Miriam E. Tucker

Once-weekly exenatide reduced hemoglobin A_1c to a significantly greater degree than did either sitagliptin or pioglitazone in DURATION-2, a 26-week randomized, double-blind trial of 491 patients with type 2 diabetes who had baseline HbA_1c levels of 8.5% or higher despite metformin treatment.

The study, funded by Amylin Pharmaceuticals and Eli Lilly, was published online to coincide with a presentation of its results by lead author Dr. Richard M. Bergenstal at the annual scientific sessions of the American Diabetes Association (Lancet 2010 June 26 [doi:10.1016/S0140-6736(10)60590-9]).

Patients received treatment in 72 sites in the United States, India, and Mexico. All had been treated with a stable metformin regimen for at least 2 months before screening and continued to take metformin throughout the study. The patients were randomized to one of three regimens: 2-mg exenatide injection once weekly plus oral placebo once daily, 100 mg oral sitagliptin once daily plus placebo injection once weekly, and 45 mg oral pioglitazone once daily with placebo injections once weekly.

Patients and staff in DURATION-2 (A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Treated With Metformin) were all blinded to treatment allocation during the 26 weeks of treatment, said Dr. Bergenstal of the International Diabetes Center at Park Nicollet, Minneapolis, and his associates.

Of the 514 participants randomized to treatment, those who received at least one treatment (491) were included in the intention-to-treat analysis. Fewer patients withdrew from treatment with sitagliptin (13%) than did those receiving exenatide once weekly (21%) or pioglitazone (21%).

At 26 weeks, mean HbA_1c values were 7.2% for exenatide, 7.7% for sitagliptin, and 7.4% for pioglitazone. From baseline to week 26, reduction in HbA_1c with once-weekly exenatide was significantly greater than with the other two drugs, at 1.5 percentage points, compared with 0.9 and 1.2 percentage points with sitagliptin and pioglitazone, respectively.

When the data were stratified by baseline HbA_1c, once-weekly exenatide was associated with a significantly greater reduction in HbA_1c than was sitagliptin in all patients, but for exenatide versus pioglitazone the difference was significant only in patients with baseline HbA_1c of 9% or higher, the investigators reported.

All three treatments improved fasting plasma glucose, but once-weekly exenatide resulted in a significantly greater reduction than did sitagliptin—32 vs. 16 mg/dL—but not pioglitazone, which produced a reduction in fasting plasma glucose of 27 mg/dL. Fasting insulin was significantly increased at week 26 with once-weekly exenatide compared with both sitagliptin and pioglitazone, they said.

Weight loss at 26 weeks was significantly greater with exenatide than with sitagliptin, 2.3 vs. 0.8 kg, while the pioglitazone group gained an average of 2.8 kg. Over 75% of the patients on once-weekly exenatide lost body weight, compared with 61% of those on sitagliptin and 21% of those on pioglitazone.

Reductions in systolic blood pressure were significantly greater with once-weekly exenatide than with sitagliptin, but did not differ from those seen with pioglitazone. Change in diastolic pressure at week 26 did not differ between the three groups. Significant improvement in HDL cholesterol was recorded with all treatments, and improvement was significantly greater with pioglitazone than with exenatide. Pioglitazone was the only treatment associated with a significant reduction in triglycerides and total cholesterol, Dr. Bergenstal and his associates noted.

The most common treatment-emergent adverse events for patients on exenatide and sitagliptin were nausea and diarrhea, whereas pioglitazone patients' most common adverse events were upper respiratory tract infection and peripheral edema. Vomiting was more common with exenatide than with sitagliptin or pioglitazone.

Adverse events leading to withdrawal from the study drug occurred in 10 patients on exenatide, 5 on sitagliptin, and 6 on pioglitazone. Of the 26 serious adverse events during treatment, one was fatal but the others resolved.

Dr. Bergenstal's institution has received consultancy fees or research grant support, or both, with receipt of travel and accommodation expenses in some cases, from Abbott Diabetes Care, Amylin, Bayer, Eli Lilly, Intuity Medical, Hygieia Medical, LifeScan, Mannkind, Medtronic-Minimed, National Institutes of Health, Novo Nordisk, ResMed, Roche, Sanofi-Aventis, United Health Group, and Valeritas; all research activity, and advisory or consultancy services were done under contract with the nonprofit International Diabetes Center at Park Nicollet. Dr. Bergenstal also owns stock in Merck. One coauthor has similar disclosures, six are employees of Amylin Pharmaceuticals, and one is an employee of Eli Lilly.

Once-weekly exenatide reduced hemoglobin A_1c to a significantly greater degree than did either sitagliptin or pioglitazone in DURATION-2, a 26-week randomized, double-blind trial of 491 patients with type 2 diabetes who had baseline HbA_1c levels of 8.5% or higher despite metformin treatment.

The study, funded by Amylin Pharmaceuticals and Eli Lilly, was published online to coincide with a presentation of its results by lead author Dr. Richard M. Bergenstal at the annual scientific sessions of the American Diabetes Association (Lancet 2010 June 26 [doi:10.1016/S0140-6736(10)60590-9]).

Patients received treatment in 72 sites in the United States, India, and Mexico. All had been treated with a stable metformin regimen for at least 2 months before screening and continued to take metformin throughout the study. The patients were randomized to one of three regimens: 2-mg exenatide injection once weekly plus oral placebo once daily, 100 mg oral sitagliptin once daily plus placebo injection once weekly, and 45 mg oral pioglitazone once daily with placebo injections once weekly.

Patients and staff in DURATION-2 (A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Treated With Metformin) were all blinded to treatment allocation during the 26 weeks of treatment, said Dr. Bergenstal of the International Diabetes Center at Park Nicollet, Minneapolis, and his associates.

Of the 514 participants randomized to treatment, those who received at least one treatment (491) were included in the intention-to-treat analysis. Fewer patients withdrew from treatment with sitagliptin (13%) than did those receiving exenatide once weekly (21%) or pioglitazone (21%).

At 26 weeks, mean HbA_1c values were 7.2% for exenatide, 7.7% for sitagliptin, and 7.4% for pioglitazone. From baseline to week 26, reduction in HbA_1c with once-weekly exenatide was significantly greater than with the other two drugs, at 1.5 percentage points, compared with 0.9 and 1.2 percentage points with sitagliptin and pioglitazone, respectively.

When the data were stratified by baseline HbA_1c, once-weekly exenatide was associated with a significantly greater reduction in HbA_1c than was sitagliptin in all patients, but for exenatide versus pioglitazone the difference was significant only in patients with baseline HbA_1c of 9% or higher, the investigators reported.

All three treatments improved fasting plasma glucose, but once-weekly exenatide resulted in a significantly greater reduction than did sitagliptin—32 vs. 16 mg/dL—but not pioglitazone, which produced a reduction in fasting plasma glucose of 27 mg/dL. Fasting insulin was significantly increased at week 26 with once-weekly exenatide compared with both sitagliptin and pioglitazone, they said.

Weight loss at 26 weeks was significantly greater with exenatide than with sitagliptin, 2.3 vs. 0.8 kg, while the pioglitazone group gained an average of 2.8 kg. Over 75% of the patients on once-weekly exenatide lost body weight, compared with 61% of those on sitagliptin and 21% of those on pioglitazone.

Reductions in systolic blood pressure were significantly greater with once-weekly exenatide than with sitagliptin, but did not differ from those seen with pioglitazone. Change in diastolic pressure at week 26 did not differ between the three groups. Significant improvement in HDL cholesterol was recorded with all treatments, and improvement was significantly greater with pioglitazone than with exenatide. Pioglitazone was the only treatment associated with a significant reduction in triglycerides and total cholesterol, Dr. Bergenstal and his associates noted.

The most common treatment-emergent adverse events for patients on exenatide and sitagliptin were nausea and diarrhea, whereas pioglitazone patients' most common adverse events were upper respiratory tract infection and peripheral edema. Vomiting was more common with exenatide than with sitagliptin or pioglitazone.

Adverse events leading to withdrawal from the study drug occurred in 10 patients on exenatide, 5 on sitagliptin, and 6 on pioglitazone. Of the 26 serious adverse events during treatment, one was fatal but the others resolved.

Dr. Bergenstal's institution has received consultancy fees or research grant support, or both, with receipt of travel and accommodation expenses in some cases, from Abbott Diabetes Care, Amylin, Bayer, Eli Lilly, Intuity Medical, Hygieia Medical, LifeScan, Mannkind, Medtronic-Minimed, National Institutes of Health, Novo Nordisk, ResMed, Roche, Sanofi-Aventis, United Health Group, and Valeritas; all research activity, and advisory or consultancy services were done under contract with the nonprofit International Diabetes Center at Park Nicollet. Dr. Bergenstal also owns stock in Merck. One coauthor has similar disclosures, six are employees of Amylin Pharmaceuticals, and one is an employee of Eli Lilly.

Once-weekly exenatide reduced hemoglobin A_1c to a significantly greater degree than did either sitagliptin or pioglitazone in DURATION-2, a 26-week randomized, double-blind trial of 491 patients with type 2 diabetes who had baseline HbA_1c levels of 8.5% or higher despite metformin treatment.

The study, funded by Amylin Pharmaceuticals and Eli Lilly, was published online to coincide with a presentation of its results by lead author Dr. Richard M. Bergenstal at the annual scientific sessions of the American Diabetes Association (Lancet 2010 June 26 [doi:10.1016/S0140-6736(10)60590-9]).

Patients received treatment in 72 sites in the United States, India, and Mexico. All had been treated with a stable metformin regimen for at least 2 months before screening and continued to take metformin throughout the study. The patients were randomized to one of three regimens: 2-mg exenatide injection once weekly plus oral placebo once daily, 100 mg oral sitagliptin once daily plus placebo injection once weekly, and 45 mg oral pioglitazone once daily with placebo injections once weekly.

Patients and staff in DURATION-2 (A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Treated With Metformin) were all blinded to treatment allocation during the 26 weeks of treatment, said Dr. Bergenstal of the International Diabetes Center at Park Nicollet, Minneapolis, and his associates.

Of the 514 participants randomized to treatment, those who received at least one treatment (491) were included in the intention-to-treat analysis. Fewer patients withdrew from treatment with sitagliptin (13%) than did those receiving exenatide once weekly (21%) or pioglitazone (21%).

At 26 weeks, mean HbA_1c values were 7.2% for exenatide, 7.7% for sitagliptin, and 7.4% for pioglitazone. From baseline to week 26, reduction in HbA_1c with once-weekly exenatide was significantly greater than with the other two drugs, at 1.5 percentage points, compared with 0.9 and 1.2 percentage points with sitagliptin and pioglitazone, respectively.

When the data were stratified by baseline HbA_1c, once-weekly exenatide was associated with a significantly greater reduction in HbA_1c than was sitagliptin in all patients, but for exenatide versus pioglitazone the difference was significant only in patients with baseline HbA_1c of 9% or higher, the investigators reported.

All three treatments improved fasting plasma glucose, but once-weekly exenatide resulted in a significantly greater reduction than did sitagliptin—32 vs. 16 mg/dL—but not pioglitazone, which produced a reduction in fasting plasma glucose of 27 mg/dL. Fasting insulin was significantly increased at week 26 with once-weekly exenatide compared with both sitagliptin and pioglitazone, they said.

Weight loss at 26 weeks was significantly greater with exenatide than with sitagliptin, 2.3 vs. 0.8 kg, while the pioglitazone group gained an average of 2.8 kg. Over 75% of the patients on once-weekly exenatide lost body weight, compared with 61% of those on sitagliptin and 21% of those on pioglitazone.

Reductions in systolic blood pressure were significantly greater with once-weekly exenatide than with sitagliptin, but did not differ from those seen with pioglitazone. Change in diastolic pressure at week 26 did not differ between the three groups. Significant improvement in HDL cholesterol was recorded with all treatments, and improvement was significantly greater with pioglitazone than with exenatide. Pioglitazone was the only treatment associated with a significant reduction in triglycerides and total cholesterol, Dr. Bergenstal and his associates noted.

The most common treatment-emergent adverse events for patients on exenatide and sitagliptin were nausea and diarrhea, whereas pioglitazone patients' most common adverse events were upper respiratory tract infection and peripheral edema. Vomiting was more common with exenatide than with sitagliptin or pioglitazone.

Adverse events leading to withdrawal from the study drug occurred in 10 patients on exenatide, 5 on sitagliptin, and 6 on pioglitazone. Of the 26 serious adverse events during treatment, one was fatal but the others resolved.

Dr. Bergenstal's institution has received consultancy fees or research grant support, or both, with receipt of travel and accommodation expenses in some cases, from Abbott Diabetes Care, Amylin, Bayer, Eli Lilly, Intuity Medical, Hygieia Medical, LifeScan, Mannkind, Medtronic-Minimed, National Institutes of Health, Novo Nordisk, ResMed, Roche, Sanofi-Aventis, United Health Group, and Valeritas; all research activity, and advisory or consultancy services were done under contract with the nonprofit International Diabetes Center at Park Nicollet. Dr. Bergenstal also owns stock in Merck. One coauthor has similar disclosures, six are employees of Amylin Pharmaceuticals, and one is an employee of Eli Lilly.

ORLANDO — Intensive glycemic control did not reduce the risk for developing advanced measures of microvascular outcomes, although it did delay the onset of albuminuria and some measures of eye complications and neuropathy among patients with longstanding type 2 diabetes at high cardiovascular risk.

