DHEA-PC Slows the Progression of Type 2 Diabetes (Non–Insulin-Dependent Diabetes Mellitus) in the ZDF/Gmi-fa/fa Rat

Abstract

The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is complex and development is manifested by initial insulin resistance coupled with elevated insulin levels in the early diabetic state with concomitant increases in circulating levels of glucose and triglycerides. This is followed by a decline in insulin levels due to pancreatic exhaustion. Our results show that administration of DHEA-PC, a phosphocholine conjugate of dehydroepiandrosterone (DHEA), delayed the development of NIDDM symptoms and the onset of type 2 diabetes in the ZDF/Gmi-fa/fa rat model. The treatment consisted of weekly implantation of subdermal osmotic infusion pumps in the rats starting at 6 weeks of age (n = 5 animals per group). For the first three weeks the pumps delivered 6 mg/day/rat followed by 12 mg/day/rat for 1 week (control group pumps delivered only carrier vehicle) after which the pumps were removed. Plasma was collected weekly from day 0 through day 58, and glucose, triglycerides, cholesterol, insulin, IGF-1, and IGF-BP3 levels were measured. Data were analyzed by two-way ANOVA. Following 3 weeks of treatment with DHEA-PC, plasma glucose levels in the treated group remained low, 150+/-9 mg/dL, while the levels in the control animals steadily increased to 320+/-100 mg/dL (p < 0.05). After the DHEA-PC treatment ended, plasma glucose plateaued for 10 days and then took 25 days to reach the level in the control animals (p < 0.05). After 2 weeks of DHEA-PC treatment, plasma triglyceride levels in the treated group remained low, 85+/-24 mg/dL, while the level in the control rats increased to 180+/-35 mg/dL (p < 0.05). After the treatment was terminated triglyceride levels in the treated group increased to control levels within 2 days. Insulin, IGF-1, IGF-BP3, cholesterol, body weight, and food consumption were not changed by DHEA-PC treatment (p < 0.05). Therefore, the delay of increases in plasma glucose and triglycerides, caused by DHEA-PC, was not the result of differences in caloric intake, increased insulin, or increased IGF-1 levels. The data suggest that DHEA-PC delayed the onset of the two most important parameters of NIDDM, namely hyperglycemia and hypertriglyceridemia. (ZDF/Gmi-fa/fa rats and their care was supplied by contract with Genetic Models Inc., Indianapolis, IN.).

Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study

“…DHEA is available as a health food supplement in the USA, but previous literature on the effects of supplemental DHEA on glucose metabolism in healthy humans is controversial [ 3 – 6 ]. Evidence from animal studies indicates that DHEA treatment could result in increased insulin-induced glucose uptake in rat models of type 2 diabetes and moderate the severity of diabetes [ 7 , 8 ]. Along the same lines, a randomised controlled trial (RCT) of elderly women and men with an age-related decrease in DHEA showed that DHEA replacement reduced abdominal fat and improved insulin sensitivity [ 9 ].…”

Association between alcohol consumption and serum dehydroepiandrosterone sulphate concentration in men with Type 2 diabetes: a link to decreased cardiovascular risk

“…Decreased serum concentrations of DHEA may contribute to insulin resistance, while DHEA supplementation appears to improve insulin sensitivity and may slow progression of Type 2 diabetes [10,11]. In addition, DHEA is considered to have a protective effect against coronary artery disease [12], and was found to inhibit atherosclerosis and plaque progression in an experimental model [13].…”

Evidence for the Biosynthesis of DHEA from Cholesterol by First-Trimester Human Placental Tissue: Source of Androgens

“…Amongst its postulated biologic roles, DHEA can inhibit glucose-6-phosphate dehydrogenase [21], reverse insulin resistance associated with glucocorticoid treatment [22] and, more importantly, in pregnancy through its immunomodulatory function by potentiation of lymphocyte activation [23]. DHEA has also been shown to have anti-atherogenic, anti-obesity and anti-diabetes activity [24,25]. A negative correlation occurred between serum insulin and DHEA-S and experimental acute hyperinsulinemia resulted in prompt decline in DHEA and DHEA-S levels [26].…”