LETTER
Relation of Adrenal Androgen to Insulin Levels
John E. Nestler
15 May 1993 | Volume 118 Issue 10 | Page 826
TO THE EDITOR:
The report by Barrett-Connor [1] that serum levels of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA-sulfate are decreased in untreated men with mild type II diabetes mellitus is thought provoking. During the past decade, it has become apparent that insulin may act as a physiologic regulator of human steroid hormone biosynthesis [2]. Although serum insulin levels were not reported in Barrett-Connor's study [1], it seems likely that the untreated men with type II diabetes mellitus were insulin resistant and hyperinsulinemic.
Insulin has been shown to lower acutely serum DHEA and DHEA-sulfate levels in men and women [2]. Conversely, amelioration of insulin resistance and hyperinsulinemia in obese insulin-resistant men, who otherwise manifest normal glucose tolerance, has resulted in a dramatic rise in serum DHEA-sulfate levels [3]. It would have been interesting to assess whether an inverse correlation existed between fasting serum insulin and adrenal androgen levels in these men.
The possible regulation of adrenal androgens by insulin is all the more intriguing because of recent evidence, including that of Barrett-Connor and colleagues [4], which suggests that DHEA exerts several potent antiatherogenic and cardioprotective actions [5]. An insulin-mediated reduction in circulating DHEA and DHEA-sulfate may serve as a mechanism for the well-described epidemiologic association between hyperinsulinemic states (such as type II diabetes mellitus, obesity, and aging) and atherosclerosis [5].
It would be most instructive if Barrett-Connor and colleagues measured serum adrenal androgen levels in these diabetic men after instituting either dietary or long-term oral hypoglycemic therapy. If insulin sensitivity were enhanced and reduction in circulating insulin were reduced, serum DHEA and DHEA-sulfate levels might concurrently rise.
1. Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med. 1992; 117:807-11.
2. Nestler JE, Strauss JF III. Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocrinol Metab Clin North Am. 1991; 20:807-23.
3. Beer NA, Jakubowicz DJ, Beer RM, Arocha IR, Nestler JE. Effects of nitrendipine on glucose tolerance and serum insulin and dehydroepiandrosterone-sulfate levels in insulin-resistant obese and hypertensive men. J Clin Endocrinol Metab. 1993; 76:178-83.
4. Barrett-Connor E, Khaw KT, Yen SS. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986; 315:1519-24.
5. Nestler JE, Clore JN, Blackard WG. Dehydroepiandrosterone: the "missing link" between hyperinsulinemia and atherosclerosis? FASEB J. 1992; 6:3073-5.
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