Advisory Committee Chair
Barbara Gower
Advisory Committee Members
Jamy Ard
Donna Arnett
Jose Fernandez
Fernando Ovalle
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) School of Health Professions
Abstract
Identification and characterization of ethnic differences in insulin dynamics, insulin sensitivity (SI), and inflammation may shed light on the greater risk for type 2 diabetes in African Americans (AA), relative to European Americans (EA). Ideally, such studies should take into account the potential confounding roles of adiposity, fat distribution, genetic background, and socioeconomic status (SES). The objectives of this study were, 1) to evaluate ethnic differences in insulin dynamics in AA and EA children and adults using robust measures of insulin secretion and clearance; 2) to identify the contributions of genetic admixture and SES to insulin dynamics; 3) to examine ethnic differences in markers of inflammation (CRP, IL6, TNF-α, and TNFRII) in AA and EA adults; and 4) to examine the association of markers of inflammation with SI after adjusting for measures of adiposity and fat distribution. Measures of SI and insulin dynamics were obtained via intravenous glucose tolerance test and mathematical modeling. Body composition was assessed with dual-energy X-ray absorptiometry, and fat distribution with computed tomography scanning. Subjects were genotyped for African and European genetic admixture. In children, African genetic admixture was independently associated with greater first-phase insulin secretion, and tended to be associated with lower insulin extraction. Total body fat masked the effect of genetic admixture on firstphase secretion. Children with lower SES have greater total insulin secretion. In adults, iii AA vs. EA women had greater early-phase β-cell responsivity, compensated by lower total-β-cell responsivity, and similar insulin extraction. AA had lower TNF-α and TNFRII, relative to EA. Significant independent associations of SI with IL6 and TNFRII were present, after adjusting for confounding variables. The greater first phase secretion in AA may serve as a risk factor for development of type 2 diabetes, by facilitating early β-cell exhaustion. While this study highlights the independent association between SI and inflammation, it is unclear whether the role of inflammation in chronic disease is similar in AA and EA. Future studies should aim at understanding the physiologic significance of greater first phase insulin secretion, and lower TNF-α and TNFRII, in AA with respect to implication for chronic disease.
Recommended Citation
Phadke, Radhika P., "Insulin Dynamics In African Americans And European Americans: Mechanistic Aspects, And Association With Inflammation" (2007). All ETDs from UAB. 3783.
https://digitalcommons.library.uab.edu/etd-collection/3783