The mixed results, from a subanalysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, suggest that the microvascular benefits of intensive therapy should be weighed against the increase in total disease-related mortality, increased weight gain, and high risk for severe hypoglycemia that emerged with the main findings of the trial 2 years ago, Dr. Faramarz Ismail-Beigi said.

“Caution should be exercised in pursuit of a strategy of intensive glycemic control for prevention of microvascular complications in patients with established type 2 diabetes and characteristics similar to those in the ACCORD trial,” Dr. Ismail-Beigi of Case Western Reserve University, Cleveland, said. The findings were released simultaneously online in the Lancet (doi:10.1016/S0140-6736(10)60576-4).

The ACCORD trial randomized 10,251 adults with type 2 diabetes to either intensive glycemic control with a target hemoglobin A_1c of less than 6.0%, or standard therapy aiming for HbA_1c values of 7.0%-7.9%. The intensive arm was stopped early in February 2008—after a median follow-up of 3.7 years—because of a 22% higher all-cause mortality in the intensive group. They were then transitioned to standard therapy for the rest of the trial, which also included blood pressure and lipid control arms (N. Engl. J. Med. 2008;358:2545-59).

At the time of that transition and at study end, the two groups did not differ in the prespecified primary composite outcome of advanced nephropathy and diabetic eye complications (development of renal failure or retinal photocoagulation or vitrectomy to treat retinopathy), or in a second composite end point that added a peripheral neuropathy outcome (score of greater than 2.0 on the Michigan neuropathy screening instrument or the first composite outcome). At the end of the study, 10.9% of the intensive group and 11.5% of the standard treatment group met the first composite end point, and 38.2% and 40.0%, respectively, met the second.

However, microvascular renal outcomes based on urinary measures were significantly reduced in the intensive glycemic therapy group. Intensive glycemia therapy led to a 21% reduction in the development of microalbuminuria at the time of transition. This effect was attenuated to 15% at study end, but remained statistically significant, Dr. Ismail-Beigi reported.

For diabetes-related eye events, three-line worsening of visual acuity was more common in the standard group than in the intensive group at both transition and study end (20.7% vs. 19.1%). Cataract extraction was also significantly reduced, by 21%, in the intensive group, compared with the standard group at study end. Other diabetes-related eye outcomes did not differ between the two groups, he said.

Peripheral neuropathy (MNSI greater than 2.0) was less common in the intensive group than in the standard group at study end (55.6% vs. 58.6%). Loss of ankle jerk reflex and light touch (10-g monofilament) perception were both rarer in the intensive vs. standard therapy groups at study end, but loss of vibratory sensation did not differ between the two groups.

In an accompanying editorial in the Lancet, Dr. Ronald Klein pointed out that the American Diabetes Association's recommendation of a hemoglobin value of less than 7.0% was based on the findings of the United Kingdom Prospective Diabetes Study (UKPDS), which showed that intensive glycemic therapy in newly diagnosed type 2 diabetes patients did reduce the risk for the same composite microvascular end points as the ones used in ACCORD (Lancet 1998;352:837-53).

However, the follow-up period of ACCORD was much shorter than that of the UKPDS, in which it took about 10 years to show efficacy of intensive glycemic control for the same advanced end points, noted Dr. Klein, of the department of ophthalmology and visual sciences at the University of Wisconsin, Madison.

“I do not believe the ACCORD experience will (or should) cause clinicians to doubt the importance of glycemic control in preventing microvascular complications,” Dr. Klein concluded.

The ACCORD trial was funded by the National Heart Lung and Blood Institute, with contributions of medications, equipment, or supplies from several manufacturers. Dr. Ismail-Beigi has received travel support from NHLBI and did not disclose any other relationships. However, several coauthors declared financial relationships with many manufacturers of diabetes-related products. Dr. Klein has worked as a consultant for AstraZeneca, Eli Lilly, GlaxoSmithKline, Takeda, Pfizer, and Novartis.

ORLANDO — Intensive glycemic control did not reduce the risk for developing advanced measures of microvascular outcomes, although it did delay the onset of albuminuria and some measures of eye complications and neuropathy among patients with longstanding type 2 diabetes at high cardiovascular risk.

The mixed results, from a subanalysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, suggest that the microvascular benefits of intensive therapy should be weighed against the increase in total disease-related mortality, increased weight gain, and high risk for severe hypoglycemia that emerged with the main findings of the trial 2 years ago, Dr. Faramarz Ismail-Beigi said.

“Caution should be exercised in pursuit of a strategy of intensive glycemic control for prevention of microvascular complications in patients with established type 2 diabetes and characteristics similar to those in the ACCORD trial,” Dr. Ismail-Beigi of Case Western Reserve University, Cleveland, said. The findings were released simultaneously online in the Lancet (doi:10.1016/S0140-6736(10)60576-4).

The ACCORD trial randomized 10,251 adults with type 2 diabetes to either intensive glycemic control with a target hemoglobin A_1c of less than 6.0%, or standard therapy aiming for HbA_1c values of 7.0%-7.9%. The intensive arm was stopped early in February 2008—after a median follow-up of 3.7 years—because of a 22% higher all-cause mortality in the intensive group. They were then transitioned to standard therapy for the rest of the trial, which also included blood pressure and lipid control arms (N. Engl. J. Med. 2008;358:2545-59).

At the time of that transition and at study end, the two groups did not differ in the prespecified primary composite outcome of advanced nephropathy and diabetic eye complications (development of renal failure or retinal photocoagulation or vitrectomy to treat retinopathy), or in a second composite end point that added a peripheral neuropathy outcome (score of greater than 2.0 on the Michigan neuropathy screening instrument or the first composite outcome). At the end of the study, 10.9% of the intensive group and 11.5% of the standard treatment group met the first composite end point, and 38.2% and 40.0%, respectively, met the second.

However, microvascular renal outcomes based on urinary measures were significantly reduced in the intensive glycemic therapy group. Intensive glycemia therapy led to a 21% reduction in the development of microalbuminuria at the time of transition. This effect was attenuated to 15% at study end, but remained statistically significant, Dr. Ismail-Beigi reported.

For diabetes-related eye events, three-line worsening of visual acuity was more common in the standard group than in the intensive group at both transition and study end (20.7% vs. 19.1%). Cataract extraction was also significantly reduced, by 21%, in the intensive group, compared with the standard group at study end. Other diabetes-related eye outcomes did not differ between the two groups, he said.

Peripheral neuropathy (MNSI greater than 2.0) was less common in the intensive group than in the standard group at study end (55.6% vs. 58.6%). Loss of ankle jerk reflex and light touch (10-g monofilament) perception were both rarer in the intensive vs. standard therapy groups at study end, but loss of vibratory sensation did not differ between the two groups.

In an accompanying editorial in the Lancet, Dr. Ronald Klein pointed out that the American Diabetes Association's recommendation of a hemoglobin value of less than 7.0% was based on the findings of the United Kingdom Prospective Diabetes Study (UKPDS), which showed that intensive glycemic therapy in newly diagnosed type 2 diabetes patients did reduce the risk for the same composite microvascular end points as the ones used in ACCORD (Lancet 1998;352:837-53).

However, the follow-up period of ACCORD was much shorter than that of the UKPDS, in which it took about 10 years to show efficacy of intensive glycemic control for the same advanced end points, noted Dr. Klein, of the department of ophthalmology and visual sciences at the University of Wisconsin, Madison.

“I do not believe the ACCORD experience will (or should) cause clinicians to doubt the importance of glycemic control in preventing microvascular complications,” Dr. Klein concluded.

The ACCORD trial was funded by the National Heart Lung and Blood Institute, with contributions of medications, equipment, or supplies from several manufacturers. Dr. Ismail-Beigi has received travel support from NHLBI and did not disclose any other relationships. However, several coauthors declared financial relationships with many manufacturers of diabetes-related products. Dr. Klein has worked as a consultant for AstraZeneca, Eli Lilly, GlaxoSmithKline, Takeda, Pfizer, and Novartis.

ORLANDO — Intensive glycemic control did not reduce the risk for developing advanced measures of microvascular outcomes, although it did delay the onset of albuminuria and some measures of eye complications and neuropathy among patients with longstanding type 2 diabetes at high cardiovascular risk.

The mixed results, from a subanalysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, suggest that the microvascular benefits of intensive therapy should be weighed against the increase in total disease-related mortality, increased weight gain, and high risk for severe hypoglycemia that emerged with the main findings of the trial 2 years ago, Dr. Faramarz Ismail-Beigi said.

“Caution should be exercised in pursuit of a strategy of intensive glycemic control for prevention of microvascular complications in patients with established type 2 diabetes and characteristics similar to those in the ACCORD trial,” Dr. Ismail-Beigi of Case Western Reserve University, Cleveland, said. The findings were released simultaneously online in the Lancet (doi:10.1016/S0140-6736(10)60576-4).

The ACCORD trial randomized 10,251 adults with type 2 diabetes to either intensive glycemic control with a target hemoglobin A_1c of less than 6.0%, or standard therapy aiming for HbA_1c values of 7.0%-7.9%. The intensive arm was stopped early in February 2008—after a median follow-up of 3.7 years—because of a 22% higher all-cause mortality in the intensive group. They were then transitioned to standard therapy for the rest of the trial, which also included blood pressure and lipid control arms (N. Engl. J. Med. 2008;358:2545-59).

At the time of that transition and at study end, the two groups did not differ in the prespecified primary composite outcome of advanced nephropathy and diabetic eye complications (development of renal failure or retinal photocoagulation or vitrectomy to treat retinopathy), or in a second composite end point that added a peripheral neuropathy outcome (score of greater than 2.0 on the Michigan neuropathy screening instrument or the first composite outcome). At the end of the study, 10.9% of the intensive group and 11.5% of the standard treatment group met the first composite end point, and 38.2% and 40.0%, respectively, met the second.

However, microvascular renal outcomes based on urinary measures were significantly reduced in the intensive glycemic therapy group. Intensive glycemia therapy led to a 21% reduction in the development of microalbuminuria at the time of transition. This effect was attenuated to 15% at study end, but remained statistically significant, Dr. Ismail-Beigi reported.

For diabetes-related eye events, three-line worsening of visual acuity was more common in the standard group than in the intensive group at both transition and study end (20.7% vs. 19.1%). Cataract extraction was also significantly reduced, by 21%, in the intensive group, compared with the standard group at study end. Other diabetes-related eye outcomes did not differ between the two groups, he said.

Peripheral neuropathy (MNSI greater than 2.0) was less common in the intensive group than in the standard group at study end (55.6% vs. 58.6%). Loss of ankle jerk reflex and light touch (10-g monofilament) perception were both rarer in the intensive vs. standard therapy groups at study end, but loss of vibratory sensation did not differ between the two groups.

In an accompanying editorial in the Lancet, Dr. Ronald Klein pointed out that the American Diabetes Association's recommendation of a hemoglobin value of less than 7.0% was based on the findings of the United Kingdom Prospective Diabetes Study (UKPDS), which showed that intensive glycemic therapy in newly diagnosed type 2 diabetes patients did reduce the risk for the same composite microvascular end points as the ones used in ACCORD (Lancet 1998;352:837-53).

However, the follow-up period of ACCORD was much shorter than that of the UKPDS, in which it took about 10 years to show efficacy of intensive glycemic control for the same advanced end points, noted Dr. Klein, of the department of ophthalmology and visual sciences at the University of Wisconsin, Madison.

“I do not believe the ACCORD experience will (or should) cause clinicians to doubt the importance of glycemic control in preventing microvascular complications,” Dr. Klein concluded.

The ACCORD trial was funded by the National Heart Lung and Blood Institute, with contributions of medications, equipment, or supplies from several manufacturers. Dr. Ismail-Beigi has received travel support from NHLBI and did not disclose any other relationships. However, several coauthors declared financial relationships with many manufacturers of diabetes-related products. Dr. Klein has worked as a consultant for AstraZeneca, Eli Lilly, GlaxoSmithKline, Takeda, Pfizer, and Novartis.

ROCKVILLE, MD. — Chronic back pain is an enormously heterogeneous and common disorder that might better be examined in observational “Framingham-like studies” than in randomized, controlled clinical trials.

The recommendation was proposed by several presenters at the workshop, sponsored by the National Center for Complementary and Alternative Medicine (NCCAM), a division of the National Institutes of Health.

With seven thematic panels and 23 speakers, the meeting included lively discussions about optimal approaches for studying a problem that affects one in four adults and costs the health care system billions of dollars annually, and for which research thus far has not yielded the kinds of interventions that can help the majority of affected patients.

“I think this is the right time to be talking about this problem. The NIH has certainly been urged by our leader, Dr. Francis Collins, to worry about research of relevance to health policy, and I can't think of a single issue that has as much resonance or potential implications for health policy as this one,” NCCAM director Dr. Josephine Briggs said.

Dr. Briggs, who was originally trained in internal medicine and nephrology, also noted, “This is not my area, but as I've learned more about back pain over the last year, I have been absolutely blown away by the magnitude of this problem and the enormous clinical difficulties in bringing relief to most patients suffering from chronic back pain…. This is totally pervasive, a huge driver of health costs.”

There was agreement among participants that chronic back pain is not simply a multifaceted biological problem, but also a psychosocial one. As such, there is little correlation between physical findings on imaging or other studies and the degree to which a patient perceives pain or experiences functional impairment. Participants also generally agreed that current treatments, including opioids and surgical approaches, are ineffective in many patients and have been associated with harm as well.

