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

Mayo Clinic College of Medicine, 200 1st Street SW, Rochester, MN 55905, USA.
Diabetes (Impact Factor: 8.1). 03/2007; 56(3):753-66. DOI: 10.2337/db06-1504
Source: PubMed


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.

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    • "Moreover, there are discrepancies concerning the effect of DHEA on glucose homeostasis in both healthy individuals and diabetic ones. There are reports showing a negative correlation between serum DHEA and insulin resistance [21] [22], while others do not show such a correlation [23]. Therefore, studies (both in vitro and in vivo) were undertaken: (i) to elucidate the mechanisms of dexamethasone and DHEA on glucose synthesis in kidney-cortex tubules grown in primary cultures and (ii) to investigate the influence of DHEA on gluconeogenesis, insulin sensitivity and plasma lipid profile in both control and dexamethasonetreated rabbits. "
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    ABSTRACT: In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several dexP-evoked effects, it seems likely, that its supplementation might be beneficial to patients treated with glucocorticoids.
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    • "However, in recent studies the DHEA administration did not reduce insulin resistance (Talaei et al. 2010) and did not improve the insulin secretion, insulin action or the pattern of postprandial glucose metabolism (Basu et al. 2007). In the type 2 diabetes mellitus lower levels of the DHEA-S have been reported (Zietz et al. 2001; Tagawa et al. 2002). "
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    ABSTRACT: Dehydroepiandrosterone (DHEA) is believed to exert, besides others, positive effects on the insulin resistance or its secretion and glucose metabolism. There are several reports dealing with the DHEA levels and its effects in the type 2 diabetes mellitus, but less information is available on the type 1 diabetic subjects. Recently, a report dealing with the lack of the age-dependent decline of the DHEA levels in the type 2 diabetic subjects was published. The aim of the present study was to answer the question whether a comparable change in the aging pattern of the DHEA and its sulphate could be detected in the type 1 diabetes mellitus. The data regarding the DHEA and dehydroepiandrosterone sulphate (DHEA-S) concentrations in the serum obtained from 116 patients with the type 1 diabetes mellitus and 259 controls were gathered from the database of the Institute of Endocrinology (Prague, Czech Republic). No significant differences in the level of the DHEA-S were found between the type 1 diabetics and controls either in men or women. However, lower DHEA levels were found in the type 1 diabetic women, but not in men. The age-dependent declines of both the DHEA and DHEA-S were similar to those in controls. In contrast to the type 2 diabetes, the levels of DHEA-S in the type 1 diabetic patients were practically identical with those in controls. In contrast to men, in women, the DHEA basal levels were lower than those seen in controls. The age dependence of both hormones followed the pattern of the decline in controls.
    Full-text · Article · Apr 2012 · Endocrine regulations
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    • ". (Continued ) Authors Dose Findings Serious side effects Morales et al. (1994) Morales et al. (1998) Nair et al. (2006) Basu et al. (2007) Same study Nestler et al. (1988) Percheron et al. (2003) Roberts and Fauble (1990) Sun et al. (2002) Van Thiel et al. (2005) Villareal and Holloszy (2004) Von Muhlen et al. (2008) Welle et al. (1990) Wolf et al. (1997) Wolkowitz et al. (1997) Yen et al. (1995) Yen et al. (1995) "
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    ABSTRACT: A major achievement from 500 million years of evolution is the establishment of a high secretion rate of dehydroepiandrosterone (DHEA) by the human adrenal glands coupled with the indroduction of menopause which stops secretion of estrogens by the ovary. Cessation of estrogen secretion at menopause eliminates the risks of endometrial hyperplasia and cancer which would result from non-opposed estrogen stimulation during the post-menopausal years. In fact, from the time of menopause, DHEA becomes the exclusive and tissue-specific source of sex steroids for all tissues except the uterus.
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