SKELETAL FAT IN ADOLESCENTS AT RISK FOR T2 DIABETES

Ut Southwestern Medical Center, Dallas TX

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is one of the most important public health issues affecting the United States. The prevalence of obesity has been steadily increasing since the 1970's and a sharp increase has occurred in the past 10 years. The obesity epidemic is present in both sexes and across all racial, ethnic, and socioeconomic groups in the United States. Obesity is linked to several health problems such as diabetes, hypertension, and heart disease. Obesity predisposes to insulin resistance (IR), and insulin resistance is a known risk factor for diabetes and cardiovascular disease in children and adults. The ability of insulin to stimulate glucose uptake into tissues varies greatly among individuals. The tissues of insulin-resistant individuals have a diminished ability to respond to insulin. One proposed mechanism for insulin resistance in obese patients is abnormal glucose metabolism in skeletal muscle due to accumulation of intracellular lipids. Thus far, there is no consensus on when to test obese patients for insulin resistance and how best to test them. Current laboratory testing includes fasting insulin levels, fasting blood glucose levels, hemoglobin A1C, and lipid profiles. However, none of these modalities directly measures intracellular lipid content in skeletal muscle, which is involved in the pathogenesis of insulin resistance. Advances in magnetic resonance imaging (MRI) technology allow us to utilize magnetic resonance spectroscopy (MRS) to quantify extracellular and intracellular compounds, including intracellular lipid concentrations. Our hypothesis is that the intracellular lipid concentration is higher in subjects with obesity compared to non-obese controls, and it is higher in obese subjects with insulin resistance compared to obese subjects without insulin resistance. We hypothesize that magnetic resonance (MR) spectroscopy will prove to be a safe, non-invasive tool to identify adolescents at increased risk for developing insulin resistance before they show changes in serum glucose, insulin, or lipids and facilitate early intervention. The purpose of this project was to determine whether there is a difference in the intracellular lipid concentration of skeletal muscle as measured by magnetic resonance spectroscopy with the 7 tesla magnet in adolescent subjects with obesity, both with and without insulin resistance, and in non-obese age matched controls without insulin resistance. The aim was to determine whether there is a difference in the intracellular lipid concentration as measured by nuclear magnetic resonance spectroscopy with the 7 tesla magnet in subjects with obesity, both with and without insulin resistance, and in non-obese age matched controls without insulin resistance.