DHEA May Reduce Abdominal Fat and Increase Insulin Sensitivity in the Elderly

Yael Waknine

November 09, 2004

Nov. 9, 2004 — Daily replacement therapy with 50 mg of dehydroepiandrosterone (DHEA) significantly decreases visceral and subcutaneous abdominal fat and significantly increases insulin sensitivity in the elderly, according to the results of a six-month, randomized, double-blind, placebo-controlled preliminary trial published in the Nov. 10 issue of JAMA.

"The accumulation of abdominal fat increases with advancing age, and there is extensive evidence that abdominal obesity increases the risk for development of insulin resistance, diabetes, and atherosclerosis," write Dennis T. Villareal, MD, and John O. Holloszy, MD, from the Division of Geriatrics and Nutritional Science at the Washington University School of Medicine in St. Louis, Missouri.

According to the authors, the increase in abdominal fat may be due in part to age-related hormonal and metabolic changes. "One such change is the decline in production of the adrenal hormone [DHEA],...[which] peaks at approximately 20 years of age and declines rapidly and markedly after age 25 years," the authors write.

DHEA has been shown in animal studies to reduce accumulation of abdominal visceral fat and protect against insulin resistance. To determine its efficacy in a human population, the investigators randomized 56 elderly subjects with age-related DHEA deficiency (28 men; mean age, 71 years [range, 65-78 years]) to receive 50 mg of DHEA per day or placebo for six months.

Subjects in both groups had similar baseline characteristics and were generally overweight; their abdominal fat was quantified using proton magnetic resonance imaging at baseline and at six months. There were no significant changes in energy intake or physical activity during the study period, as assessed using diet records and a physical activity questionnaire.

Compliance was high in the DHEA and placebo groups (97% and 95%, respectively) as confirmed by pill counts at monthly intervals. DHEA therapy was not associated with any significant adverse events.

Intent-to-treat analysis at six months showed that DHEA therapy induced a significant decrease in body weight from baseline compared with placebo (–0.9 ± 2.4 kg vs +0.6 ± 2.2 kg; P = .02), with no difference in response between men and women ( P = .74). Significant decreases in visceral fat area (–13 cm2 vs + 3 cm2; P = .001) and subcutaneous fat (–13 cm2 vs +2 cm2; P = .003) were observed in the DHEA group compared with the placebo group.

Subjects who received DHEA also showed significantly decreased insulin levels upon challenge with an oral glucose tolerance test compared with subjects in the placebo group (area under the curve, –1,119 µU/mL/2 hours vs +818 µU/mL/2 hours; P = .007). Because the glucose area under the curve remained unchanged compared with placebo ( P = .79), lowered insulin levels indicated a significant increase in insulin sensitivity for the DHEA group compared with the placebo group (+1.4 vs –0.7; P = .005).

Compared with placebo and baseline values, DHEA replacement therapy raised serum DHEA levels to the normal range in both men and women, significantly increased serum testosterone levels in women but not in men, and significantly increased estradiol levels in both men and women ( P < .001 for all). Small but significant increases in serum insulin growth factor (IGF-1) concentrations were also observed in the DHEA group compared with the placebo group ( P = .03).

"There is evidence suggesting that estrogen therapy protects postmenopausal women against abdominal fat accumulation and that increasing IGF-1 levels reduces abdominal fat," the authors comment. "Thus, it is possible that the increases in estradiol and IGF-1 levels could have played a role in the decrease inabdominal fat induced by DHEA in our study."

"We found in this preliminary study that DHEA reduced abdominal fat and improved insulin sensitivity index," the authors write, noting that larger studies will be needed to verify these findings in patient groups that are fully representative of the population at risk. "DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity," they conclude.

The authors report having received funding via a patient-oriented research career development award and grants from the General Clinical Research Center, the Diabetes Research and Training Center, the Clinical Nutrition Research Unit, and the National Institutes of Health.

JAMA. 2004;292:2243-2248

Reviewed by Gary D. Vogin, MD

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