Endo 2012

HOUSTON – A high-protein, high-carbohydrate breakfast that included a daily dessert such as cake or a cookie resulted in significantly greater weight loss through 32 weeks than an identically low-calorie weight loss diet featuring a low-carbohydrate breakfast.

That’s what Dr. Daniela Jakubowicz found in a randomized trial presented at the annual meeting of the Endocrine Society.

Courtesy Wikimedia Commons/Politikaner/Creative Commons License

"To achieve long-term weight loss, meal timing and composition must counteract weight loss compensatory mechanisms that encourage weight regain after weight loss. A high-carbohydrate and protein breakfast may prevent weight regain by reducing diet-induced compensatory changes in hunger, craving, and ghrelin suppression," said Dr. Jakubowicz of the Wolfson Medical Center at Tel Aviv University.

She reported on 193 obese, sedentary, nondiabetic subjects with an average age of 47 years and a body mass index of 32 kg/m² who were randomized to one of two weight-loss diets. Both incorporated 1,600 calories daily for men and 1,400 for women. The dessert-for-breakfast diet for women allotted 600 calories at breakfast, 500 at lunch, and 300 at dinner, while the low-carbohydrate breakfast comprised 300 calories in the morning, 500 at lunch, and 600 at dinner. The big-breakfast group consumed 60 g of carbohydrate at breakfast, compared with 15 g in the comparison group.

The two diets proved similarly effective through the first 16 weeks, with average weight losses of 15.1 kg in the low-carbohydrate breakfast group and 13.5 kg in the dessert-with-breakfast eaters. At that point, however, the trajectories diverged. Over the next 16 weeks, the low-calorie breakfast group regained an average of 11.6 kg, while the big-breakfast group lost a further 6.9 kg.

Thus, the net weight loss at 32 weeks was 20.4 kg (45 pounds) in the dessert-with-breakfast group, compared with a scant 3.5 kg (7.7 lb) in the low-carbohydrate group.

What’s the explanation?

"More important than the speed of weight loss is that patients feel satiety – less hunger – and that they prevent craving," the endocrinologist said. "Several studies have now shown that diets that avoid chocolates and cookies and carbohydrates increase the addiction to carbohydrates – they increase the craving. So instead, if you eat a snack in the morning every day, after a while you become less addicted to these foods. Also, protein in the morning increases satiety. We know that if you have enough protein in the morning you’re not hungry all day."

Indeed, these points were born out in patient self-assessments conducted using visual analog scales at weeks 16 and 32. Scores for hunger were significantly lower and satiety scores significantly higher in the dessert-for-breakfast group at both time points. In addition, this group had significantly lower craving scores for fatty foods, sweets, and fast food. Dietary compliance was significantly better in the big-breakfast group than in controls from week 8 on. At week 32, for example, the big-breakfast group averaged 5 episodes of noncompliance per week, compared with 15 in controls.

Moreover, levels of ghrelin – the so-called hunger hormone – were suppressed by 45% in the dessert-with-breakfast group 2 hours after breakfast at week 32, compared with a 30% reduction in controls. The insulin response to a standardized test meal was significantly lower in the big-breakfast group as well.

In a separate randomized trial Dr. Jakubowicz conducted in 93 obese, sedentary, nondiabetic women, placing the big meal of the day at breakfast resulted in significantly greater weight loss, waist circumference shrinkage, and salutary lipid changes than when dinner was the big meal.

Both groups were placed on a 1,400-calorie-per-day diet. One diet entailed 700 calories at breakfast and 200 at dinner, while the other featured 200 calories at breakfast and 700 at dinner. After 12 weeks, the big-breakfast group lost an average of 8.7 kg, while the big-dinner group lost 3.3 kg. Waist circumference decreased by 7 cm from a baseline of 110 cm in the big-breakfast group, compared with a 2-cm reduction in controls.

Triglyceride levels improved from 180 mg/dL at baseline to 129 mg/dL at 12 weeks in the big-breakfast group, while they worsened from a baseline of 178 mg/dL to 195 mg/dL in the big-dinner group.

"It’s important to note that triglycerides increased on the big-dinner diet even though the people lost weight. The management of lipids after eating carbohydrates at night is worse than with the same carbohydrates in the morning," she concluded.

The average LDL cholesterol level in the big-breakfast group dropped from 160 mg/dL at baseline to 151 mg/dL, a significantly greater effect than seen in the big-dinner group, whose LDL went from 164 mg/dL at baseline to 162 mg/dL at 12 weeks.

Dr. Jakubowicz reported having no financial conflicts.

HOUSTON – A high-protein, high-carbohydrate breakfast that included a daily dessert such as cake or a cookie resulted in significantly greater weight loss through 32 weeks than an identically low-calorie weight loss diet featuring a low-carbohydrate breakfast.

That’s what Dr. Daniela Jakubowicz found in a randomized trial presented at the annual meeting of the Endocrine Society.

Courtesy Wikimedia Commons/Politikaner/Creative Commons License

"To achieve long-term weight loss, meal timing and composition must counteract weight loss compensatory mechanisms that encourage weight regain after weight loss. A high-carbohydrate and protein breakfast may prevent weight regain by reducing diet-induced compensatory changes in hunger, craving, and ghrelin suppression," said Dr. Jakubowicz of the Wolfson Medical Center at Tel Aviv University.

She reported on 193 obese, sedentary, nondiabetic subjects with an average age of 47 years and a body mass index of 32 kg/m² who were randomized to one of two weight-loss diets. Both incorporated 1,600 calories daily for men and 1,400 for women. The dessert-for-breakfast diet for women allotted 600 calories at breakfast, 500 at lunch, and 300 at dinner, while the low-carbohydrate breakfast comprised 300 calories in the morning, 500 at lunch, and 600 at dinner. The big-breakfast group consumed 60 g of carbohydrate at breakfast, compared with 15 g in the comparison group.

The two diets proved similarly effective through the first 16 weeks, with average weight losses of 15.1 kg in the low-carbohydrate breakfast group and 13.5 kg in the dessert-with-breakfast eaters. At that point, however, the trajectories diverged. Over the next 16 weeks, the low-calorie breakfast group regained an average of 11.6 kg, while the big-breakfast group lost a further 6.9 kg.

Thus, the net weight loss at 32 weeks was 20.4 kg (45 pounds) in the dessert-with-breakfast group, compared with a scant 3.5 kg (7.7 lb) in the low-carbohydrate group.

What’s the explanation?

"More important than the speed of weight loss is that patients feel satiety – less hunger – and that they prevent craving," the endocrinologist said. "Several studies have now shown that diets that avoid chocolates and cookies and carbohydrates increase the addiction to carbohydrates – they increase the craving. So instead, if you eat a snack in the morning every day, after a while you become less addicted to these foods. Also, protein in the morning increases satiety. We know that if you have enough protein in the morning you’re not hungry all day."

Indeed, these points were born out in patient self-assessments conducted using visual analog scales at weeks 16 and 32. Scores for hunger were significantly lower and satiety scores significantly higher in the dessert-for-breakfast group at both time points. In addition, this group had significantly lower craving scores for fatty foods, sweets, and fast food. Dietary compliance was significantly better in the big-breakfast group than in controls from week 8 on. At week 32, for example, the big-breakfast group averaged 5 episodes of noncompliance per week, compared with 15 in controls.

Moreover, levels of ghrelin – the so-called hunger hormone – were suppressed by 45% in the dessert-with-breakfast group 2 hours after breakfast at week 32, compared with a 30% reduction in controls. The insulin response to a standardized test meal was significantly lower in the big-breakfast group as well.

In a separate randomized trial Dr. Jakubowicz conducted in 93 obese, sedentary, nondiabetic women, placing the big meal of the day at breakfast resulted in significantly greater weight loss, waist circumference shrinkage, and salutary lipid changes than when dinner was the big meal.

Both groups were placed on a 1,400-calorie-per-day diet. One diet entailed 700 calories at breakfast and 200 at dinner, while the other featured 200 calories at breakfast and 700 at dinner. After 12 weeks, the big-breakfast group lost an average of 8.7 kg, while the big-dinner group lost 3.3 kg. Waist circumference decreased by 7 cm from a baseline of 110 cm in the big-breakfast group, compared with a 2-cm reduction in controls.

Triglyceride levels improved from 180 mg/dL at baseline to 129 mg/dL at 12 weeks in the big-breakfast group, while they worsened from a baseline of 178 mg/dL to 195 mg/dL in the big-dinner group.

"It’s important to note that triglycerides increased on the big-dinner diet even though the people lost weight. The management of lipids after eating carbohydrates at night is worse than with the same carbohydrates in the morning," she concluded.

The average LDL cholesterol level in the big-breakfast group dropped from 160 mg/dL at baseline to 151 mg/dL, a significantly greater effect than seen in the big-dinner group, whose LDL went from 164 mg/dL at baseline to 162 mg/dL at 12 weeks.

Dr. Jakubowicz reported having no financial conflicts.

HOUSTON – A high-protein, high-carbohydrate breakfast that included a daily dessert such as cake or a cookie resulted in significantly greater weight loss through 32 weeks than an identically low-calorie weight loss diet featuring a low-carbohydrate breakfast.

That’s what Dr. Daniela Jakubowicz found in a randomized trial presented at the annual meeting of the Endocrine Society.

Courtesy Wikimedia Commons/Politikaner/Creative Commons License

"To achieve long-term weight loss, meal timing and composition must counteract weight loss compensatory mechanisms that encourage weight regain after weight loss. A high-carbohydrate and protein breakfast may prevent weight regain by reducing diet-induced compensatory changes in hunger, craving, and ghrelin suppression," said Dr. Jakubowicz of the Wolfson Medical Center at Tel Aviv University.

She reported on 193 obese, sedentary, nondiabetic subjects with an average age of 47 years and a body mass index of 32 kg/m² who were randomized to one of two weight-loss diets. Both incorporated 1,600 calories daily for men and 1,400 for women. The dessert-for-breakfast diet for women allotted 600 calories at breakfast, 500 at lunch, and 300 at dinner, while the low-carbohydrate breakfast comprised 300 calories in the morning, 500 at lunch, and 600 at dinner. The big-breakfast group consumed 60 g of carbohydrate at breakfast, compared with 15 g in the comparison group.

The two diets proved similarly effective through the first 16 weeks, with average weight losses of 15.1 kg in the low-carbohydrate breakfast group and 13.5 kg in the dessert-with-breakfast eaters. At that point, however, the trajectories diverged. Over the next 16 weeks, the low-calorie breakfast group regained an average of 11.6 kg, while the big-breakfast group lost a further 6.9 kg.

Thus, the net weight loss at 32 weeks was 20.4 kg (45 pounds) in the dessert-with-breakfast group, compared with a scant 3.5 kg (7.7 lb) in the low-carbohydrate group.

What’s the explanation?

