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Autonomic Function

Autonomic Function and Insulin Dynamics in Childhood Obesity

Obesity is a major risk factor for several chronic diseases and has reached epidemic proportions throughout the world. Unfortunately, obesity usually begins and worsens in the pediatric age group and those who become obese in childhood stay obese as adults. Hyperinsulinism, insulin resistance, and obesity are linked through reciprocal control mechanisms, although the debate continues on which comes first. Autonomic nervous system function is associated with insulin dynamics and obesity in adults.

The purpose of this study is to find the relationship between insulin and autonomic nervous function in obese children.

The specific aims of this research are:

1. To assess and categorize insulin dynamics (insulin hypersecretion vs. insulin resistance) in obese children.
2. To examine demographic differences in the expression of insulin dynamics in obese children.
3. To examine correlations between sympathetic vs. parasympathetic tone, and insulin dynamics in obese children. This diagnostic trial is a cross-sectional study to assess and categorize insulin dynamics and examine correlations with autonomic tone in obese children, age 0-17 years, who have met the inclusion and exclusion criteria. The subjects will undergo the three-hour OGTT with simultaneous Holter monitoring to obtain autonomic (AFT) data and will be photographed at the back of the neck for grading of acanthosis nigricans. The selected metabolic parameters will be correlated with each demographic parameters, insulin dynamics, and AFT data.

Robert H. Lustig, MD, principal investigator

Oxidative Stress and Peripheral Nerve Function in Type 1 Diabetes

A large body of evidence has indicated that the damaging effects of hyperglycemia (high glucose) are linked to interactions between glucose and oxygen metabolism or “oxidative stress”. Oxygen provides energy and sustains life, and most of the end products of this process, such as water and carbon dioxide, are harmless. Some of the end products of oxygen metabolism, commonly designated oxygen free radicals, have unpaired electrons, which are unstable and toxic to the body. Glucose generates free radicals both in vitro (in a test tube) and in vivo (in an animal) which when excessive damages those tissues (kidneys, eyes, nerves and pancreas) vulnerable to the adverse effects of chronic hyperglycemia. This theory has been proven correct in experimental animals but has been hard to test in human diabetes where complications develop very slowly over time and interventions are difficult to evaluate.

The present research will focus on the effect of diabetes and oxidative stress on beta cell function (insulin secretion) in early Type 1 diabetes. This problem is clinically important because the preservation of residual beta cell function during the first five years of diabetes leads to improvement in glycemic control (lower sugars) and has a long-lasting benefit with respect to the prevention of complications.

The aims of these studies are 1) to gather information from healthy individuals to define normal values for test that measure specific nervous system functions, and 2) to determine whether chemical measures of oxidative stress relates to nerve function in diabetes. Chemical test on blood and urine samples and autonomic function tests will be used. These tests evaluate the function of nerves going to the heart, blood vessels, skin, and sweat glands. These nerves control important bodily functions and are damaged in diabetes. The procedures used to assess nervous system function in these studies will include measuring a) heart rate changes during deep breathing, b) heart rate changes while breathing into a tube at a constant pressure, c) ability to sweat, and d) ability to detect changes in temperature stimulus.

Robert Hoeldtke, MD; Ann Cashion, PhD, and Sandra Holmes, PhD candidate—investigators.