Several speakers pointed out that the extensive heterogeneity in causes, presentations, and functional impact of chronic back pain has made it difficult to define “case-ness,” which in turn makes it impossible to compare studies on the problem and determine the extent to which results from any given study can be extrapolated to another.

Indeed, even the most commonly used definition of “chronic”—pain lasting longer than 3 or 6 months—is limiting in that it doesn't account for other parameters such as pain intensity, associated psychological dysfunction, or degree of functional impairment, noted Michael Von Korff, Sc.D., senior investigator at Group Health Research Institute, Seattle.

He described an alternative “prognostic risk score” that would not only classify patients with back pain but would also help to determine their probability of future clinically significant back pain. The score, derived from a study of 1,213 primary care back pain patients, utilizes measurements of degrees of pain intensity, interference with activities, persistence, number of pain sites, and depression to define risk levels corresponding to a 50% and an 80% probability of future clinically significant pain (Pain 2005;117:304–13).

Such an “empirically grounded” approach, he said, could help distinguish patients at low risk who could be managed conservatively from those at greater risk for whom intervention could be initiated early, rather than waiting for the passage of time until they meet the “chronic” criteria. Moreover, “it avoids labeling patients as hopeless, with immutable back pain, when change for the better is always possible and often likely.”

Indeed, noted Dr. Gary Franklin, a research professor in environmental and occupational health sciences at the University of Washington, Seattle, the Food and Drug Administration uses only pain as a primary outcome measure for drug trials, with function and quality of life as secondary outcomes. “The FDA needs to consider using a composite measure,” he commented.

Several speakers questioned whether the randomized clinical trial, widely considered the “gold standard” type of study for the efficacy of drugs, is really the best type of trial to examine aspects of such a heterogeneous problem as chronic back pain, and whether longitudinal observational “Framingham-like” study might be more appropriate to determine what happens to patients with chronic back pain over time.

In an interview, workshop cochair Dr. Partap Khalsa, program officer of the division of intramural research at NCCAM, noted that the best clinical guidelines currently available for managing chronic low back pain are those developed jointly by the American College of Physicians and the American Pain Society. They advise clinicians to conduct a focused history and physical to help determine etiology, and only perform diagnostic imaging in selected patients with severe or progressive neurologic deficits or in whom serious underlying conditions are suspected based on the history and physical exam (Ann. Intern. Med. 2007;147:478–91).

For the 80%–90% of patients with chronic back pain for whom no specific cause can be found, the guidelines advise that physicians educate patients about appropriate self-care and prescribe acetaminophen or NSAIDs as first-line therapy. For patients in whom pain persists, nonpharmacologic approaches such as exercise and spinal manipulation may be tried, along with other “interdisciplinary” approaches such as acupuncture, massage therapy, yoga, cognitive-behavioral therapy, or progressive relaxation therapy.

A main goal of the workshop, Dr. Khalsa said, was to move beyond those measures to design approaches that can prevent chronic pain in the first place. “It's much better to be able to do something when the patient first walks in the door to identify and predict—and hopefully prevent—a long-term chronic, debilitating problem.”

Disclosures: Dr. Khalsa and Dr. Briggs are government employees with no financial conflicts. Dr. von Korff said he received funding only from the NIH, and Dr. Franklin stated that he has no disclosures.

ROCKVILLE, MD. — Chronic back pain is an enormously heterogeneous and common disorder that might better be examined in observational “Framingham-like studies” than in randomized, controlled clinical trials.

The recommendation was proposed by several presenters at the workshop, sponsored by the National Center for Complementary and Alternative Medicine (NCCAM), a division of the National Institutes of Health.

With seven thematic panels and 23 speakers, the meeting included lively discussions about optimal approaches for studying a problem that affects one in four adults and costs the health care system billions of dollars annually, and for which research thus far has not yielded the kinds of interventions that can help the majority of affected patients.

“I think this is the right time to be talking about this problem. The NIH has certainly been urged by our leader, Dr. Francis Collins, to worry about research of relevance to health policy, and I can't think of a single issue that has as much resonance or potential implications for health policy as this one,” NCCAM director Dr. Josephine Briggs said.

Dr. Briggs, who was originally trained in internal medicine and nephrology, also noted, “This is not my area, but as I've learned more about back pain over the last year, I have been absolutely blown away by the magnitude of this problem and the enormous clinical difficulties in bringing relief to most patients suffering from chronic back pain…. This is totally pervasive, a huge driver of health costs.”

There was agreement among participants that chronic back pain is not simply a multifaceted biological problem, but also a psychosocial one. As such, there is little correlation between physical findings on imaging or other studies and the degree to which a patient perceives pain or experiences functional impairment. Participants also generally agreed that current treatments, including opioids and surgical approaches, are ineffective in many patients and have been associated with harm as well.

Several speakers pointed out that the extensive heterogeneity in causes, presentations, and functional impact of chronic back pain has made it difficult to define “case-ness,” which in turn makes it impossible to compare studies on the problem and determine the extent to which results from any given study can be extrapolated to another.

Indeed, even the most commonly used definition of “chronic”—pain lasting longer than 3 or 6 months—is limiting in that it doesn't account for other parameters such as pain intensity, associated psychological dysfunction, or degree of functional impairment, noted Michael Von Korff, Sc.D., senior investigator at Group Health Research Institute, Seattle.

He described an alternative “prognostic risk score” that would not only classify patients with back pain but would also help to determine their probability of future clinically significant back pain. The score, derived from a study of 1,213 primary care back pain patients, utilizes measurements of degrees of pain intensity, interference with activities, persistence, number of pain sites, and depression to define risk levels corresponding to a 50% and an 80% probability of future clinically significant pain (Pain 2005;117:304–13).

Such an “empirically grounded” approach, he said, could help distinguish patients at low risk who could be managed conservatively from those at greater risk for whom intervention could be initiated early, rather than waiting for the passage of time until they meet the “chronic” criteria. Moreover, “it avoids labeling patients as hopeless, with immutable back pain, when change for the better is always possible and often likely.”

Indeed, noted Dr. Gary Franklin, a research professor in environmental and occupational health sciences at the University of Washington, Seattle, the Food and Drug Administration uses only pain as a primary outcome measure for drug trials, with function and quality of life as secondary outcomes. “The FDA needs to consider using a composite measure,” he commented.

Several speakers questioned whether the randomized clinical trial, widely considered the “gold standard” type of study for the efficacy of drugs, is really the best type of trial to examine aspects of such a heterogeneous problem as chronic back pain, and whether longitudinal observational “Framingham-like” study might be more appropriate to determine what happens to patients with chronic back pain over time.

In an interview, workshop cochair Dr. Partap Khalsa, program officer of the division of intramural research at NCCAM, noted that the best clinical guidelines currently available for managing chronic low back pain are those developed jointly by the American College of Physicians and the American Pain Society. They advise clinicians to conduct a focused history and physical to help determine etiology, and only perform diagnostic imaging in selected patients with severe or progressive neurologic deficits or in whom serious underlying conditions are suspected based on the history and physical exam (Ann. Intern. Med. 2007;147:478–91).

For the 80%–90% of patients with chronic back pain for whom no specific cause can be found, the guidelines advise that physicians educate patients about appropriate self-care and prescribe acetaminophen or NSAIDs as first-line therapy. For patients in whom pain persists, nonpharmacologic approaches such as exercise and spinal manipulation may be tried, along with other “interdisciplinary” approaches such as acupuncture, massage therapy, yoga, cognitive-behavioral therapy, or progressive relaxation therapy.

A main goal of the workshop, Dr. Khalsa said, was to move beyond those measures to design approaches that can prevent chronic pain in the first place. “It's much better to be able to do something when the patient first walks in the door to identify and predict—and hopefully prevent—a long-term chronic, debilitating problem.”

Disclosures: Dr. Khalsa and Dr. Briggs are government employees with no financial conflicts. Dr. von Korff said he received funding only from the NIH, and Dr. Franklin stated that he has no disclosures.

ROCKVILLE, MD. — Chronic back pain is an enormously heterogeneous and common disorder that might better be examined in observational “Framingham-like studies” than in randomized, controlled clinical trials.

The recommendation was proposed by several presenters at the workshop, sponsored by the National Center for Complementary and Alternative Medicine (NCCAM), a division of the National Institutes of Health.

With seven thematic panels and 23 speakers, the meeting included lively discussions about optimal approaches for studying a problem that affects one in four adults and costs the health care system billions of dollars annually, and for which research thus far has not yielded the kinds of interventions that can help the majority of affected patients.

“I think this is the right time to be talking about this problem. The NIH has certainly been urged by our leader, Dr. Francis Collins, to worry about research of relevance to health policy, and I can't think of a single issue that has as much resonance or potential implications for health policy as this one,” NCCAM director Dr. Josephine Briggs said.

Dr. Briggs, who was originally trained in internal medicine and nephrology, also noted, “This is not my area, but as I've learned more about back pain over the last year, I have been absolutely blown away by the magnitude of this problem and the enormous clinical difficulties in bringing relief to most patients suffering from chronic back pain…. This is totally pervasive, a huge driver of health costs.”

There was agreement among participants that chronic back pain is not simply a multifaceted biological problem, but also a psychosocial one. As such, there is little correlation between physical findings on imaging or other studies and the degree to which a patient perceives pain or experiences functional impairment. Participants also generally agreed that current treatments, including opioids and surgical approaches, are ineffective in many patients and have been associated with harm as well.

Several speakers pointed out that the extensive heterogeneity in causes, presentations, and functional impact of chronic back pain has made it difficult to define “case-ness,” which in turn makes it impossible to compare studies on the problem and determine the extent to which results from any given study can be extrapolated to another.

Indeed, even the most commonly used definition of “chronic”—pain lasting longer than 3 or 6 months—is limiting in that it doesn't account for other parameters such as pain intensity, associated psychological dysfunction, or degree of functional impairment, noted Michael Von Korff, Sc.D., senior investigator at Group Health Research Institute, Seattle.

He described an alternative “prognostic risk score” that would not only classify patients with back pain but would also help to determine their probability of future clinically significant back pain. The score, derived from a study of 1,213 primary care back pain patients, utilizes measurements of degrees of pain intensity, interference with activities, persistence, number of pain sites, and depression to define risk levels corresponding to a 50% and an 80% probability of future clinically significant pain (Pain 2005;117:304–13).

Such an “empirically grounded” approach, he said, could help distinguish patients at low risk who could be managed conservatively from those at greater risk for whom intervention could be initiated early, rather than waiting for the passage of time until they meet the “chronic” criteria. Moreover, “it avoids labeling patients as hopeless, with immutable back pain, when change for the better is always possible and often likely.”

Indeed, noted Dr. Gary Franklin, a research professor in environmental and occupational health sciences at the University of Washington, Seattle, the Food and Drug Administration uses only pain as a primary outcome measure for drug trials, with function and quality of life as secondary outcomes. “The FDA needs to consider using a composite measure,” he commented.

Several speakers questioned whether the randomized clinical trial, widely considered the “gold standard” type of study for the efficacy of drugs, is really the best type of trial to examine aspects of such a heterogeneous problem as chronic back pain, and whether longitudinal observational “Framingham-like” study might be more appropriate to determine what happens to patients with chronic back pain over time.

In an interview, workshop cochair Dr. Partap Khalsa, program officer of the division of intramural research at NCCAM, noted that the best clinical guidelines currently available for managing chronic low back pain are those developed jointly by the American College of Physicians and the American Pain Society. They advise clinicians to conduct a focused history and physical to help determine etiology, and only perform diagnostic imaging in selected patients with severe or progressive neurologic deficits or in whom serious underlying conditions are suspected based on the history and physical exam (Ann. Intern. Med. 2007;147:478–91).

For the 80%–90% of patients with chronic back pain for whom no specific cause can be found, the guidelines advise that physicians educate patients about appropriate self-care and prescribe acetaminophen or NSAIDs as first-line therapy. For patients in whom pain persists, nonpharmacologic approaches such as exercise and spinal manipulation may be tried, along with other “interdisciplinary” approaches such as acupuncture, massage therapy, yoga, cognitive-behavioral therapy, or progressive relaxation therapy.

A main goal of the workshop, Dr. Khalsa said, was to move beyond those measures to design approaches that can prevent chronic pain in the first place. “It's much better to be able to do something when the patient first walks in the door to identify and predict—and hopefully prevent—a long-term chronic, debilitating problem.”

Disclosures: Dr. Khalsa and Dr. Briggs are government employees with no financial conflicts. Dr. von Korff said he received funding only from the NIH, and Dr. Franklin stated that he has no disclosures.

Major Finding: BMI failed to detect obesity in 37% and falsely detected it in 5% in a study of 1,234 adults who had both BMI and DXA measurements.

Data Source: Medical chart review of private adult outpatients.

Disclosures: Study funded by the nonprofit PATH (Place for Achieving Total Health) Research Foundation NY. Dr. Braverman, director of the PATH centers in New York and Philadelphia, had no other financial disclosures.

BOSTON — Dual energy x-ray absorptiometry was a more accurate predictor of obesity than was body mass index in a retrospective comparison of the two measures in 1,234 adults.