"More important than the speed of weight loss is that patients feel satiety – less hunger – and that they prevent craving," the endocrinologist said. "Several studies have now shown that diets that avoid chocolates and cookies and carbohydrates increase the addiction to carbohydrates – they increase the craving. So instead, if you eat a snack in the morning every day, after a while you become less addicted to these foods. Also, protein in the morning increases satiety. We know that if you have enough protein in the morning you’re not hungry all day."

Indeed, these points were born out in patient self-assessments conducted using visual analog scales at weeks 16 and 32. Scores for hunger were significantly lower and satiety scores significantly higher in the dessert-for-breakfast group at both time points. In addition, this group had significantly lower craving scores for fatty foods, sweets, and fast food. Dietary compliance was significantly better in the big-breakfast group than in controls from week 8 on. At week 32, for example, the big-breakfast group averaged 5 episodes of noncompliance per week, compared with 15 in controls.

Moreover, levels of ghrelin – the so-called hunger hormone – were suppressed by 45% in the dessert-with-breakfast group 2 hours after breakfast at week 32, compared with a 30% reduction in controls. The insulin response to a standardized test meal was significantly lower in the big-breakfast group as well.

In a separate randomized trial Dr. Jakubowicz conducted in 93 obese, sedentary, nondiabetic women, placing the big meal of the day at breakfast resulted in significantly greater weight loss, waist circumference shrinkage, and salutary lipid changes than when dinner was the big meal.

Both groups were placed on a 1,400-calorie-per-day diet. One diet entailed 700 calories at breakfast and 200 at dinner, while the other featured 200 calories at breakfast and 700 at dinner. After 12 weeks, the big-breakfast group lost an average of 8.7 kg, while the big-dinner group lost 3.3 kg. Waist circumference decreased by 7 cm from a baseline of 110 cm in the big-breakfast group, compared with a 2-cm reduction in controls.

Triglyceride levels improved from 180 mg/dL at baseline to 129 mg/dL at 12 weeks in the big-breakfast group, while they worsened from a baseline of 178 mg/dL to 195 mg/dL in the big-dinner group.

"It’s important to note that triglycerides increased on the big-dinner diet even though the people lost weight. The management of lipids after eating carbohydrates at night is worse than with the same carbohydrates in the morning," she concluded.

The average LDL cholesterol level in the big-breakfast group dropped from 160 mg/dL at baseline to 151 mg/dL, a significantly greater effect than seen in the big-dinner group, whose LDL went from 164 mg/dL at baseline to 162 mg/dL at 12 weeks.

Dr. Jakubowicz reported having no financial conflicts.

Doctors and patients can make good progress in controlling a chronic disease, and then life may intervene, sometimes in a violent, chaotic way.

The civil war now being fought in Syria presents a question for physicians around the world that was raised in a poster presentation by Syrian physicians presented at the Endocrine Society’s annual meeting: How best to manage metabolic control, blood pressure, lipids, and gonadal and sexual function in a crisis setting? All of these may be affected by the stress of conflict, lack of access to health resources, and other factors.

Courtesy flickr user FreedomHouse (Creative Commons)

Mainstream news coverage of the Syrian conflict tends to emphasize death tolls and ground gained or lost by the warring parties. Dr. Saad Sakkal and associates at the Aleppo (Syria) Care Center took a more personalized look at 200 patients with diabetes who were being seen quarterly at the center’s endocrine/diabetes clinic before and during the war.

In the 6 months of July-December 2010, before the civil unrest started, patients showed an average 8–mm Hg drop in systolic blood pressure, a 7–mm Hg decline in diastolic blood pressure, a decrease of 37 mg/dL in fasting blood sugar results, and a 62 mg/dL decrease in 2-hour postprandial glucose results. Their hemoglobin A_1c levels improved on average by 2.5% and insulin doses decreased by 22%. Triglyceride levels decreased by 59 mg/dL and the triglyceride:HDL ratio improved by an average of 1.31.

Measures of gonadal and sexual dysfunction (such as libido, erectile dysfunction, and gonadal hormone deficiencies) improved in 17 of 37 patients with one of these dysfunctions at baseline.

The civil unrest wiped out those gains, and then some.

After the civil unrest started, in the 6 months of July-December 2011, the average blood pressure rose by 26/8–mm Hg on average, fasting blood sugar results increased by 47 mg/dL, 2-hour postprandial glucose levels increased by 128 mg/dL, average HbA_1c levels increased by 2%, and insulin doses increased by 25%. Cholesterol and triglyceride levels increased, and the triglyceride:HDL ratio worsened by an average of 1.72.

Measures of gonadal and sexual dysfunction worsened in 16 patients. Although previous studies have shown that stress affects metabolic control in general, there are few or no prior data on the influence of civil unrest on gonadal and sexual dysfunction in patients with diabetes, Dr. Sakkal reported.

Although the stress producer in the study was "civil unrest," which now has progressed to all-out civil war, it’s reasonable to think that the same health problems might occur in other disasters with long-term effects, such as tsunamis, hurricanes, earthquakes, and perhaps even poverty.

Avoiding death is the primary goal in these situations, of course, but the Syrian physicians also are hard at work helping the living live. How can physicians best help survivors with a chronic illness deal with the effects of a stressful situation?

The study excluded patients with new-onset diabetes or other new illnesses. Dr. Sakkal reported having no financial disclosures.

–Sherry Boschert (on Twitter @sherryboschert)

Doctors and patients can make good progress in controlling a chronic disease, and then life may intervene, sometimes in a violent, chaotic way.

The civil war now being fought in Syria presents a question for physicians around the world that was raised in a poster presentation by Syrian physicians presented at the Endocrine Society’s annual meeting: How best to manage metabolic control, blood pressure, lipids, and gonadal and sexual function in a crisis setting? All of these may be affected by the stress of conflict, lack of access to health resources, and other factors.

Courtesy flickr user FreedomHouse (Creative Commons)

Mainstream news coverage of the Syrian conflict tends to emphasize death tolls and ground gained or lost by the warring parties. Dr. Saad Sakkal and associates at the Aleppo (Syria) Care Center took a more personalized look at 200 patients with diabetes who were being seen quarterly at the center’s endocrine/diabetes clinic before and during the war.

In the 6 months of July-December 2010, before the civil unrest started, patients showed an average 8–mm Hg drop in systolic blood pressure, a 7–mm Hg decline in diastolic blood pressure, a decrease of 37 mg/dL in fasting blood sugar results, and a 62 mg/dL decrease in 2-hour postprandial glucose results. Their hemoglobin A_1c levels improved on average by 2.5% and insulin doses decreased by 22%. Triglyceride levels decreased by 59 mg/dL and the triglyceride:HDL ratio improved by an average of 1.31.

Measures of gonadal and sexual dysfunction (such as libido, erectile dysfunction, and gonadal hormone deficiencies) improved in 17 of 37 patients with one of these dysfunctions at baseline.

The civil unrest wiped out those gains, and then some.

After the civil unrest started, in the 6 months of July-December 2011, the average blood pressure rose by 26/8–mm Hg on average, fasting blood sugar results increased by 47 mg/dL, 2-hour postprandial glucose levels increased by 128 mg/dL, average HbA_1c levels increased by 2%, and insulin doses increased by 25%. Cholesterol and triglyceride levels increased, and the triglyceride:HDL ratio worsened by an average of 1.72.

Measures of gonadal and sexual dysfunction worsened in 16 patients. Although previous studies have shown that stress affects metabolic control in general, there are few or no prior data on the influence of civil unrest on gonadal and sexual dysfunction in patients with diabetes, Dr. Sakkal reported.

Although the stress producer in the study was "civil unrest," which now has progressed to all-out civil war, it’s reasonable to think that the same health problems might occur in other disasters with long-term effects, such as tsunamis, hurricanes, earthquakes, and perhaps even poverty.

Avoiding death is the primary goal in these situations, of course, but the Syrian physicians also are hard at work helping the living live. How can physicians best help survivors with a chronic illness deal with the effects of a stressful situation?

The study excluded patients with new-onset diabetes or other new illnesses. Dr. Sakkal reported having no financial disclosures.

–Sherry Boschert (on Twitter @sherryboschert)

Doctors and patients can make good progress in controlling a chronic disease, and then life may intervene, sometimes in a violent, chaotic way.

The civil war now being fought in Syria presents a question for physicians around the world that was raised in a poster presentation by Syrian physicians presented at the Endocrine Society’s annual meeting: How best to manage metabolic control, blood pressure, lipids, and gonadal and sexual function in a crisis setting? All of these may be affected by the stress of conflict, lack of access to health resources, and other factors.

Courtesy flickr user FreedomHouse (Creative Commons)

Mainstream news coverage of the Syrian conflict tends to emphasize death tolls and ground gained or lost by the warring parties. Dr. Saad Sakkal and associates at the Aleppo (Syria) Care Center took a more personalized look at 200 patients with diabetes who were being seen quarterly at the center’s endocrine/diabetes clinic before and during the war.

In the 6 months of July-December 2010, before the civil unrest started, patients showed an average 8–mm Hg drop in systolic blood pressure, a 7–mm Hg decline in diastolic blood pressure, a decrease of 37 mg/dL in fasting blood sugar results, and a 62 mg/dL decrease in 2-hour postprandial glucose results. Their hemoglobin A_1c levels improved on average by 2.5% and insulin doses decreased by 22%. Triglyceride levels decreased by 59 mg/dL and the triglyceride:HDL ratio improved by an average of 1.31.

Measures of gonadal and sexual dysfunction (such as libido, erectile dysfunction, and gonadal hormone deficiencies) improved in 17 of 37 patients with one of these dysfunctions at baseline.

The civil unrest wiped out those gains, and then some.

After the civil unrest started, in the 6 months of July-December 2011, the average blood pressure rose by 26/8–mm Hg on average, fasting blood sugar results increased by 47 mg/dL, 2-hour postprandial glucose levels increased by 128 mg/dL, average HbA_1c levels increased by 2%, and insulin doses increased by 25%. Cholesterol and triglyceride levels increased, and the triglyceride:HDL ratio worsened by an average of 1.72.

Measures of gonadal and sexual dysfunction worsened in 16 patients. Although previous studies have shown that stress affects metabolic control in general, there are few or no prior data on the influence of civil unrest on gonadal and sexual dysfunction in patients with diabetes, Dr. Sakkal reported.

Although the stress producer in the study was "civil unrest," which now has progressed to all-out civil war, it’s reasonable to think that the same health problems might occur in other disasters with long-term effects, such as tsunamis, hurricanes, earthquakes, and perhaps even poverty.

Avoiding death is the primary goal in these situations, of course, but the Syrian physicians also are hard at work helping the living live. How can physicians best help survivors with a chronic illness deal with the effects of a stressful situation?

The study excluded patients with new-onset diabetes or other new illnesses. Dr. Sakkal reported having no financial disclosures.

–Sherry Boschert (on Twitter @sherryboschert)

HOUSTON – Use of a gonadotropin-releasing hormone antagonist showed early promise as a novel therapy for rheumatoid arthritis in a brief, proof-of-concept study that was presented at the annual meeting of the Endocrine Society.

