Defense Date

2011

Document Type

Thesis

Degree Name

Master of Pharmaceutical Sciences

Department

Pharmaceutical Sciences

First Advisor

Kai I. Cheang

Abstract

Introduction: Obese women are predisposed to greater risks of insulin resistance and compensatory hyperinsulinemia. Likewise, African-Americans, appear to be inherently insulin resistant and hyperinsulinemic even after controlling for obesity. Hyperinsulinemia has been attributed to insulin resistance and a compensatory insulin hyper-secretion by the pancreas, as well as decreased insulin clearance, notably in obesity. Pharmacological agents that may worsen insulin resistance/hyperinsulinemia in obese women is of clinical relevance. Previous data from our group suggested that combined oral contraceptives (COCs) may worsen insulin sensitivity particularly in obese women, but limited information on insulin clearance is available in obese women or African-American women. Objective: The objective of the study is to evaluate and compare the effect of a COC containing ethinyl estradiol and norgestimate on insulin clearance among lean and obese pre-menopausal women and among African-American obese vs. non African-American obese women. Method: Plasma insulin clearance was calculated from plasma insulin concentrations, following frequently sampled intravenous glucose tolerance test. Changes in insulin clearance, during six months of COC use were analyzed by repeated measures analysis. Result: Six months of COC use showed no significant change in insulin clearance in all women (p=0.3713). Furthermore, there were no divergent effects on insulin clearance among lean (n=13) and obese (n=14) women (p=0.6703) and among African-American obese (n=7) and non African-American obese (n=7) women (p=0.0957). Changes in insulin clearance, following six months of COC administration was found to be positively correlated with changes in insulin sensitivity (r=0.385, p=0.0099) and negatively correlated with changes in acute insulin response to glucose (r=-0.432, p=0.0034). Discussion: In the present study, COC administration did not show any differential effect on insulin clearance in lean vs. obese women. Future studies evaluating the effects of hormonal agents on insulin-glucose dynamics may focus on mechanisms of hormone-mediated insulin resistance and compensatory hyperinsulinemia rather than insulin clearance.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

September 2011

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