Despite its widespread use, BMI is not an accurate indicator of body fat. Direct measures of adiposity, such as those obtained by dual energy x-ray absorptiometry (DXA), are far more precise, Dr. Eric R. Braverman and his associates reported in a poster at the meeting.

“We have a big problem with the BMI. You could retitle it the 'baloney mass index.' It's a mathematical equation. … The scientific standard is clearly subpar compared to our other endocrinology standards,” Dr. Braverman of the department of neurological surgery at Weill Cornell Medical College, New York, said at a press briefing.

Dr. Braverman and his colleagues analyzed medical records of 1,234 private adult outpatients (490 men, 744 women) who had both BMI and DXA measurements during 2003-2009.

The subjects had a mean age of 51 years, a mean BMI of 26.2 kg/m

When the researchers used BMI, 249 (20%) were classified as obese. DXA measurement showed that of those 249, 95% (237) were obese and 5% (12) were nonobese on the basis of body fat percentage.

When the researchers used DXA, 689 (56%) were classified as obese. Of those 689, 34% (237) were obese and 66% (452) were not obese based on BMI.

Thus, 37% of patients were misclassified by BMI: A total of 452 were found to be obese by DXA but nonobese by BMI and 12 were obese by BMI but not by DXA.

The 66% of patients classified as obese by DXA but who were “missed” by BMI had lower muscle and lean body mass, Dr. Braverman and his associates noted.

The BMI measurement of obesity in this study was approximately identical to the national percentage of obesity, which is also determined by BMI. “However, we have shown that BMI is a highly insensitive measure, resulting in an underdiagnosis of obesity. If we can extrapolate from the rest of our data on the national scale, it is very likely that obesity is a much bigger epidemic than is currently acknowledged,” the investigators said in the poster.

Dr. Braverman said in an interview that he foresees DXA becoming a routine part of clinical practice in the future, to measure bone density as well as assess obesity.

“In the 21st century, the physical is really quite outdated and almost no yield to silent disease that every endocrinologist works in. DXA and an efficiency system that can deliver it at $3 a test will make it simply a part of the physical,” he said.

'We have a big problem with the BMI. You could retitle it the “baloney mass index.”'

Source DR. BRAVERMAN

Major Finding: BMI failed to detect obesity in 37% and falsely detected it in 5% in a study of 1,234 adults who had both BMI and DXA measurements.

Data Source: Medical chart review of private adult outpatients.

Disclosures: Study funded by the nonprofit PATH (Place for Achieving Total Health) Research Foundation NY. Dr. Braverman, director of the PATH centers in New York and Philadelphia, had no other financial disclosures.

BOSTON — Dual energy x-ray absorptiometry was a more accurate predictor of obesity than was body mass index in a retrospective comparison of the two measures in 1,234 adults.

Despite its widespread use, BMI is not an accurate indicator of body fat. Direct measures of adiposity, such as those obtained by dual energy x-ray absorptiometry (DXA), are far more precise, Dr. Eric R. Braverman and his associates reported in a poster at the meeting.

“We have a big problem with the BMI. You could retitle it the 'baloney mass index.' It's a mathematical equation. … The scientific standard is clearly subpar compared to our other endocrinology standards,” Dr. Braverman of the department of neurological surgery at Weill Cornell Medical College, New York, said at a press briefing.

Dr. Braverman and his colleagues analyzed medical records of 1,234 private adult outpatients (490 men, 744 women) who had both BMI and DXA measurements during 2003-2009.

The subjects had a mean age of 51 years, a mean BMI of 26.2 kg/m

When the researchers used BMI, 249 (20%) were classified as obese. DXA measurement showed that of those 249, 95% (237) were obese and 5% (12) were nonobese on the basis of body fat percentage.

When the researchers used DXA, 689 (56%) were classified as obese. Of those 689, 34% (237) were obese and 66% (452) were not obese based on BMI.

Thus, 37% of patients were misclassified by BMI: A total of 452 were found to be obese by DXA but nonobese by BMI and 12 were obese by BMI but not by DXA.

The 66% of patients classified as obese by DXA but who were “missed” by BMI had lower muscle and lean body mass, Dr. Braverman and his associates noted.

The BMI measurement of obesity in this study was approximately identical to the national percentage of obesity, which is also determined by BMI. “However, we have shown that BMI is a highly insensitive measure, resulting in an underdiagnosis of obesity. If we can extrapolate from the rest of our data on the national scale, it is very likely that obesity is a much bigger epidemic than is currently acknowledged,” the investigators said in the poster.

Dr. Braverman said in an interview that he foresees DXA becoming a routine part of clinical practice in the future, to measure bone density as well as assess obesity.

“In the 21st century, the physical is really quite outdated and almost no yield to silent disease that every endocrinologist works in. DXA and an efficiency system that can deliver it at $3 a test will make it simply a part of the physical,” he said.

'We have a big problem with the BMI. You could retitle it the “baloney mass index.”'

Source DR. BRAVERMAN

Major Finding: BMI failed to detect obesity in 37% and falsely detected it in 5% in a study of 1,234 adults who had both BMI and DXA measurements.

Data Source: Medical chart review of private adult outpatients.

Disclosures: Study funded by the nonprofit PATH (Place for Achieving Total Health) Research Foundation NY. Dr. Braverman, director of the PATH centers in New York and Philadelphia, had no other financial disclosures.

BOSTON — Dual energy x-ray absorptiometry was a more accurate predictor of obesity than was body mass index in a retrospective comparison of the two measures in 1,234 adults.

Despite its widespread use, BMI is not an accurate indicator of body fat. Direct measures of adiposity, such as those obtained by dual energy x-ray absorptiometry (DXA), are far more precise, Dr. Eric R. Braverman and his associates reported in a poster at the meeting.

“We have a big problem with the BMI. You could retitle it the 'baloney mass index.' It's a mathematical equation. … The scientific standard is clearly subpar compared to our other endocrinology standards,” Dr. Braverman of the department of neurological surgery at Weill Cornell Medical College, New York, said at a press briefing.

Dr. Braverman and his colleagues analyzed medical records of 1,234 private adult outpatients (490 men, 744 women) who had both BMI and DXA measurements during 2003-2009.

The subjects had a mean age of 51 years, a mean BMI of 26.2 kg/m

When the researchers used BMI, 249 (20%) were classified as obese. DXA measurement showed that of those 249, 95% (237) were obese and 5% (12) were nonobese on the basis of body fat percentage.

When the researchers used DXA, 689 (56%) were classified as obese. Of those 689, 34% (237) were obese and 66% (452) were not obese based on BMI.

Thus, 37% of patients were misclassified by BMI: A total of 452 were found to be obese by DXA but nonobese by BMI and 12 were obese by BMI but not by DXA.

The 66% of patients classified as obese by DXA but who were “missed” by BMI had lower muscle and lean body mass, Dr. Braverman and his associates noted.

The BMI measurement of obesity in this study was approximately identical to the national percentage of obesity, which is also determined by BMI. “However, we have shown that BMI is a highly insensitive measure, resulting in an underdiagnosis of obesity. If we can extrapolate from the rest of our data on the national scale, it is very likely that obesity is a much bigger epidemic than is currently acknowledged,” the investigators said in the poster.

Dr. Braverman said in an interview that he foresees DXA becoming a routine part of clinical practice in the future, to measure bone density as well as assess obesity.

“In the 21st century, the physical is really quite outdated and almost no yield to silent disease that every endocrinologist works in. DXA and an efficiency system that can deliver it at $3 a test will make it simply a part of the physical,” he said.

'We have a big problem with the BMI. You could retitle it the “baloney mass index.”'

Source DR. BRAVERMAN

BOSTON — Dual x-ray absorptiometry was a more accurate predictor of obesity than was body mass index in a retrospective comparison of the two measures in 1,234 adults.

Despite its widespread use, BMI is not an accurate indicator of body fat. Direct measures of adiposity, such as those obtained by dual x-ray absorptiometry (DXA), are far more precise, Dr. Eric R. Braverman and his associates reported in a poster at the meeting.

Records of 1,234 private adult outpatients (490 men, 744 women) who had both BMI and DXA measurements during 2003–2009 were analyzed. They had a mean age of 51 years, a mean BMI of 26.2 kg/m

Thus, 37% of patients were misclassified by BMI: 452 were found to be obese by DXA but nonobese by BMI and 12 were obese by BMI but not by DXA. The 66% of patients classified as obese by DXA but who were “missed” by BMI had lower muscle and lean body mass, said Dr. Braverman of the department of neurological surgery at Weill Cornell Medical College, New York.

“We have shown that BMI is a highly insensitive measure, resulting in an underdiagnosis of obesity. If we can extrapolate from the rest of our data on the national scale, it is very likely that obesity is a much bigger epidemic than is currently acknowledged,” they said.

This study was funded by the private nonprofit PATH Foundation in New York. Dr. Braverman stated that he had no other financial disclosures.

The 66% of patients classified as obese by DXA but who were 'missed' by BMI had lower muscle mass.

Source DR. BRAVERMAN

BOSTON — Dual x-ray absorptiometry was a more accurate predictor of obesity than was body mass index in a retrospective comparison of the two measures in 1,234 adults.

Despite its widespread use, BMI is not an accurate indicator of body fat. Direct measures of adiposity, such as those obtained by dual x-ray absorptiometry (DXA), are far more precise, Dr. Eric R. Braverman and his associates reported in a poster at the meeting.

Records of 1,234 private adult outpatients (490 men, 744 women) who had both BMI and DXA measurements during 2003–2009 were analyzed. They had a mean age of 51 years, a mean BMI of 26.2 kg/m

Thus, 37% of patients were misclassified by BMI: 452 were found to be obese by DXA but nonobese by BMI and 12 were obese by BMI but not by DXA. The 66% of patients classified as obese by DXA but who were “missed” by BMI had lower muscle and lean body mass, said Dr. Braverman of the department of neurological surgery at Weill Cornell Medical College, New York.

“We have shown that BMI is a highly insensitive measure, resulting in an underdiagnosis of obesity. If we can extrapolate from the rest of our data on the national scale, it is very likely that obesity is a much bigger epidemic than is currently acknowledged,” they said.

This study was funded by the private nonprofit PATH Foundation in New York. Dr. Braverman stated that he had no other financial disclosures.

The 66% of patients classified as obese by DXA but who were 'missed' by BMI had lower muscle mass.

Source DR. BRAVERMAN

BOSTON — Dual x-ray absorptiometry was a more accurate predictor of obesity than was body mass index in a retrospective comparison of the two measures in 1,234 adults.

Despite its widespread use, BMI is not an accurate indicator of body fat. Direct measures of adiposity, such as those obtained by dual x-ray absorptiometry (DXA), are far more precise, Dr. Eric R. Braverman and his associates reported in a poster at the meeting.

Records of 1,234 private adult outpatients (490 men, 744 women) who had both BMI and DXA measurements during 2003–2009 were analyzed. They had a mean age of 51 years, a mean BMI of 26.2 kg/m

Thus, 37% of patients were misclassified by BMI: 452 were found to be obese by DXA but nonobese by BMI and 12 were obese by BMI but not by DXA. The 66% of patients classified as obese by DXA but who were “missed” by BMI had lower muscle and lean body mass, said Dr. Braverman of the department of neurological surgery at Weill Cornell Medical College, New York.

“We have shown that BMI is a highly insensitive measure, resulting in an underdiagnosis of obesity. If we can extrapolate from the rest of our data on the national scale, it is very likely that obesity is a much bigger epidemic than is currently acknowledged,” they said.

This study was funded by the private nonprofit PATH Foundation in New York. Dr. Braverman stated that he had no other financial disclosures.

The 66% of patients classified as obese by DXA but who were 'missed' by BMI had lower muscle mass.

Source DR. BRAVERMAN

BOSTON — Vietnam veterans exposed to Agent Orange were found to have a threefold increased risk of Graves' disease in an analysis of electronic medical records of more than 200,000 vets who served during the Vietnam era.

The herbicide Agent Orange was sprayed over South Vietnam between 1962 and 1971, ultimately covering nearly 20% of the country's surface.

Much of the concern over its use stemmed from the dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) it was contaminated with during the production process.

Awareness of its persistent toxicity in biological tissue now spans at least 35 years, Dr. Ajay Varanasi said at the annual meeting.

Evidence of thyroid tissue damage arising from TCDD has been observed in animals and humans, said Dr. Varanasi of the State University of New York at Buffalo and the VA Western New York Health Care System.

The study included Department of Veterans Affairs electronic medical records data from 224,048 veterans born between 1925 and 1953 who were followed in upstate New York.

Of those, 23,939 were classified as having been exposed to Agent Orange. Only about 10% of veterans from the Vietnam era actually set foot in Vietnam, but it can be assumed that nearly all who did were exposed to Agent Orange, he noted.

The exposed group did not differ significantly from the 200,109 nonexposed veterans in terms of age (average 62 years), race (about 1 in 5 were African American), smoking history (more than 90% were smokers), and sex (92% of the exposed and 89% of the nonexposed were men).

Diabetes, however, was significantly more common among the exposed, 24% vs. 14%.

The substantial increase in type 2 diabetes among Vietnam veterans has been described previously and is well recognized, he noted.

Graves' disease was diagnosed in 54 exposed and 148 nonexposed vets, for an odds ratio (OR) of 3.05.

Hypothyroidism was significantly more prevalent in the nonexposed group, with 7,273 receiving the diagnosis vs. 740 exposed veterans (OR 0.85). There were no significant differences in the rates of thyroid cancer (OR 1.16) or thyroid nodules (OR 1.14).