Five days of subcutaneous injections of cetrorelix (Cetrotide) that were aimed at rapidly reducing levels of luteinizing hormone and follicle-stimulating hormone safely improved signs and symptoms of RA and reduced tumor necrosis factor–alpha levels in a 99-patient, placebo-controlled, randomized trial. Larger and longer-term clinical trials of GnRH antagonists as a potential treatment for RA are planned, according to Dr. Anita Kass of Betanien Hospital in Skien, Norway.

All study participants had active RA and were on stable doses of disease-modifying antirheumatic drugs. They were randomized to placebo or subcutaneous cetrorelix dosed at 5 mg on days 1-3 and 3 mg on days 4-5.

Outcomes were assessed on day 5, when LH and FSH levels in the cetrorelix arm were at their nadir. At that time, an ACR 20 (American College of Rheumatology scale, based on a 20% improvement in specified criteria) response was documented in 40% of patients on cetrorelix, compared with 18% of controls. Remission according to the DAS28 (Disease Activity Score, including a 28-joint count) was achieved in 13% of patients on the GnRH antagonist, compared with none on placebo. The erythrocyte sedimentation rate had declined by a mean of 1.06 mm/hour, compared with baseline, in the active treatment group, compared with a 5.04-mm/hour increase in controls.

In addition, the cetrorelix group had a mean 0.58 log pg/mL decrease in TNF-alpha compared with baseline, whereas controls experienced a 0.02 log pg/mL reduction. All of these differences between the cetrorelix and control groups were statistically significant.

The reduction in DAS28 score by day 5 was 0.82 in the cetrorelix group and 0.57 in controls, a trend that didn’t reach significance.

Adverse events in the two study arms did not differ.

Dr. Kass credited the impetus for this line of clinical investigation to earlier work by other investigators at the Weizmann Institute of Science in Rehovot, Israel. They showed that GnRH and GnRH-II are produced by T cells, and that the hormones have roles that extend beyond the reproductive system to include immune system regulation. The hormones trigger T-cell chemotaxis and homing to specific organs (Nat. Med. 2002;8:1421-6).

This proof-of-concept study was supported by the Norwegian Health and Rehabilitation Organization. The presenter reported having no financial conflicts.

HOUSTON – Use of a gonadotropin-releasing hormone antagonist showed early promise as a novel therapy for rheumatoid arthritis in a brief, proof-of-concept study that was presented at the annual meeting of the Endocrine Society.

Five days of subcutaneous injections of cetrorelix (Cetrotide) that were aimed at rapidly reducing levels of luteinizing hormone and follicle-stimulating hormone safely improved signs and symptoms of RA and reduced tumor necrosis factor–alpha levels in a 99-patient, placebo-controlled, randomized trial. Larger and longer-term clinical trials of GnRH antagonists as a potential treatment for RA are planned, according to Dr. Anita Kass of Betanien Hospital in Skien, Norway.

All study participants had active RA and were on stable doses of disease-modifying antirheumatic drugs. They were randomized to placebo or subcutaneous cetrorelix dosed at 5 mg on days 1-3 and 3 mg on days 4-5.

Outcomes were assessed on day 5, when LH and FSH levels in the cetrorelix arm were at their nadir. At that time, an ACR 20 (American College of Rheumatology scale, based on a 20% improvement in specified criteria) response was documented in 40% of patients on cetrorelix, compared with 18% of controls. Remission according to the DAS28 (Disease Activity Score, including a 28-joint count) was achieved in 13% of patients on the GnRH antagonist, compared with none on placebo. The erythrocyte sedimentation rate had declined by a mean of 1.06 mm/hour, compared with baseline, in the active treatment group, compared with a 5.04-mm/hour increase in controls.

In addition, the cetrorelix group had a mean 0.58 log pg/mL decrease in TNF-alpha compared with baseline, whereas controls experienced a 0.02 log pg/mL reduction. All of these differences between the cetrorelix and control groups were statistically significant.

The reduction in DAS28 score by day 5 was 0.82 in the cetrorelix group and 0.57 in controls, a trend that didn’t reach significance.

Adverse events in the two study arms did not differ.

Dr. Kass credited the impetus for this line of clinical investigation to earlier work by other investigators at the Weizmann Institute of Science in Rehovot, Israel. They showed that GnRH and GnRH-II are produced by T cells, and that the hormones have roles that extend beyond the reproductive system to include immune system regulation. The hormones trigger T-cell chemotaxis and homing to specific organs (Nat. Med. 2002;8:1421-6).

This proof-of-concept study was supported by the Norwegian Health and Rehabilitation Organization. The presenter reported having no financial conflicts.

HOUSTON – Use of a gonadotropin-releasing hormone antagonist showed early promise as a novel therapy for rheumatoid arthritis in a brief, proof-of-concept study that was presented at the annual meeting of the Endocrine Society.

Five days of subcutaneous injections of cetrorelix (Cetrotide) that were aimed at rapidly reducing levels of luteinizing hormone and follicle-stimulating hormone safely improved signs and symptoms of RA and reduced tumor necrosis factor–alpha levels in a 99-patient, placebo-controlled, randomized trial. Larger and longer-term clinical trials of GnRH antagonists as a potential treatment for RA are planned, according to Dr. Anita Kass of Betanien Hospital in Skien, Norway.

All study participants had active RA and were on stable doses of disease-modifying antirheumatic drugs. They were randomized to placebo or subcutaneous cetrorelix dosed at 5 mg on days 1-3 and 3 mg on days 4-5.

Outcomes were assessed on day 5, when LH and FSH levels in the cetrorelix arm were at their nadir. At that time, an ACR 20 (American College of Rheumatology scale, based on a 20% improvement in specified criteria) response was documented in 40% of patients on cetrorelix, compared with 18% of controls. Remission according to the DAS28 (Disease Activity Score, including a 28-joint count) was achieved in 13% of patients on the GnRH antagonist, compared with none on placebo. The erythrocyte sedimentation rate had declined by a mean of 1.06 mm/hour, compared with baseline, in the active treatment group, compared with a 5.04-mm/hour increase in controls.

In addition, the cetrorelix group had a mean 0.58 log pg/mL decrease in TNF-alpha compared with baseline, whereas controls experienced a 0.02 log pg/mL reduction. All of these differences between the cetrorelix and control groups were statistically significant.

The reduction in DAS28 score by day 5 was 0.82 in the cetrorelix group and 0.57 in controls, a trend that didn’t reach significance.

Adverse events in the two study arms did not differ.

Dr. Kass credited the impetus for this line of clinical investigation to earlier work by other investigators at the Weizmann Institute of Science in Rehovot, Israel. They showed that GnRH and GnRH-II are produced by T cells, and that the hormones have roles that extend beyond the reproductive system to include immune system regulation. The hormones trigger T-cell chemotaxis and homing to specific organs (Nat. Med. 2002;8:1421-6).

This proof-of-concept study was supported by the Norwegian Health and Rehabilitation Organization. The presenter reported having no financial conflicts.

HOUSTON – Denosumab continued to achieve reduced fractures rates, progressively rising bone mineral density, and sustained reduction in bone turnover biomarkers through 6 years of continuous use in the ongoing 7-year extension of the landmark FREEDOM trial.

FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) was the pivotal phase III, double-blind, placebo-controlled, 3-year randomized trial that led to marketing approval of denosumab (Prolia) at 60 mg subcutaneously every 6 months for treatment of postmenopausal osteoporosis (N. Engl. J. Med. 2009;361:756-65).

The FREEDOM extension study is evaluating the long-term safety and efficacy of denosumab for an additional 7 years. Thus, participants who were in the active treatment arm of the original study will receive denosumab for a total of 10 years, whereas patients who crossed over to denosumab after 3 years on placebo will be on the novel RANKL (receptor-activated nuclear factor–kappaB ligand) inhibitor for 7 years.

At the conference, Dr. Henry G. Bone presented updated study results through 6 years. In all, 4,550 postmenopausal women from the original randomized trial were enrolled in the extension and have been followed for an additional 3 years.

In the original FREEDOM trial, 3 years of denosumab resulted in a 10.1% increase in BMD in the lumbar spine, compared with baseline. With an additional 3 years of open-label therapy, this figure has increased to 15.1%. The gain in the crossover group paralleled that seen with active therapy in the original trial; that is, after 6 years – the last 3 on open-label denosumab – those patients had a 9.4% increase over baseline in lumbar spine BMD, reported Dr. Bone, chief of the endocrinology department at St. John Hospital and Medical Center, Detroit, and director of the Michigan Bone and Mineral Clinic.

Total hip BMD rose from a 5.7% increase over baseline after 3 years of denosumab to a 7.5% increase after 6 years. The crossover group had a 4.8% increase at this site after 3 years of active therapy.

During the first 3 years of the FREEDOM trial, new vertebral fractures occurred in 2.3% of the denosumab group, compared with 7.2% of placebo-treated controls. During the subsequent 3 years of open-label therapy, the original denosumab cohort had a 3.5% incidence of new vertebral fractures. Because it would have been unethical to have a placebo arm during those second 3 years, statistical modeling using a method known as "virtual twins" was used to project outcomes had the original control group remained on placebo. Their expected rate of new vertebral fractures during the first 3 years of the extension study was 6.3%.

The incidence of nonvertebral fractures during the 3-year, double-blind phase of FREEDOM was 8.0% in the placebo arm and significantly lower, at 6.5%, in the denosumab group. During the second 3-year period of denosumab therapy, the incidence was 3.8%.

"It’s interesting that the nonvertebral fracture rate in the second 3 years is actually quite a bit lower than in the first 3 years, suggesting there may be an additional benefit of long treatment," Dr. Bone said.

The projected rate of new nonvertebral fractures during years 4-6 in the "virtual twins" was 7.5%.

Turning to safety issues, the endocrinologist said that there were two adjudicated cases of osteonecrosis of the jaw during 6 years of denosumab therapy, and two more in the control group that occurred after crossover to active treatment. There has been one documented case of atypical femoral fracture during 6 consecutive years on denosumab. There has been one serious skin infection in the control group after they were crossed to 3 years of denosumab, and several more during years 4-6 in the long-term extension group.

The FREEDOM study extension is sponsored by Amgen. The presenter is a consultant to and on the speakers bureau for the company.

HOUSTON – Denosumab continued to achieve reduced fractures rates, progressively rising bone mineral density, and sustained reduction in bone turnover biomarkers through 6 years of continuous use in the ongoing 7-year extension of the landmark FREEDOM trial.

FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) was the pivotal phase III, double-blind, placebo-controlled, 3-year randomized trial that led to marketing approval of denosumab (Prolia) at 60 mg subcutaneously every 6 months for treatment of postmenopausal osteoporosis (N. Engl. J. Med. 2009;361:756-65).

