Effects of raloxifene on insulin sensitivity, beta-cell function, and hepatic insulin extraction in normal postmenopausal women.
OBJECTIVE
To investigate the effect of raloxifene on insulin sensitivity, beta-cell function, hepatic insulin clearance, and glucose tolerance in postmenopausal women.


METHODS
Prospective study.


METHODS
University of Texas Medical Branch at Galveston, Texas.


METHODS
Twenty normal postmenopausal women.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nagamani
Manubai
M
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-0587, USA. mnagaman@utmb.edu
Szymajda
Alexandria
A
Sepilian
Vicken
V
Urban
Randall J
RJ
Gilkison
Charles
C
D001786:Blood Glucose / Q000187:drug effects*; D002096:C-Peptide / Q000097:blood; D005215:Fasting / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000378:metabolism*; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D012016:Reference Values; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; D020849:Raloxifene Hydrochloride; D020845:Selective Estrogen Receptor Modulators; C517652:hemoglobin A1c protein, human