In a multivariate analysis, Agent Orange exposure was independently associated with an increased risk of Graves' disease (OR 2.76), whereas smoking history (OR 1.42), diabetes (OR 1.05), and race (OR 1.22 for African American vs. other) were not, Dr. Varanasi reported.

Recent literature indicates that TCDD, which acts primarily by binding to the transcription factor aryl hydrocarbon receptor (AhR) and prolonging its activation, can have both immune-suppressing and immune-promoting effects in humans.

The dioxin may play a role in normal immune responses as well (Trends Immunol. 2009;30:447-54).

Data also suggest that TCDD exposure, along with endogenous AhR ligands, can promote Th17 cell differentiation and expansion. In one study, the proportion of peripheral Th17 cells in patients with autoimmune thyroid disease was higher than in controls, and the proportion of these cells in patients with intractable Graves' disease was higher than in patients with Graves' that was in remission (Thyroid 2009;19:495-501).

An increased prevalence of combined thyroid disorders—thyrotoxicosis, goiter, hypothyroidism, and thyroid adenoma—was seen in accidentally exposed German workers (Occup. Environ. Med. 1994;51:479-86). However, other studies of TCDD and thyroid function have produced less-consistent findings (Occup. Environ. Med. 1999;56:270-6).

“In view of known immune-modulating effects of TCDD, our finding of an increased prevalence of Graves' disease in Vietnam veterans potentially exposed to TCDD warrants further investigation,” Dr. Varanasi concluded.

Disclosures: This study was funded by the Department of Veterans Affairs, and Dr. Varanasi stated that he had no other disclosures.

BOSTON — Vietnam veterans exposed to Agent Orange were found to have a threefold increased risk of Graves' disease in an analysis of electronic medical records of more than 200,000 vets who served during the Vietnam era.

The herbicide Agent Orange was sprayed over South Vietnam between 1962 and 1971, ultimately covering nearly 20% of the country's surface.

Much of the concern over its use stemmed from the dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) it was contaminated with during the production process.

Awareness of its persistent toxicity in biological tissue now spans at least 35 years, Dr. Ajay Varanasi said at the annual meeting.

Evidence of thyroid tissue damage arising from TCDD has been observed in animals and humans, said Dr. Varanasi of the State University of New York at Buffalo and the VA Western New York Health Care System.

The study included Department of Veterans Affairs electronic medical records data from 224,048 veterans born between 1925 and 1953 who were followed in upstate New York.

Of those, 23,939 were classified as having been exposed to Agent Orange. Only about 10% of veterans from the Vietnam era actually set foot in Vietnam, but it can be assumed that nearly all who did were exposed to Agent Orange, he noted.

The exposed group did not differ significantly from the 200,109 nonexposed veterans in terms of age (average 62 years), race (about 1 in 5 were African American), smoking history (more than 90% were smokers), and sex (92% of the exposed and 89% of the nonexposed were men).

Diabetes, however, was significantly more common among the exposed, 24% vs. 14%.

The substantial increase in type 2 diabetes among Vietnam veterans has been described previously and is well recognized, he noted.

Graves' disease was diagnosed in 54 exposed and 148 nonexposed vets, for an odds ratio (OR) of 3.05.

Hypothyroidism was significantly more prevalent in the nonexposed group, with 7,273 receiving the diagnosis vs. 740 exposed veterans (OR 0.85). There were no significant differences in the rates of thyroid cancer (OR 1.16) or thyroid nodules (OR 1.14).

In a multivariate analysis, Agent Orange exposure was independently associated with an increased risk of Graves' disease (OR 2.76), whereas smoking history (OR 1.42), diabetes (OR 1.05), and race (OR 1.22 for African American vs. other) were not, Dr. Varanasi reported.

Recent literature indicates that TCDD, which acts primarily by binding to the transcription factor aryl hydrocarbon receptor (AhR) and prolonging its activation, can have both immune-suppressing and immune-promoting effects in humans.

The dioxin may play a role in normal immune responses as well (Trends Immunol. 2009;30:447-54).

Data also suggest that TCDD exposure, along with endogenous AhR ligands, can promote Th17 cell differentiation and expansion. In one study, the proportion of peripheral Th17 cells in patients with autoimmune thyroid disease was higher than in controls, and the proportion of these cells in patients with intractable Graves' disease was higher than in patients with Graves' that was in remission (Thyroid 2009;19:495-501).

An increased prevalence of combined thyroid disorders—thyrotoxicosis, goiter, hypothyroidism, and thyroid adenoma—was seen in accidentally exposed German workers (Occup. Environ. Med. 1994;51:479-86). However, other studies of TCDD and thyroid function have produced less-consistent findings (Occup. Environ. Med. 1999;56:270-6).

“In view of known immune-modulating effects of TCDD, our finding of an increased prevalence of Graves' disease in Vietnam veterans potentially exposed to TCDD warrants further investigation,” Dr. Varanasi concluded.

Disclosures: This study was funded by the Department of Veterans Affairs, and Dr. Varanasi stated that he had no other disclosures.

BOSTON — Vietnam veterans exposed to Agent Orange were found to have a threefold increased risk of Graves' disease in an analysis of electronic medical records of more than 200,000 vets who served during the Vietnam era.

The herbicide Agent Orange was sprayed over South Vietnam between 1962 and 1971, ultimately covering nearly 20% of the country's surface.

Much of the concern over its use stemmed from the dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) it was contaminated with during the production process.

Awareness of its persistent toxicity in biological tissue now spans at least 35 years, Dr. Ajay Varanasi said at the annual meeting.

Evidence of thyroid tissue damage arising from TCDD has been observed in animals and humans, said Dr. Varanasi of the State University of New York at Buffalo and the VA Western New York Health Care System.

The study included Department of Veterans Affairs electronic medical records data from 224,048 veterans born between 1925 and 1953 who were followed in upstate New York.

Of those, 23,939 were classified as having been exposed to Agent Orange. Only about 10% of veterans from the Vietnam era actually set foot in Vietnam, but it can be assumed that nearly all who did were exposed to Agent Orange, he noted.

The exposed group did not differ significantly from the 200,109 nonexposed veterans in terms of age (average 62 years), race (about 1 in 5 were African American), smoking history (more than 90% were smokers), and sex (92% of the exposed and 89% of the nonexposed were men).

Diabetes, however, was significantly more common among the exposed, 24% vs. 14%.

The substantial increase in type 2 diabetes among Vietnam veterans has been described previously and is well recognized, he noted.

Graves' disease was diagnosed in 54 exposed and 148 nonexposed vets, for an odds ratio (OR) of 3.05.

Hypothyroidism was significantly more prevalent in the nonexposed group, with 7,273 receiving the diagnosis vs. 740 exposed veterans (OR 0.85). There were no significant differences in the rates of thyroid cancer (OR 1.16) or thyroid nodules (OR 1.14).

In a multivariate analysis, Agent Orange exposure was independently associated with an increased risk of Graves' disease (OR 2.76), whereas smoking history (OR 1.42), diabetes (OR 1.05), and race (OR 1.22 for African American vs. other) were not, Dr. Varanasi reported.

Recent literature indicates that TCDD, which acts primarily by binding to the transcription factor aryl hydrocarbon receptor (AhR) and prolonging its activation, can have both immune-suppressing and immune-promoting effects in humans.

The dioxin may play a role in normal immune responses as well (Trends Immunol. 2009;30:447-54).

Data also suggest that TCDD exposure, along with endogenous AhR ligands, can promote Th17 cell differentiation and expansion. In one study, the proportion of peripheral Th17 cells in patients with autoimmune thyroid disease was higher than in controls, and the proportion of these cells in patients with intractable Graves' disease was higher than in patients with Graves' that was in remission (Thyroid 2009;19:495-501).

An increased prevalence of combined thyroid disorders—thyrotoxicosis, goiter, hypothyroidism, and thyroid adenoma—was seen in accidentally exposed German workers (Occup. Environ. Med. 1994;51:479-86). However, other studies of TCDD and thyroid function have produced less-consistent findings (Occup. Environ. Med. 1999;56:270-6).

“In view of known immune-modulating effects of TCDD, our finding of an increased prevalence of Graves' disease in Vietnam veterans potentially exposed to TCDD warrants further investigation,” Dr. Varanasi concluded.

Disclosures: This study was funded by the Department of Veterans Affairs, and Dr. Varanasi stated that he had no other disclosures.

Major Finding: After implementation of a computerized antibiotic stewardship system, the rate of appropriate prescribing rose from 8% to 92% for tigecycline and from 19% to 91% for linezolid.

Data Source: A study conducted during two 4-month periods at a 214-bed hospital.

Disclosures: Dr. Po reported that he had no disclosures.

ATLANTA — A computerized antibiotic stewardship system for tigecycline and linezolid led to an overall decrease in prescriptions of both medications and a significant increase in their appropriate use in a 214-bed community hospital.

A physician order entry system with decision support “provides a nonconfrontational, evidence-based system that can be rapidly implemented,” Dr. John Leander Po and his associates said in a poster at the conference.

Previous strategies to reduce unnecessary use of antibiotics have included prior authorization, prescriber feedback/education, and antibiotic order forms. But little is known about the effectiveness of a computerized interface that is triggered whenever a prescription is entered, requiring input, said Dr. Po and his associates, of Banner Estrella Medical Center, Phoenix.

The onscreen system used in this study was designed to limit utilization of tigecycline and linezolid outside of Food and Drug Administration–approved indications. The FDA has approved the drugs for treatment of patients infected with a multidrug-resistant organism with no other options, for those at risk of penicillin or vancomycin anaphylaxis with no other options, or as second-line therapy for pneumonia, urinary tract infection, and staphylococcal infection. The interface also delivered recommendations for alternative antibiotics, with hyperlinks to evidence-based articles.

Antimicrobial use was monitored, and direct feedback was delivered to the prescriber—primarily hospitalists, surgeons, and emergency physicians—when inappropriate use of either antimicrobial occurred.

During the 4 months before the intervention, 36 prescriptions for tigecycline were ordered, compared with 12 during the 4 months with the computerized system in place. The proportion of appropriate orders rose significantly, from 8% (3) to 92% (11). Examples of inappropriate use in the preintervention phase included for empiric postoperative prophylaxis; for gastroenteritis; when a single, narrow-spectrum antibiotic was indicated (i.e., vancomycin); and in a patient without penicillin allergy.

During the intervention, the one inappropriate tigecycline prescription was for a postcolectomy patient with fever and negative blood cultures and no evidence of penicillin allergy.

Similarly, total linezolid prescriptions fell from 168 to 3 with the computerized system, and the proportion of appropriate orders also increased significantly, from 19% to 91%. Inappropriate linezolid use prior to the intervention included empiric therapy for skin and soft tissue infection (SSTI) and initial therapy for methicillin-resistant Staphylococcus aureus bacteremia and endocarditis. After the intervention, inappropriate use included empiric SSTI therapy, initial therapy for osteomyelitis, and vancomycin-resistant urinary tract infection with a negative urinalysis, Dr. Po and his associates reported.

The computerized system used in this study could serve as a model to reduce inappropriate prescribing of other antimicrobial agents, they commented.

My Take

Getting to the Root Cause of Inappropriate Prescribing

The study by Dr. Po and his associates offers several insights that are relevant to hospitalists. Clearly, the findings speak to the need for improvement in antimicrobial stewardship. We're doing better than we have in the past, but we still need to think before we prescribe. The system used in this study is a simple method designed to catch us if we don't.

A system that walks the user through a clear algorithm can not only steer us toward evidence-based best practice but also provide education at the point of care. Yes, we all know about appropriate antimicrobial prescribing, but there is tremendous variation around the country. Better standardization of these practices could lead to improved care and resource utilization.

The literature supports the use of decision-support systems, particularly for busy clinicians who are working in high-volume institutions. Sometimes we get overwhelmed, and these computerized systems can help us opt into the best standard of care. That's also why checklists have received so much attention lately. They use a similar approach and have been shown to improve outcomes.

However, the idea that pop-up alerts are the answer to everything comes with a price. After a while, too many alerts can lead to “alert fatigue,” and you stop paying attention. Just as we need to adopt more judicious use of our medications, technology needs to be applied judiciously as well.

Downstream alerts are a useful safety-net solution that can help reduce practice deviations. But it is always important to understand and investigate the root cause of why deviations occur in the first place. It's important for clinicians to step back, figure out why this is happening, and address it at the outset.

Major Finding: After implementation of a computerized antibiotic stewardship system, the rate of appropriate prescribing rose from 8% to 92% for tigecycline and from 19% to 91% for linezolid.

Data Source: A study conducted during two 4-month periods at a 214-bed hospital.

Disclosures: Dr. Po reported that he had no disclosures.

ATLANTA — A computerized antibiotic stewardship system for tigecycline and linezolid led to an overall decrease in prescriptions of both medications and a significant increase in their appropriate use in a 214-bed community hospital.

A physician order entry system with decision support “provides a nonconfrontational, evidence-based system that can be rapidly implemented,” Dr. John Leander Po and his associates said in a poster at the conference.

Previous strategies to reduce unnecessary use of antibiotics have included prior authorization, prescriber feedback/education, and antibiotic order forms. But little is known about the effectiveness of a computerized interface that is triggered whenever a prescription is entered, requiring input, said Dr. Po and his associates, of Banner Estrella Medical Center, Phoenix.

