and who should be retested again in 3-6 months, he said.

Another gray area is the use of HbA_1c to define prediabetes (patients at high risk for developing diabetes or cardiovascular disease). The statements from the various groups differ somewhat in how they address this. “I think everyone agrees that for at-risk patients, that's a little bit more of a judgment call,” Dr. Bergenstal said.

The International Expert Committee suggested avoiding the concept of prediabetes because the risk is a continuum with a fairly steady rise in risk as HbA_1c levels increase. They identified HbA_1c levels of 6.0%–6.4% as “very high risk” while noting that people with lower HbA_1c levels also may have increased risk for diabetes if other risk factors are present.

The ADA's 2010 clinical practice recommendations declare HbA_1c levels of 5.7%–6.4% to be indicative of high risk, and state that patients with these levels may be referred to as having prediabetes, Dr. Bergenstal said. “At 5.7% we thought the risk was really quite high, and that people deserved to have some kind of program” to prevent diabetes.

The American Association of Clinical Endocrinologists suggested that an HbA_1c level of 5.5%–6.4% may be a better cut-off to identify higher-risk patients.

Unlike the glucose tests, HbA_1c testing does not require patients to fast before testing and carries several other advantages. Each of the statements supporting HbA_1c testing for diabetes diagnosis acknowledged a number of caveats, however, such as recognition that marginally elevated HbA_1c values in certain ethnic groups do not necessarily indicate diabetes. HbA_1c testing should not be used for diabetes diagnosis in patients with conditions that impair the correlation between HbA_1c and average blood glucose, such as iron deficiency or renal disease.

Only standardized, validated laboratory assays for HbA_1c were endorsed. Some of the newer point-of-care tests may be sufficiently accurate, but others are not, and more testing is needed before these can be endorsed for diabetes diagnosis, he said.

Disclosures: Dr. Bergenstal has held stock in Merck & Co. and participated in research or consulted for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly & Co., Intuity Medical, Lifescan (Johnson & Johnson), Mannkind, Medtronic, Merck, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

'Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?'

Source DR. BERGENSTAL

SAN DIEGO — The risk for gastric cancer was more than 200 times higher in patients with gastric intestinal metaplasia on initial or repeat upper endoscopy, compared with the control population, in a retrospective study of 11,600 male veterans.

Of the cohort of 354 veterans, 3% were diagnosed with gastric intestinal metaplasia (GIM) over a 19-year period; the researchers compared their records with those of 355 randomly selected patients seen at the GI clinic of the Brooklyn campus of the Veterans Affairs New York Harbor Healthcare System.

Among veterans with GIM, 6% (21 patients) were diagnosed with gastric cancer, a rate 200-fold higher than the rate in the control group, Dr. Naveen Anand and his associates reported at the annual meeting of the American College of Gastroenterology.

Half of the cancer diagnoses were made on the initial endoscopy, and half were made on follow-up endoscopy, said Dr. Anand, a chief resident at the State University of New York Downstate Medical Center, Brooklyn. Repeat endoscopies were performed on 53% of the cohort (including 11% who underwent four or more endoscopies).

Patients with GIM—especially patients in these higher-risk subgroups—should undergo regular endoscopic surveillance with careful histologic diagnosis of GIM based on biopsies at multiple gastric locations, Dr. Anand suggested. He acknowledged the cost of increased surveillance, but noted that the gastric cancer rate in patients with GIM is similar to that in patients with severe dysplasia. “If patients have severe dysplasia on biopsy, we will bring these patients back for follow-up. So, if we're seeing similar rates of progression to cancer from GIM, these patients probably should be followed up.”

He and his associates were surprised to find that having a history of Helicobacter pylori infection did not significantly influence pathology results. He attributed that to early intervention (that is, treatment that was initiated whenever H. pylori was diagnosed by histology).

Patients with GIM were more likely to be 70-90 years old, whereas those without GIM were more likely to be aged 50-70 years. About half of patients in the GIM and control groups were black and half were white, and there were few veterans of other races or ethnicities. The mean age in blacks was significantly older than in whites (75 vs. 71 years), and blacks accounted for 67% of patients who developed gastric cancer, Dr. Anand said.

“We believe there is a long lead time between the premalignant lesion and intestinal metaplasia and intestinal-type gastric carcinoma, similar to what we see in colon cancer and cervical cancer, which gives us an opportunity for possible surveillance and even possible intervention,” he said.

Disclosures: The investigators reported no conflicts of interest.

SAN DIEGO — The risk for gastric cancer was more than 200 times higher in patients with gastric intestinal metaplasia on initial or repeat upper endoscopy, compared with the control population, in a retrospective study of 11,600 male veterans.

Of the cohort of 354 veterans, 3% were diagnosed with gastric intestinal metaplasia (GIM) over a 19-year period; the researchers compared their records with those of 355 randomly selected patients seen at the GI clinic of the Brooklyn campus of the Veterans Affairs New York Harbor Healthcare System.

Among veterans with GIM, 6% (21 patients) were diagnosed with gastric cancer, a rate 200-fold higher than the rate in the control group, Dr. Naveen Anand and his associates reported at the annual meeting of the American College of Gastroenterology.

Half of the cancer diagnoses were made on the initial endoscopy, and half were made on follow-up endoscopy, said Dr. Anand, a chief resident at the State University of New York Downstate Medical Center, Brooklyn. Repeat endoscopies were performed on 53% of the cohort (including 11% who underwent four or more endoscopies).

Patients with GIM—especially patients in these higher-risk subgroups—should undergo regular endoscopic surveillance with careful histologic diagnosis of GIM based on biopsies at multiple gastric locations, Dr. Anand suggested. He acknowledged the cost of increased surveillance, but noted that the gastric cancer rate in patients with GIM is similar to that in patients with severe dysplasia. “If patients have severe dysplasia on biopsy, we will bring these patients back for follow-up. So, if we're seeing similar rates of progression to cancer from GIM, these patients probably should be followed up.”

He and his associates were surprised to find that having a history of Helicobacter pylori infection did not significantly influence pathology results. He attributed that to early intervention (that is, treatment that was initiated whenever H. pylori was diagnosed by histology).

Patients with GIM were more likely to be 70-90 years old, whereas those without GIM were more likely to be aged 50-70 years. About half of patients in the GIM and control groups were black and half were white, and there were few veterans of other races or ethnicities. The mean age in blacks was significantly older than in whites (75 vs. 71 years), and blacks accounted for 67% of patients who developed gastric cancer, Dr. Anand said.

“We believe there is a long lead time between the premalignant lesion and intestinal metaplasia and intestinal-type gastric carcinoma, similar to what we see in colon cancer and cervical cancer, which gives us an opportunity for possible surveillance and even possible intervention,” he said.

Disclosures: The investigators reported no conflicts of interest.

SAN DIEGO — The risk for gastric cancer was more than 200 times higher in patients with gastric intestinal metaplasia on initial or repeat upper endoscopy, compared with the control population, in a retrospective study of 11,600 male veterans.

Of the cohort of 354 veterans, 3% were diagnosed with gastric intestinal metaplasia (GIM) over a 19-year period; the researchers compared their records with those of 355 randomly selected patients seen at the GI clinic of the Brooklyn campus of the Veterans Affairs New York Harbor Healthcare System.

Among veterans with GIM, 6% (21 patients) were diagnosed with gastric cancer, a rate 200-fold higher than the rate in the control group, Dr. Naveen Anand and his associates reported at the annual meeting of the American College of Gastroenterology.

Half of the cancer diagnoses were made on the initial endoscopy, and half were made on follow-up endoscopy, said Dr. Anand, a chief resident at the State University of New York Downstate Medical Center, Brooklyn. Repeat endoscopies were performed on 53% of the cohort (including 11% who underwent four or more endoscopies).

Patients with GIM—especially patients in these higher-risk subgroups—should undergo regular endoscopic surveillance with careful histologic diagnosis of GIM based on biopsies at multiple gastric locations, Dr. Anand suggested. He acknowledged the cost of increased surveillance, but noted that the gastric cancer rate in patients with GIM is similar to that in patients with severe dysplasia. “If patients have severe dysplasia on biopsy, we will bring these patients back for follow-up. So, if we're seeing similar rates of progression to cancer from GIM, these patients probably should be followed up.”

He and his associates were surprised to find that having a history of Helicobacter pylori infection did not significantly influence pathology results. He attributed that to early intervention (that is, treatment that was initiated whenever H. pylori was diagnosed by histology).

Patients with GIM were more likely to be 70-90 years old, whereas those without GIM were more likely to be aged 50-70 years. About half of patients in the GIM and control groups were black and half were white, and there were few veterans of other races or ethnicities. The mean age in blacks was significantly older than in whites (75 vs. 71 years), and blacks accounted for 67% of patients who developed gastric cancer, Dr. Anand said.

“We believe there is a long lead time between the premalignant lesion and intestinal metaplasia and intestinal-type gastric carcinoma, similar to what we see in colon cancer and cervical cancer, which gives us an opportunity for possible surveillance and even possible intervention,” he said.

Disclosures: The investigators reported no conflicts of interest.

SAN FRANCISCO — The first update in recommendations for dietary intake of vitamin D since 1997 is expected in May, and is likely to endorse a conservative change from the status quo, one expert predicted.

The Institute of Medicine's Food and Nutrition Board has been reviewing the literature, including consideration of associations between serum vitamin D levels and disease indicators. “The grapevine says they are going to come in very conservative. They are going to require evidence from randomized, controlled trials, and those don't really exist today,” Dr. Neil Binkley said at a meeting sponsored by the American Diabetes Association.

The current Dietary Reference Intake (or Recommended Dietary Allowance) defines “adequate” intake as 200 IU/day for people up to age 50 years, 400 IU/day for those aged 51-70 years, and 600 IU/day for people older than 70 years.

Dr. Binkley, of the University of Wisconsin, Madison, expects the new intake recommendation for older adults to roughly double from 400 IU/day to 800 or maybe 1,000 IU/day.

“This will be an evolution,” he said. “I think the next iteration coming out in May is going to be a step up, but it's probably not going to get us all the way there.”

Recent data suggest that much higher daily intakes are needed to keep serum 25-hydroxyvitamin D levels (25[OH]D) in desired ranges, he explained. Generally, levels below 10 ng/mL indicate vitamin D deficiency, 10-30 ng/mL reflects vitamin D insufficiency, and a 25(OH)D level above 30 ng/mL is considered optimal.

Optimal levels may differ by bodily system, he noted. Serum 25(OH)D levels greater than 40 ng/mL may be best for bone health, while leg function appears to be better with levels above 38 ng/mL. A level above 36 ng/mL has been associated with reduced risk for colorectal cancer, and levels of 36-40 ng/mL have been linked to lower risk for periodontal disease.

