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Query: UMLS:C0028754 (obesity)
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Seven to eight thousand Pima Indians are presently living in the southwestern desert of Arizona. The prevalence of type II diabetes in this population exceeds 45% and more than 75% of the Pimas are obese. In 1962, Neel proposed that obesity in populations like the Pima Indians might be the expression of a "thrifty gene" which becomes detrimental with progress. Since 1982, longitudinal studies have been conducted including measurements of metabolic rate in 200 non-diabetic Pima Indians and have shown that 1) at any given body weight and body composition, there is quite a large variability in the resting metabolic rate which is not accounted for by intra-individual variability or errors of the methods; 2) metabolic rate after adjustment for body composition and body weight is a familial trait; 3) a low metabolic rate is a risk factor for body weight gain; 4) in response to body weight gain, there is a "normalization" of the resting metabolic rate. These studies are the first showing that a "thrifty" metabolic rate can play a role in the development of obesity.
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PMID:Energy expenditure in the obese: is there a thrifty gene? 219 19

The contributions of diminished insulin sensitivity and decreased insulin response to the development of non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Nondiabetics in high-risk populations for NIDDM, including Pima Indians and Mexican Americans, are characterized by obesity and hyperinsulinemia relative to nondiabetics in the lower-risk white population. However, it is not clear to what extent diminished insulin sensitivity in the high-risk groups reflects obesity per se or is an inherent characteristic of these groups. Insulin sensitivity and secretion were determined in 10 nonobese, normoglycemic Mexican Americans (mean body mass index [BMI], 23.8 kg/m2) and 11 normoglycemic non-Hispanic whites (mean BMI, 22.5 kg/m2) using the intravenous glucose tolerance test (IVGTT) and the minimal model approach of Bergman et al. Age, BMI, sum of skinfolds, and the ratio of waist-to-hip circumference (WHR) were similar in both ethnic groups. Mexican Americans had decreased insulin sensitivity compared with non-Hispanic whites (4.06 +/- 0.72 in Mexican Americans v 7.56 +/- 1.13 in non-Hispanic whites, P = .017). The areas under the C-peptide and insulin curves were significantly greater in Mexican Americans than in non-Hispanic whites (P less than .01), suggesting greater insulin secretion in the former. This study provides evidence for diminished insulin sensitivity and increased insulin response in young, nonobese, normoglycemic Mexican Americans.
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PMID:Diminished insulin sensitivity and increased insulin response in nonobese, nondiabetic Mexican Americans. 219 35

The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2873 Pima Indians aged 18-92 yr (mean 37 yr). Age- and sex-adjusted to the Pima population, the prevalence of hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg, or receiving drug treatment) was 7.1% for subjects with normal glucose tolerance compared with 13.0% for subjects with impaired glucose tolerance (IGT) and 19.8% for those with non-insulin-dependent diabetes mellitus (NIDDM) (P less than 0.001). The prevalence ratio of hypertension was 1.8 (95% confidence interval [CI] 1.2-2.5) for IGT and 2.6 (95% CI 2.0-3.2) for NIDDM compared with normal glucose tolerance, controlled for age, sex, and body mass index (BMI). In logistic regression analysis, hypertension was positively related to age, male sex, BMI, glucose tolerance, and fasting but not 2-h postload serum insulin concentration. Among subjects not taking antihypertensive drugs, however, neither fasting nor 2-h postload serum insulin was significantly related to hypertension. Furthermore, in 2033 subjects receiving neither antihypertensive nor antidiabetic drugs, blood pressure was not significantly correlated to fasting insulin concentration, and 2-h postload serum insulin was negatively correlated with diastolic blood pressure. In conclusion, insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians.
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PMID:Insulin and hypertension. Relationship to obesity and glucose intolerance in Pima Indians. 222 16

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.
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PMID:Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. 224 Feb 3

A high-dietary fat intake may be an important environmental factor leading to obesity in some people. The mechanism could be either a decrease in energy expenditure and/or an increase in caloric intake. To determine the relative importance of these mechanisms we measured 24-h energy expenditure in a whole body calorimeter in 14 nondiabetic subjects and in six subjects with non-insulin-dependent diabetes mellitus, eating isocaloric, weight-maintenance, high-fat, and high-carbohydrate diets. All subjects were Pima Indians. In nondiabetics, the mean total 24-h energy expenditure was similar (2,436 +/- 103 vs. 2,359 +/- 82 kcal/day) on high-fat and high-carbohydrate diets, respectively. The means for sleeping and resting metabolic rates, thermic effect of food, and spontaneous physical activity were unchanged. Similar results were obtained in the diabetic subjects. In summary, using a whole body calorimeter, we found no evidence of a decrease in 24-h energy expenditure on a high-fat diet compared with a high-carbohydrate diet.
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PMID:Energy expenditure in humans: effects of dietary fat and carbohydrate. 230 78

