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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Available from: Michael D Jensen, Jul 16, 2014
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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.
    Endocrine regulations 04/2012; 46(2):67-71. DOI:10.4149/endo_2012_02_67
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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. Intracrinology, a term coined in 1988, describes the local formation, action and inactivation of sex steroids from the inactive sex steroid precursor DHEA. Over the past 25 years most, if not all, the genes encoding the human steroidogenic and steroid-inactivating enzymes have been cloned and sequenced and their enzymatic activity characterized. The problem with DHEA, however, is that its secretion decreases from the age of 30 years and is already decreased, on average, by 60% at time of menopause. In addition, there is a large variability in the circulating levels of DHEA with some post-menopausal women having barely detectable serum concentrations of the steroid while others have normal values. Since there is no feedback mechanism controlling DHEA secretion within 'normal' values, women with low DHEA will remain with such a deficit of sex steroids for their remaining lifetime. Since there is no other significant source of sex steroids after menopause, one can reasonably believe that low DHEA is involved, in association with the aging process, in a series of medical problems classically associated with post-menopause, namely osteoporosis, muscle loss, vaginal atrophy, fat accumulation, hot flashes, skin atrophy, type 2 diabetes, memory loss, cognition loss and possibly Alzheimer's disease. A recent randomized, placebo-controlled study has shown that all the signs and symptoms of vaginal atrophy, a classical problem recognized to be due to the hormone deficiency of menopause, can be rapidly improved or corrected by local administration of DHEA without systemic exposure to estrogens. In addition, the four domains of sexual dysfucntion are improved. For the other problems of menopause, although similar large scale, randomized and placebo-controlled studies usually remain to be performed, the available evidence already strongly suggests that they could be improved, corrected or even prevented by exogenous DHEA. In men, the contribution of adrenal DHEA to the total androgen pool has been measured at 40% in 65-75-year-old men. Such data stress the necessity of blocking both the testicular and adrenal sources of androgens in order to achieve optimal benefits in prostate cancer therapy. On the other hand, the comparable decrease in serum DHEA levels observed in both sexes has less consequence in men who continue to receive a practically constant supply of testicular sex steroids during their whole life. In fact, in men, the appearance of hormone-deficiency symptoms common to women is observed at a later age and with a lower degree of severity. Consequently, DHEA replacement has shown much more easily measurable beneficial effects in women. Most importantly, despite the non-scientific and unfortunate availability of DHEA as a food supplement in the United States, a situation that discourages rigorous clinical trials on the crucial physiological and therapeutic role of DHEA, no serious adverse event related to DHEA has ever been reported in the world literature (thousands of subjects exposed) or in the monitoring of adverse events by the FDA (millions of subjects exposed), thus indicating, as expected from its known physiology, the excellent safety profile of DHEA. With today's knowledge, one can reasonably suggest that DHEA offers the promise of a safe and efficient replacement therapy for the multiple problems related to hormone deficiency after menopause without the risks associated with estrogen-based or any other treatments.
    Progress in brain research 01/2010; 182:97-148. DOI:10.1016/S0079-6123(10)82004-7 · 2.83 Impact Factor
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    ABSTRACT: This chapter focused on rat models of genetic hypertension since (1) they are widely used and (2) they allow renal function and especially RBF to be measured with a relative accuracy. The various techniques used to obtain RBF (microspheres, pulsed Doppler, ultrasonic transit time, and laser Doppler methods) are presented with their major advantages and limitations. The most frequently used experimental conditions are described since they largely influence the data. Finally, the results obtained in various strains of genetically hypertensive rats are summarized with a special emphasis on the existence of preglomerular vasoconstriction in most of these strains, which makes them close to a “multiple, micro-Goldblatt renal hypertension”.
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