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Advisory Committee Chair

Edmond K Kabagambe

Advisory Committee Members

Donna K Arnett

Gary R Cutter

Frank A Franklin

Fernando Ovalle

Document Type

Dissertation

Date of Award

2011

Degree Name by School

Doctor of Public Health (DrPH) School of Public Health

Abstract

Both animal and human models suggest that fenofibrate, a medication widely prescribed to decrease triglycerides, also decreases insulin resistance. In the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort, which included 780 individual who took 160 mg of micronized fenofibrate daily for three weeks, fenofibrate was found to decrease HOMA-IR by -0.24 units, (95% CI: -0.32, -0.14), insulin by -0.65 uU/mL (95% CI: -0.97, -0.34) and glucose by 2.46 mg/dL (95% CI: -2.51, -2.42). In a meta-analysis of 19 studies that included 1,297 individuals without diabetes and 196 individuals with diabetes treated with fenofibrate for three weeks or longer, fenofibrate was found to decrease HOMA-IR by 0.46 units (95% CI: -0.70, -0.22), insulin by 1.23 uU/mL (95% CI: -2.37, -0.09) and glucose concentrations by 2.86 mg/dL (95% CI: -5.01, -0.71). Change in adiponectin is a potential mediator of the relationship between fenofibrate use and insulin resistance. The relationship between fenofibrate use, changes in adiponectin concentrations and change in HOMA-IR was examined in the GOLDN cohort and significant relationships were found between fenofibrate use and change in adiponectin but not between change in adiponectin and change in HOMA-IR. Thus, changes in adiponectin do not mediate the relationship between fenofibrate use and change in HOMA-IR. These studies provide support for the hypothesis that fenofibrate use decreases insulin resistance. However, this relationship is not mediated by changes in adiponectin concentrations. Future studies should examine these relationships using a control group so the impact of fenofibrate use on changes in insulin resistance can be more accurately quantified. Further research is also needed to determine if the observed changes in insulin resistance are clinically meaningful.

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