Race Adiposity Interactions Regulate Mechanisms Determining Insulin Sensitivity

Study Overview
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Brief Summary
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This research study will examine how ethnic/racial background, body composition (%body fat), and the location of body fat affect the ability of the hormone insulin to promote uptake of blood sugar in persons who are 19 to 45 years of age. When insulin is ineffective in promoting blood sugar uptake, this condition is termed insulin resistance. Insulin resistance plays a major role in the development of chronic metabolic diseases (such as type 2 diabetes, cardiovascular disease, and cancer), many of which differ with race. Previous studies suggest that insulin resistance is higher in African-Americans (AA) vs. European-Americans (EA). However, results from these studies remain unclear due to different testing measures used for insulin resistance as well as differences in body fat between individuals. Results from this research study may help explain why insulin resistance differs with genetic background and may guide development of personalized treatment strategies with implications for several chronic metabolic diseases (e.g., type 2 diabetes, cardiovascular disease, and cancer).

Detailed Description
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Insulin resistance plays a major role in the etiology of chronic metabolic diseases, many of which differ with race/ethnicity. Previous studies using mainly indirect methods suggest that insulin sensitivity is lower in AA vs. EA. Our preliminary data using the reference standard glucose clamp indicate that in lean individuals, insulin sensitivity is lower among AA, while in obese individuals, insulin sensitivity is higher among AA. We hypothesize that this race/body mass index (BMI) interaction may be explained in part by significantly lower visceral and hepatic fat accumulation in AA. Conversely, based on our preliminary data, we hypothesize that inherently greater oxidative stress impairs insulin sensitivity even in AA, explaining lower insulin sensitivity in lean AA vs. EA. We propose to test these hypotheses by prospectively comparing skeletal muscle and hepatic insulin sensitivity in healthy lean, overweight, and obese AA and EA using the hyperinsulinemic isoglycemic glucose clamp. Analysis of ancestral genes will permit simultaneous assessment of the contribution of ancestry to main outcomes.

Official Title
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Race Adiposity Interactions Regulate Mechanisms Determining Insulin Sensitivity

Conditions
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Insulin Sensitivity, Fat; Liver

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: African American or Caucasian Body Mass Index 19-45 Do NOT have diabetes Exercise less than 2 hours per week Are willing to travel to UAB for 2 screens and 4 testing visits Exclusion Criteria: Diabetes Any major medical conditions or medications that interfere with study outcomes

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| African American Females<br>No intervention | |
| African American Males<br>No intervention | |
| Caucasian Females<br>No intervention | |
| Caucasian Males<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperinsulinemic isoglycemic glucose clamp |  | 5 years |