The FREEDOM extension study is evaluating the long-term safety and efficacy of denosumab for an additional 7 years. Thus, participants who were in the active treatment arm of the original study will receive denosumab for a total of 10 years, whereas patients who crossed over to denosumab after 3 years on placebo will be on the novel RANKL (receptor-activated nuclear factor–kappaB ligand) inhibitor for 7 years.

At the conference, Dr. Henry G. Bone presented updated study results through 6 years. In all, 4,550 postmenopausal women from the original randomized trial were enrolled in the extension and have been followed for an additional 3 years.

In the original FREEDOM trial, 3 years of denosumab resulted in a 10.1% increase in BMD in the lumbar spine, compared with baseline. With an additional 3 years of open-label therapy, this figure has increased to 15.1%. The gain in the crossover group paralleled that seen with active therapy in the original trial; that is, after 6 years – the last 3 on open-label denosumab – those patients had a 9.4% increase over baseline in lumbar spine BMD, reported Dr. Bone, chief of the endocrinology department at St. John Hospital and Medical Center, Detroit, and director of the Michigan Bone and Mineral Clinic.

Total hip BMD rose from a 5.7% increase over baseline after 3 years of denosumab to a 7.5% increase after 6 years. The crossover group had a 4.8% increase at this site after 3 years of active therapy.

During the first 3 years of the FREEDOM trial, new vertebral fractures occurred in 2.3% of the denosumab group, compared with 7.2% of placebo-treated controls. During the subsequent 3 years of open-label therapy, the original denosumab cohort had a 3.5% incidence of new vertebral fractures. Because it would have been unethical to have a placebo arm during those second 3 years, statistical modeling using a method known as "virtual twins" was used to project outcomes had the original control group remained on placebo. Their expected rate of new vertebral fractures during the first 3 years of the extension study was 6.3%.

The incidence of nonvertebral fractures during the 3-year, double-blind phase of FREEDOM was 8.0% in the placebo arm and significantly lower, at 6.5%, in the denosumab group. During the second 3-year period of denosumab therapy, the incidence was 3.8%.

"It’s interesting that the nonvertebral fracture rate in the second 3 years is actually quite a bit lower than in the first 3 years, suggesting there may be an additional benefit of long treatment," Dr. Bone said.

The projected rate of new nonvertebral fractures during years 4-6 in the "virtual twins" was 7.5%.

Turning to safety issues, the endocrinologist said that there were two adjudicated cases of osteonecrosis of the jaw during 6 years of denosumab therapy, and two more in the control group that occurred after crossover to active treatment. There has been one documented case of atypical femoral fracture during 6 consecutive years on denosumab. There has been one serious skin infection in the control group after they were crossed to 3 years of denosumab, and several more during years 4-6 in the long-term extension group.

The FREEDOM study extension is sponsored by Amgen. The presenter is a consultant to and on the speakers bureau for the company.

HOUSTON – Denosumab continued to achieve reduced fractures rates, progressively rising bone mineral density, and sustained reduction in bone turnover biomarkers through 6 years of continuous use in the ongoing 7-year extension of the landmark FREEDOM trial.

FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) was the pivotal phase III, double-blind, placebo-controlled, 3-year randomized trial that led to marketing approval of denosumab (Prolia) at 60 mg subcutaneously every 6 months for treatment of postmenopausal osteoporosis (N. Engl. J. Med. 2009;361:756-65).

The FREEDOM extension study is evaluating the long-term safety and efficacy of denosumab for an additional 7 years. Thus, participants who were in the active treatment arm of the original study will receive denosumab for a total of 10 years, whereas patients who crossed over to denosumab after 3 years on placebo will be on the novel RANKL (receptor-activated nuclear factor–kappaB ligand) inhibitor for 7 years.

At the conference, Dr. Henry G. Bone presented updated study results through 6 years. In all, 4,550 postmenopausal women from the original randomized trial were enrolled in the extension and have been followed for an additional 3 years.

In the original FREEDOM trial, 3 years of denosumab resulted in a 10.1% increase in BMD in the lumbar spine, compared with baseline. With an additional 3 years of open-label therapy, this figure has increased to 15.1%. The gain in the crossover group paralleled that seen with active therapy in the original trial; that is, after 6 years – the last 3 on open-label denosumab – those patients had a 9.4% increase over baseline in lumbar spine BMD, reported Dr. Bone, chief of the endocrinology department at St. John Hospital and Medical Center, Detroit, and director of the Michigan Bone and Mineral Clinic.

Total hip BMD rose from a 5.7% increase over baseline after 3 years of denosumab to a 7.5% increase after 6 years. The crossover group had a 4.8% increase at this site after 3 years of active therapy.

During the first 3 years of the FREEDOM trial, new vertebral fractures occurred in 2.3% of the denosumab group, compared with 7.2% of placebo-treated controls. During the subsequent 3 years of open-label therapy, the original denosumab cohort had a 3.5% incidence of new vertebral fractures. Because it would have been unethical to have a placebo arm during those second 3 years, statistical modeling using a method known as "virtual twins" was used to project outcomes had the original control group remained on placebo. Their expected rate of new vertebral fractures during the first 3 years of the extension study was 6.3%.

The incidence of nonvertebral fractures during the 3-year, double-blind phase of FREEDOM was 8.0% in the placebo arm and significantly lower, at 6.5%, in the denosumab group. During the second 3-year period of denosumab therapy, the incidence was 3.8%.

"It’s interesting that the nonvertebral fracture rate in the second 3 years is actually quite a bit lower than in the first 3 years, suggesting there may be an additional benefit of long treatment," Dr. Bone said.

The projected rate of new nonvertebral fractures during years 4-6 in the "virtual twins" was 7.5%.

Turning to safety issues, the endocrinologist said that there were two adjudicated cases of osteonecrosis of the jaw during 6 years of denosumab therapy, and two more in the control group that occurred after crossover to active treatment. There has been one documented case of atypical femoral fracture during 6 consecutive years on denosumab. There has been one serious skin infection in the control group after they were crossed to 3 years of denosumab, and several more during years 4-6 in the long-term extension group.

The FREEDOM study extension is sponsored by Amgen. The presenter is a consultant to and on the speakers bureau for the company.

HOUSTON – Off-label use of sitagliptin to treat patients with postprandial hypoglycemia significantly reduced the symptoms of reactive hypoglycemia in a preliminary randomized, controlled, double-blind trial of 28 adults.

The 13 patients who took 100 mg/day of sitagliptin (Januvia) for 2 weeks and the 15 control patients on an identical placebo did not differ in baseline characteristics or in prerandomization measures of insulin and blood sugar levels from 5-hour meal tolerance tests. The 440-calorie meal contained 100 g of carbohydrates, which usually would trigger reactive hypoglycemia symptoms in these patients.

After treatment, the sitagliptin group rated the intensity of reactive hypoglycemia symptoms significantly lower than did the control group – 2 vs. 5 – on a visual analog scale of 1-10, in which 0 represented no symptoms and 10 was greatest symptom intensity, Dr. Paloma Almeda-Valdés and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

Patients in the sitagliptin group reported significant reductions in the symptoms of anxiety, palpitations, shakiness (tremor), diaphoresis, dizziness, tingling, difficulty concentrating, and weakness, said Dr. Almeda-Valdés of Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City.

Sitagliptin is approved to lower glucose levels in adults with type 2 diabetes. It increases glucagon-like peptide1 circulating levels, which improves the early-phase secretion of insulin.

Meal tolerance tests after 2 weeks of treatment showed that the sitagliptin group had significantly higher levels of insulin within 30 minutes of the test, with areas under the curve of 2,278 mcU/mL per minute compared with 2,106 mcU/mL per minute in the control group.

The increased insulin concentration in this early phase after the meal was associated with significantly higher glucose concentrations later on, 1-5 hours after the meal. The glucose areas under the curve in the late phase of the meal tolerance test were 90,030 mg/dL per minute in the sitagliptin group and 84,165 mg/dL per minute in the control group.

These biochemical changes were associated with the reductions in symptom severity in the sitagliptin group, Dr. Almeda-Valdés said.

"The hypothesis is that sitagliptin restores insulin secretion in these patients, and this was associated with higher glucose levels in the late phase" and thus less hypoglycemia, she said in an interview.

The study defined symptomatic reactive hypoglycemia as the presence of symptoms associated with a 2- to 4-hour postprandial capillary glucose less than 65 mg/dL that disappeared with carbohydrate ingestion.

Merck, which markets sitagliptin, provided funding, the drug, and the placebo for the study. Dr. Almeda-Valdés reported having no other disclosures.

HOUSTON – Off-label use of sitagliptin to treat patients with postprandial hypoglycemia significantly reduced the symptoms of reactive hypoglycemia in a preliminary randomized, controlled, double-blind trial of 28 adults.

The 13 patients who took 100 mg/day of sitagliptin (Januvia) for 2 weeks and the 15 control patients on an identical placebo did not differ in baseline characteristics or in prerandomization measures of insulin and blood sugar levels from 5-hour meal tolerance tests. The 440-calorie meal contained 100 g of carbohydrates, which usually would trigger reactive hypoglycemia symptoms in these patients.

After treatment, the sitagliptin group rated the intensity of reactive hypoglycemia symptoms significantly lower than did the control group – 2 vs. 5 – on a visual analog scale of 1-10, in which 0 represented no symptoms and 10 was greatest symptom intensity, Dr. Paloma Almeda-Valdés and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

Patients in the sitagliptin group reported significant reductions in the symptoms of anxiety, palpitations, shakiness (tremor), diaphoresis, dizziness, tingling, difficulty concentrating, and weakness, said Dr. Almeda-Valdés of Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City.

Sitagliptin is approved to lower glucose levels in adults with type 2 diabetes. It increases glucagon-like peptide1 circulating levels, which improves the early-phase secretion of insulin.

Meal tolerance tests after 2 weeks of treatment showed that the sitagliptin group had significantly higher levels of insulin within 30 minutes of the test, with areas under the curve of 2,278 mcU/mL per minute compared with 2,106 mcU/mL per minute in the control group.

The increased insulin concentration in this early phase after the meal was associated with significantly higher glucose concentrations later on, 1-5 hours after the meal. The glucose areas under the curve in the late phase of the meal tolerance test were 90,030 mg/dL per minute in the sitagliptin group and 84,165 mg/dL per minute in the control group.

These biochemical changes were associated with the reductions in symptom severity in the sitagliptin group, Dr. Almeda-Valdés said.

"The hypothesis is that sitagliptin restores insulin secretion in these patients, and this was associated with higher glucose levels in the late phase" and thus less hypoglycemia, she said in an interview.

The study defined symptomatic reactive hypoglycemia as the presence of symptoms associated with a 2- to 4-hour postprandial capillary glucose less than 65 mg/dL that disappeared with carbohydrate ingestion.

Merck, which markets sitagliptin, provided funding, the drug, and the placebo for the study. Dr. Almeda-Valdés reported having no other disclosures.

HOUSTON – Off-label use of sitagliptin to treat patients with postprandial hypoglycemia significantly reduced the symptoms of reactive hypoglycemia in a preliminary randomized, controlled, double-blind trial of 28 adults.

