Effects of raloxifene on insulin sensitivity, β-cell function, and hepatic insulin extraction in normal postmenopausal women

Abstract

To investigate the effect of raloxifene on insulin sensitivity, beta-cell function, hepatic insulin clearance, and glucose tolerance in postmenopausal women. Prospective study. University of Texas Medical Branch at Galveston, Texas. Twenty normal postmenopausal women. An oral glucose tolerance test (OGTT) was performed on all study participants before and after treatment with 60 mg of raloxifene daily for 3 months. Blood samples were obtained at baseline and 1, 2, and 3 hours after 75-g oral glucose administration for measurement of glucose, insulin, proinsulin, and c-peptide levels. Insulin tolerance test (ITT) and euglycemic clamp studies were also performed before and after treatment. Glucose and insulin area under curve (AUC) were calculated. The c-peptide to insulin ratio was determined to assess hepatic clearance of insulin. The homeostasis model assessment (HOMA) was used to calculate the index of insulin resistance (HOMA-IR) and beta-cell function (HOMA-%beta). Insulin sensitivity was assessed by insulin tolerance test and glucose infusion rate (GIR) during euglycemic clamp studies. There was no change in fasting or AUC glucose levels. Fasting insulin levels were not statistically significantly different, but the insulin levels at 2 hours and insulin AUC were higher after treatment compared with before treatment. Proinsulin, c-peptide levels, and HOMA-%beta did not change. The c-peptide to insulin molar ratio was statistically significantly decreased after treatment. There was no change in insulin sensitivity. These results indicate that raloxifene has no adverse effect on insulin sensitivity or glucose tolerance, and it does not affect beta-cell function. After glucose load, raloxifene decreases hepatic insulin extraction and thus conserves insulin, which may be beneficial to patients with decreased beta-cell reserve or those predisposed to type 2 diabetes.