All ETDs from UAB

Advisory Committee Chair

W Timothy Garvey

Advisory Committee Members

George Howard

Barbara A Gower

Douglas R Moellering

Timothy Mark Beasley

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Obesity is associated with elevated risk for morbidity and mortality and has become an epidemic both in the United States and around the world. Insulin resistance is essentially involved in the pathogenic process of cardiometabolic diseases in obese people, which involves defects in glucose production by the liver and insulin-stimulated glucose uptake and utilization by peripheral tissues. Insulin resistance appears at an early stage of life and is the first step in the development of cardiometabolic diseases. Long-term insulin resistance will induce metabolic syndrome and prediabetes and eventually will cause type 2 diabetes and cardiovascular diseases. Obesity may exacerbate insulin resistance and progression of cardiometabolic diseases. However, general adiposity explains only a minor portion of the variability in insulin resistance among non-diabetic individuals. A broad range of perturbations of the macronutrient intermediary metabolism contribute to the development of insulin resistance. The relationship between plasma acylcarnitine profiles and insulin resistance has been studied using primarily surrogate measures of insulin sensitivity, which is of limited accuracy. In our study, we were the first to assess the association between plasma acylcarnitine profiles and insulin sensitivity by the gold standard measure, the hyperinsulinemic-euglycemic clamp. The clamp quantifies total-body insulin action under the condition that the vast proportion of in vivo glucose uptake takes place in skeletal muscles. With about 70% of the adult population overweight or obese, it is not feasible to treat everyone with medical or surgical therapy. It is important to develop a risk assessment tool that can identify patients who can most benefit from weight loss interventions, rationally identify the best treatment modality and intensity, improve benefit-risk ratios, and optimize patient outcomes. Here, we developed a diabetes scoring system based on our newly developed cardiometabolic disease staging system (CMDS) to guide the selection of treatment modality and intensity for weight management in obese people. Body Mass Index is widely used as a population-based tool to assess adiposity. However, its performance on individual levels is limited, and it also fails to directly reflect risk for obesity-related comorbidities. We also developed a novel adiposity index to reflect both body adiposity and health risks.

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