The 13 patients who took 100 mg/day of sitagliptin (Januvia) for 2 weeks and the 15 control patients on an identical placebo did not differ in baseline characteristics or in prerandomization measures of insulin and blood sugar levels from 5-hour meal tolerance tests. The 440-calorie meal contained 100 g of carbohydrates, which usually would trigger reactive hypoglycemia symptoms in these patients.

After treatment, the sitagliptin group rated the intensity of reactive hypoglycemia symptoms significantly lower than did the control group – 2 vs. 5 – on a visual analog scale of 1-10, in which 0 represented no symptoms and 10 was greatest symptom intensity, Dr. Paloma Almeda-Valdés and her associates reported in a poster presentation at the annual meeting of the Endocrine Society.

Patients in the sitagliptin group reported significant reductions in the symptoms of anxiety, palpitations, shakiness (tremor), diaphoresis, dizziness, tingling, difficulty concentrating, and weakness, said Dr. Almeda-Valdés of Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City.

Sitagliptin is approved to lower glucose levels in adults with type 2 diabetes. It increases glucagon-like peptide1 circulating levels, which improves the early-phase secretion of insulin.

Meal tolerance tests after 2 weeks of treatment showed that the sitagliptin group had significantly higher levels of insulin within 30 minutes of the test, with areas under the curve of 2,278 mcU/mL per minute compared with 2,106 mcU/mL per minute in the control group.

The increased insulin concentration in this early phase after the meal was associated with significantly higher glucose concentrations later on, 1-5 hours after the meal. The glucose areas under the curve in the late phase of the meal tolerance test were 90,030 mg/dL per minute in the sitagliptin group and 84,165 mg/dL per minute in the control group.

These biochemical changes were associated with the reductions in symptom severity in the sitagliptin group, Dr. Almeda-Valdés said.

"The hypothesis is that sitagliptin restores insulin secretion in these patients, and this was associated with higher glucose levels in the late phase" and thus less hypoglycemia, she said in an interview.

The study defined symptomatic reactive hypoglycemia as the presence of symptoms associated with a 2- to 4-hour postprandial capillary glucose less than 65 mg/dL that disappeared with carbohydrate ingestion.

Merck, which markets sitagliptin, provided funding, the drug, and the placebo for the study. Dr. Almeda-Valdés reported having no other disclosures.

HOUSTON – Diet-induced weight loss with or without an accompanying exercise training program improved insulin sensitivity and other key cardiometabolic risk factors in an obese elderly population, a randomized trial showed.

However, exercise training alone in the absence of weight loss had no effect on insulin sensitivity in the 52-week-long clinical trial.

"This is actually a novel finding in this population of obese older adults, and it suggests a distinct complementary effect of regular exercise only in the setting of prerequisite weight loss," observed Dr. Matthew F. Bouchonville of the University of New Mexico, Albuquerque.

He reported on 107 obese subjects with a mean body mass index of 37 kg/m², all of whom were at least 65 years old. Sixty percent were women. Participants were randomized to one of four groups: a 52-week supervised dietary intervention with the goal of a 10% loss in body weight at 6 months and maintenance of that slimmed-down weight during the following 6 months; an exercise program; a combined diet-and-exercise intervention; or a control group. Essentially the study compared the metabolic effects of weight loss without exercise, versus exercise without weight loss, versus both interventions.

The primary outcome was change in insulin sensitivity index (ISI) over 1 year as measured via a 75-g oral glucose tolerance test. At 6 months, there was nearly a 40% increase in ISI in both weight-loss interventions – that is, the diet-only and diet-plus-exercise groups – with no significant difference between the two. Moreover, the exercise-only intervention had no effect on ISI; it was identical to that in the control group. Thus, at that intermediate 6-month time point there didn’t seem to be any added value for an exercise program in terms of enhancement of insulin sensitivity, Dr. Bouchonville explained.

But that changed as patients were followed from the 6-month mark out to 12 months. During that period, insulin sensitivity continued to improve in the diet-only group such that at 1 year their ISI was 70% better than at baseline, while the ISI in the diet-plus-exercise group showed an even more robust improvement: an 86% gain over baseline. The exercise training–only group still showed no change in insulin sensitivity at 12 months.

"The combination of these interventions is associated with an even greater improvement in insulin sensitivity," Dr. Bouchonville said. "This lends support to the recommendation that lifestyle interventions directed at this population incorporate both diet-induced weight loss and also regular exercise."

That recommendation was made on the basis of an earlier analysis of the data showing that the combination of weight loss and exercise training provided greater improvement in physical function and reduction in physical frailty than did either intervention alone (N. Engl. J. Med. 2011;364:1218-29).

This new analysis of the randomized trial data focused on change in insulin sensitivity because insulin resistance has been implicated as the main driving force behind the metabolic syndrome, the physician continued.

The same pattern seen with regard to change in insulin sensitivity recurred for the other cardiometabolic risk factors serving as secondary outcomes in the study: that is, no effect for exercise alone, but significant improvements noted in both the diet and diet-plus-exercise groups. For example, abdominal adiposity as measured by MRI decreased by an average of nearly 800 cc and C-reactive protein dropped on average by nearly 2 mg/dL in the combined intervention group, while triglyceride levels declined by 25-30 mg/dL in both of the weight loss interventions. Blood pressure also improved significantly, but again, only in the weight-loss interventions, not with exercise alone.

Audience members expressed surprise that the exercise training program alone did not have a significant impact on insulin sensitivity or the other cardiometabolic risk factors. They wondered if the exercise was not sufficiently intensive. Dr. Bouchonville replied that all indications are that it was. The program entailed three 90-minute group workouts per week led by a physical therapist. Each session included aerobic exercise, resistance training, and balance and flexibility exercises. Participants gradually reached 70%-85% of their peak heart rate. Their peak oxygen consumption improved significantly over time, as did their physical function scores, although the improvements on these measures were even greater in the combined diet-plus-exercise arm.

The diet intervention was pretty intensive. Patients met weekly with a dietician who prescribed a balanced diet that included 1 g of high-quality protein per kilo of body weight while maintaining an energy deficit of 500-750 kcal per day. They kept food diaries, and there were weekly weigh-ins. Body weight fell by 10% in the diet-only group and 9% in the diet-plus-exercise group but did not decrease in the exercise or control groups.

Dr. Bouchonville explained that this study was undertaken because the appropriate treatment for obese older adults has been controversial. Until now, some have argued that it’s prohibitively difficult to achieve lasting weight loss in this population because of unhealthy diet habits and a sedentary lifestyle. It has also been asserted that weight loss in the elderly could worsen frailty by accelerating age-related loss of muscle mass.

It is essential to determine the best evidence-based approach to the treatment of obese older adults because it is a population growing by leaps and bounds, he stressed. The Census Bureau estimates that 20% of the U.S. population will be age 65 years or older by 2030, while the Centers for Disease Control and Prevention predicts that by then 42% of Americans will be obese.

The clinical trial was funded by the National Institutes of Health. The presenter reported having no financial conflicts.

HOUSTON – Diet-induced weight loss with or without an accompanying exercise training program improved insulin sensitivity and other key cardiometabolic risk factors in an obese elderly population, a randomized trial showed.

However, exercise training alone in the absence of weight loss had no effect on insulin sensitivity in the 52-week-long clinical trial.

"This is actually a novel finding in this population of obese older adults, and it suggests a distinct complementary effect of regular exercise only in the setting of prerequisite weight loss," observed Dr. Matthew F. Bouchonville of the University of New Mexico, Albuquerque.

He reported on 107 obese subjects with a mean body mass index of 37 kg/m², all of whom were at least 65 years old. Sixty percent were women. Participants were randomized to one of four groups: a 52-week supervised dietary intervention with the goal of a 10% loss in body weight at 6 months and maintenance of that slimmed-down weight during the following 6 months; an exercise program; a combined diet-and-exercise intervention; or a control group. Essentially the study compared the metabolic effects of weight loss without exercise, versus exercise without weight loss, versus both interventions.

The primary outcome was change in insulin sensitivity index (ISI) over 1 year as measured via a 75-g oral glucose tolerance test. At 6 months, there was nearly a 40% increase in ISI in both weight-loss interventions – that is, the diet-only and diet-plus-exercise groups – with no significant difference between the two. Moreover, the exercise-only intervention had no effect on ISI; it was identical to that in the control group. Thus, at that intermediate 6-month time point there didn’t seem to be any added value for an exercise program in terms of enhancement of insulin sensitivity, Dr. Bouchonville explained.

But that changed as patients were followed from the 6-month mark out to 12 months. During that period, insulin sensitivity continued to improve in the diet-only group such that at 1 year their ISI was 70% better than at baseline, while the ISI in the diet-plus-exercise group showed an even more robust improvement: an 86% gain over baseline. The exercise training–only group still showed no change in insulin sensitivity at 12 months.

"The combination of these interventions is associated with an even greater improvement in insulin sensitivity," Dr. Bouchonville said. "This lends support to the recommendation that lifestyle interventions directed at this population incorporate both diet-induced weight loss and also regular exercise."

That recommendation was made on the basis of an earlier analysis of the data showing that the combination of weight loss and exercise training provided greater improvement in physical function and reduction in physical frailty than did either intervention alone (N. Engl. J. Med. 2011;364:1218-29).

This new analysis of the randomized trial data focused on change in insulin sensitivity because insulin resistance has been implicated as the main driving force behind the metabolic syndrome, the physician continued.

The same pattern seen with regard to change in insulin sensitivity recurred for the other cardiometabolic risk factors serving as secondary outcomes in the study: that is, no effect for exercise alone, but significant improvements noted in both the diet and diet-plus-exercise groups. For example, abdominal adiposity as measured by MRI decreased by an average of nearly 800 cc and C-reactive protein dropped on average by nearly 2 mg/dL in the combined intervention group, while triglyceride levels declined by 25-30 mg/dL in both of the weight loss interventions. Blood pressure also improved significantly, but again, only in the weight-loss interventions, not with exercise alone.

Audience members expressed surprise that the exercise training program alone did not have a significant impact on insulin sensitivity or the other cardiometabolic risk factors. They wondered if the exercise was not sufficiently intensive. Dr. Bouchonville replied that all indications are that it was. The program entailed three 90-minute group workouts per week led by a physical therapist. Each session included aerobic exercise, resistance training, and balance and flexibility exercises. Participants gradually reached 70%-85% of their peak heart rate. Their peak oxygen consumption improved significantly over time, as did their physical function scores, although the improvements on these measures were even greater in the combined diet-plus-exercise arm.

The diet intervention was pretty intensive. Patients met weekly with a dietician who prescribed a balanced diet that included 1 g of high-quality protein per kilo of body weight while maintaining an energy deficit of 500-750 kcal per day. They kept food diaries, and there were weekly weigh-ins. Body weight fell by 10% in the diet-only group and 9% in the diet-plus-exercise group but did not decrease in the exercise or control groups.

