All ETDs from UAB

Advisory Committee Chair

Barbara Gower

Advisory Committee Members

Jose Fernandez

Jamy Ard

John Clancy

Timothy Garvey

Document Type

Dissertation

Date of Award

2006

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

African Americans (AA) exhibit greater insulin responses following either an oral or intravenous glucose challenge relative to their European American (EA) counterparts. The etiology of this difference is not fully understood nor has it been confirmed with a more physiologically relevant mixed meal. Insulin secretion is regulated by a variety of factors. Significant among these are the enteric peptides glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The role of the incretin system in the ethnic differences in post challenge insulinemia has received little attention. Hence, the purpose of the study was two-fold. First, determine whether AA have higher fasting concentrations of GLP-1 and/ or GIP relative to EA and determine the contribution of these differences to the greater acute insulin response (AIRg) of AA following an intravenous glucose challenge. Second, determine whether postprandial concentrations of insulin are higher among AA relative to EA and assess the role of postprandial GLP-1 and GIP concentrations in this difference. Sixty-one children were recruited and provided consent to participate in two overnight stays during which an intravenous glucose tolerance test and a mixed meal tolerance test were administered. AA had higher AIRg, lower insulin sensitivity, higher fasting insulin, and lower basal insulin clearance compared to their EA counterparts. Fasting concentrations of GLP-1 and GIP were not different by ethnicity and were not related to AIRg. AA had significantly higher postprandial insulin responses (P<0.01) relative to EA. AA had lower postprandial GLP-1 responses relative to EA (P=0.04). GLP-1 responses were not ii associated with insulin responses (P>0.05). However, early GIP responses were significantly associated with the early insulin response. The early postprandial insulin response remained significantly higher in AA after accounting for differences in maturation, insulin sensitivity, and the early GIP response (P<0.05). However, after accounting for insulin clearance, ethnicity was no longer an independent predictor of the early insulin response (P=0.53). In conclusion, incretins are unlikely to factor in the higher relative insulin responses of AA. The importance of lower GLP-1 among AA remains to be determined. Lower insulin clearance among AA may explain a large portion of their postprandial hyperinsulinemia.

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