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Effects of raloxifene on insulin sensitivity, beta-cell function, and hepatic insulin extraction in normal
Manubai Nagamani1, Alexandria Szymajda, Vicken Sepilian
1Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-0587, USA. mnagaman@utmb.edu
Objective:
To investigate the effect of raloxifene on insulin sensitivity, beta-cell function, hepatic insulin clearance, and glucose tolerance in postmenopausal women.
Design:
Prospective study.
Setting:
University of Texas Medical Branch at Galveston, Texas.
Patient(S):
Twenty normal postmenopausal women.
Intervention(S):
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.
Main Outcome Measure(S):
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.
Result(S):
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.
Conclusion(S):
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.