Dr. Bouchonville explained that this study was undertaken because the appropriate treatment for obese older adults has been controversial. Until now, some have argued that it’s prohibitively difficult to achieve lasting weight loss in this population because of unhealthy diet habits and a sedentary lifestyle. It has also been asserted that weight loss in the elderly could worsen frailty by accelerating age-related loss of muscle mass.

It is essential to determine the best evidence-based approach to the treatment of obese older adults because it is a population growing by leaps and bounds, he stressed. The Census Bureau estimates that 20% of the U.S. population will be age 65 years or older by 2030, while the Centers for Disease Control and Prevention predicts that by then 42% of Americans will be obese.

The clinical trial was funded by the National Institutes of Health. The presenter reported having no financial conflicts.

HOUSTON – Diet-induced weight loss with or without an accompanying exercise training program improved insulin sensitivity and other key cardiometabolic risk factors in an obese elderly population, a randomized trial showed.

However, exercise training alone in the absence of weight loss had no effect on insulin sensitivity in the 52-week-long clinical trial.

"This is actually a novel finding in this population of obese older adults, and it suggests a distinct complementary effect of regular exercise only in the setting of prerequisite weight loss," observed Dr. Matthew F. Bouchonville of the University of New Mexico, Albuquerque.

He reported on 107 obese subjects with a mean body mass index of 37 kg/m², all of whom were at least 65 years old. Sixty percent were women. Participants were randomized to one of four groups: a 52-week supervised dietary intervention with the goal of a 10% loss in body weight at 6 months and maintenance of that slimmed-down weight during the following 6 months; an exercise program; a combined diet-and-exercise intervention; or a control group. Essentially the study compared the metabolic effects of weight loss without exercise, versus exercise without weight loss, versus both interventions.

The primary outcome was change in insulin sensitivity index (ISI) over 1 year as measured via a 75-g oral glucose tolerance test. At 6 months, there was nearly a 40% increase in ISI in both weight-loss interventions – that is, the diet-only and diet-plus-exercise groups – with no significant difference between the two. Moreover, the exercise-only intervention had no effect on ISI; it was identical to that in the control group. Thus, at that intermediate 6-month time point there didn’t seem to be any added value for an exercise program in terms of enhancement of insulin sensitivity, Dr. Bouchonville explained.

But that changed as patients were followed from the 6-month mark out to 12 months. During that period, insulin sensitivity continued to improve in the diet-only group such that at 1 year their ISI was 70% better than at baseline, while the ISI in the diet-plus-exercise group showed an even more robust improvement: an 86% gain over baseline. The exercise training–only group still showed no change in insulin sensitivity at 12 months.

"The combination of these interventions is associated with an even greater improvement in insulin sensitivity," Dr. Bouchonville said. "This lends support to the recommendation that lifestyle interventions directed at this population incorporate both diet-induced weight loss and also regular exercise."

That recommendation was made on the basis of an earlier analysis of the data showing that the combination of weight loss and exercise training provided greater improvement in physical function and reduction in physical frailty than did either intervention alone (N. Engl. J. Med. 2011;364:1218-29).

This new analysis of the randomized trial data focused on change in insulin sensitivity because insulin resistance has been implicated as the main driving force behind the metabolic syndrome, the physician continued.

The same pattern seen with regard to change in insulin sensitivity recurred for the other cardiometabolic risk factors serving as secondary outcomes in the study: that is, no effect for exercise alone, but significant improvements noted in both the diet and diet-plus-exercise groups. For example, abdominal adiposity as measured by MRI decreased by an average of nearly 800 cc and C-reactive protein dropped on average by nearly 2 mg/dL in the combined intervention group, while triglyceride levels declined by 25-30 mg/dL in both of the weight loss interventions. Blood pressure also improved significantly, but again, only in the weight-loss interventions, not with exercise alone.

Audience members expressed surprise that the exercise training program alone did not have a significant impact on insulin sensitivity or the other cardiometabolic risk factors. They wondered if the exercise was not sufficiently intensive. Dr. Bouchonville replied that all indications are that it was. The program entailed three 90-minute group workouts per week led by a physical therapist. Each session included aerobic exercise, resistance training, and balance and flexibility exercises. Participants gradually reached 70%-85% of their peak heart rate. Their peak oxygen consumption improved significantly over time, as did their physical function scores, although the improvements on these measures were even greater in the combined diet-plus-exercise arm.

The diet intervention was pretty intensive. Patients met weekly with a dietician who prescribed a balanced diet that included 1 g of high-quality protein per kilo of body weight while maintaining an energy deficit of 500-750 kcal per day. They kept food diaries, and there were weekly weigh-ins. Body weight fell by 10% in the diet-only group and 9% in the diet-plus-exercise group but did not decrease in the exercise or control groups.

Dr. Bouchonville explained that this study was undertaken because the appropriate treatment for obese older adults has been controversial. Until now, some have argued that it’s prohibitively difficult to achieve lasting weight loss in this population because of unhealthy diet habits and a sedentary lifestyle. It has also been asserted that weight loss in the elderly could worsen frailty by accelerating age-related loss of muscle mass.

It is essential to determine the best evidence-based approach to the treatment of obese older adults because it is a population growing by leaps and bounds, he stressed. The Census Bureau estimates that 20% of the U.S. population will be age 65 years or older by 2030, while the Centers for Disease Control and Prevention predicts that by then 42% of Americans will be obese.

The clinical trial was funded by the National Institutes of Health. The presenter reported having no financial conflicts.

HOUSTON – A decline in testosterone is not an inevitable result of aging in men, according to a large population-based, longitudinal study.

"There’s an often-spoken-about concept that there is a decrease in testosterone with increasing age in men. Some people have even gone so far as to talk about an ‘andropause,’ or sudden drop in testosterone at some particular critical point in time reached in middle age. But we showed there’s almost no change in testosterone with age. At baseline, the mean serum total testosterone was 16.2 nmol/L, and at 5 years of follow-up it was 15.6. So essentially there is no age effect," declared Dr. Gary A. Wittert, professor of medicine at the University of Adelaide (South Australia).

He is director of the ongoing longitudinal MAILES (Male Adelaide Inflammation Lifestyle Environment Study). For this analysis of testosterone trends over time, he reported on 1,382 community-dwelling MAILES participants who averaged 54 years of age at entry. None was on medications that were known to affect hormones.

Although there was no significant change in testosterone over the course of 5 years in the overall group, some men did experience a significant decline in levels. A multivariate linear regression analysis identified several potent predictors of a progressive fall in testosterone (unmarried status, being depressed at baseline and at follow-up, cardiovascular disease, obesity, and weight gain during follow-up).

"It is critical that doctors understand that declining testosterone levels are not a natural part of aging and that they are most likely due to health-related behaviors or health status itself – particularly the burden of chronic disease, obesity, and depression," he said.

Counsel patients that the most important thing they can do to maintain their manhood, "or their mojo, is to prevent obesity. I think the most important target for preventing the decline in testosterone and all its consequences is to deal with the rapidly increasing obesity epidemic and maintain the healthiest possible lifestyle," Dr. Wittert said.

Men who maintained a normal weight had no change over time in testosterone. Those who lost weight showed a modest increase in the hormone. And men who transitioned from normal weight at baseline to obesity at follow-up showed a reduction in testosterone with no compensatory increase in luteinizing hormone levels, suggesting a central failure at the hypothalamic/pituitary level, he continued.

Dr. Wittert is the principal investigator in a six-center Australian prospective randomized trial that’s looking at whether testosterone replacement therapy plus a lifestyle intervention prevents progression from prediabetes to diabetes in hypogonadal men older than age 50 who are at increased risk. The control arm in the study, which is just beginning enrollment, will receive placebo plus the lifestyle intervention.

One of the hypotheses being tested is whether testosterone replacement improves motivation to engage in lifestyle change, a benefit that Dr. Wittert and others have observed anecdotally. Secondary end points in the study include the effect of testosterone replacement on cardiovascular disease risk and on bone health.

Testosterone levels tended to decline in smokers who quit. That’s clearly not a valid reason to continue smoking. Yet this intriguing relationship between smoking and testosterone is worthy of further investigation, in Dr. Wittert’s view.

The study is being funded by the National Health and Medical Research Council of Australia.

HOUSTON – A decline in testosterone is not an inevitable result of aging in men, according to a large population-based, longitudinal study.

"There’s an often-spoken-about concept that there is a decrease in testosterone with increasing age in men. Some people have even gone so far as to talk about an ‘andropause,’ or sudden drop in testosterone at some particular critical point in time reached in middle age. But we showed there’s almost no change in testosterone with age. At baseline, the mean serum total testosterone was 16.2 nmol/L, and at 5 years of follow-up it was 15.6. So essentially there is no age effect," declared Dr. Gary A. Wittert, professor of medicine at the University of Adelaide (South Australia).

He is director of the ongoing longitudinal MAILES (Male Adelaide Inflammation Lifestyle Environment Study). For this analysis of testosterone trends over time, he reported on 1,382 community-dwelling MAILES participants who averaged 54 years of age at entry. None was on medications that were known to affect hormones.

Although there was no significant change in testosterone over the course of 5 years in the overall group, some men did experience a significant decline in levels. A multivariate linear regression analysis identified several potent predictors of a progressive fall in testosterone (unmarried status, being depressed at baseline and at follow-up, cardiovascular disease, obesity, and weight gain during follow-up).

"It is critical that doctors understand that declining testosterone levels are not a natural part of aging and that they are most likely due to health-related behaviors or health status itself – particularly the burden of chronic disease, obesity, and depression," he said.

Counsel patients that the most important thing they can do to maintain their manhood, "or their mojo, is to prevent obesity. I think the most important target for preventing the decline in testosterone and all its consequences is to deal with the rapidly increasing obesity epidemic and maintain the healthiest possible lifestyle," Dr. Wittert said.

Men who maintained a normal weight had no change over time in testosterone. Those who lost weight showed a modest increase in the hormone. And men who transitioned from normal weight at baseline to obesity at follow-up showed a reduction in testosterone with no compensatory increase in luteinizing hormone levels, suggesting a central failure at the hypothalamic/pituitary level, he continued.

Dr. Wittert is the principal investigator in a six-center Australian prospective randomized trial that’s looking at whether testosterone replacement therapy plus a lifestyle intervention prevents progression from prediabetes to diabetes in hypogonadal men older than age 50 who are at increased risk. The control arm in the study, which is just beginning enrollment, will receive placebo plus the lifestyle intervention.

One of the hypotheses being tested is whether testosterone replacement improves motivation to engage in lifestyle change, a benefit that Dr. Wittert and others have observed anecdotally. Secondary end points in the study include the effect of testosterone replacement on cardiovascular disease risk and on bone health.

Testosterone levels tended to decline in smokers who quit. That’s clearly not a valid reason to continue smoking. Yet this intriguing relationship between smoking and testosterone is worthy of further investigation, in Dr. Wittert’s view.

