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Obesity

Cardiovascular Risks in African-American Obese Adolescents

Obesity is a national health problem of the highest urgency. The overwhelming majority of obese adults had their excessive weight gain begin during childhood. In all age groups, obesity has been associated with several chronic conditions, including type 2 diabetes mellitus (T2D), hypertension (HTN) and increased risk for cardiovascular disease (CVD). It has been suggested that African-Americans (AA) have a higher risk for obesity, T2D and CVD in all ages. Obesity and associated co-morbidities are very costly conditions in the United States (U.S.). Efforts for a successful prevention or early intervention are very cost-effective. The purpose of this study is to determine if a lifestyle intervention (LSI) will be successful in controlling weight and decreasing risk factors for T2D and CVD. Two hundred AA children between 8-12 years of age will be recruited and randomized to either lifestyle intervention group (LSIG) or intervention comparison group (ICG).The LSIG will undergo an intensive approach, including nutritional, behavioral management, exercise, and family education. The ICG will receive conventional standardized care including dietary and exercise counseling 4 times a year.All children will undergo complete clinical, nutritional, cardiovascular, and metabolic evaluation at baseline and yearly thereafter for three years. We will determine if LSI leads to decreased BMI and reduced risk factors for T2D and CVD. This study will also enhance the understanding of the natural history and pathogenesis of obesity, T2D and CVD in AA children. If our intervention proves to have beneficial impact on the above named conditions, our results can be immediately extrapolated into practical clinical venues with relatively low cost.

Hypothesis:Lifestyle changes in AA children at risk for diabetes and cardiovascular disease will result in weight loss, improvement of insulin resistance, preservation of pancreatic b-cell function, and reduction of T2D and CVD risk factors.

Specific Aims:
1)To recruit a cohort of 200 obese AA children at high risk for T2D and CVD, including hyperinsulinemia, insulin resistance, and family history of diabetes or abnormal lipid metabolism.
2)To establish a partnership with physicians and institutions involved in the care of AA children in the Greater Memphis Area (GMA) for identification, referral and follow-up of obese individuals with increased risk for T2D and CVD.
3)To determine if randomization into LSI, including promotion of a healthier diet and increased physical activity, will induce and sustain a reduction in relative weight loss in obese AA children.
4) To determine if randomization into LSI improves insulin resistance and pancreatic B-cell function.
5)To determine if LSI will improve exercise tolerance and reduce known cardiovascular risk factors.

George Burghan, MD, principal investigator

Pedro Velasquez-Mieyer, MD, co-investigator
Patricia Cowan, PhD, co-investigator

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