Lipid-induced beta-cell dysfunction in vivo in models of progressive beta-cell failure.

We determined the effect of 48-h elevation of plasma free fatty acids (FFA) on insulin secretion during hyperglycemic clamps in control female Wistar rats (group a) and in the following female rat models of progressive beta-cell dysfunction: lean Zucker diabetic fatty (ZDF) rats, both wild-type (group b) and heterozygous for the fa mutation in the leptin receptor gene (group c); obese (fa/fa) Zucker rats (nonprediabetic; group d); obese prediabetic (fa/fa) ZDF rats (group e); and obese (fa/fa) diabetic ZDF rats (group f). FFA induced insulin resistance in all groups but increased C-peptide levels (index of absolute insulin secretion) only in obese prediabetic ZDF rats. Insulin secretion corrected for insulin sensitivity using a hyperbolic or power relationship (disposition index or compensation index, respectively, both indexes of beta-cell function) was decreased by FFA.

Post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial on the effects of three years of raloxifene treatment on glycemic control and cardiovascular disease risk factors in women with and without type 2 diabetes.

Background: The long-term effects of the selective estrogen-receptor modulator raloxifene hydrochloride on glycemic control and markers of cardiovascular disease risk in postmenopausal women with type 2 diabetes mellitus are unknown.

Objective: The aim of this analysis was to compare the effects of 3-year treatment with raloxifene 60 mg/d versus placebo on glycemic control and markers of cardiovascular disease risk in osteoporotic postmenopausal women with and without type 2 diabetes.

Methods: In this analysis, we included women from the Multiple Outcomes of Raloxifene Evaluation trial (a multicenter, double-masked trial) who were randomized to receive raloxifene 60 mg/d (n = 2557) or placebo (n = 2576).

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years.

Objective: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known.