Race Adiposity Interactions Regulate Mechanisms Determining Insulin Sensitivity

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).

Study Overview

• Status: Completed
• Conditions: Insulin Sensitivity; Fat; Liver

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 126

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

African American and Caucasian Males and Females between 19-45 years old

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
African American Females; No intervention
African American Males; No intervention
Caucasian Females; No intervention
Caucasian Males; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hyperinsulinemic isoglycemic glucose clamp	5 years

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Barbara Gower, PhD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Fisher G, Tay J, Warren JL, Garvey WT, Yarar-Fisher C, Gower BA. Sex and race contribute to variation in mitochondrial function and insulin sensitivity. Physiol Rep. 2021 Oct;9(19):e15049. doi: 10.14814/phy2.15049.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2014
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 3, 2017

Study Record Updates

• Last Update Posted (Actual): July 16, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Hyperinsulinism; Hypersensitivity; Insulin Resistance
• Other Study ID Numbers: 2237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No