Insulin Sensitivity in Children with low Birth Weight

Louisiana State Univ Hsc New Orleans, New Orleans LA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Low birth weight is associated with impaired insulin sensitivity later in life. The relationship may be due to intrauterine growth retardation, which causes metabolic disorders and ultimately promotes diabetes mellitus, especially in genetically vulnerable individuals. However, the relationship, if present, is not well established in African Americans. Only one study has attempted to examine the relationships between low birth weight, ethnicity and insulin sensitivity in children under 14 years of age but, none during the critical period of obesity development (adiposity rebound at 7-9y). More importantly, mechanisms connecting low birth weight to impaired insulin sensitivity have yet to be identified. These mechanisms may originate in the intrauterine environment, be exacerbated in susceptible populations, and be further promoted by an early environment conducive to obesity. We propose that young African American children with low birth weight may be predisposed genetically and behaviorally to the early manifestation of subtle, nonsymptomatic metabolic abnormalities that work synergistically to create a childhood obesity phenotype. The metabolic abnormalities increasing the propensity to obesity and type 2 diabetes may originate earlier than previously proposed. In adults insulin sensitivity is correlated negatively with lipid depots in the skeletal muscle (intramyocellular lipids = IMCL) and in the liver long before the development of diabetes. Non-invasive techniques for examining the relationship of skeletal muscle and liver lipids to insulin sensitivity have not been applied to prepubertal African American or Caucasian youth with low birth weight. In this study we propose to examine the relationship of birth weight (low vs. normal) and ethnicity (African American vs. Caucasian) to insulin sensitivity in 7-9 year old African American and Caucasian children (with and without adjusting for total body fat). We will explore potential mechanisms of the impaired insulin sensitivity observed in 7-9 year old prepubertal children by examining the relationships between insulin sensitivity and ectopic fat deposition (triglyceride content in skeletal muscle and liver), abdominal fat, resting energy metabolism (REE and respiratory quotient [RQ]) and cardiovascular disease risk factors (lipid profiles and blood pressure). Insulin Sensitivity will be measured by Frequently Sampled Intravenous Glucose Tolerance Test (FSIGTT), triglyceride contents in skeletal muscle and liver by Nuclear Magnetic Resonance Spectroscopy (1H-MRS) and energy metabolism by ventilated hood indirect calorimetry. [unreadable] [unreadable]