One study calculated that 2,600 IU/day of vitamin D supplementation would be needed to ensure that 97.5% of older women have 25(OH)D levels at or above desirable levels (J. Nutr. 2006;136:1123-6). Other experts recommend that between 2,000 and 4,000 IU/day be consumed to reduce risks for cancer and autoimmune disease, Dr. Binkley said.

He aims for levels above 40 ng/mL in his patients to consistently hit targets above 30 ng/mL. As a rule of thumb, for each 1,000 IU of supplemental vitamin D₃, circulating 25(OH)D rises by about 6 ng/mL. For a patient with a serum 25(OH)D level of 20 ng/mL, taking 2,000 IU/day of vitamin D₃ would boost serum levels to about 32 ng/mL, and more than 3,000 IU/day would be needed to reach 40 ng/mL.

People are unlikely to get adequate vitamin D from sunlight, and fortified foods contain about 40-100 IU per serving. “If we truly do need 1,000, 2,000, or 4,000 IU/day, that means you'd need to drink between 10 and 40 glasses of milk per day to get your vitamin D requirement” at current fortification levels, he said. “I'm hopeful that after the Institute of Medicine meets, food fortification will go up.”

The American Academy of Pediatrics in 2008 recommended that children and adolescents get 400 IU/day of vitamin D, double the current Dietary Reference Intake. The National Osteoporosis Foundation recommends that people up to age 50 ingest 400-800 IU/day, and that adults aged 50 or older get 800-1,000 IU/day.

Observational studies suggest that low vitamin D levels are related to increased risk for diabetes. Several studies found that children who received vitamin D supplementation had a lower risk for type 1 diabetes, and the Nurses Health Study found a link between low vitamin D status and higher risk for type 2 diabetes over 20 years of follow-up.

Two prospective studies with 36 patients each found no effect of vitamin D supplementation on diabetes risk, but these studies were too small, Dr. Binkley said. A post hoc analysis of a randomized, controlled trial of 800 IU/day of vitamin D for fracture prevention in 3,314 women over age 70 found no protective effect against development of type 2 diabetes, but compliance with vitamin D supplements was poor, he noted (Age Ageing 2009;38:606-9).

The Women's Health Study also found no reduction in risk for diabetes after a median 7-year follow-up in 33,951 women randomized to 1,000 mg/day of calcium plus 400 IU/day of vitamin D or placebo (Diabetes Care 2008;31:701-7). The vitamin D dose was too low, Dr. Binkley said, and the compliance rate was only around 60%.

“We need larger studies, with higher vitamin D doses,” he said.

Disclosures: Dr. Binkley reported no relevant conflicts of interest.

SAN FRANCISCO — The first update in recommendations for dietary intake of vitamin D since 1997 is expected in May, and is likely to endorse a conservative change from the status quo, one expert predicted.

The Institute of Medicine's Food and Nutrition Board has been reviewing the literature, including consideration of associations between serum vitamin D levels and disease indicators. “The grapevine says they are going to come in very conservative. They are going to require evidence from randomized, controlled trials, and those don't really exist today,” Dr. Neil Binkley said at a meeting sponsored by the American Diabetes Association.

The current Dietary Reference Intake (or Recommended Dietary Allowance) defines “adequate” intake as 200 IU/day for people up to age 50 years, 400 IU/day for those aged 51-70 years, and 600 IU/day for people older than 70 years.

Dr. Binkley, of the University of Wisconsin, Madison, expects the new intake recommendation for older adults to roughly double from 400 IU/day to 800 or maybe 1,000 IU/day.

“This will be an evolution,” he said. “I think the next iteration coming out in May is going to be a step up, but it's probably not going to get us all the way there.”

Recent data suggest that much higher daily intakes are needed to keep serum 25-hydroxyvitamin D levels (25[OH]D) in desired ranges, he explained. Generally, levels below 10 ng/mL indicate vitamin D deficiency, 10-30 ng/mL reflects vitamin D insufficiency, and a 25(OH)D level above 30 ng/mL is considered optimal.

Optimal levels may differ by bodily system, he noted. Serum 25(OH)D levels greater than 40 ng/mL may be best for bone health, while leg function appears to be better with levels above 38 ng/mL. A level above 36 ng/mL has been associated with reduced risk for colorectal cancer, and levels of 36-40 ng/mL have been linked to lower risk for periodontal disease.

One study calculated that 2,600 IU/day of vitamin D supplementation would be needed to ensure that 97.5% of older women have 25(OH)D levels at or above desirable levels (J. Nutr. 2006;136:1123-6). Other experts recommend that between 2,000 and 4,000 IU/day be consumed to reduce risks for cancer and autoimmune disease, Dr. Binkley said.

He aims for levels above 40 ng/mL in his patients to consistently hit targets above 30 ng/mL. As a rule of thumb, for each 1,000 IU of supplemental vitamin D₃, circulating 25(OH)D rises by about 6 ng/mL. For a patient with a serum 25(OH)D level of 20 ng/mL, taking 2,000 IU/day of vitamin D₃ would boost serum levels to about 32 ng/mL, and more than 3,000 IU/day would be needed to reach 40 ng/mL.

People are unlikely to get adequate vitamin D from sunlight, and fortified foods contain about 40-100 IU per serving. “If we truly do need 1,000, 2,000, or 4,000 IU/day, that means you'd need to drink between 10 and 40 glasses of milk per day to get your vitamin D requirement” at current fortification levels, he said. “I'm hopeful that after the Institute of Medicine meets, food fortification will go up.”

The American Academy of Pediatrics in 2008 recommended that children and adolescents get 400 IU/day of vitamin D, double the current Dietary Reference Intake. The National Osteoporosis Foundation recommends that people up to age 50 ingest 400-800 IU/day, and that adults aged 50 or older get 800-1,000 IU/day.

Observational studies suggest that low vitamin D levels are related to increased risk for diabetes. Several studies found that children who received vitamin D supplementation had a lower risk for type 1 diabetes, and the Nurses Health Study found a link between low vitamin D status and higher risk for type 2 diabetes over 20 years of follow-up.

Two prospective studies with 36 patients each found no effect of vitamin D supplementation on diabetes risk, but these studies were too small, Dr. Binkley said. A post hoc analysis of a randomized, controlled trial of 800 IU/day of vitamin D for fracture prevention in 3,314 women over age 70 found no protective effect against development of type 2 diabetes, but compliance with vitamin D supplements was poor, he noted (Age Ageing 2009;38:606-9).

The Women's Health Study also found no reduction in risk for diabetes after a median 7-year follow-up in 33,951 women randomized to 1,000 mg/day of calcium plus 400 IU/day of vitamin D or placebo (Diabetes Care 2008;31:701-7). The vitamin D dose was too low, Dr. Binkley said, and the compliance rate was only around 60%.

“We need larger studies, with higher vitamin D doses,” he said.

Disclosures: Dr. Binkley reported no relevant conflicts of interest.

SAN FRANCISCO — The first update in recommendations for dietary intake of vitamin D since 1997 is expected in May, and is likely to endorse a conservative change from the status quo, one expert predicted.

The Institute of Medicine's Food and Nutrition Board has been reviewing the literature, including consideration of associations between serum vitamin D levels and disease indicators. “The grapevine says they are going to come in very conservative. They are going to require evidence from randomized, controlled trials, and those don't really exist today,” Dr. Neil Binkley said at a meeting sponsored by the American Diabetes Association.

The current Dietary Reference Intake (or Recommended Dietary Allowance) defines “adequate” intake as 200 IU/day for people up to age 50 years, 400 IU/day for those aged 51-70 years, and 600 IU/day for people older than 70 years.

Dr. Binkley, of the University of Wisconsin, Madison, expects the new intake recommendation for older adults to roughly double from 400 IU/day to 800 or maybe 1,000 IU/day.

“This will be an evolution,” he said. “I think the next iteration coming out in May is going to be a step up, but it's probably not going to get us all the way there.”

Recent data suggest that much higher daily intakes are needed to keep serum 25-hydroxyvitamin D levels (25[OH]D) in desired ranges, he explained. Generally, levels below 10 ng/mL indicate vitamin D deficiency, 10-30 ng/mL reflects vitamin D insufficiency, and a 25(OH)D level above 30 ng/mL is considered optimal.

Optimal levels may differ by bodily system, he noted. Serum 25(OH)D levels greater than 40 ng/mL may be best for bone health, while leg function appears to be better with levels above 38 ng/mL. A level above 36 ng/mL has been associated with reduced risk for colorectal cancer, and levels of 36-40 ng/mL have been linked to lower risk for periodontal disease.

One study calculated that 2,600 IU/day of vitamin D supplementation would be needed to ensure that 97.5% of older women have 25(OH)D levels at or above desirable levels (J. Nutr. 2006;136:1123-6). Other experts recommend that between 2,000 and 4,000 IU/day be consumed to reduce risks for cancer and autoimmune disease, Dr. Binkley said.

He aims for levels above 40 ng/mL in his patients to consistently hit targets above 30 ng/mL. As a rule of thumb, for each 1,000 IU of supplemental vitamin D₃, circulating 25(OH)D rises by about 6 ng/mL. For a patient with a serum 25(OH)D level of 20 ng/mL, taking 2,000 IU/day of vitamin D₃ would boost serum levels to about 32 ng/mL, and more than 3,000 IU/day would be needed to reach 40 ng/mL.

People are unlikely to get adequate vitamin D from sunlight, and fortified foods contain about 40-100 IU per serving. “If we truly do need 1,000, 2,000, or 4,000 IU/day, that means you'd need to drink between 10 and 40 glasses of milk per day to get your vitamin D requirement” at current fortification levels, he said. “I'm hopeful that after the Institute of Medicine meets, food fortification will go up.”

The American Academy of Pediatrics in 2008 recommended that children and adolescents get 400 IU/day of vitamin D, double the current Dietary Reference Intake. The National Osteoporosis Foundation recommends that people up to age 50 ingest 400-800 IU/day, and that adults aged 50 or older get 800-1,000 IU/day.

Observational studies suggest that low vitamin D levels are related to increased risk for diabetes. Several studies found that children who received vitamin D supplementation had a lower risk for type 1 diabetes, and the Nurses Health Study found a link between low vitamin D status and higher risk for type 2 diabetes over 20 years of follow-up.

Two prospective studies with 36 patients each found no effect of vitamin D supplementation on diabetes risk, but these studies were too small, Dr. Binkley said. A post hoc analysis of a randomized, controlled trial of 800 IU/day of vitamin D for fracture prevention in 3,314 women over age 70 found no protective effect against development of type 2 diabetes, but compliance with vitamin D supplements was poor, he noted (Age Ageing 2009;38:606-9).

