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.

Whether sedentary energy expenditure is normal or lower in elderly people has not yet been clearly established. Twenty-four-hour energy expenditure (24EE) and its different components were measured by use of a respiratory chamber in elderly (17 male, 21 female; 71 +/- 6 y, mean +/- SD; 71.2 +/- 13.5 kg; 32 +/- 8% fat) and young (33 male, 31 female; 24 +/- 4 y; 84.5 +/- 23.1 kg; 25 +/- 13% fat) subjects. The elderly subjects had lower mean height (P less than 0.001), weight (P less than 0.01), and fat-free mass (P less than 0.001) but higher percent body fat (P less than 0.01) than did the young adults. Absolute 24EE, basal metabolic rate (BMR), and sleeping metabolic rate were significantly lower (P less than 0.01) in the elderly subjects than in the young subjects. However, after differences in fat-free mass, fat mass, and sex were adjusted for, only BMR was found to be lower in the elderly subjects (P less than 0.01). Despite a reduced adjusted BMR in older subjects, sedentary 24EE was decreased only in proportion to their reduced body size, suggesting that the lower energy intake reported in elderly people might be mainly related to lower physical activity in free-living conditions.

Healthy, nondiabetic Pima Indians [103 males, 77 females; 27 +/- 6 (SD) yr, 97 +/- 25 kg, 33 +/- 9% body fat] were studied in a respiratory chamber in which spontaneous physical activity (SPA) was measured by two microwave sensors. SPA, defined as the percentage of time the subjects were active, varied widely from 4.4 to 17.5%. It was higher in males (9.3 +/- 2.0%) than in females (8.6 +/- 2.3%; P less than 0.05) and was not related to body fatness in either sex. However, SPA accounted for a significant portion of the daily energy expenditure (24-h EE) in males (1,389 +/- 423 kJ/day) and females (1,163 +/- 351 kJ/day) and correlated positively with 24-h EE adjusted for differences in fat-free mass, fat mass, age, and sex (r = 0.42, P less than 0.0001). In 88 siblings, family membership accounted for 57% of the variance in SPA (r(i) = 0.57, P less than 0.02). Body composition was reassessed in a subgroup of 123 subjects (65 males, 58 females) 33 +/- 14 mo later. In males only, SPA correlated inversely to the rate of subsequent body weight change (r = -0.25, P less than 0.05) and the rate of fat-mass change (r = -0.35, P less than 0.005). We conclude that spontaneous physical activity is a familial trait that may play a role in the pathogenesis of obesity.

No abstract

Impaired glucose tolerance often presages the development of non-insulin-dependent diabetes mellitus. We have studied insulin action and secretion in 24 Pima Indians before and after the development of impaired glucose tolerance and in 254 other subjects representing the whole spectrum of glucose tolerance, including subjects with overt non-insulin-dependent diabetes. The transition from normal to impaired glucose tolerance was associated with a decrease in glucose uptake during hyperinsulinemia, from 0.018 to 0.016 mmol per minute (from 3.3 to 2.8 mg per kilogram of fat-free body mass per minute) (P less than 0.0003). Mean plasma insulin concentrations increased during an oral glucose-tolerance test, from 1200 to 1770 pmol per liter (from 167 to 247 microU per milliliter). In 151 subjects with normal glucose tolerance, the insulin concentration measured during an oral glucose-tolerance test correlated with the plasma glucose concentration (r = 0.48, P less than or equal to 0.0001). This relation was used to predict an insulin concentration of 1550 pmol per liter (216 microU per milliliter) in subjects with impaired glucose tolerance (actual value, 1590 pmol per liter [222 microU per milliliter]; P not significant), suggesting that these subjects had normal secretion of insulin. In contrast, plasma insulin concentrations in the diabetics decreased as glucose concentrations increased (r = -0.75, P less than or equal to 0.0001), suggesting deficient secretion of insulin. This relative insulin deficiency first appears at the lower end of the second (diabetic) mode seen in population frequency distributions of plasma glucose concentrations. Our data show that impaired glucose tolerance in our study population is primarily due to impaired insulin action. In patients with non-insulin-dependent diabetes mellitus, by contrast, impaired insulin action and insulin secretory failure are both present.