Obesity is the consequence of an imbalance between energy intake and energy expenditure. Recent studies have suggested that the sympathetic nervous system (SNS) may be an important determinant of the rate of energy expenditure in man. Indirect assessments of the sympathetic nervous activity in Pima Indians have recently shown impaired SNS-mediated energy expenditure in this obesity-prone population. We plan to perform direct microelectrode nerve recording of the sympathetic innervation of the lower leg to directly assess SNS activity and examine its potential role in the regulation of metabolic rate and the development of obesity. Measurements will be performed in the basal state, in response to glucose feeding (75 g OGTT) and in response to glucose/insulin infusion. These studies also will help to disassociate the effect of insulin and glucose on the stimulation of SNS activity. Energy expenditure measurements will be performed over 24 hours in the respiratory chamber and for 2 1/2 hours before and during the euglycemic clamp. Results also will be used to determine possible racial differences between Pimas and Caucasians, since the risk for obesity is markedly different in these populations. To exclude the possibility of a "normal" SNS activity but with peripheral resistance to the action of norepineprine, we will perform adrenergic stimulation by isoproterenol to measure peripheral adrenergic sensitivity.

Obesity is the consequence of an imbalance between energy intake and energy expenditure. Recent studies have suggested that the sympathetic nervous system (SNS) may be an important determinant of the rate of energy expenditure in man. Indirect assessments of the sympathetic nervous activity in Pima Indians have recently shown impaired SNS-mediated energy expenditure in this obesity-prone population. We plan to perform direct microelectrode nerve recording of the sympathetic innervation of the lower leg to directly assess SNS activity and examine its potential role in the regulation of metabolic rate and the development of obesity. Measurements will be performed in the basal state, in response to glucose feeding (75 g OGTT), in response to a standard meal, and in response to glucose/insulin infusion. These studies also will help to disassociate the effect of insulin and glucose on the stimulation of SNS activity. The association between postprandial changes in SNS activity and subjective ratings of hunger and fullness also will be studied. Energy expenditure measurements will be performed over 24 hours in the respiratory chamber and for 2 1/2 hours before and during the euglycemic clamp. Results also will be used to determine possible racial differences between Pimas and Caucasians, since the risk for obesity is markedly different in these populations. To exclude the possibility of a "normal" SNS activity but with peripheral resistance to the action of norepineprine, we will perform adrenergic stimulation by isoproterenol to measure peripheral adrenergic sensitivity.

• INCLUSION CRITERIA:

Male and female Pima Indians, age 4 years old and older.

Male and female Caucasians, age 4 years old and older.

Offspring of Diabetic and Non-Diabetic mothers will be recruited.

Male and female monozygotic and dizygotic twins of any racial background between the ages of 4-7 will be considered for study.

Indian subjects will be recruited from the Gila River Indian Community.

Only children found in good health on the basis of the medical history and physical examination will be accepted into the study.