The onscreen system used in this study was designed to limit utilization of tigecycline and linezolid outside of Food and Drug Administration–approved indications. The FDA has approved the drugs for treatment of patients infected with a multidrug-resistant organism with no other options, for those at risk of penicillin or vancomycin anaphylaxis with no other options, or as second-line therapy for pneumonia, urinary tract infection, and staphylococcal infection. The interface also delivered recommendations for alternative antibiotics, with hyperlinks to evidence-based articles.

Antimicrobial use was monitored, and direct feedback was delivered to the prescriber—primarily hospitalists, surgeons, and emergency physicians—when inappropriate use of either antimicrobial occurred.

During the 4 months before the intervention, 36 prescriptions for tigecycline were ordered, compared with 12 during the 4 months with the computerized system in place. The proportion of appropriate orders rose significantly, from 8% (3) to 92% (11). Examples of inappropriate use in the preintervention phase included for empiric postoperative prophylaxis; for gastroenteritis; when a single, narrow-spectrum antibiotic was indicated (i.e., vancomycin); and in a patient without penicillin allergy.

During the intervention, the one inappropriate tigecycline prescription was for a postcolectomy patient with fever and negative blood cultures and no evidence of penicillin allergy.

Similarly, total linezolid prescriptions fell from 168 to 3 with the computerized system, and the proportion of appropriate orders also increased significantly, from 19% to 91%. Inappropriate linezolid use prior to the intervention included empiric therapy for skin and soft tissue infection (SSTI) and initial therapy for methicillin-resistant Staphylococcus aureus bacteremia and endocarditis. After the intervention, inappropriate use included empiric SSTI therapy, initial therapy for osteomyelitis, and vancomycin-resistant urinary tract infection with a negative urinalysis, Dr. Po and his associates reported.

The computerized system used in this study could serve as a model to reduce inappropriate prescribing of other antimicrobial agents, they commented.

My Take

Getting to the Root Cause of Inappropriate Prescribing

The study by Dr. Po and his associates offers several insights that are relevant to hospitalists. Clearly, the findings speak to the need for improvement in antimicrobial stewardship. We're doing better than we have in the past, but we still need to think before we prescribe. The system used in this study is a simple method designed to catch us if we don't.

A system that walks the user through a clear algorithm can not only steer us toward evidence-based best practice but also provide education at the point of care. Yes, we all know about appropriate antimicrobial prescribing, but there is tremendous variation around the country. Better standardization of these practices could lead to improved care and resource utilization.

The literature supports the use of decision-support systems, particularly for busy clinicians who are working in high-volume institutions. Sometimes we get overwhelmed, and these computerized systems can help us opt into the best standard of care. That's also why checklists have received so much attention lately. They use a similar approach and have been shown to improve outcomes.

However, the idea that pop-up alerts are the answer to everything comes with a price. After a while, too many alerts can lead to “alert fatigue,” and you stop paying attention. Just as we need to adopt more judicious use of our medications, technology needs to be applied judiciously as well.

Downstream alerts are a useful safety-net solution that can help reduce practice deviations. But it is always important to understand and investigate the root cause of why deviations occur in the first place. It's important for clinicians to step back, figure out why this is happening, and address it at the outset.

Major Finding: After implementation of a computerized antibiotic stewardship system, the rate of appropriate prescribing rose from 8% to 92% for tigecycline and from 19% to 91% for linezolid.

Data Source: A study conducted during two 4-month periods at a 214-bed hospital.

Disclosures: Dr. Po reported that he had no disclosures.

ATLANTA — A computerized antibiotic stewardship system for tigecycline and linezolid led to an overall decrease in prescriptions of both medications and a significant increase in their appropriate use in a 214-bed community hospital.

A physician order entry system with decision support “provides a nonconfrontational, evidence-based system that can be rapidly implemented,” Dr. John Leander Po and his associates said in a poster at the conference.

Previous strategies to reduce unnecessary use of antibiotics have included prior authorization, prescriber feedback/education, and antibiotic order forms. But little is known about the effectiveness of a computerized interface that is triggered whenever a prescription is entered, requiring input, said Dr. Po and his associates, of Banner Estrella Medical Center, Phoenix.

The onscreen system used in this study was designed to limit utilization of tigecycline and linezolid outside of Food and Drug Administration–approved indications. The FDA has approved the drugs for treatment of patients infected with a multidrug-resistant organism with no other options, for those at risk of penicillin or vancomycin anaphylaxis with no other options, or as second-line therapy for pneumonia, urinary tract infection, and staphylococcal infection. The interface also delivered recommendations for alternative antibiotics, with hyperlinks to evidence-based articles.

Antimicrobial use was monitored, and direct feedback was delivered to the prescriber—primarily hospitalists, surgeons, and emergency physicians—when inappropriate use of either antimicrobial occurred.

During the 4 months before the intervention, 36 prescriptions for tigecycline were ordered, compared with 12 during the 4 months with the computerized system in place. The proportion of appropriate orders rose significantly, from 8% (3) to 92% (11). Examples of inappropriate use in the preintervention phase included for empiric postoperative prophylaxis; for gastroenteritis; when a single, narrow-spectrum antibiotic was indicated (i.e., vancomycin); and in a patient without penicillin allergy.

During the intervention, the one inappropriate tigecycline prescription was for a postcolectomy patient with fever and negative blood cultures and no evidence of penicillin allergy.

Similarly, total linezolid prescriptions fell from 168 to 3 with the computerized system, and the proportion of appropriate orders also increased significantly, from 19% to 91%. Inappropriate linezolid use prior to the intervention included empiric therapy for skin and soft tissue infection (SSTI) and initial therapy for methicillin-resistant Staphylococcus aureus bacteremia and endocarditis. After the intervention, inappropriate use included empiric SSTI therapy, initial therapy for osteomyelitis, and vancomycin-resistant urinary tract infection with a negative urinalysis, Dr. Po and his associates reported.

The computerized system used in this study could serve as a model to reduce inappropriate prescribing of other antimicrobial agents, they commented.

My Take

Getting to the Root Cause of Inappropriate Prescribing

The study by Dr. Po and his associates offers several insights that are relevant to hospitalists. Clearly, the findings speak to the need for improvement in antimicrobial stewardship. We're doing better than we have in the past, but we still need to think before we prescribe. The system used in this study is a simple method designed to catch us if we don't.

A system that walks the user through a clear algorithm can not only steer us toward evidence-based best practice but also provide education at the point of care. Yes, we all know about appropriate antimicrobial prescribing, but there is tremendous variation around the country. Better standardization of these practices could lead to improved care and resource utilization.

The literature supports the use of decision-support systems, particularly for busy clinicians who are working in high-volume institutions. Sometimes we get overwhelmed, and these computerized systems can help us opt into the best standard of care. That's also why checklists have received so much attention lately. They use a similar approach and have been shown to improve outcomes.

However, the idea that pop-up alerts are the answer to everything comes with a price. After a while, too many alerts can lead to “alert fatigue,” and you stop paying attention. Just as we need to adopt more judicious use of our medications, technology needs to be applied judiciously as well.

Downstream alerts are a useful safety-net solution that can help reduce practice deviations. But it is always important to understand and investigate the root cause of why deviations occur in the first place. It's important for clinicians to step back, figure out why this is happening, and address it at the outset.

BOSTON — It's still not clear why mortality was higher with the intensive glycemic control strategy of the ACCORD trial, but new analyses of the data highlight the fact that higher glucose levels, not lower, remain the most likely culprit.

At a special evening session held during the annual meeting of the American Association of Clinical Endocrinologists, researchers from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial summarized results of recent subanalyses of the trial data and suggested ways in which the new findings, while still lacking an ultimate conclusion, might nonetheless help inform clinical decisions—at least among patients who resemble the study population.

In ACCORD, all-cause mortality was greater among patients randomized to intensive glycemic control, with the aim of getting patients to a hemoglobin A_1c below 6%. When the glycemic arm of the study was stopped early, at 3.4 years rather than the planned 5.6 years of follow-up, the hazard ratio was 1.22, compared with standard treatment (N. Engl. J. Med. 2008;358:2545–59).

Panel moderator Dr. Faramarz Ismail-Beigi said that the overall conclusion from the glycemia arm of the ACCORD trial pertains only to that patient group: In older patients with a longer duration of diabetes and established cardiovascular risk factors, attempting to achieve normoglycemia does not reduce all-cause or cardiovascular mortality and may increase the risk.

However, he said, it's important to remember that the 10,194 patients enrolled in ACCORD did not represent the entire type 2 diabetes population. The ACCORD patients had an average age of 62 years, a 10-year duration of diabetes, and a median HbA_1c of 8.1%. A third had experienced prior cardiovascular events.

“This cohort represents a little bit less than half of all U.S. patients with type 2 diabetes. So it represents a large group of people, but not everybody. We're not talking about people who are newly diagnosed with diabetes, middle-aged, or younger,” said Dr. Ismail-Beigi, professor of medicine at Case Western Reserve University, Cleveland.

Several possible mechanisms to explain the results were put forward at the time the glycemia arm of ACCORD was stopped in 2008, including hypoglycemia, weight gain, individual drugs, drug combinations, or the rapid reduction of glucose levels early in the trial. But now, new data refute some of these hypotheses.

Dr. Elizabeth R. Seaquist, professor of medicine and director of the Center for Diabetes Research at the University of Minnesota, Minneapolis, presented just-published data showing that the excess risk of all-cause mortality associated with intensive treatment in ACCORD was associated with persistently high HbA_1c rather than low HbA_1c, regardless of treatment group assignment.

Average HbA_1c was the strongest predictor of death for both groups: A 1-percentage-point increase was linked with a 22% increase in mortality, after adjustment for a variety of potentially confounding baseline factors. When each group was examined separately, the relationship between HbA_1c and death was much stronger among those in the intensive treatment group, with a statistically significant 66% increase in all-cause mortality for every 1-percentage-point higher HbA_1c vs. a nonsignificant 14% increase for the standard treatment group.

The greatest excess risk of death associated with the intensive treatment group occurred among the patients whose average HbA_1c remained above 7% despite their treatment assignment. In the intensive treatment group, there was a steady increase in mortality as the HbA_1c rose from 6% to 9%, whereas no such relationship was seen in the standard treatment group. The excess mortality in the intensive group was seen only at an HbA_1c above 7%, not below, Dr. Seaquist reported.

The relationship between mortality and the last HbA_1c recorded before death and the decrease in HbA_1c over the first year did not differ between the two groups, suggesting that the rate of change in HbA_1c from baseline was not associated with increased risk of death. “These analyses do not support the view that rapid reduction of glucose levels or lower average A_1c independent of other factors led to the excess risk of death,” she said.

Dr. Saul Genuth, professor of medicine at Case Western Reserve University, summarized findings from two studies published last year suggesting that severe hypoglycemia was a risk factor for increased mortality in ACCORD, but that the relationship between hypoglycemia and mortality did not explain the difference in outcomes between the intensive and standard treatment groups.

Patients with poorer glycemic control had a greater risk for hypoglycemia in both groups, and among those who experienced severe hypoglycemia, the risk of death was actually lower in the intensive treatment arm, he said.

The frequency of severe hypoglycemia events requiring medical assistance was 4.3 per 100 person-years for the intensive arm, compared with 1.4 for standard treatment. There was a slow decline in severe hypoglycemic events over the 3.4 years of the trial in the intensive group, whereas the rate remained steady in the standard treatment group. “This should encourage all of us to keep educating our patients about preventing hypoglycemia,” Dr. Genuth said.

Baseline characteristics linked with increased risk for severe hypoglycemia included African American race, male gender, increased age, and longer diabetes duration. Higher BMI actually protected against severe hypoglycemia, presumably owing to greater insulin resistance. Insulin treatment at baseline nearly doubled the risk of severe hypoglycemia in the intensive group, but quadrupled it in the standard group (BMJ 2010;340:b5444).

Among just the patients with no severe hypoglycemic events, the mortality risk was increased by 25% in the intensive treatment group compared with standard treatment, similar to the 22% increase for the entire intensive treatment group, suggesting that severe hypoglycemia was not the reason for the increased deaths in the intensive group, he said.

Importantly, the higher the average HbA_1c achieved and maintained during the trial, the more the incidence of severe hypoglycemia increased. The risk of hypoglycemia was greatest among those whose HbA_1c barely declined in the first 4 months of treatment, and was least among those whose HbA_1c fell rapidly.

Finger-stick data implied that the occurrence of severe hypoglycemia identifies patients with type 2 diabetes at increased risk for death, particularly in those whose HbA1_c does not respond to intensification of treatment, Dr. Genuth concluded (BMJ 2010;340:b4909).

More ACCORD data are due to be published during 2010, including results on microvascular outcomes.

Disclosures: ACCORD was funded by the National Institutes of Health and the Centers for Disease Control and Prevention, with supplies and medications contributed by 13 companies. Dr. Ismail-Beigi is a consultant to Eli Lilly. Dr. Seaquist and Dr. Genuth reported no relevant disclosures.

BOSTON — It's still not clear why mortality was higher with the intensive glycemic control strategy of the ACCORD trial, but new analyses of the data highlight the fact that higher glucose levels, not lower, remain the most likely culprit.