The Women's Health Study also found no reduction in risk for diabetes after a median 7-year follow-up in 33,951 women randomized to 1,000 mg/day of calcium plus 400 IU/day of vitamin D or placebo (Diabetes Care 2008;31:701-7). The vitamin D dose was too low, Dr. Binkley said, and the compliance rate was only around 60%.

“We need larger studies, with higher vitamin D doses,” he said.

Disclosures: Dr. Binkley reported no relevant conflicts of interest.

SAN FRANCISCO — People with HIV infection tend to have more risk factors for bone loss than do people without HIV, and antiretroviral medications may be adding to that risk.

The specific role of antiretroviral therapy in bone loss has been controversial: Some studies say there is no association, but others suggest that the drugs do contribute to bone loss. Results of two small but well -conducted studies recently tipped the emphasis toward concern about the differential effects of antiretrovirals on bone mineral density, Dr. Dolores Shoback said at a meeting on HIV management sponsored by the University of California, San Francisco.

One randomized, controlled trial of 71 HIV-infected patients suggested that antiretroviral regimens that contain a protease inhibitor booster have a greater negative impact on spinal bone density than do regimens without a boosted protease inhibitor, said Dr. Shoback, professor of medicine at UCSF.

At baseline, 31% of the patients were osteopenic and 3% were osteoporotic. Bone densities were retested after 48 weeks of combination HIV therapy with a nonnucleoside reverse transcriptase inhibitor (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTIs), or an NNRTI and a boosted protease inhibitor, or two NRTIs and a boosted protease inhibitor. On average, the cohort as a whole lost 4% of lumbar spine bone mineral density and 3% of hip bone density during those 48 weeks (AIDS 2009;23:817-24).

The groups treated with boosted protease inhibitors lost significantly more spinal density—4.4% when combined with an NNRTI and 5.8% when combined with NRTIs—compared with the NNRTI-plus-NRTI arm (1.5%). Changes in hip bone density did not differ significantly by treatment group.

The second study randomized 50 HIV-infected patients to treatment with lopinavir/ritonavir plus zidovudine/lamivudine (ZDV/3TC) or lopinavir/ritonavir plus nevirapine, with bone densities compared at baseline and 2 years. At the start, up to 31% were osteopenic and up to 4% were osteoporotic. The ZDV/3TC group lost 6.3% of bone mineral density in the hip and 5.1% in the spine, compared with smaller losses of 2.3% in the hip and 2.6% in the spine in the nevirapine group. Spinal density decreased mainly in the first year and then stabilized, but hip density continued to fall in the second year (AIDS 2009;23:1367-76).

The investigators speculated that ZDV/3TC increased osteoclastic activity. “I think there probably is, in fact, a signal here,” Dr. Shoback said.

The evidence does not support changing antiretroviral regimens if bone mineral density is low, she added, but physicians should pay attention to nutrition (especially calcium and vitamin D), lifestyle factors, and weight-bearing exercise in patients with HIV.

Ongoing immune activation in HIV infection leads to high levels of cytokines. “There pretty much isn't a cytokine that doesn't have a negative effect on bone,” she said. Also, five of six cross-sectional studies found low levels of hydroxyvitamin D in patients with HIV. Compared with the HIV-negative population, people with HIV have higher rates of smoking and alcohol use, are more likely to be treated with steroids, and are more likely to have periods of immobilization and illness, bouts of weight loss, hypogonadism (in men), and amenorrhea (in women).

Dr. Shoback has been a speaker for Novartis.

HIV patients on antiretroviral regimens with a protease inhibitor booster have shown greater bone loss.

Source DR. SHOBACK

SAN FRANCISCO — People with HIV infection tend to have more risk factors for bone loss than do people without HIV, and antiretroviral medications may be adding to that risk.

The specific role of antiretroviral therapy in bone loss has been controversial: Some studies say there is no association, but others suggest that the drugs do contribute to bone loss. Results of two small but well -conducted studies recently tipped the emphasis toward concern about the differential effects of antiretrovirals on bone mineral density, Dr. Dolores Shoback said at a meeting on HIV management sponsored by the University of California, San Francisco.

One randomized, controlled trial of 71 HIV-infected patients suggested that antiretroviral regimens that contain a protease inhibitor booster have a greater negative impact on spinal bone density than do regimens without a boosted protease inhibitor, said Dr. Shoback, professor of medicine at UCSF.

At baseline, 31% of the patients were osteopenic and 3% were osteoporotic. Bone densities were retested after 48 weeks of combination HIV therapy with a nonnucleoside reverse transcriptase inhibitor (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTIs), or an NNRTI and a boosted protease inhibitor, or two NRTIs and a boosted protease inhibitor. On average, the cohort as a whole lost 4% of lumbar spine bone mineral density and 3% of hip bone density during those 48 weeks (AIDS 2009;23:817-24).

The groups treated with boosted protease inhibitors lost significantly more spinal density—4.4% when combined with an NNRTI and 5.8% when combined with NRTIs—compared with the NNRTI-plus-NRTI arm (1.5%). Changes in hip bone density did not differ significantly by treatment group.

The second study randomized 50 HIV-infected patients to treatment with lopinavir/ritonavir plus zidovudine/lamivudine (ZDV/3TC) or lopinavir/ritonavir plus nevirapine, with bone densities compared at baseline and 2 years. At the start, up to 31% were osteopenic and up to 4% were osteoporotic. The ZDV/3TC group lost 6.3% of bone mineral density in the hip and 5.1% in the spine, compared with smaller losses of 2.3% in the hip and 2.6% in the spine in the nevirapine group. Spinal density decreased mainly in the first year and then stabilized, but hip density continued to fall in the second year (AIDS 2009;23:1367-76).

The investigators speculated that ZDV/3TC increased osteoclastic activity. “I think there probably is, in fact, a signal here,” Dr. Shoback said.

The evidence does not support changing antiretroviral regimens if bone mineral density is low, she added, but physicians should pay attention to nutrition (especially calcium and vitamin D), lifestyle factors, and weight-bearing exercise in patients with HIV.

Ongoing immune activation in HIV infection leads to high levels of cytokines. “There pretty much isn't a cytokine that doesn't have a negative effect on bone,” she said. Also, five of six cross-sectional studies found low levels of hydroxyvitamin D in patients with HIV. Compared with the HIV-negative population, people with HIV have higher rates of smoking and alcohol use, are more likely to be treated with steroids, and are more likely to have periods of immobilization and illness, bouts of weight loss, hypogonadism (in men), and amenorrhea (in women).

Dr. Shoback has been a speaker for Novartis.

HIV patients on antiretroviral regimens with a protease inhibitor booster have shown greater bone loss.

Source DR. SHOBACK

SAN FRANCISCO — People with HIV infection tend to have more risk factors for bone loss than do people without HIV, and antiretroviral medications may be adding to that risk.

The specific role of antiretroviral therapy in bone loss has been controversial: Some studies say there is no association, but others suggest that the drugs do contribute to bone loss. Results of two small but well -conducted studies recently tipped the emphasis toward concern about the differential effects of antiretrovirals on bone mineral density, Dr. Dolores Shoback said at a meeting on HIV management sponsored by the University of California, San Francisco.

One randomized, controlled trial of 71 HIV-infected patients suggested that antiretroviral regimens that contain a protease inhibitor booster have a greater negative impact on spinal bone density than do regimens without a boosted protease inhibitor, said Dr. Shoback, professor of medicine at UCSF.

At baseline, 31% of the patients were osteopenic and 3% were osteoporotic. Bone densities were retested after 48 weeks of combination HIV therapy with a nonnucleoside reverse transcriptase inhibitor (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTIs), or an NNRTI and a boosted protease inhibitor, or two NRTIs and a boosted protease inhibitor. On average, the cohort as a whole lost 4% of lumbar spine bone mineral density and 3% of hip bone density during those 48 weeks (AIDS 2009;23:817-24).

The groups treated with boosted protease inhibitors lost significantly more spinal density—4.4% when combined with an NNRTI and 5.8% when combined with NRTIs—compared with the NNRTI-plus-NRTI arm (1.5%). Changes in hip bone density did not differ significantly by treatment group.

The second study randomized 50 HIV-infected patients to treatment with lopinavir/ritonavir plus zidovudine/lamivudine (ZDV/3TC) or lopinavir/ritonavir plus nevirapine, with bone densities compared at baseline and 2 years. At the start, up to 31% were osteopenic and up to 4% were osteoporotic. The ZDV/3TC group lost 6.3% of bone mineral density in the hip and 5.1% in the spine, compared with smaller losses of 2.3% in the hip and 2.6% in the spine in the nevirapine group. Spinal density decreased mainly in the first year and then stabilized, but hip density continued to fall in the second year (AIDS 2009;23:1367-76).

The investigators speculated that ZDV/3TC increased osteoclastic activity. “I think there probably is, in fact, a signal here,” Dr. Shoback said.

The evidence does not support changing antiretroviral regimens if bone mineral density is low, she added, but physicians should pay attention to nutrition (especially calcium and vitamin D), lifestyle factors, and weight-bearing exercise in patients with HIV.

Ongoing immune activation in HIV infection leads to high levels of cytokines. “There pretty much isn't a cytokine that doesn't have a negative effect on bone,” she said. Also, five of six cross-sectional studies found low levels of hydroxyvitamin D in patients with HIV. Compared with the HIV-negative population, people with HIV have higher rates of smoking and alcohol use, are more likely to be treated with steroids, and are more likely to have periods of immobilization and illness, bouts of weight loss, hypogonadism (in men), and amenorrhea (in women).

Dr. Shoback has been a speaker for Novartis.

HIV patients on antiretroviral regimens with a protease inhibitor booster have shown greater bone loss.

Source DR. SHOBACK

Postmenopausal women improved their physical fitness and reported reductions in the severity of menopausal symptoms after 12–24 weeks of aerobic exercise in three 70-minute sessions per week.

The 65 women (mean age 50.1 years) rated symptom severity on the self-administered Menopause Rating Scale questionnaire at baseline, 12 weeks, and 24 weeks in the uncontrolled study. The program of aerobic and calisthenic exercise aimed for 75%-80% of maximal heart rate according to the Karvonen method and consisted of 10 minutes of warm-up exercises; 40 minutes of aerobics; 15 minutes of exercise targeting the abdomen, hip, and leg muscles; and 5 minutes for cool-down and stretching.

Participants reported significant decreases in the severity of hot flushes, night sweats, cardiac symptoms, muscle and joint pain, sleeping disorder symptoms, depressive mood, irritability, anxiety, exhaustion, sexual problems, and urinary symptoms between the start and the end of the study, Dr. Selma Karacan of Selcuk University in Konya, Turkey reported.

