Two Years of Treatment With Dehydroepiandrosterone Does Not Improve Insulin Secretion, Insulin Action, or Postprandial Glucose Turnover in Elderly Men or Women

Abstract

To determine if dehydroepiandrosterone (DHEA) replacement improves insulin secretion, insulin action, and/or postprandial glucose metabolism, 112 elderly subjects with relative DHEA deficiency ingested a labeled mixed meal and underwent a frequently sampled intravenous glucose tolerance test before and after 2 years of either DHEA or placebo. Despite restoring DHEA sulphate concentrations to values observed in young men and women, the changes over time in fasting and postprandial glucose concentrations, meal appearance, glucose disposal, and endogenous glucose production were identical to those observed after 2 years of placebo. The change over time in postmeal and intravenous glucose tolerance test insulin and C-peptide concentrations did not differ in men treated with DHEA or placebo. In contrast, postmeal and intravenous glucose tolerance test change over time in insulin and C-peptide concentrations were greater (P < 0.05) in women after DHEA than after placebo. However, since DHEA tended to decrease insulin action, the change over time in disposition indexes did not differ between DHEA-and placebo-treated women, indicating that the slight increase in insulin secretion was a compensatory response to a slight decrease in insulin action. We conclude that 2 years of replacement of DHEA in elderly men and women does not improve insulin secretion, insulin action, or the pattern of postprandial glucose metabolism. Diabetes 56:753-766, 2007 P lasma dehydroepiandrosterone (DHEA) concentrations and glucose tolerance both decrease with age (1-6). In addition, plasma DHEA concentrations have been reported to be inversely correlated with BMI, visceral fat, plasma insulin concentrations, and insulin action (1,7-10). Furthermore, treatment with DHEA increases glucose uptake in vitro and improves glucose tolerance in mice, decreases body fat in fa/fa rats, prevents diabetes in ob/ob mice, and enhances glucose-induced insulin secretion in Wistar rats (11-17). These observations have led to speculation that the agerelated fall in DHEA concentrations either causes or exacerbates glucose intolerance and likely has contributed to the widespread empirical use of DHEA as a putative "anti-aging" drug.Studies in humans examining the effects of DHEA on carbohydrate metabolism have been less convincing. Whereas DHEA replacement improves insulin action in individuals with absolute DHEA deficiency (18), it has been reported to improve (19 -21), have no effect (22-25), or decrease (26) insulin action in subjects with intact adrenals. However, all of the above have studied a relatively small number of patients (i.e., less than 15 patients per group) for a relatively short period of time (i.e., Յ12 months). In addition, to our knowledge, no study has concurrently assessed the effect of DHEA replacement on insulin secretion and action, leaving open the question as to whether a change in one of the parameters observed in some studies is a primary effect of DHEA or merely represents a compensatory response to a change in the other.We have rec...

Effect of 2 Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance, and Postprandial Glucose Turnover in Elderly Men

“…We also observed that DHEA replacement did not alter net insulin action measured with the unlabeled meal minimal model (21). To our knowledge, the effects of testosterone replacement on insulin secretion, insulin action, and postprandial glucose turnover have not been previously evaluated in elderly men.…”

The effect of Dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance

“…18 In another study, a two-week intake of DHEA by type 2 diabetic men improved glucose control and HOMA-IR. 19 Other results however have shown that a two year intake of DHEA had no effect on insulin sensitivity 3,20 and quality of life. 20 In a study by Yamauchi et al, it was found that in diabetic men DHEA levels were significantly lower compared to men with IGT but DHEA levels were not related to insulin levels.…”

“…19 Other results however have shown that a two year intake of DHEA had no effect on insulin sensitivity 3,20 and quality of life. 20 In a study by Yamauchi et al, it was found that in diabetic men DHEA levels were significantly lower compared to men with IGT but DHEA levels were not related to insulin levels. 21 Analogous results were found by Jedrzejuk et al who studied the effect of DHEA intake for three months and found that this treatment had no effect on cholesterol, triglyceride and insulin sensitivity.…”

Late-onset hypogonadism or ADAM: treatment

“…The few studies that have addressed this issue suggest that DHEA has no effect on the metabolism of carbohydrates (B). 25 …”

“…36 The beneficial effects of ART on metabolic syndrome components appear to be specific to testosterone, given that chronic replacement with DHEA does not improve the secretion or action of insulin and postprandial glycemia in women and elderly men (B). 40 …”