Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

Energy expenditure varies among people, independent of body size and composition, and persons with a "low" metabolic rate seem to be at higher risk of gaining weight. To assess the importance of skeletal muscle metabolism as a determinant of metabolic rate, 24-h energy expenditure, basal metabolic rate (BMR), and sleeping metabolic rate (SMR) were measured by indirect calorimetry in 14 subjects (7 males, 7 females; 30±6 yr Jmean±SDJ 79.1±173 kg; 22±7% body fat), and compared to forearm oxygen uptake. Values of energy expenditure were adjusted for individual differences in fat-free mass, fat mass, age, and sex. Adjusted BMR and SMR, expressed as deviations from predicted values, correlated with forearm resting oxygen uptake (ml 02/liter forearm) (r = 0.72, P < 0.005 and r = 0.53, P = 0.05, respectively). These findings suggest that differences in resting muscle metabolism account for part of the variance in metabolic rate among individuals and may play a role in the pathogenesis of obesity. (J. Clin. Invest. 1990.

Subcutaneous and visceral fat distribution as related to sex, age, and overweight was studied in 130 subjects and 10 women with Cushing's disease. Fat depots were evaluated by computed tomography at one thoracic and one abdominal level. Adipose tissue (density range - 50 to 250 Hansfield units) was highlighted and the fat areas were measured by a laser planimeter. The ratio between subcutaneous and visceral fat areas (S:V ratio) was assumed as an index. Ratios of both nonobese and obese groups were significantly higher in females than in males. Ratios decreased markedly over age 60. There was a significant inverse correlation between age and S:V ratios in females (r = 0.65; p less than 0.001) and in males (r = 0.61; p less than 0.001). Statistically significant correlations were found between S:V ratios at thoracic and abdominal levels. In Cushing's patients, the S:V ratio at the abdominal level was significantly lower than in controls matched for age, sex, and body mass index.

Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally-and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5±1.8 y (mean±SD).Results: (a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P < 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally-(r = 0.19, P < 0.01) and maximallystimulating (r = 0.34, P < 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data.We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians. (J.