All ETDs from UAB

Advisory Committee Chair

W Timothy Garvey

Advisory Committee Members

T Mark Beasley

Krista Casazza

Jose R Fernandez

Barbara A Gower

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Insulin resistance (IR) is central to the pathogenesis of cardiometabolic disorders. Early detection, along with appropriate interventions, is paramount to reduce the morbidity and mortality of IR-related diseases. The gold standard measurement for IR is the hyperinsulinemic-euglycemic clamp, which is markedly sophisticated for clinical evaluation but costly and invasive for clinical practice. Several alternative surrogate indicators of IR have been identified and used by clinicians, including insulin sensitivity indices derived from plasma glucose and insulin values, as well as other indicators that are independent of direct insulin measurements. In addition, lipid panel and lipoprotein subclass profile have emerged as markers of IR, and the cluster of abnormalities that define Metabolic Syndrome also have been used to predict IR and related outcomes in clinical settings. Race can confound the utility of IR indicators; however, there is no data to demonstrate which indicators may more accurately represent insulin dynamics and homeostasis in different populations. Although it is known that intervention strategies can improve IR, it is not clear whether the effect of interventions in insulin-related outcomes can be accurately captured by traditionally used methods. Thus, three specific aims were investigated in this project. First, we determined the predictability of commonly used insulin sensitivity indices compared to the hyperinsulinemic-euglycemic clamp in European Americans (EA) and African Americans (AA), demonstrating differences between groups and that the most reliable indices were the Matsuda index and the simple index assessing insulin sensitivity using oral glucose tolerance test. Second, we evaluated the relationship between IR and lipoprotein subclass profile between EAs and AAs, showing an association between IR and lipid subclass profile beyond the conventional lipid panel. Third, we determined changes in lipoprotein subclass profile and insulin sensitivity after a short-term very low calorie diet, verifying concomitant favorable changes in the Matsuda index and lipoprotein subclass profile after the intervention. Taken together, our findings demonstrated that the Matsuda index and lipoprotein subclass profile are appropriate markers for identifying and monitoring IR in a mixed-race population during regular screening and during diet-related interventions. Our work supports the need for race-specific tools in the evaluation of insulin-related outcomes.

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