Some symptoms showed improvement by 12 weeks and further significant improvements by 24 weeks, including vasomotor symptoms, muscle and joint pain, psychological symptoms, and sexual problems. The women reported no significant change in vaginal dryness (Sci. Sports 2009 [doi:10.1016/j.scispo.2009.07.004]).

Significant improvements also were seen in resting heart rate, systolic and diastolic blood pressures, flexibility, aerobic power, and the ability to perform sit-ups, push-ups, and right or left hand grips. Body weight, body mass index, body fat percentage, and fat weight decreased significantly, with no change in lean body mass values.

Dr. Karacan reported having no conflicts of interest.

Postmenopausal women improved their physical fitness and reported reductions in the severity of menopausal symptoms after 12–24 weeks of aerobic exercise in three 70-minute sessions per week.

The 65 women (mean age 50.1 years) rated symptom severity on the self-administered Menopause Rating Scale questionnaire at baseline, 12 weeks, and 24 weeks in the uncontrolled study. The program of aerobic and calisthenic exercise aimed for 75%-80% of maximal heart rate according to the Karvonen method and consisted of 10 minutes of warm-up exercises; 40 minutes of aerobics; 15 minutes of exercise targeting the abdomen, hip, and leg muscles; and 5 minutes for cool-down and stretching.

Participants reported significant decreases in the severity of hot flushes, night sweats, cardiac symptoms, muscle and joint pain, sleeping disorder symptoms, depressive mood, irritability, anxiety, exhaustion, sexual problems, and urinary symptoms between the start and the end of the study, Dr. Selma Karacan of Selcuk University in Konya, Turkey reported.

Some symptoms showed improvement by 12 weeks and further significant improvements by 24 weeks, including vasomotor symptoms, muscle and joint pain, psychological symptoms, and sexual problems. The women reported no significant change in vaginal dryness (Sci. Sports 2009 [doi:10.1016/j.scispo.2009.07.004]).

Significant improvements also were seen in resting heart rate, systolic and diastolic blood pressures, flexibility, aerobic power, and the ability to perform sit-ups, push-ups, and right or left hand grips. Body weight, body mass index, body fat percentage, and fat weight decreased significantly, with no change in lean body mass values.

Dr. Karacan reported having no conflicts of interest.

Postmenopausal women improved their physical fitness and reported reductions in the severity of menopausal symptoms after 12–24 weeks of aerobic exercise in three 70-minute sessions per week.

The 65 women (mean age 50.1 years) rated symptom severity on the self-administered Menopause Rating Scale questionnaire at baseline, 12 weeks, and 24 weeks in the uncontrolled study. The program of aerobic and calisthenic exercise aimed for 75%-80% of maximal heart rate according to the Karvonen method and consisted of 10 minutes of warm-up exercises; 40 minutes of aerobics; 15 minutes of exercise targeting the abdomen, hip, and leg muscles; and 5 minutes for cool-down and stretching.

Participants reported significant decreases in the severity of hot flushes, night sweats, cardiac symptoms, muscle and joint pain, sleeping disorder symptoms, depressive mood, irritability, anxiety, exhaustion, sexual problems, and urinary symptoms between the start and the end of the study, Dr. Selma Karacan of Selcuk University in Konya, Turkey reported.

Some symptoms showed improvement by 12 weeks and further significant improvements by 24 weeks, including vasomotor symptoms, muscle and joint pain, psychological symptoms, and sexual problems. The women reported no significant change in vaginal dryness (Sci. Sports 2009 [doi:10.1016/j.scispo.2009.07.004]).

Significant improvements also were seen in resting heart rate, systolic and diastolic blood pressures, flexibility, aerobic power, and the ability to perform sit-ups, push-ups, and right or left hand grips. Body weight, body mass index, body fat percentage, and fat weight decreased significantly, with no change in lean body mass values.

Dr. Karacan reported having no conflicts of interest.

Major Finding: Food and Drug Administration warnings and consensus recommendations have not increased testing for glucose levels and lipid profiles in Medicaid patients who are starting second-generation antipsychotics.

Data Source: Retrospective, population-based case-control study of data on 312,978 patients receiving Medicaid in three states.

Disclosures: The study was funded by Pfizer, which makes ziprasidone. The investigator has received research funds from Eli Lilly and Co., maker of olanzapine. Several other investigators have received funding from or been consultants to those and other companies that make second-generation antipsychotics.

Clinicians reduced prescriptions for one second-generation antipsychotic medication associated with metabolic problems after the Food and Drug Administration required warnings in 2003 about increased risk for diabetes and hyperlipidemia with that class of drugs, a new study shows.

Clinicians did not increase metabolic testing, however, despite recommendations issued at that time by the American Diabetes Association (ADA) and the American Psychiatric Association (APA) to test glucose and lipid levels in all patients who start a second-generation antipsychotic, a large controlled study found.

The study looked at 109,451 Medicaid recipients who started second-generation antipsychotic medications, and a control cohort of 203,527 patients who began taking albuterol but did not receive a second-generation antipsychotic.

Before the FDA warnings and the ADA/APA recommendations, 27% of patients who started a second-generation antipsychotic underwent baseline serum glucose testing, compared with 26% of control patients. Clinicians got baseline lipid tests in 10% of patients starting a second-generation antipsychotic and 11% of controls.

The only statistically significant change in testing rates during or after issuance of the warnings and guidelines was a clinically insignificant 2% increase in baseline lipid testing in patients starting a second-generation antipsychotic, Elaine H. Morrato, Dr. P.H., and her associates reported (Arch. Gen. Psychiatry 2010;67:17–24).

Previous studies have shown that the warnings produced no clinically meaningful change in glucose and lipid monitoring in commercially insured patients. The current retrospective cohort study is the first to find a similar pattern in a Medicaid population, reported Dr. Morrato of the University of Colorado, Denver.

The FDA compelled drug manufacturers to change labels for second-generation antipsychotics starting in December 2003 and to mail “Dear healthcare professional” letters to neuropsychiatric health care providers through August 2004 to warn of increased risk for hyperglycemia and diabetes with use of second-generation antipsychotics and to recommend monitoring of glucose levels in patients with diabetes, risk factors for diabetes, or hyperglycemia.

Concurrently, ADA and APA consensus statements described the metabolic risks of second-generation antipsychotics and provided a monitoring protocol that included baseline tests of glucose levels and lipid profiles.

The current study used data from patients in California, Missouri, and Oregon during a prewarning period (January 2002 through November 2003), a warning period during which the letters were mailed and the ADA/APA recommendations came out (December 2003 through August 2004), and a postwarning period (September 2004 through December 2005).

Prescriptions for clozapine were excluded from the study because of the drug's unique requirement for neutropenia-related testing.

Although the warnings and recommendations did not increase rates of metabolic testing in patients starting second-generation antipsychotics, clinicians did reduce their use of olanzapine, which would be consistent with intent to reduce metabolic risk, the investigators noted.

Before the FDA warnings, olanzapine use was already declining by 5% per year, compared with other second-generation antipsychotics; during the warning period, olanzapine use declined by 20% per year.

Use of a second-generation antipsychotic with lower metabolic risk—aripiprazole—increased significantly during the warning period but not the postwarning period, a change that might have been attributable more to California's elimination of the need for prior authorization for aripiprazole prescriptions during that time than to concerns about diabetes and hyperglycemia, Dr. Morrato and her associates suggested. The warnings by the FDA and the ADA/APA recommendations did not affect the use of quetiapine, ziprasidone, or risperidone.

People with serious mental illness are 1.5-2 times more likely to develop dyslipidemia, hypertension, obesity, and type 2 diabetes, compared with the general population.

More effort is needed to increase screening for diabetes and dyslipidemia in patients receiving second-generation antipsychotics and monitoring for metabolic side effects of these drugs, the authors suggested.

In some previous studies, 60%-80% of psychiatrists reported that they do regularly monitor glucose and lipid levels in patients taking second-generation antipsychotics, and two-thirds of community mental health centers reported having protocols or procedures to screen patients for diabetes and dyslipidemia.

More research is needed to understand the discrepancy between these reports and the low rates of screening found in the current study.

Major Finding: Food and Drug Administration warnings and consensus recommendations have not increased testing for glucose levels and lipid profiles in Medicaid patients who are starting second-generation antipsychotics.

Data Source: Retrospective, population-based case-control study of data on 312,978 patients receiving Medicaid in three states.

Disclosures: The study was funded by Pfizer, which makes ziprasidone. The investigator has received research funds from Eli Lilly and Co., maker of olanzapine. Several other investigators have received funding from or been consultants to those and other companies that make second-generation antipsychotics.

Clinicians reduced prescriptions for one second-generation antipsychotic medication associated with metabolic problems after the Food and Drug Administration required warnings in 2003 about increased risk for diabetes and hyperlipidemia with that class of drugs, a new study shows.

Clinicians did not increase metabolic testing, however, despite recommendations issued at that time by the American Diabetes Association (ADA) and the American Psychiatric Association (APA) to test glucose and lipid levels in all patients who start a second-generation antipsychotic, a large controlled study found.

The study looked at 109,451 Medicaid recipients who started second-generation antipsychotic medications, and a control cohort of 203,527 patients who began taking albuterol but did not receive a second-generation antipsychotic.

Before the FDA warnings and the ADA/APA recommendations, 27% of patients who started a second-generation antipsychotic underwent baseline serum glucose testing, compared with 26% of control patients. Clinicians got baseline lipid tests in 10% of patients starting a second-generation antipsychotic and 11% of controls.

The only statistically significant change in testing rates during or after issuance of the warnings and guidelines was a clinically insignificant 2% increase in baseline lipid testing in patients starting a second-generation antipsychotic, Elaine H. Morrato, Dr. P.H., and her associates reported (Arch. Gen. Psychiatry 2010;67:17–24).

Previous studies have shown that the warnings produced no clinically meaningful change in glucose and lipid monitoring in commercially insured patients. The current retrospective cohort study is the first to find a similar pattern in a Medicaid population, reported Dr. Morrato of the University of Colorado, Denver.

The FDA compelled drug manufacturers to change labels for second-generation antipsychotics starting in December 2003 and to mail “Dear healthcare professional” letters to neuropsychiatric health care providers through August 2004 to warn of increased risk for hyperglycemia and diabetes with use of second-generation antipsychotics and to recommend monitoring of glucose levels in patients with diabetes, risk factors for diabetes, or hyperglycemia.

Concurrently, ADA and APA consensus statements described the metabolic risks of second-generation antipsychotics and provided a monitoring protocol that included baseline tests of glucose levels and lipid profiles.

The current study used data from patients in California, Missouri, and Oregon during a prewarning period (January 2002 through November 2003), a warning period during which the letters were mailed and the ADA/APA recommendations came out (December 2003 through August 2004), and a postwarning period (September 2004 through December 2005).

