All ETDs from UAB

Advisory Committee Chair

Barbara A Gower

Advisory Committee Members

Betty E Darnell

Jose R Fernandez

Robert A Oster

Cynthia K Sites

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Background: Evidence suggests that intrauterine exposure to elevated glucose concentrations may be a mediating factor in prenatal programming of offspring disease risk. However, studies examining the effects of maternal glucose concentration on measures of body composition, insulin sensitivity, and ß-cell response in prepubertal children are limited. Therefore, the objective of this study was to determine the associations of maternal glucose concentration with children's fat mass, insulin sensitivity, and ß-cell response using robust and physiologic measures. Methods: Participants were 40 children aged 5-10 years. Children's insulin sensitivity index (SI) and measures of basal, static, dynamic, and total ß-cell response were determined by mathematical modeling using insulin, glucose, and c-peptide values following a liquid meal tolerance test. Dual-energy X-ray absorptiometry was used for the determination of children's total fat mass, total lean mass and percent total body fat. Maternal glucose concentration was determined following a 50-g, 1-hour oral glucose challenge test at 24-28 weeks' gestation and ranged from 75-229 mg/dl. Independent associations of maternal gestational glucose with children's total fat mass, SI, and ß-cell response indices were determined by multiple linear regression analyses. Results: Maternal gestational glucose was significantly, positively associated with children's fat mass independent of energy intake, physical activity, total lean mass, and socioeconomic status (Parameter Estimate ± SE: 1.18 ± 0.19, P<0.001). A significant, inverse association was observed for maternal gestational glucose with children's SI independent of ethnicity, body composition, and socioeconomic status (Parameter Estimate ± SE: -0.87 ± 0.23, P<0.01). Maternal gestational glucose was significantly and positively associated with basal ß-cell response, static ß-cell response, and basal insulin secretion rate independent of body composition and SI (Parameter Estimate ± SE: 0.63 ± 0.26, 1.04 ± 0.43, & 0.62 ± 0.28, respectively, P<0.05 for all). Conclusions: These results suggest that maternal gestational glucose affects prenatal programming of children's adiposity, insulin sensitivity, and ß-cell response, which is evident at 5-10 years of age. Fetal programming of insulin sensitivity and ß-cell function appears to occur at both the level of the pancreas and the level of insulin target tissues such as skeletal muscle and liver.

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