At a special evening session held during the annual meeting of the American Association of Clinical Endocrinologists, researchers from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial summarized results of recent subanalyses of the trial data and suggested ways in which the new findings, while still lacking an ultimate conclusion, might nonetheless help inform clinical decisions—at least among patients who resemble the study population.

In ACCORD, all-cause mortality was greater among patients randomized to intensive glycemic control, with the aim of getting patients to a hemoglobin A_1c below 6%. When the glycemic arm of the study was stopped early, at 3.4 years rather than the planned 5.6 years of follow-up, the hazard ratio was 1.22, compared with standard treatment (N. Engl. J. Med. 2008;358:2545–59).

Panel moderator Dr. Faramarz Ismail-Beigi said that the overall conclusion from the glycemia arm of the ACCORD trial pertains only to that patient group: In older patients with a longer duration of diabetes and established cardiovascular risk factors, attempting to achieve normoglycemia does not reduce all-cause or cardiovascular mortality and may increase the risk.

However, he said, it's important to remember that the 10,194 patients enrolled in ACCORD did not represent the entire type 2 diabetes population. The ACCORD patients had an average age of 62 years, a 10-year duration of diabetes, and a median HbA_1c of 8.1%. A third had experienced prior cardiovascular events.

“This cohort represents a little bit less than half of all U.S. patients with type 2 diabetes. So it represents a large group of people, but not everybody. We're not talking about people who are newly diagnosed with diabetes, middle-aged, or younger,” said Dr. Ismail-Beigi, professor of medicine at Case Western Reserve University, Cleveland.

Several possible mechanisms to explain the results were put forward at the time the glycemia arm of ACCORD was stopped in 2008, including hypoglycemia, weight gain, individual drugs, drug combinations, or the rapid reduction of glucose levels early in the trial. But now, new data refute some of these hypotheses.

Dr. Elizabeth R. Seaquist, professor of medicine and director of the Center for Diabetes Research at the University of Minnesota, Minneapolis, presented just-published data showing that the excess risk of all-cause mortality associated with intensive treatment in ACCORD was associated with persistently high HbA_1c rather than low HbA_1c, regardless of treatment group assignment.

Average HbA_1c was the strongest predictor of death for both groups: A 1-percentage-point increase was linked with a 22% increase in mortality, after adjustment for a variety of potentially confounding baseline factors. When each group was examined separately, the relationship between HbA_1c and death was much stronger among those in the intensive treatment group, with a statistically significant 66% increase in all-cause mortality for every 1-percentage-point higher HbA_1c vs. a nonsignificant 14% increase for the standard treatment group.

The greatest excess risk of death associated with the intensive treatment group occurred among the patients whose average HbA_1c remained above 7% despite their treatment assignment. In the intensive treatment group, there was a steady increase in mortality as the HbA_1c rose from 6% to 9%, whereas no such relationship was seen in the standard treatment group. The excess mortality in the intensive group was seen only at an HbA_1c above 7%, not below, Dr. Seaquist reported.

The relationship between mortality and the last HbA_1c recorded before death and the decrease in HbA_1c over the first year did not differ between the two groups, suggesting that the rate of change in HbA_1c from baseline was not associated with increased risk of death. “These analyses do not support the view that rapid reduction of glucose levels or lower average A_1c independent of other factors led to the excess risk of death,” she said.

Dr. Saul Genuth, professor of medicine at Case Western Reserve University, summarized findings from two studies published last year suggesting that severe hypoglycemia was a risk factor for increased mortality in ACCORD, but that the relationship between hypoglycemia and mortality did not explain the difference in outcomes between the intensive and standard treatment groups.

Patients with poorer glycemic control had a greater risk for hypoglycemia in both groups, and among those who experienced severe hypoglycemia, the risk of death was actually lower in the intensive treatment arm, he said.

The frequency of severe hypoglycemia events requiring medical assistance was 4.3 per 100 person-years for the intensive arm, compared with 1.4 for standard treatment. There was a slow decline in severe hypoglycemic events over the 3.4 years of the trial in the intensive group, whereas the rate remained steady in the standard treatment group. “This should encourage all of us to keep educating our patients about preventing hypoglycemia,” Dr. Genuth said.

Baseline characteristics linked with increased risk for severe hypoglycemia included African American race, male gender, increased age, and longer diabetes duration. Higher BMI actually protected against severe hypoglycemia, presumably owing to greater insulin resistance. Insulin treatment at baseline nearly doubled the risk of severe hypoglycemia in the intensive group, but quadrupled it in the standard group (BMJ 2010;340:b5444).

Among just the patients with no severe hypoglycemic events, the mortality risk was increased by 25% in the intensive treatment group compared with standard treatment, similar to the 22% increase for the entire intensive treatment group, suggesting that severe hypoglycemia was not the reason for the increased deaths in the intensive group, he said.

Importantly, the higher the average HbA_1c achieved and maintained during the trial, the more the incidence of severe hypoglycemia increased. The risk of hypoglycemia was greatest among those whose HbA_1c barely declined in the first 4 months of treatment, and was least among those whose HbA_1c fell rapidly.

Finger-stick data implied that the occurrence of severe hypoglycemia identifies patients with type 2 diabetes at increased risk for death, particularly in those whose HbA1_c does not respond to intensification of treatment, Dr. Genuth concluded (BMJ 2010;340:b4909).

More ACCORD data are due to be published during 2010, including results on microvascular outcomes.

Disclosures: ACCORD was funded by the National Institutes of Health and the Centers for Disease Control and Prevention, with supplies and medications contributed by 13 companies. Dr. Ismail-Beigi is a consultant to Eli Lilly. Dr. Seaquist and Dr. Genuth reported no relevant disclosures.

BOSTON — It's still not clear why mortality was higher with the intensive glycemic control strategy of the ACCORD trial, but new analyses of the data highlight the fact that higher glucose levels, not lower, remain the most likely culprit.

At a special evening session held during the annual meeting of the American Association of Clinical Endocrinologists, researchers from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial summarized results of recent subanalyses of the trial data and suggested ways in which the new findings, while still lacking an ultimate conclusion, might nonetheless help inform clinical decisions—at least among patients who resemble the study population.

In ACCORD, all-cause mortality was greater among patients randomized to intensive glycemic control, with the aim of getting patients to a hemoglobin A_1c below 6%. When the glycemic arm of the study was stopped early, at 3.4 years rather than the planned 5.6 years of follow-up, the hazard ratio was 1.22, compared with standard treatment (N. Engl. J. Med. 2008;358:2545–59).

Panel moderator Dr. Faramarz Ismail-Beigi said that the overall conclusion from the glycemia arm of the ACCORD trial pertains only to that patient group: In older patients with a longer duration of diabetes and established cardiovascular risk factors, attempting to achieve normoglycemia does not reduce all-cause or cardiovascular mortality and may increase the risk.

However, he said, it's important to remember that the 10,194 patients enrolled in ACCORD did not represent the entire type 2 diabetes population. The ACCORD patients had an average age of 62 years, a 10-year duration of diabetes, and a median HbA_1c of 8.1%. A third had experienced prior cardiovascular events.

“This cohort represents a little bit less than half of all U.S. patients with type 2 diabetes. So it represents a large group of people, but not everybody. We're not talking about people who are newly diagnosed with diabetes, middle-aged, or younger,” said Dr. Ismail-Beigi, professor of medicine at Case Western Reserve University, Cleveland.

Several possible mechanisms to explain the results were put forward at the time the glycemia arm of ACCORD was stopped in 2008, including hypoglycemia, weight gain, individual drugs, drug combinations, or the rapid reduction of glucose levels early in the trial. But now, new data refute some of these hypotheses.

Dr. Elizabeth R. Seaquist, professor of medicine and director of the Center for Diabetes Research at the University of Minnesota, Minneapolis, presented just-published data showing that the excess risk of all-cause mortality associated with intensive treatment in ACCORD was associated with persistently high HbA_1c rather than low HbA_1c, regardless of treatment group assignment.

Average HbA_1c was the strongest predictor of death for both groups: A 1-percentage-point increase was linked with a 22% increase in mortality, after adjustment for a variety of potentially confounding baseline factors. When each group was examined separately, the relationship between HbA_1c and death was much stronger among those in the intensive treatment group, with a statistically significant 66% increase in all-cause mortality for every 1-percentage-point higher HbA_1c vs. a nonsignificant 14% increase for the standard treatment group.

The greatest excess risk of death associated with the intensive treatment group occurred among the patients whose average HbA_1c remained above 7% despite their treatment assignment. In the intensive treatment group, there was a steady increase in mortality as the HbA_1c rose from 6% to 9%, whereas no such relationship was seen in the standard treatment group. The excess mortality in the intensive group was seen only at an HbA_1c above 7%, not below, Dr. Seaquist reported.

The relationship between mortality and the last HbA_1c recorded before death and the decrease in HbA_1c over the first year did not differ between the two groups, suggesting that the rate of change in HbA_1c from baseline was not associated with increased risk of death. “These analyses do not support the view that rapid reduction of glucose levels or lower average A_1c independent of other factors led to the excess risk of death,” she said.

Dr. Saul Genuth, professor of medicine at Case Western Reserve University, summarized findings from two studies published last year suggesting that severe hypoglycemia was a risk factor for increased mortality in ACCORD, but that the relationship between hypoglycemia and mortality did not explain the difference in outcomes between the intensive and standard treatment groups.

Patients with poorer glycemic control had a greater risk for hypoglycemia in both groups, and among those who experienced severe hypoglycemia, the risk of death was actually lower in the intensive treatment arm, he said.

The frequency of severe hypoglycemia events requiring medical assistance was 4.3 per 100 person-years for the intensive arm, compared with 1.4 for standard treatment. There was a slow decline in severe hypoglycemic events over the 3.4 years of the trial in the intensive group, whereas the rate remained steady in the standard treatment group. “This should encourage all of us to keep educating our patients about preventing hypoglycemia,” Dr. Genuth said.

Baseline characteristics linked with increased risk for severe hypoglycemia included African American race, male gender, increased age, and longer diabetes duration. Higher BMI actually protected against severe hypoglycemia, presumably owing to greater insulin resistance. Insulin treatment at baseline nearly doubled the risk of severe hypoglycemia in the intensive group, but quadrupled it in the standard group (BMJ 2010;340:b5444).

Among just the patients with no severe hypoglycemic events, the mortality risk was increased by 25% in the intensive treatment group compared with standard treatment, similar to the 22% increase for the entire intensive treatment group, suggesting that severe hypoglycemia was not the reason for the increased deaths in the intensive group, he said.

Importantly, the higher the average HbA_1c achieved and maintained during the trial, the more the incidence of severe hypoglycemia increased. The risk of hypoglycemia was greatest among those whose HbA_1c barely declined in the first 4 months of treatment, and was least among those whose HbA_1c fell rapidly.

Finger-stick data implied that the occurrence of severe hypoglycemia identifies patients with type 2 diabetes at increased risk for death, particularly in those whose HbA1_c does not respond to intensification of treatment, Dr. Genuth concluded (BMJ 2010;340:b4909).

More ACCORD data are due to be published during 2010, including results on microvascular outcomes.

Disclosures: ACCORD was funded by the National Institutes of Health and the Centers for Disease Control and Prevention, with supplies and medications contributed by 13 companies. Dr. Ismail-Beigi is a consultant to Eli Lilly. Dr. Seaquist and Dr. Genuth reported no relevant disclosures.

Major Finding: Graves' disease was diagnosed in 54 of 23,939 veterans exposed to Agent Orange and 148 of 200,109 nonexposed veterans (OR 3.05).

Data Source: Electronic database analysis of veterans born between 1925 and 1953.

Disclosures: Study was funded by the Department of Veteran's Affairs. Dr. Varanasi had no other disclosures.

BOSTON — Vietnam veterans exposed to Agent Orange were found to have a threefold increased risk of Graves' disease in an analysis of electronic medical records of more than 200,000 vets who served during the Vietnam era.

The herbicide Agent Orange was sprayed over South Vietnam between 1962 and 1971, ultimately covering nearly 20% of the country's surface. Much of the concern over its use stemmed from the dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) it was contaminated with during production. Its persistent toxicity in biological tissue has been known for 35 years, Dr. Ajay Varanasi said at the annual meeting of the American Association of Clinical Endocrinologists.

Evidence of thyroid tissue damage arising from TCDD has been observed in animals and humans, said Dr. Varanasi of the State University of New York at Buffalo and the VA Western New York Health Care System.

The study included Department of Veterans Affairs electronic medical records data from 224,048 veterans born between 1925 and 1953 who were followed in upstate New York. Of those, 23,939 were classified as having been exposed to Agent Orange. Only about 10% of veterans from the Vietnam era actually set foot in Vietnam, but it can be assumed that nearly all who did were exposed to Agent Orange, he noted.

The exposed group did not differ significantly from the 200,109 nonexposed veterans in terms of age (average 62 years), race (1/5 were African American), smoking history (more than 90% were smokers), and sex (92% of the exposed and 89% of the nonexposed were men).

Diabetes, however, was significantly more common among the exposed, 24% vs. 14%. The substantial increase in type 2 diabetes among Vietnam veterans has been described previously and is well recognized, he noted.

Graves' disease was diagnosed in 54 exposed and 148 nonexposed vets, for an odds ratio (OR) of 3.05. Hypothyroidism was significantly more prevalent in the nonexposed group, with 7,273 receiving the diagnosis vs. 740 exposed veterans (OR 0.85). There were no significant differences in the rates of thyroid cancer (OR 1.16) or thyroid nodules (OR 1.14).