Prescriptions for clozapine were excluded from the study because of the drug's unique requirement for neutropenia-related testing.

Although the warnings and recommendations did not increase rates of metabolic testing in patients starting second-generation antipsychotics, clinicians did reduce their use of olanzapine, which would be consistent with intent to reduce metabolic risk, the investigators noted.

Before the FDA warnings, olanzapine use was already declining by 5% per year, compared with other second-generation antipsychotics; during the warning period, olanzapine use declined by 20% per year.

Use of a second-generation antipsychotic with lower metabolic risk—aripiprazole—increased significantly during the warning period but not the postwarning period, a change that might have been attributable more to California's elimination of the need for prior authorization for aripiprazole prescriptions during that time than to concerns about diabetes and hyperglycemia, Dr. Morrato and her associates suggested. The warnings by the FDA and the ADA/APA recommendations did not affect the use of quetiapine, ziprasidone, or risperidone.

People with serious mental illness are 1.5-2 times more likely to develop dyslipidemia, hypertension, obesity, and type 2 diabetes, compared with the general population.

More effort is needed to increase screening for diabetes and dyslipidemia in patients receiving second-generation antipsychotics and monitoring for metabolic side effects of these drugs, the authors suggested.

In some previous studies, 60%-80% of psychiatrists reported that they do regularly monitor glucose and lipid levels in patients taking second-generation antipsychotics, and two-thirds of community mental health centers reported having protocols or procedures to screen patients for diabetes and dyslipidemia.

More research is needed to understand the discrepancy between these reports and the low rates of screening found in the current study.

Major Finding: Food and Drug Administration warnings and consensus recommendations have not increased testing for glucose levels and lipid profiles in Medicaid patients who are starting second-generation antipsychotics.

Data Source: Retrospective, population-based case-control study of data on 312,978 patients receiving Medicaid in three states.

Disclosures: The study was funded by Pfizer, which makes ziprasidone. The investigator has received research funds from Eli Lilly and Co., maker of olanzapine. Several other investigators have received funding from or been consultants to those and other companies that make second-generation antipsychotics.

Clinicians reduced prescriptions for one second-generation antipsychotic medication associated with metabolic problems after the Food and Drug Administration required warnings in 2003 about increased risk for diabetes and hyperlipidemia with that class of drugs, a new study shows.

Clinicians did not increase metabolic testing, however, despite recommendations issued at that time by the American Diabetes Association (ADA) and the American Psychiatric Association (APA) to test glucose and lipid levels in all patients who start a second-generation antipsychotic, a large controlled study found.

The study looked at 109,451 Medicaid recipients who started second-generation antipsychotic medications, and a control cohort of 203,527 patients who began taking albuterol but did not receive a second-generation antipsychotic.

Before the FDA warnings and the ADA/APA recommendations, 27% of patients who started a second-generation antipsychotic underwent baseline serum glucose testing, compared with 26% of control patients. Clinicians got baseline lipid tests in 10% of patients starting a second-generation antipsychotic and 11% of controls.

The only statistically significant change in testing rates during or after issuance of the warnings and guidelines was a clinically insignificant 2% increase in baseline lipid testing in patients starting a second-generation antipsychotic, Elaine H. Morrato, Dr. P.H., and her associates reported (Arch. Gen. Psychiatry 2010;67:17–24).

Previous studies have shown that the warnings produced no clinically meaningful change in glucose and lipid monitoring in commercially insured patients. The current retrospective cohort study is the first to find a similar pattern in a Medicaid population, reported Dr. Morrato of the University of Colorado, Denver.

The FDA compelled drug manufacturers to change labels for second-generation antipsychotics starting in December 2003 and to mail “Dear healthcare professional” letters to neuropsychiatric health care providers through August 2004 to warn of increased risk for hyperglycemia and diabetes with use of second-generation antipsychotics and to recommend monitoring of glucose levels in patients with diabetes, risk factors for diabetes, or hyperglycemia.

Concurrently, ADA and APA consensus statements described the metabolic risks of second-generation antipsychotics and provided a monitoring protocol that included baseline tests of glucose levels and lipid profiles.

The current study used data from patients in California, Missouri, and Oregon during a prewarning period (January 2002 through November 2003), a warning period during which the letters were mailed and the ADA/APA recommendations came out (December 2003 through August 2004), and a postwarning period (September 2004 through December 2005).

Prescriptions for clozapine were excluded from the study because of the drug's unique requirement for neutropenia-related testing.

Although the warnings and recommendations did not increase rates of metabolic testing in patients starting second-generation antipsychotics, clinicians did reduce their use of olanzapine, which would be consistent with intent to reduce metabolic risk, the investigators noted.

Before the FDA warnings, olanzapine use was already declining by 5% per year, compared with other second-generation antipsychotics; during the warning period, olanzapine use declined by 20% per year.

Use of a second-generation antipsychotic with lower metabolic risk—aripiprazole—increased significantly during the warning period but not the postwarning period, a change that might have been attributable more to California's elimination of the need for prior authorization for aripiprazole prescriptions during that time than to concerns about diabetes and hyperglycemia, Dr. Morrato and her associates suggested. The warnings by the FDA and the ADA/APA recommendations did not affect the use of quetiapine, ziprasidone, or risperidone.

People with serious mental illness are 1.5-2 times more likely to develop dyslipidemia, hypertension, obesity, and type 2 diabetes, compared with the general population.

More effort is needed to increase screening for diabetes and dyslipidemia in patients receiving second-generation antipsychotics and monitoring for metabolic side effects of these drugs, the authors suggested.

In some previous studies, 60%-80% of psychiatrists reported that they do regularly monitor glucose and lipid levels in patients taking second-generation antipsychotics, and two-thirds of community mental health centers reported having protocols or procedures to screen patients for diabetes and dyslipidemia.

More research is needed to understand the discrepancy between these reports and the low rates of screening found in the current study.

SAN FRANCISCO — It's okay to push for a rapid drop in high hemoglobin A_1c levels and tight glycemic control in patients with diabetes, but it's probably smart to ease up if there's no response within a year.

That's the key message from the recent major trials of aggressive glycemic control, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.

Many patients—but not all—can get their HbA_1c level below 7% and help prevent microvascular disease, if that's a goal the patient embraces and the physician provides the right therapies.

“Push hard, work with a team, make good choices, and if there's no response, be careful. Don't keep pushing, pushing, pushing,” said Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center in Saint Louis Park, Minn.

HbA_1c levels plummeted in the first year of intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N. Engl. J. Med. 2008;358:2545-59) but decreased more gradually in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560-72).

Contrary to what many have presumed, however, the increased risk of death in the ACCORD trial in the intensive-therapy group compared with the standard-therapy group was not associated with the fast decrease in HbA_1c, he said.

In a yet-to-be-published analysis, there was no increased mortality in ACCORD patients whose HbA_1c declined in the first year, and there was increased mortality if the HbA_1c did not drop. “It's just the opposite of what you might think. If you drop rapidly, you do fine. If you don't drop, you are at risk of dying,” probably because “there's something going on in your life or in your physiology” that increases risk, Dr. Bergenstal said.

Pushing hard to get the HbA_1c level below 6% may be overkill if the patient is not responding, he added. This was the goal of intensive therapy in the ACCORD trial, which was associated with increased cardiovascular risk. The unpublished analysis, however, showed that patients on intensive therapy who achieved lower HbA_1c levels were less likely to die.

“So, yes, the ACCORD intensive group had higher mortality” compared with the standard-therapy group “but it was people who could not get to goal,” Dr. Bergenstal explained. “If you are working hard, hard, hard and not getting a response, that is the person you back off on. They're not going to get to goal, and you're probably going to cause more harm than benefit.” This shouldn't be an excuse for not trying to get HbA_1c down initially, however, at least to less than 7%, he added.

Lessons to be learned from these studies and the other recent major trial of tight glucose control, the Veterans Affairs Diabetes Trial (VADT), go far beyond management of HbA_1c, Dr. Bergenstal said. “I think relying on the A_1c alone is causing part of the problem” in getting too few patients to glycemic goals, he said.

Organizing a clinical practice for success is a team effort that should include a nurse, educator, and/or pharmacist who can help monitor patients between physician visits and initiate a change in therapy according to an agreed-upon algorithm that serves as a checklist, not a cookbook, he suggested. A team helps motivate patient lifestyle changes and helps patients cope with pain or depression.

It's very important that patients and physicians agree on the goals of therapy, and that the right therapies are chosen to meet those goals, he added. Some patients, for example, may be more afraid of increasing their risk for hypoglycemic episodes with intensive therapy than of the risk for complications from higher HbA_1c levels. Others may be more concerned about avoiding the weight gain associated with some medications than about lowering HbA_1c levels.

Dr. Bergenstal has held stock in Merck & Co. and participated in research or been a consultant for that company as well as Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly and Co., Intuity Medical, LifeScan (Johnson & Johnson), Mannkind Corp., Medtronic, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

SAN FRANCISCO — It's okay to push for a rapid drop in high hemoglobin A_1c levels and tight glycemic control in patients with diabetes, but it's probably smart to ease up if there's no response within a year.

That's the key message from the recent major trials of aggressive glycemic control, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.

Many patients—but not all—can get their HbA_1c level below 7% and help prevent microvascular disease, if that's a goal the patient embraces and the physician provides the right therapies.

“Push hard, work with a team, make good choices, and if there's no response, be careful. Don't keep pushing, pushing, pushing,” said Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center in Saint Louis Park, Minn.

HbA_1c levels plummeted in the first year of intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N. Engl. J. Med. 2008;358:2545-59) but decreased more gradually in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560-72).

Contrary to what many have presumed, however, the increased risk of death in the ACCORD trial in the intensive-therapy group compared with the standard-therapy group was not associated with the fast decrease in HbA_1c, he said.

In a yet-to-be-published analysis, there was no increased mortality in ACCORD patients whose HbA_1c declined in the first year, and there was increased mortality if the HbA_1c did not drop. “It's just the opposite of what you might think. If you drop rapidly, you do fine. If you don't drop, you are at risk of dying,” probably because “there's something going on in your life or in your physiology” that increases risk, Dr. Bergenstal said.

Pushing hard to get the HbA_1c level below 6% may be overkill if the patient is not responding, he added. This was the goal of intensive therapy in the ACCORD trial, which was associated with increased cardiovascular risk. The unpublished analysis, however, showed that patients on intensive therapy who achieved lower HbA_1c levels were less likely to die.

“So, yes, the ACCORD intensive group had higher mortality” compared with the standard-therapy group “but it was people who could not get to goal,” Dr. Bergenstal explained. “If you are working hard, hard, hard and not getting a response, that is the person you back off on. They're not going to get to goal, and you're probably going to cause more harm than benefit.” This shouldn't be an excuse for not trying to get HbA_1c down initially, however, at least to less than 7%, he added.