The study is being funded by the National Health and Medical Research Council of Australia.

HOUSTON – A decline in testosterone is not an inevitable result of aging in men, according to a large population-based, longitudinal study.

"There’s an often-spoken-about concept that there is a decrease in testosterone with increasing age in men. Some people have even gone so far as to talk about an ‘andropause,’ or sudden drop in testosterone at some particular critical point in time reached in middle age. But we showed there’s almost no change in testosterone with age. At baseline, the mean serum total testosterone was 16.2 nmol/L, and at 5 years of follow-up it was 15.6. So essentially there is no age effect," declared Dr. Gary A. Wittert, professor of medicine at the University of Adelaide (South Australia).

He is director of the ongoing longitudinal MAILES (Male Adelaide Inflammation Lifestyle Environment Study). For this analysis of testosterone trends over time, he reported on 1,382 community-dwelling MAILES participants who averaged 54 years of age at entry. None was on medications that were known to affect hormones.

Although there was no significant change in testosterone over the course of 5 years in the overall group, some men did experience a significant decline in levels. A multivariate linear regression analysis identified several potent predictors of a progressive fall in testosterone (unmarried status, being depressed at baseline and at follow-up, cardiovascular disease, obesity, and weight gain during follow-up).

"It is critical that doctors understand that declining testosterone levels are not a natural part of aging and that they are most likely due to health-related behaviors or health status itself – particularly the burden of chronic disease, obesity, and depression," he said.

Counsel patients that the most important thing they can do to maintain their manhood, "or their mojo, is to prevent obesity. I think the most important target for preventing the decline in testosterone and all its consequences is to deal with the rapidly increasing obesity epidemic and maintain the healthiest possible lifestyle," Dr. Wittert said.

Men who maintained a normal weight had no change over time in testosterone. Those who lost weight showed a modest increase in the hormone. And men who transitioned from normal weight at baseline to obesity at follow-up showed a reduction in testosterone with no compensatory increase in luteinizing hormone levels, suggesting a central failure at the hypothalamic/pituitary level, he continued.

Dr. Wittert is the principal investigator in a six-center Australian prospective randomized trial that’s looking at whether testosterone replacement therapy plus a lifestyle intervention prevents progression from prediabetes to diabetes in hypogonadal men older than age 50 who are at increased risk. The control arm in the study, which is just beginning enrollment, will receive placebo plus the lifestyle intervention.

One of the hypotheses being tested is whether testosterone replacement improves motivation to engage in lifestyle change, a benefit that Dr. Wittert and others have observed anecdotally. Secondary end points in the study include the effect of testosterone replacement on cardiovascular disease risk and on bone health.

Testosterone levels tended to decline in smokers who quit. That’s clearly not a valid reason to continue smoking. Yet this intriguing relationship between smoking and testosterone is worthy of further investigation, in Dr. Wittert’s view.

The study is being funded by the National Health and Medical Research Council of Australia.

HOUSTON – The antimalarial/immunomodulatory drug chloroquine might take on a new life as a treatment for patients with the metabolic syndrome.

In a randomized, double-blind trial involving 277 healthy Singapore volunteers assigned to low-dose chloroquine or placebo, mean triglyceride levels after 12 weeks were 77.9 mg/dL in the chloroquine group, an 11% reduction compared with the mean 87.7 mg/dL in controls.

Moreover, the total cholesterol–high-density lipoprotein ratio at the 12-week mark was 3.31 mg/dL in the chloroquine group, 7% better than the 3.51 mg/dL in controls, according to Dr. Lawrence Lee of the National University of Singapore.

"This cheap and safe treatment should be investigated further for reducing the risk of cardiovascular disease, especially in high-risk patients, such as those who are obese or diabetic, where the effect could be more clinically significant," he noted at the annual meeting of the Endocrine Society.

Twelve weeks of low-dose chloroquine had no impact on HDL, insulin levels, blood glucose, or the homeostatic model assessment (HOMA) insulin sensitivity index.

The chloroquine regimen consisted of 300 mg/day for the first 7 days followed by 300 mg once weekly for the next 11 weeks.

Previous animal studies by investigators at Washington University at St. Louis showed that daily doses of chloroquine or hydroxychloroquine reduced insulin resistance and improved lipid metabolism, most likely via activation of the ataxia telangiectasis mutated (ATM) gene (Cell Metab. 2006;4:377-89).

This work has led to ongoing large prospective clinical trials of daily chloroquine as a treatment for dyslipidemia and insulin resistance.

Dr. Lee and coworkers hypothesized that low-dose, once-weekly chloroquine could also be effective in metabolic syndrome, and with a more favorable safety profile than that of daily therapy. This study in healthy volunteers was a prelude to further studies in patients with metabolic syndrome.

The current study was actually a substudy of the Chloroquine for Influenza Prevention (CHIP) trial, in which 1,500 healthy volunteers were randomized to chloroquine or placebo, and which established that chloroquine does not prevent influenza (Lancet Infect. Dis. 2011; 677-83).

Dr. Lee reported having no financial conflicts. The CHIP trial was funded by the National Medical Research Council of Singapore.

HOUSTON – The antimalarial/immunomodulatory drug chloroquine might take on a new life as a treatment for patients with the metabolic syndrome.

In a randomized, double-blind trial involving 277 healthy Singapore volunteers assigned to low-dose chloroquine or placebo, mean triglyceride levels after 12 weeks were 77.9 mg/dL in the chloroquine group, an 11% reduction compared with the mean 87.7 mg/dL in controls.

Moreover, the total cholesterol–high-density lipoprotein ratio at the 12-week mark was 3.31 mg/dL in the chloroquine group, 7% better than the 3.51 mg/dL in controls, according to Dr. Lawrence Lee of the National University of Singapore.

"This cheap and safe treatment should be investigated further for reducing the risk of cardiovascular disease, especially in high-risk patients, such as those who are obese or diabetic, where the effect could be more clinically significant," he noted at the annual meeting of the Endocrine Society.

Twelve weeks of low-dose chloroquine had no impact on HDL, insulin levels, blood glucose, or the homeostatic model assessment (HOMA) insulin sensitivity index.

The chloroquine regimen consisted of 300 mg/day for the first 7 days followed by 300 mg once weekly for the next 11 weeks.

Previous animal studies by investigators at Washington University at St. Louis showed that daily doses of chloroquine or hydroxychloroquine reduced insulin resistance and improved lipid metabolism, most likely via activation of the ataxia telangiectasis mutated (ATM) gene (Cell Metab. 2006;4:377-89).

This work has led to ongoing large prospective clinical trials of daily chloroquine as a treatment for dyslipidemia and insulin resistance.

Dr. Lee and coworkers hypothesized that low-dose, once-weekly chloroquine could also be effective in metabolic syndrome, and with a more favorable safety profile than that of daily therapy. This study in healthy volunteers was a prelude to further studies in patients with metabolic syndrome.

The current study was actually a substudy of the Chloroquine for Influenza Prevention (CHIP) trial, in which 1,500 healthy volunteers were randomized to chloroquine or placebo, and which established that chloroquine does not prevent influenza (Lancet Infect. Dis. 2011; 677-83).

Dr. Lee reported having no financial conflicts. The CHIP trial was funded by the National Medical Research Council of Singapore.

HOUSTON – The antimalarial/immunomodulatory drug chloroquine might take on a new life as a treatment for patients with the metabolic syndrome.

In a randomized, double-blind trial involving 277 healthy Singapore volunteers assigned to low-dose chloroquine or placebo, mean triglyceride levels after 12 weeks were 77.9 mg/dL in the chloroquine group, an 11% reduction compared with the mean 87.7 mg/dL in controls.

Moreover, the total cholesterol–high-density lipoprotein ratio at the 12-week mark was 3.31 mg/dL in the chloroquine group, 7% better than the 3.51 mg/dL in controls, according to Dr. Lawrence Lee of the National University of Singapore.

"This cheap and safe treatment should be investigated further for reducing the risk of cardiovascular disease, especially in high-risk patients, such as those who are obese or diabetic, where the effect could be more clinically significant," he noted at the annual meeting of the Endocrine Society.

Twelve weeks of low-dose chloroquine had no impact on HDL, insulin levels, blood glucose, or the homeostatic model assessment (HOMA) insulin sensitivity index.

The chloroquine regimen consisted of 300 mg/day for the first 7 days followed by 300 mg once weekly for the next 11 weeks.

Previous animal studies by investigators at Washington University at St. Louis showed that daily doses of chloroquine or hydroxychloroquine reduced insulin resistance and improved lipid metabolism, most likely via activation of the ataxia telangiectasis mutated (ATM) gene (Cell Metab. 2006;4:377-89).

This work has led to ongoing large prospective clinical trials of daily chloroquine as a treatment for dyslipidemia and insulin resistance.

Dr. Lee and coworkers hypothesized that low-dose, once-weekly chloroquine could also be effective in metabolic syndrome, and with a more favorable safety profile than that of daily therapy. This study in healthy volunteers was a prelude to further studies in patients with metabolic syndrome.

The current study was actually a substudy of the Chloroquine for Influenza Prevention (CHIP) trial, in which 1,500 healthy volunteers were randomized to chloroquine or placebo, and which established that chloroquine does not prevent influenza (Lancet Infect. Dis. 2011; 677-83).

Dr. Lee reported having no financial conflicts. The CHIP trial was funded by the National Medical Research Council of Singapore.

HOUSTON – Metformin was associated with more modest reports of pain among patients with lumbar radiculopathy.

In a retrospective case-control study presented at the annual meeting of the Endocrine Society, 46 patients who were taking metformin and sought care for lumbar radiculopathy pain averaged a 1.85-point lower score on a 0-10 point "having pain now," scale as did 94 controls, 18 of whom had type 2 diabetes. The two groups were matched for their number of pain medications. None had peripheral neuropathy or other diabetic complications, reported Dr. Magdalena Szkudlinska of the University of Arizona, Tucson.

Mechanistic studies were conducted in animal models. Other researchers have identified AMPK (adenosine monophosphate–activated protein kinase) as a potential therapeutic target in chronic neuropathic pain conditions. The proposed mechanism involves activation of AMPK by metformin, with resultant inhibition of the mTOR (mammalian target of rapamycin) pathway leading to reduced sensory neuron excitability and decreased chronic neuropathic pain (Nat. Cell Biol. 2011;13:1016-23).

Moreover, Dr. Szkudlinska added, metformin has proved "remarkably effective" in reducing nociceptor sensitization and pain in animal models (Mol. Pain 2011 Sept. 21 [doi:10.1186/1744-8069-7-70]).

"We propose that these results, combined with the preclinical rationale, warrant a larger prospective study testing the effectiveness of metformin on chronic neuropathic pain," she declared.

Her retrospective lumbar radiculopathy study was supported by the National Institutes of Health. She declared having no financial conflicts.

HOUSTON – Metformin was associated with more modest reports of pain among patients with lumbar radiculopathy.