In a multivariate analysis, Agent Orange exposure was independently associated with an increased risk of Graves' disease (OR 2.76), whereas smoking history (OR 1.42), diabetes (OR 1.05), and race (OR 1.22 for African American vs. other) were not, Dr. Varanasi reported.

Recent literature indicates that TCDD can have both immune-suppressing and immune-promoting effects in humans. The dioxin may play a role in normal immune responses as well (Trends Immunol. 2009;30:447–54).

Data also suggest that TCDD exposure can promote Th17-cell differentiation and expansion. In one study, the proportion of peripheral Th17 cells in patients with autoimmune thyroid disease was higher than in controls, and the proportion of these cells in patients with intractable Graves' disease was higher than in patients with Graves' that was in remission (Thyroid 2009;19:495–501).

An increased prevalence of combined thyroid disorders—thyrotoxicosis, goiter, hypothyroidism, and thyroid adenoma—was seen in accidentally exposed German workers (Occup. Environ. Med. 1994;51:479–86). However, other studies of TCDD and thyroid function have produced less-consistent findings (Occup. Environ. Med. 1999;56:270–6).

“Our finding of an increased prevalence of Graves' disease in Vietnam veterans potentially exposed to TCDD warrants further investigation,” Dr. Varanasi concluded.

Major Finding: Graves' disease was diagnosed in 54 of 23,939 veterans exposed to Agent Orange and 148 of 200,109 nonexposed veterans (OR 3.05).

Data Source: Electronic database analysis of veterans born between 1925 and 1953.

Disclosures: Study was funded by the Department of Veteran's Affairs. Dr. Varanasi had no other disclosures.

BOSTON — Vietnam veterans exposed to Agent Orange were found to have a threefold increased risk of Graves' disease in an analysis of electronic medical records of more than 200,000 vets who served during the Vietnam era.

The herbicide Agent Orange was sprayed over South Vietnam between 1962 and 1971, ultimately covering nearly 20% of the country's surface. Much of the concern over its use stemmed from the dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) it was contaminated with during production. Its persistent toxicity in biological tissue has been known for 35 years, Dr. Ajay Varanasi said at the annual meeting of the American Association of Clinical Endocrinologists.

Evidence of thyroid tissue damage arising from TCDD has been observed in animals and humans, said Dr. Varanasi of the State University of New York at Buffalo and the VA Western New York Health Care System.

The study included Department of Veterans Affairs electronic medical records data from 224,048 veterans born between 1925 and 1953 who were followed in upstate New York. Of those, 23,939 were classified as having been exposed to Agent Orange. Only about 10% of veterans from the Vietnam era actually set foot in Vietnam, but it can be assumed that nearly all who did were exposed to Agent Orange, he noted.

The exposed group did not differ significantly from the 200,109 nonexposed veterans in terms of age (average 62 years), race (1/5 were African American), smoking history (more than 90% were smokers), and sex (92% of the exposed and 89% of the nonexposed were men).

Diabetes, however, was significantly more common among the exposed, 24% vs. 14%. The substantial increase in type 2 diabetes among Vietnam veterans has been described previously and is well recognized, he noted.

Graves' disease was diagnosed in 54 exposed and 148 nonexposed vets, for an odds ratio (OR) of 3.05. Hypothyroidism was significantly more prevalent in the nonexposed group, with 7,273 receiving the diagnosis vs. 740 exposed veterans (OR 0.85). There were no significant differences in the rates of thyroid cancer (OR 1.16) or thyroid nodules (OR 1.14).

In a multivariate analysis, Agent Orange exposure was independently associated with an increased risk of Graves' disease (OR 2.76), whereas smoking history (OR 1.42), diabetes (OR 1.05), and race (OR 1.22 for African American vs. other) were not, Dr. Varanasi reported.

Recent literature indicates that TCDD can have both immune-suppressing and immune-promoting effects in humans. The dioxin may play a role in normal immune responses as well (Trends Immunol. 2009;30:447–54).

Data also suggest that TCDD exposure can promote Th17-cell differentiation and expansion. In one study, the proportion of peripheral Th17 cells in patients with autoimmune thyroid disease was higher than in controls, and the proportion of these cells in patients with intractable Graves' disease was higher than in patients with Graves' that was in remission (Thyroid 2009;19:495–501).

An increased prevalence of combined thyroid disorders—thyrotoxicosis, goiter, hypothyroidism, and thyroid adenoma—was seen in accidentally exposed German workers (Occup. Environ. Med. 1994;51:479–86). However, other studies of TCDD and thyroid function have produced less-consistent findings (Occup. Environ. Med. 1999;56:270–6).

“Our finding of an increased prevalence of Graves' disease in Vietnam veterans potentially exposed to TCDD warrants further investigation,” Dr. Varanasi concluded.

Major Finding: Graves' disease was diagnosed in 54 of 23,939 veterans exposed to Agent Orange and 148 of 200,109 nonexposed veterans (OR 3.05).

Data Source: Electronic database analysis of veterans born between 1925 and 1953.

Disclosures: Study was funded by the Department of Veteran's Affairs. Dr. Varanasi had no other disclosures.

BOSTON — Vietnam veterans exposed to Agent Orange were found to have a threefold increased risk of Graves' disease in an analysis of electronic medical records of more than 200,000 vets who served during the Vietnam era.

The herbicide Agent Orange was sprayed over South Vietnam between 1962 and 1971, ultimately covering nearly 20% of the country's surface. Much of the concern over its use stemmed from the dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) it was contaminated with during production. Its persistent toxicity in biological tissue has been known for 35 years, Dr. Ajay Varanasi said at the annual meeting of the American Association of Clinical Endocrinologists.

Evidence of thyroid tissue damage arising from TCDD has been observed in animals and humans, said Dr. Varanasi of the State University of New York at Buffalo and the VA Western New York Health Care System.

The study included Department of Veterans Affairs electronic medical records data from 224,048 veterans born between 1925 and 1953 who were followed in upstate New York. Of those, 23,939 were classified as having been exposed to Agent Orange. Only about 10% of veterans from the Vietnam era actually set foot in Vietnam, but it can be assumed that nearly all who did were exposed to Agent Orange, he noted.

The exposed group did not differ significantly from the 200,109 nonexposed veterans in terms of age (average 62 years), race (1/5 were African American), smoking history (more than 90% were smokers), and sex (92% of the exposed and 89% of the nonexposed were men).

Diabetes, however, was significantly more common among the exposed, 24% vs. 14%. The substantial increase in type 2 diabetes among Vietnam veterans has been described previously and is well recognized, he noted.

Graves' disease was diagnosed in 54 exposed and 148 nonexposed vets, for an odds ratio (OR) of 3.05. Hypothyroidism was significantly more prevalent in the nonexposed group, with 7,273 receiving the diagnosis vs. 740 exposed veterans (OR 0.85). There were no significant differences in the rates of thyroid cancer (OR 1.16) or thyroid nodules (OR 1.14).

In a multivariate analysis, Agent Orange exposure was independently associated with an increased risk of Graves' disease (OR 2.76), whereas smoking history (OR 1.42), diabetes (OR 1.05), and race (OR 1.22 for African American vs. other) were not, Dr. Varanasi reported.

Recent literature indicates that TCDD can have both immune-suppressing and immune-promoting effects in humans. The dioxin may play a role in normal immune responses as well (Trends Immunol. 2009;30:447–54).

Data also suggest that TCDD exposure can promote Th17-cell differentiation and expansion. In one study, the proportion of peripheral Th17 cells in patients with autoimmune thyroid disease was higher than in controls, and the proportion of these cells in patients with intractable Graves' disease was higher than in patients with Graves' that was in remission (Thyroid 2009;19:495–501).

An increased prevalence of combined thyroid disorders—thyrotoxicosis, goiter, hypothyroidism, and thyroid adenoma—was seen in accidentally exposed German workers (Occup. Environ. Med. 1994;51:479–86). However, other studies of TCDD and thyroid function have produced less-consistent findings (Occup. Environ. Med. 1999;56:270–6).

“Our finding of an increased prevalence of Graves' disease in Vietnam veterans potentially exposed to TCDD warrants further investigation,” Dr. Varanasi concluded.

Major Finding: A total of 5 infants (0.15%) became infected in the NICU during the screening period, versus 29 (1.11%) during the period when screening was not performed.

Data Source: A retrospective study of 5,893 infants seen over two 42-month periods.

Disclosures: None was reported.

BETHESDA, MD. — Nasal screening for methicillin-resistant Staphylococcus aureus significantly reduced the infection rate in a neonatal intensive care unit, in a retrospective study of 5,893 infants seen over two 42-month periods.

Some U.S. states have enacted legislation for mandatory screening for nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) among inpatients in high-risk inpatient units, but there is still ongoing debate about the value of such screening, Dr. Jeremias L. Murillo said in a poster presented at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Records from January 2006 to June 2009, when all patients admitted to the NICU were screened for nasal carriage of MRSA, were compared with those from an equivalent 42-month period from July 2002 to December 2005, when no nasal screenings were performed. All MRSA infections were identified from a microbiology database and confirmed by chart review.

Nasal screenings were performed via rapid polymerase chain reaction testing, and infants found positive were decolonized with topical mupirocin, with contact isolation maintained until decolonization was completed.

There were no significant differences in birth weight or gestational age between the 3,269 infants who were screened and the 2,624 who were not.

A total of 5 infants (0.15%) became infected in the NICU during the screening period, compared with 29 (1.11%) during the period when screening was not performed, Dr. Murillo of Children's Hospital of New Jersey and Beth Israel Medical Center, Newark, reported.

In an interview, Dr. Murillo noted that in 2002 it took an average of 72 days from the time of admission before the infants became infected, compared with only 14 days in 2005, just before his hospital began screening.

“We felt that the shortened time frame was because the babies were coming into the NICU already colonized with MRSA and were therefore getting infected earlier,” he commented.

Major Finding: A total of 5 infants (0.15%) became infected in the NICU during the screening period, versus 29 (1.11%) during the period when screening was not performed.

Data Source: A retrospective study of 5,893 infants seen over two 42-month periods.

Disclosures: None was reported.

BETHESDA, MD. — Nasal screening for methicillin-resistant Staphylococcus aureus significantly reduced the infection rate in a neonatal intensive care unit, in a retrospective study of 5,893 infants seen over two 42-month periods.

Some U.S. states have enacted legislation for mandatory screening for nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) among inpatients in high-risk inpatient units, but there is still ongoing debate about the value of such screening, Dr. Jeremias L. Murillo said in a poster presented at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Records from January 2006 to June 2009, when all patients admitted to the NICU were screened for nasal carriage of MRSA, were compared with those from an equivalent 42-month period from July 2002 to December 2005, when no nasal screenings were performed. All MRSA infections were identified from a microbiology database and confirmed by chart review.

Nasal screenings were performed via rapid polymerase chain reaction testing, and infants found positive were decolonized with topical mupirocin, with contact isolation maintained until decolonization was completed.

There were no significant differences in birth weight or gestational age between the 3,269 infants who were screened and the 2,624 who were not.

A total of 5 infants (0.15%) became infected in the NICU during the screening period, compared with 29 (1.11%) during the period when screening was not performed, Dr. Murillo of Children's Hospital of New Jersey and Beth Israel Medical Center, Newark, reported.

In an interview, Dr. Murillo noted that in 2002 it took an average of 72 days from the time of admission before the infants became infected, compared with only 14 days in 2005, just before his hospital began screening.

“We felt that the shortened time frame was because the babies were coming into the NICU already colonized with MRSA and were therefore getting infected earlier,” he commented.

Major Finding: A total of 5 infants (0.15%) became infected in the NICU during the screening period, versus 29 (1.11%) during the period when screening was not performed.

Data Source: A retrospective study of 5,893 infants seen over two 42-month periods.

Disclosures: None was reported.

BETHESDA, MD. — Nasal screening for methicillin-resistant Staphylococcus aureus significantly reduced the infection rate in a neonatal intensive care unit, in a retrospective study of 5,893 infants seen over two 42-month periods.

Some U.S. states have enacted legislation for mandatory screening for nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) among inpatients in high-risk inpatient units, but there is still ongoing debate about the value of such screening, Dr. Jeremias L. Murillo said in a poster presented at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

Records from January 2006 to June 2009, when all patients admitted to the NICU were screened for nasal carriage of MRSA, were compared with those from an equivalent 42-month period from July 2002 to December 2005, when no nasal screenings were performed. All MRSA infections were identified from a microbiology database and confirmed by chart review.

Nasal screenings were performed via rapid polymerase chain reaction testing, and infants found positive were decolonized with topical mupirocin, with contact isolation maintained until decolonization was completed.

There were no significant differences in birth weight or gestational age between the 3,269 infants who were screened and the 2,624 who were not.

A total of 5 infants (0.15%) became infected in the NICU during the screening period, compared with 29 (1.11%) during the period when screening was not performed, Dr. Murillo of Children's Hospital of New Jersey and Beth Israel Medical Center, Newark, reported.

In an interview, Dr. Murillo noted that in 2002 it took an average of 72 days from the time of admission before the infants became infected, compared with only 14 days in 2005, just before his hospital began screening.

“We felt that the shortened time frame was because the babies were coming into the NICU already colonized with MRSA and were therefore getting infected earlier,” he commented.