Lessons to be learned from these studies and the other recent major trial of tight glucose control, the Veterans Affairs Diabetes Trial (VADT), go far beyond management of HbA_1c, Dr. Bergenstal said. “I think relying on the A_1c alone is causing part of the problem” in getting too few patients to glycemic goals, he said.

Organizing a clinical practice for success is a team effort that should include a nurse, educator, and/or pharmacist who can help monitor patients between physician visits and initiate a change in therapy according to an agreed-upon algorithm that serves as a checklist, not a cookbook, he suggested. A team helps motivate patient lifestyle changes and helps patients cope with pain or depression.

It's very important that patients and physicians agree on the goals of therapy, and that the right therapies are chosen to meet those goals, he added. Some patients, for example, may be more afraid of increasing their risk for hypoglycemic episodes with intensive therapy than of the risk for complications from higher HbA_1c levels. Others may be more concerned about avoiding the weight gain associated with some medications than about lowering HbA_1c levels.

Dr. Bergenstal has held stock in Merck & Co. and participated in research or been a consultant for that company as well as Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly and Co., Intuity Medical, LifeScan (Johnson & Johnson), Mannkind Corp., Medtronic, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

SAN FRANCISCO — It's okay to push for a rapid drop in high hemoglobin A_1c levels and tight glycemic control in patients with diabetes, but it's probably smart to ease up if there's no response within a year.

That's the key message from the recent major trials of aggressive glycemic control, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association.

Many patients—but not all—can get their HbA_1c level below 7% and help prevent microvascular disease, if that's a goal the patient embraces and the physician provides the right therapies.

“Push hard, work with a team, make good choices, and if there's no response, be careful. Don't keep pushing, pushing, pushing,” said Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center in Saint Louis Park, Minn.

HbA_1c levels plummeted in the first year of intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N. Engl. J. Med. 2008;358:2545-59) but decreased more gradually in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560-72).

Contrary to what many have presumed, however, the increased risk of death in the ACCORD trial in the intensive-therapy group compared with the standard-therapy group was not associated with the fast decrease in HbA_1c, he said.

In a yet-to-be-published analysis, there was no increased mortality in ACCORD patients whose HbA_1c declined in the first year, and there was increased mortality if the HbA_1c did not drop. “It's just the opposite of what you might think. If you drop rapidly, you do fine. If you don't drop, you are at risk of dying,” probably because “there's something going on in your life or in your physiology” that increases risk, Dr. Bergenstal said.

Pushing hard to get the HbA_1c level below 6% may be overkill if the patient is not responding, he added. This was the goal of intensive therapy in the ACCORD trial, which was associated with increased cardiovascular risk. The unpublished analysis, however, showed that patients on intensive therapy who achieved lower HbA_1c levels were less likely to die.

“So, yes, the ACCORD intensive group had higher mortality” compared with the standard-therapy group “but it was people who could not get to goal,” Dr. Bergenstal explained. “If you are working hard, hard, hard and not getting a response, that is the person you back off on. They're not going to get to goal, and you're probably going to cause more harm than benefit.” This shouldn't be an excuse for not trying to get HbA_1c down initially, however, at least to less than 7%, he added.

Lessons to be learned from these studies and the other recent major trial of tight glucose control, the Veterans Affairs Diabetes Trial (VADT), go far beyond management of HbA_1c, Dr. Bergenstal said. “I think relying on the A_1c alone is causing part of the problem” in getting too few patients to glycemic goals, he said.

Organizing a clinical practice for success is a team effort that should include a nurse, educator, and/or pharmacist who can help monitor patients between physician visits and initiate a change in therapy according to an agreed-upon algorithm that serves as a checklist, not a cookbook, he suggested. A team helps motivate patient lifestyle changes and helps patients cope with pain or depression.

It's very important that patients and physicians agree on the goals of therapy, and that the right therapies are chosen to meet those goals, he added. Some patients, for example, may be more afraid of increasing their risk for hypoglycemic episodes with intensive therapy than of the risk for complications from higher HbA_1c levels. Others may be more concerned about avoiding the weight gain associated with some medications than about lowering HbA_1c levels.

Dr. Bergenstal has held stock in Merck & Co. and participated in research or been a consultant for that company as well as Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly and Co., Intuity Medical, LifeScan (Johnson & Johnson), Mannkind Corp., Medtronic, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

SAN FRANCISCO — The use of a hemoglobin A_1c level of 6.5% or higher to diagnose type 2 diabetes is now mainstream, with formal endorsements from three major U.S. medical associations in 2010 supporting an International Expert Committee's 2009 consensus recommendations.

The World Health Organization and other groups are likely to follow suit, though with greater emphasis on this as an alternative to conventional means of diagnosing diabetes in regions that don't have easy access to standardized assays for HbA_1c, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association

He welcomed the change, and the rationale for using HbA_1c to diagnose diabetes. “Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?” asked Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center, Saint Louis Park, Minn.

The International Expert Committee, with members appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation, got the ball rolling by publishing a consensus opinion in July 2009 to make HbA_1c the preferred test for diagnosing type 2 diabetes (Diabetes Care 2009;32:1327-34).

The ADA translated the international consensus into clinical practice recommendations that were published in its annual update on standards of care in January 2010 (Diabetes Care 2010;33: S11–61). The ADA backed away from calling HbA1_c the preferred test, instead saying it's one of four diagnostic options, but acknowledged that it may become the most popular diagnostic test for type 2 diabetes.

The other, conventional diagnostic criteria are a fasting plasma glucose level of at least 126 mg/dL, an oral glucose tolerance test result of 200 mg/dL or higher, or classic symptoms of hyperglycemia plus a randomly obtained glucose level of at least 200 mg/dL.

The Endocrine Society endorsed the ADA clinical practice recommendations in a separate statement issued Jan. 20, 2010. The American Association of Clinical Endocrinologists followed with its own supportive statement on Feb. 1, 2010.

Inevitably, clinicians will have patients whose HbA_1c and glucose results conflict, Dr. Bergenstal noted. If one is abnormal and the other is not, repeat the abnormal test, the ADA recommendations say. “If that is still abnormal, you've made the diagnosis,” he said. If, instead, you perform a third test method for confirmation and the result meets diagnostic criteria, diabetes is confirmed, he added.

Results are less clear when a patient has one normal and one abnormal test result, and repeating the abnormal test produces a normal result. “Then you have someone who is obviously on the edge” and who should be retested again in 3–6 months, he said.

Another gray area is the use of HbA_1c to define prediabetes (patients at high risk for developing diabetes or cardiovascular disease). The statements from the various groups differ somewhat in how they address this.

“I think everyone agrees that for at-risk patients, that's a little bit more of a judgment call,” Dr. Bergenstal said.

The International Expert Committee suggested avoiding the concept of prediabetes because the risk is a continuum with a fairly steady rise in risk as HbA_1c levels increase. They identified HbA_1c levels of 6.0%-6.4% as “very high risk” while noting that people with lower HbA_1c levels also may have increased risk for diabetes if other risk factors are present. The Committee recommended starting preventive strategies depending on the intensity with which a clinician wants to deploy any available resources, he said.

The ADA's 2010 clinical practice recommendations declare HbA_1c levels of 5.7%-6.4% to be indicative of high risk, and state that patients with these levels may be referred to as having prediabetes, Dr. Bergenstal said. “At 5.7% we thought the risk was really quite high, and that people deserved to have some kind of program” to prevent diabetes.

The American Association of Clinical Endocrinologists suggested that an HbA_1c level of 5.5%-6.4% may be a better cut-off to identify higher-risk patients.

Unlike the glucose tests, HbA_1c testing does not require patients to fast before testing, and carries several other advantages. Each of the statements supporting HbA_1c testing for diabetes diagnosis acknowledged a number of caveats, however, such as recognition that marginally elevated HbA_1c values in certain ethnic groups do not necessarily indicate diabetes. HbA_1c testing should not be used for diabetes diagnosis in patients with conditions that impair the correlation between HbA_1c and average blood glucose, such as iron deficiency or renal disease.

Only standardized, validated laboratory assays for HbA_1c were endorsed. Some of the newer point-of-care tests may be sufficiently accurate, but others are not, and more testing is needed before these can be endorsed for diabetes diagnosis, he said.

Dr. Bergenstal has held stock in Merck & Co. and participated in research or consulted for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly & Co., Intuity Medical, Lifescan (Johnson & Johnson), Mannkind, Medtronic, Merck, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

If tests are inconclusive, a patient 'who is obviously on the edge' should be retested again in 3–6 months.

Source DR. BERGENSTAL

SAN FRANCISCO — The use of a hemoglobin A_1c level of 6.5% or higher to diagnose type 2 diabetes is now mainstream, with formal endorsements from three major U.S. medical associations in 2010 supporting an International Expert Committee's 2009 consensus recommendations.

The World Health Organization and other groups are likely to follow suit, though with greater emphasis on this as an alternative to conventional means of diagnosing diabetes in regions that don't have easy access to standardized assays for HbA_1c, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association

He welcomed the change, and the rationale for using HbA_1c to diagnose diabetes. “Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?” asked Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center, Saint Louis Park, Minn.

The International Expert Committee, with members appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation, got the ball rolling by publishing a consensus opinion in July 2009 to make HbA_1c the preferred test for diagnosing type 2 diabetes (Diabetes Care 2009;32:1327-34).

The ADA translated the international consensus into clinical practice recommendations that were published in its annual update on standards of care in January 2010 (Diabetes Care 2010;33: S11–61). The ADA backed away from calling HbA1_c the preferred test, instead saying it's one of four diagnostic options, but acknowledged that it may become the most popular diagnostic test for type 2 diabetes.

The other, conventional diagnostic criteria are a fasting plasma glucose level of at least 126 mg/dL, an oral glucose tolerance test result of 200 mg/dL or higher, or classic symptoms of hyperglycemia plus a randomly obtained glucose level of at least 200 mg/dL.

The Endocrine Society endorsed the ADA clinical practice recommendations in a separate statement issued Jan. 20, 2010. The American Association of Clinical Endocrinologists followed with its own supportive statement on Feb. 1, 2010.

Inevitably, clinicians will have patients whose HbA_1c and glucose results conflict, Dr. Bergenstal noted. If one is abnormal and the other is not, repeat the abnormal test, the ADA recommendations say. “If that is still abnormal, you've made the diagnosis,” he said. If, instead, you perform a third test method for confirmation and the result meets diagnostic criteria, diabetes is confirmed, he added.

Results are less clear when a patient has one normal and one abnormal test result, and repeating the abnormal test produces a normal result. “Then you have someone who is obviously on the edge” and who should be retested again in 3–6 months, he said.