In a retrospective case-control study presented at the annual meeting of the Endocrine Society, 46 patients who were taking metformin and sought care for lumbar radiculopathy pain averaged a 1.85-point lower score on a 0-10 point "having pain now," scale as did 94 controls, 18 of whom had type 2 diabetes. The two groups were matched for their number of pain medications. None had peripheral neuropathy or other diabetic complications, reported Dr. Magdalena Szkudlinska of the University of Arizona, Tucson.

Mechanistic studies were conducted in animal models. Other researchers have identified AMPK (adenosine monophosphate–activated protein kinase) as a potential therapeutic target in chronic neuropathic pain conditions. The proposed mechanism involves activation of AMPK by metformin, with resultant inhibition of the mTOR (mammalian target of rapamycin) pathway leading to reduced sensory neuron excitability and decreased chronic neuropathic pain (Nat. Cell Biol. 2011;13:1016-23).

Moreover, Dr. Szkudlinska added, metformin has proved "remarkably effective" in reducing nociceptor sensitization and pain in animal models (Mol. Pain 2011 Sept. 21 [doi:10.1186/1744-8069-7-70]).

"We propose that these results, combined with the preclinical rationale, warrant a larger prospective study testing the effectiveness of metformin on chronic neuropathic pain," she declared.

Her retrospective lumbar radiculopathy study was supported by the National Institutes of Health. She declared having no financial conflicts.

HOUSTON – Metformin was associated with more modest reports of pain among patients with lumbar radiculopathy.

In a retrospective case-control study presented at the annual meeting of the Endocrine Society, 46 patients who were taking metformin and sought care for lumbar radiculopathy pain averaged a 1.85-point lower score on a 0-10 point "having pain now," scale as did 94 controls, 18 of whom had type 2 diabetes. The two groups were matched for their number of pain medications. None had peripheral neuropathy or other diabetic complications, reported Dr. Magdalena Szkudlinska of the University of Arizona, Tucson.

Mechanistic studies were conducted in animal models. Other researchers have identified AMPK (adenosine monophosphate–activated protein kinase) as a potential therapeutic target in chronic neuropathic pain conditions. The proposed mechanism involves activation of AMPK by metformin, with resultant inhibition of the mTOR (mammalian target of rapamycin) pathway leading to reduced sensory neuron excitability and decreased chronic neuropathic pain (Nat. Cell Biol. 2011;13:1016-23).

Moreover, Dr. Szkudlinska added, metformin has proved "remarkably effective" in reducing nociceptor sensitization and pain in animal models (Mol. Pain 2011 Sept. 21 [doi:10.1186/1744-8069-7-70]).

"We propose that these results, combined with the preclinical rationale, warrant a larger prospective study testing the effectiveness of metformin on chronic neuropathic pain," she declared.

Her retrospective lumbar radiculopathy study was supported by the National Institutes of Health. She declared having no financial conflicts.

HOUSTON – Patients with surgically treated hyperthyroidism have a lingering elevation in cardiovascular risk that persists for at least 2 decades post thyroidectomy, according to a Finnish national study.

“This is the first study to show increased risk of hospitalization for cardiovascular disease after thyroid surgery. The elevated risk is sustained 20 years after surgery. This is in line with previous studies done in patients treated with radioactive iodine. Thus, it’s probably the disease rather than the treatment that affects the patient’s heart permanently,” said Dr. Saara Metso of Tampere (Finland) University Hospital.

At the annual meeting of the Endocrine Society, she presented a population-based cohort study involving 4,334 hyperthyroid patients treated with thyroidectomy at any hospital in Finland during 1986-2007, along with 12,991 controls drawn from the general population.

The hospitalization rate for all cardiovascular causes during a median 10.5 years of follow-up was 240.5 per 10,000 person-years in the thyroidectomy group, compared with 206.2 per 10,000 person-years among controls.

These rates translated into a highly significant 17% increased risk of cardiovascular hospitalization in patients after they have undergone thyroidectomy. The risk, however, was not elevated across the board for all forms of cardiovascular disease. For example, there was no significant difference between patients and controls in hospitalization rates for coronary artery disease, cerebrovascular disease, or heart failure. On the other hand, patients with surgically treated hyperthyroidism had a 27% greater rate of hospitalization for hypertension; a 51% increase in admissions for atrial fibrillation; and a 54% greater hospitalization rate for nonbacterial endo-, peri- and myocardial diseases, valvular diseases, and cardiomyopathy, she continued.

Dr. Metso noted that a recent meta-analysis of six studies featuring long-term follow-up of patients treated for hyperthyroidism showed that the subjects had a 19% increase in cardiovascular mortality relative to age- and sex-matched controls (Eur. J. Endocrinol. 2011;165:491-7). However, most of these patients had been treated with radioiodine. This is what prompted Dr. Metso and her coinvestigators to take a close look at surgically treated patients. The most common causes of their surgically treated hyperthyroidism were Graves disease in 48% of patients, multinodular goiter in 33%, and toxic adenoma in 6%.

Several audience members, while quick to praise the Finnish study as an important advance in the field, expressed a wish that Dr. Metso and her coworkers would have included radioiodine-treated hyperthyroid patients as a control group. Audience members also would have welcomed information on postthyroidectomy thyroid replacement hormone dosing to assess whether that could be a potential contributor to the observed increase in cardiovascular risk in thyroidectomized patients.

“It’s hard to understand how the adverse cardiovascular effects could last 2 decades after the end of hyperthyroidism,” one physician commented.

The Finnish national study was funded by the Pirkanmaa Hospital Research Fund. Dr. Metso reported having no financial conflicts.

HOUSTON – Patients with surgically treated hyperthyroidism have a lingering elevation in cardiovascular risk that persists for at least 2 decades post thyroidectomy, according to a Finnish national study.

“This is the first study to show increased risk of hospitalization for cardiovascular disease after thyroid surgery. The elevated risk is sustained 20 years after surgery. This is in line with previous studies done in patients treated with radioactive iodine. Thus, it’s probably the disease rather than the treatment that affects the patient’s heart permanently,” said Dr. Saara Metso of Tampere (Finland) University Hospital.

At the annual meeting of the Endocrine Society, she presented a population-based cohort study involving 4,334 hyperthyroid patients treated with thyroidectomy at any hospital in Finland during 1986-2007, along with 12,991 controls drawn from the general population.

The hospitalization rate for all cardiovascular causes during a median 10.5 years of follow-up was 240.5 per 10,000 person-years in the thyroidectomy group, compared with 206.2 per 10,000 person-years among controls.

These rates translated into a highly significant 17% increased risk of cardiovascular hospitalization in patients after they have undergone thyroidectomy. The risk, however, was not elevated across the board for all forms of cardiovascular disease. For example, there was no significant difference between patients and controls in hospitalization rates for coronary artery disease, cerebrovascular disease, or heart failure. On the other hand, patients with surgically treated hyperthyroidism had a 27% greater rate of hospitalization for hypertension; a 51% increase in admissions for atrial fibrillation; and a 54% greater hospitalization rate for nonbacterial endo-, peri- and myocardial diseases, valvular diseases, and cardiomyopathy, she continued.

Dr. Metso noted that a recent meta-analysis of six studies featuring long-term follow-up of patients treated for hyperthyroidism showed that the subjects had a 19% increase in cardiovascular mortality relative to age- and sex-matched controls (Eur. J. Endocrinol. 2011;165:491-7). However, most of these patients had been treated with radioiodine. This is what prompted Dr. Metso and her coinvestigators to take a close look at surgically treated patients. The most common causes of their surgically treated hyperthyroidism were Graves disease in 48% of patients, multinodular goiter in 33%, and toxic adenoma in 6%.

Several audience members, while quick to praise the Finnish study as an important advance in the field, expressed a wish that Dr. Metso and her coworkers would have included radioiodine-treated hyperthyroid patients as a control group. Audience members also would have welcomed information on postthyroidectomy thyroid replacement hormone dosing to assess whether that could be a potential contributor to the observed increase in cardiovascular risk in thyroidectomized patients.

“It’s hard to understand how the adverse cardiovascular effects could last 2 decades after the end of hyperthyroidism,” one physician commented.

The Finnish national study was funded by the Pirkanmaa Hospital Research Fund. Dr. Metso reported having no financial conflicts.

HOUSTON – Patients with surgically treated hyperthyroidism have a lingering elevation in cardiovascular risk that persists for at least 2 decades post thyroidectomy, according to a Finnish national study.

“This is the first study to show increased risk of hospitalization for cardiovascular disease after thyroid surgery. The elevated risk is sustained 20 years after surgery. This is in line with previous studies done in patients treated with radioactive iodine. Thus, it’s probably the disease rather than the treatment that affects the patient’s heart permanently,” said Dr. Saara Metso of Tampere (Finland) University Hospital.

At the annual meeting of the Endocrine Society, she presented a population-based cohort study involving 4,334 hyperthyroid patients treated with thyroidectomy at any hospital in Finland during 1986-2007, along with 12,991 controls drawn from the general population.

The hospitalization rate for all cardiovascular causes during a median 10.5 years of follow-up was 240.5 per 10,000 person-years in the thyroidectomy group, compared with 206.2 per 10,000 person-years among controls.

These rates translated into a highly significant 17% increased risk of cardiovascular hospitalization in patients after they have undergone thyroidectomy. The risk, however, was not elevated across the board for all forms of cardiovascular disease. For example, there was no significant difference between patients and controls in hospitalization rates for coronary artery disease, cerebrovascular disease, or heart failure. On the other hand, patients with surgically treated hyperthyroidism had a 27% greater rate of hospitalization for hypertension; a 51% increase in admissions for atrial fibrillation; and a 54% greater hospitalization rate for nonbacterial endo-, peri- and myocardial diseases, valvular diseases, and cardiomyopathy, she continued.

Dr. Metso noted that a recent meta-analysis of six studies featuring long-term follow-up of patients treated for hyperthyroidism showed that the subjects had a 19% increase in cardiovascular mortality relative to age- and sex-matched controls (Eur. J. Endocrinol. 2011;165:491-7). However, most of these patients had been treated with radioiodine. This is what prompted Dr. Metso and her coinvestigators to take a close look at surgically treated patients. The most common causes of their surgically treated hyperthyroidism were Graves disease in 48% of patients, multinodular goiter in 33%, and toxic adenoma in 6%.

Several audience members, while quick to praise the Finnish study as an important advance in the field, expressed a wish that Dr. Metso and her coworkers would have included radioiodine-treated hyperthyroid patients as a control group. Audience members also would have welcomed information on postthyroidectomy thyroid replacement hormone dosing to assess whether that could be a potential contributor to the observed increase in cardiovascular risk in thyroidectomized patients.

“It’s hard to understand how the adverse cardiovascular effects could last 2 decades after the end of hyperthyroidism,” one physician commented.

The Finnish national study was funded by the Pirkanmaa Hospital Research Fund. Dr. Metso reported having no financial conflicts.