The contribution of reduced energy expenditure to the development of obesity has been a point of controversy. We measured 24-hour energy expenditure (adjusted for body composition, age, and sex), in a respiratory chamber, in 95 southwestern American Indians. Energy expenditure correlated with the rate of change in body weight over a two-year follow-up period (r = -0.39, P less than 0.001). The estimated risk of gaining more than 7.5 kg in body weight was increased fourfold in persons with a low adjusted 24-hour energy expenditure (200 kcal per day below predicted values) as compared with persons with a high 24-hour energy expenditure (200 kcal per day above predicted values; P less than 0.01). In another 126 subjects, the adjusted metabolic rate at rest at the initial visit was also found to predict the gain in body weight over a four-year follow-up period. When the 15 subjects who gained more than 10 kg were compared with the remaining 111 subjects, the initial mean (+/- SD) adjusted metabolic rate at rest was lower in those who gained weight (1694 +/- 103 vs. 1764 +/- 109 kcal per day; P less than 0.02) and increased to 1813 +/- 134 kcal per day (P less than 0.01) after a mean weight gain of 15.7 +/- 5.7 kg. In a group of 94 siblings from 36 families, values for adjusted 24-hour energy expenditure aggregated in families (intraclass correlation = 0.48). We conclude that a low rate of energy expenditure may contribute to the aggregation of obesity in families.

We have compared the capillary density and muscle fiber type of musculus vastus lateralis with in vivo insulin action determined by the euglycemic clamp (M value) in 23 Caucasians and 41 Pima Indian nondiabetic men. M value was significantly correlated with capillary density (r = 0.63; P < 0.0001), percent type I fibers (r = 0.29; P < 0.02), and percent type 2B fibers (r = -0.38; P < 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P . 0.0001; r = -0.47, P . 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -039; P < 0.002). These results suggest that diffusion distance from capillary to muscle cells or some associated biochemical change, and fiber type, could play a role in determining in vivo insulin action. The association of muscle fiber type with body fat distribution may indicate that central obesity is only one aspect of a more generalized metabolic syndrome. The data may provide at least a partial explanation for the insulin resistance associated with obesity and for the altered kinetics of insulin action in the obese.

The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker.

Human obesity is known to be a familial disorder. We studied 130 nondiabetic adult southwestern American Indians (74 men and 56 women) from 54 families to determine whether the resting metabolic rate, as measured by indirect calorimetry, is a familial trait that is independent of individual differences in fat-free mass (estimated mass of metabolically active tissue), age, and sex. We found that most of the variance in the resting metabolic rate (83 percent, P less than 0.0001) was accounted for by three covariates--fat-free mass, age, and sex--and that fat-free mass was the most important determinant. Family membership accounted for an additional 11 percent (P less than 0.0001) of the variance in the resting metabolic rate. Thus, resting metabolic rate is a familial trait in this population, and it is independent of differences in fat-free mass, age, and sex. We also found that persons from families with lower resting metabolic rates were no more obese than persons from families with higher metabolic rates. This finding may be partly explained by the close correlation between fat-free mass and percentage of body fat (r = 0.81, P less than 0.0001), which indicates that the resting metabolic rate, as adjusted for fat-free mass, is already partly adjusted for obesity. Only prospective studies will elucidate whether the familial dependence of the resting metabolic rate is a contributing mechanism to the familial predisposition to obesity.