Another gray area is the use of HbA_1c to define prediabetes (patients at high risk for developing diabetes or cardiovascular disease). The statements from the various groups differ somewhat in how they address this.

“I think everyone agrees that for at-risk patients, that's a little bit more of a judgment call,” Dr. Bergenstal said.

The International Expert Committee suggested avoiding the concept of prediabetes because the risk is a continuum with a fairly steady rise in risk as HbA_1c levels increase. They identified HbA_1c levels of 6.0%-6.4% as “very high risk” while noting that people with lower HbA_1c levels also may have increased risk for diabetes if other risk factors are present. The Committee recommended starting preventive strategies depending on the intensity with which a clinician wants to deploy any available resources, he said.

The ADA's 2010 clinical practice recommendations declare HbA_1c levels of 5.7%-6.4% to be indicative of high risk, and state that patients with these levels may be referred to as having prediabetes, Dr. Bergenstal said. “At 5.7% we thought the risk was really quite high, and that people deserved to have some kind of program” to prevent diabetes.

The American Association of Clinical Endocrinologists suggested that an HbA_1c level of 5.5%-6.4% may be a better cut-off to identify higher-risk patients.

Unlike the glucose tests, HbA_1c testing does not require patients to fast before testing, and carries several other advantages. Each of the statements supporting HbA_1c testing for diabetes diagnosis acknowledged a number of caveats, however, such as recognition that marginally elevated HbA_1c values in certain ethnic groups do not necessarily indicate diabetes. HbA_1c testing should not be used for diabetes diagnosis in patients with conditions that impair the correlation between HbA_1c and average blood glucose, such as iron deficiency or renal disease.

Only standardized, validated laboratory assays for HbA_1c were endorsed. Some of the newer point-of-care tests may be sufficiently accurate, but others are not, and more testing is needed before these can be endorsed for diabetes diagnosis, he said.

Dr. Bergenstal has held stock in Merck & Co. and participated in research or consulted for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly & Co., Intuity Medical, Lifescan (Johnson & Johnson), Mannkind, Medtronic, Merck, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

If tests are inconclusive, a patient 'who is obviously on the edge' should be retested again in 3–6 months.

Source DR. BERGENSTAL

SAN FRANCISCO — The use of a hemoglobin A_1c level of 6.5% or higher to diagnose type 2 diabetes is now mainstream, with formal endorsements from three major U.S. medical associations in 2010 supporting an International Expert Committee's 2009 consensus recommendations.

The World Health Organization and other groups are likely to follow suit, though with greater emphasis on this as an alternative to conventional means of diagnosing diabetes in regions that don't have easy access to standardized assays for HbA_1c, Dr. Richard M. Bergenstal said at a meeting sponsored by the American Diabetes Association

He welcomed the change, and the rationale for using HbA_1c to diagnose diabetes. “Why do we follow it so closely once you're diagnosed, but pay no attention to it before you're diagnosed?” asked Dr. Bergenstal, president of medicine and science for the ADA and executive director of the International Diabetes Center, Saint Louis Park, Minn.

The International Expert Committee, with members appointed by the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation, got the ball rolling by publishing a consensus opinion in July 2009 to make HbA_1c the preferred test for diagnosing type 2 diabetes (Diabetes Care 2009;32:1327-34).

The ADA translated the international consensus into clinical practice recommendations that were published in its annual update on standards of care in January 2010 (Diabetes Care 2010;33: S11–61). The ADA backed away from calling HbA1_c the preferred test, instead saying it's one of four diagnostic options, but acknowledged that it may become the most popular diagnostic test for type 2 diabetes.

The other, conventional diagnostic criteria are a fasting plasma glucose level of at least 126 mg/dL, an oral glucose tolerance test result of 200 mg/dL or higher, or classic symptoms of hyperglycemia plus a randomly obtained glucose level of at least 200 mg/dL.

The Endocrine Society endorsed the ADA clinical practice recommendations in a separate statement issued Jan. 20, 2010. The American Association of Clinical Endocrinologists followed with its own supportive statement on Feb. 1, 2010.

Inevitably, clinicians will have patients whose HbA_1c and glucose results conflict, Dr. Bergenstal noted. If one is abnormal and the other is not, repeat the abnormal test, the ADA recommendations say. “If that is still abnormal, you've made the diagnosis,” he said. If, instead, you perform a third test method for confirmation and the result meets diagnostic criteria, diabetes is confirmed, he added.

Results are less clear when a patient has one normal and one abnormal test result, and repeating the abnormal test produces a normal result. “Then you have someone who is obviously on the edge” and who should be retested again in 3–6 months, he said.

Another gray area is the use of HbA_1c to define prediabetes (patients at high risk for developing diabetes or cardiovascular disease). The statements from the various groups differ somewhat in how they address this.

“I think everyone agrees that for at-risk patients, that's a little bit more of a judgment call,” Dr. Bergenstal said.

The International Expert Committee suggested avoiding the concept of prediabetes because the risk is a continuum with a fairly steady rise in risk as HbA_1c levels increase. They identified HbA_1c levels of 6.0%-6.4% as “very high risk” while noting that people with lower HbA_1c levels also may have increased risk for diabetes if other risk factors are present. The Committee recommended starting preventive strategies depending on the intensity with which a clinician wants to deploy any available resources, he said.

The ADA's 2010 clinical practice recommendations declare HbA_1c levels of 5.7%-6.4% to be indicative of high risk, and state that patients with these levels may be referred to as having prediabetes, Dr. Bergenstal said. “At 5.7% we thought the risk was really quite high, and that people deserved to have some kind of program” to prevent diabetes.

The American Association of Clinical Endocrinologists suggested that an HbA_1c level of 5.5%-6.4% may be a better cut-off to identify higher-risk patients.

Unlike the glucose tests, HbA_1c testing does not require patients to fast before testing, and carries several other advantages. Each of the statements supporting HbA_1c testing for diabetes diagnosis acknowledged a number of caveats, however, such as recognition that marginally elevated HbA_1c values in certain ethnic groups do not necessarily indicate diabetes. HbA_1c testing should not be used for diabetes diagnosis in patients with conditions that impair the correlation between HbA_1c and average blood glucose, such as iron deficiency or renal disease.

Only standardized, validated laboratory assays for HbA_1c were endorsed. Some of the newer point-of-care tests may be sufficiently accurate, but others are not, and more testing is needed before these can be endorsed for diabetes diagnosis, he said.

Dr. Bergenstal has held stock in Merck & Co. and participated in research or consulted for Abbott Diabetes Care, Amylin Pharmaceuticals, Bayer, Eli Lilly & Co., Intuity Medical, Lifescan (Johnson & Johnson), Mannkind, Medtronic, Merck, Novo Nordisk, ResMed, Roche Diagnostics Corp., Sanofi-Aventis, Pfizer, and Takeda Pharmaceuticals.

If tests are inconclusive, a patient 'who is obviously on the edge' should be retested again in 3–6 months.

Source DR. BERGENSTAL

Major Finding: Women who had ever used hormone therapy had a 14% higher risk for cataract extraction and current HT users had an 18% higher risk, compared with women who never used HT.

Data Source: A 98-month Swedish prospective study of 30,861 postmenopausal women.

Disclosures: Dr. Lindblad and her associates reported having no conflicts of interest related to the study, which was funded by Swedish government agencies and research foundations.

Women who used hormone therapy were more likely to need cataract surgery, a risk potentiated by drinking alcohol, a large Swedish prospective study found.

In a 98-month study of 30,861 postmenopausal women, those who had ever used hormone therapy (HT) had a 14% higher risk for cataract extraction and current HT users had an 18% higher risk, compared with women who had never used HT, in a multivariate adjusted analysis, Dr. Birgitta Ejdervik Lindblad and her associates reported. The study appears in the journal Ophthalmology (doi:10.1016/j.ophtha.2009.07.046).

Cataract extraction was even more likely in women who were using HT and drank alcohol. Among current HT users, any alcohol consumption was associated with a 29% higher risk for cataract extraction, and those who drank more than one alcoholic drink per day had a 42% higher risk, compared with women who were neither using HT nor drinking alcohol. (One drink was defined as about 13 g of alcohol, roughly equal to one glass of wine, bottle of beer, or drink of liquor.) Drinking alcohol has been associated with increased levels of plasma estrogen in postmenopausal women in prior studies.

Investigators collected data from women in the Swedish Mammography Cohort who completed questionnaires in September 1997 about hormone status, use of hormone therapy, and lifestyle factors. The researchers followed them through October 2005 and compared their names with those on Swedish registers of cataract surgeries, which identified 4,324 women who underwent cataract surgery during the study period.

Among women aged 65 years or older, the risk for cataract surgery was 73% higher in those using hormone therapy, compared with women who never used HT, after the researchers adjusted for the effects of alcohol consumption, smoking, diabetes, hypertension, steroid or vitamin use, body mass index, and education level.

Longer use of HT was associated with a higher risk for cataract extraction in a linear fashion, added Dr. Lindblad of the Karolinska Institute, Stockholm. Current users of hormone therapy reported a longer duration of HT (a mean of 6 years) compared with past users (4 years). Women who used HT for more than 10 years had a 20% higher risk of cataract extraction, compared with women who never used HT.

Dr. Lindblad and her associates advised caution in comparing their study with those conducted outside of Sweden because HT preparations and clinical practices vary between countries. Hormone therapy with estrogen alone is more common in the United States. And U.S. versions of HT for postmenopausal symptoms like hot flushes most commonly use conjugated estrogens alone or in combination with progesteronelike progestins, while in Sweden the predominant hormone therapy is a combination of estradiol with testosteronelike progestins. The different chemistries might have different effects on the body.

Major Finding: Women who had ever used hormone therapy had a 14% higher risk for cataract extraction and current HT users had an 18% higher risk, compared with women who never used HT.

Data Source: A 98-month Swedish prospective study of 30,861 postmenopausal women.

Disclosures: Dr. Lindblad and her associates reported having no conflicts of interest related to the study, which was funded by Swedish government agencies and research foundations.

Women who used hormone therapy were more likely to need cataract surgery, a risk potentiated by drinking alcohol, a large Swedish prospective study found.

In a 98-month study of 30,861 postmenopausal women, those who had ever used hormone therapy (HT) had a 14% higher risk for cataract extraction and current HT users had an 18% higher risk, compared with women who had never used HT, in a multivariate adjusted analysis, Dr. Birgitta Ejdervik Lindblad and her associates reported. The study appears in the journal Ophthalmology (doi:10.1016/j.ophtha.2009.07.046).

Cataract extraction was even more likely in women who were using HT and drank alcohol. Among current HT users, any alcohol consumption was associated with a 29% higher risk for cataract extraction, and those who drank more than one alcoholic drink per day had a 42% higher risk, compared with women who were neither using HT nor drinking alcohol. (One drink was defined as about 13 g of alcohol, roughly equal to one glass of wine, bottle of beer, or drink of liquor.) Drinking alcohol has been associated with increased levels of plasma estrogen in postmenopausal women in prior studies.

Investigators collected data from women in the Swedish Mammography Cohort who completed questionnaires in September 1997 about hormone status, use of hormone therapy, and lifestyle factors. The researchers followed them through October 2005 and compared their names with those on Swedish registers of cataract surgeries, which identified 4,324 women who underwent cataract surgery during the study period.

Among women aged 65 years or older, the risk for cataract surgery was 73% higher in those using hormone therapy, compared with women who never used HT, after the researchers adjusted for the effects of alcohol consumption, smoking, diabetes, hypertension, steroid or vitamin use, body mass index, and education level.

Longer use of HT was associated with a higher risk for cataract extraction in a linear fashion, added Dr. Lindblad of the Karolinska Institute, Stockholm. Current users of hormone therapy reported a longer duration of HT (a mean of 6 years) compared with past users (4 years). Women who used HT for more than 10 years had a 20% higher risk of cataract extraction, compared with women who never used HT.

Dr. Lindblad and her associates advised caution in comparing their study with those conducted outside of Sweden because HT preparations and clinical practices vary between countries. Hormone therapy with estrogen alone is more common in the United States. And U.S. versions of HT for postmenopausal symptoms like hot flushes most commonly use conjugated estrogens alone or in combination with progesteronelike progestins, while in Sweden the predominant hormone therapy is a combination of estradiol with testosteronelike progestins. The different chemistries might have different effects on the body.

Major Finding: Women who had ever used hormone therapy had a 14% higher risk for cataract extraction and current HT users had an 18% higher risk, compared with women who never used HT.

Data Source: A 98-month Swedish prospective study of 30,861 postmenopausal women.

Disclosures: Dr. Lindblad and her associates reported having no conflicts of interest related to the study, which was funded by Swedish government agencies and research foundations.

Women who used hormone therapy were more likely to need cataract surgery, a risk potentiated by drinking alcohol, a large Swedish prospective study found.

In a 98-month study of 30,861 postmenopausal women, those who had ever used hormone therapy (HT) had a 14% higher risk for cataract extraction and current HT users had an 18% higher risk, compared with women who had never used HT, in a multivariate adjusted analysis, Dr. Birgitta Ejdervik Lindblad and her associates reported. The study appears in the journal Ophthalmology (doi:10.1016/j.ophtha.2009.07.046).

Cataract extraction was even more likely in women who were using HT and drank alcohol. Among current HT users, any alcohol consumption was associated with a 29% higher risk for cataract extraction, and those who drank more than one alcoholic drink per day had a 42% higher risk, compared with women who were neither using HT nor drinking alcohol. (One drink was defined as about 13 g of alcohol, roughly equal to one glass of wine, bottle of beer, or drink of liquor.) Drinking alcohol has been associated with increased levels of plasma estrogen in postmenopausal women in prior studies.

Investigators collected data from women in the Swedish Mammography Cohort who completed questionnaires in September 1997 about hormone status, use of hormone therapy, and lifestyle factors. The researchers followed them through October 2005 and compared their names with those on Swedish registers of cataract surgeries, which identified 4,324 women who underwent cataract surgery during the study period.

Among women aged 65 years or older, the risk for cataract surgery was 73% higher in those using hormone therapy, compared with women who never used HT, after the researchers adjusted for the effects of alcohol consumption, smoking, diabetes, hypertension, steroid or vitamin use, body mass index, and education level.

Longer use of HT was associated with a higher risk for cataract extraction in a linear fashion, added Dr. Lindblad of the Karolinska Institute, Stockholm. Current users of hormone therapy reported a longer duration of HT (a mean of 6 years) compared with past users (4 years). Women who used HT for more than 10 years had a 20% higher risk of cataract extraction, compared with women who never used HT.

Dr. Lindblad and her associates advised caution in comparing their study with those conducted outside of Sweden because HT preparations and clinical practices vary between countries. Hormone therapy with estrogen alone is more common in the United States. And U.S. versions of HT for postmenopausal symptoms like hot flushes most commonly use conjugated estrogens alone or in combination with progesteronelike progestins, while in Sweden the predominant hormone therapy is a combination of estradiol with testosteronelike progestins. The different chemistries might have different effects on the body.

Major Finding: Six months of 70-minute aerobic exercise sessions three days per week significantly reduced the severity of menopausal symptoms while improving physical fitness.

Data Source: An uncontrolled study in 65 postmenopausal women.

Disclosures: None reported.

Postmenopausal women improved their physical fitness and reported reductions in the severity of menopausal symptoms after 12–24 weeks of aerobic exercise in three 70-minute sessions per week.

The 65 women (mean age, 50.1 years) rated the severity of menopausal symptoms on the self-administered Menopause Rating Scale questionnaire at baseline, 12 weeks, and 24 weeks in the uncontrolled study. The program of aerobic and calisthenic exercise aimed for 75%–80% of maximal heart rate according to the Karvonen method and consisted of 10 minutes of warm-up exercises; 40 minutes of aerobics; 15 minutes of exercise targeting the abdomen, hip, and leg muscles; and 5 minutes for cooldown and stretching.

Participants reported significant decreases in the severity of hot flushes, night sweats, cardiac symptoms, muscle and joint pain, sleeping disorder symptoms, depressive mood, irritability, anxiety, exhaustion, sexual problems, and urinary symptoms between the start and end of the study, Dr. Selma Karacan of Selcuk University in Konya, Turkey, reported (Sci. Sports 2009 [doi:10.1016/j.scispo.2009.07.004]).

Some of the symptoms showed improvement by 12 weeks and further significant improvements by 24 weeks, including vasomotor symptoms, muscle and joint pain, psychological symptoms, and sexual problems. The women reported no significant change in vaginal dryness.

Significant improvements also were seen in resting heart rate, systolic and diastolic blood pressures, flexibility, aerobic power, and the ability to perform sit-ups, push-ups, and right or left hand grips. Body weight, body mass index, body fat percentage, and fat weight decreased significantly, with no change in lean body mass values.

The findings support results from previous observational studies of physically active postmenopausal women compared with age-matched, sedentary control women. No randomized controlled trials have looked at the efficacy of exercise in managing hot flushes.

The current study suggests that a high level of cardiorespiratory fitness may help reduce menopausal symptoms, Dr. Karacan concluded.

Major Finding: Six months of 70-minute aerobic exercise sessions three days per week significantly reduced the severity of menopausal symptoms while improving physical fitness.

Data Source: An uncontrolled study in 65 postmenopausal women.

Disclosures: None reported.

Postmenopausal women improved their physical fitness and reported reductions in the severity of menopausal symptoms after 12–24 weeks of aerobic exercise in three 70-minute sessions per week.

The 65 women (mean age, 50.1 years) rated the severity of menopausal symptoms on the self-administered Menopause Rating Scale questionnaire at baseline, 12 weeks, and 24 weeks in the uncontrolled study. The program of aerobic and calisthenic exercise aimed for 75%–80% of maximal heart rate according to the Karvonen method and consisted of 10 minutes of warm-up exercises; 40 minutes of aerobics; 15 minutes of exercise targeting the abdomen, hip, and leg muscles; and 5 minutes for cooldown and stretching.

Participants reported significant decreases in the severity of hot flushes, night sweats, cardiac symptoms, muscle and joint pain, sleeping disorder symptoms, depressive mood, irritability, anxiety, exhaustion, sexual problems, and urinary symptoms between the start and end of the study, Dr. Selma Karacan of Selcuk University in Konya, Turkey, reported (Sci. Sports 2009 [doi:10.1016/j.scispo.2009.07.004]).

Some of the symptoms showed improvement by 12 weeks and further significant improvements by 24 weeks, including vasomotor symptoms, muscle and joint pain, psychological symptoms, and sexual problems. The women reported no significant change in vaginal dryness.

Significant improvements also were seen in resting heart rate, systolic and diastolic blood pressures, flexibility, aerobic power, and the ability to perform sit-ups, push-ups, and right or left hand grips. Body weight, body mass index, body fat percentage, and fat weight decreased significantly, with no change in lean body mass values.

The findings support results from previous observational studies of physically active postmenopausal women compared with age-matched, sedentary control women. No randomized controlled trials have looked at the efficacy of exercise in managing hot flushes.

The current study suggests that a high level of cardiorespiratory fitness may help reduce menopausal symptoms, Dr. Karacan concluded.

Major Finding: Six months of 70-minute aerobic exercise sessions three days per week significantly reduced the severity of menopausal symptoms while improving physical fitness.

Data Source: An uncontrolled study in 65 postmenopausal women.

Disclosures: None reported.

Postmenopausal women improved their physical fitness and reported reductions in the severity of menopausal symptoms after 12–24 weeks of aerobic exercise in three 70-minute sessions per week.

The 65 women (mean age, 50.1 years) rated the severity of menopausal symptoms on the self-administered Menopause Rating Scale questionnaire at baseline, 12 weeks, and 24 weeks in the uncontrolled study. The program of aerobic and calisthenic exercise aimed for 75%–80% of maximal heart rate according to the Karvonen method and consisted of 10 minutes of warm-up exercises; 40 minutes of aerobics; 15 minutes of exercise targeting the abdomen, hip, and leg muscles; and 5 minutes for cooldown and stretching.

Participants reported significant decreases in the severity of hot flushes, night sweats, cardiac symptoms, muscle and joint pain, sleeping disorder symptoms, depressive mood, irritability, anxiety, exhaustion, sexual problems, and urinary symptoms between the start and end of the study, Dr. Selma Karacan of Selcuk University in Konya, Turkey, reported (Sci. Sports 2009 [doi:10.1016/j.scispo.2009.07.004]).

Some of the symptoms showed improvement by 12 weeks and further significant improvements by 24 weeks, including vasomotor symptoms, muscle and joint pain, psychological symptoms, and sexual problems. The women reported no significant change in vaginal dryness.

Significant improvements also were seen in resting heart rate, systolic and diastolic blood pressures, flexibility, aerobic power, and the ability to perform sit-ups, push-ups, and right or left hand grips. Body weight, body mass index, body fat percentage, and fat weight decreased significantly, with no change in lean body mass values.

The findings support results from previous observational studies of physically active postmenopausal women compared with age-matched, sedentary control women. No randomized controlled trials have looked at the efficacy of exercise in managing hot flushes.

The current study suggests that a high level of cardiorespiratory fitness may help reduce menopausal symptoms, Dr. Karacan concluded.