The prevalence of diagnosed diabetes among American Indians in New Mexico with varied genetic and cultural backgrounds is reported. Utilizing community-based registries, the prevalence in persons ages 35 years and older ranged from 9.8 percent among Jicarilla Apache Indians to 28.2 percent among Zuni Indians. All rates were significantly higher than the U.S. rate of 5.3 percent for the same age group. In addition, in three of the five tribal groups examined, the rates of diagnosed diabetes in Indians less than 35 years of age (range from 0.5 percent to 1.3 percent) were significantly higher than the U.S. rate of 0.4 percent for the same age group. The prevalence rates of diagnosed diabetes found in this study of American Indians in New Mexico were intermediate between those for the United States as a whole and the Pima Indians of southern Arizona. Reasons for the variations and the relative contribution of obesity, fitness, or genetic risk in the development of diabetes need further study.
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PMID:Tribal differences in diabetes: prevalence among American Indians in New Mexico. 251 3

The role of the sympathetic nervous system in free fatty acid (FFA) mobilization was assessed in this study. FFA turnover rate using 1-14C-palmitic acid and metabolic rate by using indirect calorimetry were measured in ten white and 12 Pima Indian males after an overnight fast and during propranolol infusion (120 micrograms/kg fat-free mass [FFM] bolus and 1.2 micrograms/kg FFM/min). Baseline FFA turnovers were similar in both racial groups and decreased similarly following propranolol infusion (-16% +/- 4%; P less than .001, n = 22). This decrease was greater in more obese subjects (decrease in FFA turnover v % body fat, r = -.59, P less than .01, n = 22). Propranolol also induced an increase in lipid oxidation, which was more marked in the subjects with a high ratio of abdomen to thigh circumference (A/T ratio) (r = .63, P less than .01, n = 22). On average the resting metabolic rate (RMR) was unchanged during propranolol infusion, but individuals with lower A/T ratio had greater decreases in RMR than subjects with higher A/T ratio (r = .48, P less than .05). Assuming that the change in FFA turnover following beta-blockade is proportional to the role that the catecholamines (and therefore the sympathetic nervous system) play in mobilization of FFA, the greater fall in FFA turnover after propranolol infusion in more obese subjects suggests that they have a higher basal sympathetic activity. Furthermore, the lack of decrease in metabolic rate in response to beta-blockade in persons with a high A/T ratio could be the reflection of an even greater SNS activity in individuals with central obesity.
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PMID:The effect of propranolol on free fatty acid mobilization and resting metabolic rate. 272 82

We studied insulin binding, receptor autophosphorylation, and insulin action in isolated adipocytes from 23 Pima Indians with varying degrees of obesity over a range of glucose tolerance. [125I]Insulin binding varied widely and did not correlate with fasting plasma immunoreactive insulin levels or insulin sensitivity, as assessed by the ED50 values of insulin stimulation of glucose transport or insulin inhibition of lipolysis in isolated abdominal wall adipocytes obtained by biopsy from the patients. In contrast there was a significant correlation between loss of stimulation of autophosphorylation in solubilized receptors and loss of insulin sensitivity for both stimulation of glucose transport (r = -0.59; P less than 0.005) and inhibition of lipolysis (r = -0.54; P less than 0.01). There was also a significant inverse correlation between insulin's ability to stimulate receptor autophosphorylation and in vivo insulin resistance, as assessed by fasting plasma insulin levels (r = -0.46; P less than 0.05). These data indicate a significant correlation between changes in sensitivity of glucose transport and antilipolysis to insulin and receptor kinase activity in those patients and suggest that defective coupling of insulin binding to insulin action at the level of phosphorylation of the insulin receptor may cause the insulin resistance in this group of patients.
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PMID:Alterations in insulin receptor autophosphorylation in insulin resistance: correlation with altered sensitivity to glucose transport and antilipolysis to insulin. 283 14

Among 384 Pima Indians with impaired glucose tolerance according to World Health Organization criteria who were followed for 1.6 to 11.5 years (median, 3.3), non-insulin-dependent diabetes mellitus (NIDDM) developed in 118 (31 percent), glucose tolerance remained impaired in 100 (26 percent), and glucose tolerance returned to normal in 166 (43 percent). The cumulative incidence of NIDDM was 25 and 61 percent at 5 and 10 years, respectively. The risk of development of diabetes was 6.3 times (95 percent confidence interval, 3.8 to 10.6) as high as in a normoglycemic control group (n = 752). Variables predicting deterioration to NIDDM were age up to the age of 40, after which increasing age had a beneficial effect; higher plasma glucose levels during fasting and after carbohydrate loading; and higher serum insulin levels after fasting and lower levels after carbohydrate loading, suggesting that insulin resistance and decreased beta-cell responsiveness are important determinants of the clinical outcome of impaired glucose tolerance. Obese subjects had 2.9 times (95 percent confidence interval, 2.0 to 10.9) the incidence of NIDDM as the nonobese. Obesity was not, however, predictive of progression to NIDDM after an adjustment for plasma glucose and serum insulin levels. We conclude that in this population approximately one fourth of subjects with impaired glucose tolerance have NIDDM at five years and two thirds at 10 years (approximately one third revert to normal) and that age and plasma glucose and insulin levels are the best predictors of clinical outcome.
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PMID:The natural history of impaired glucose tolerance in the Pima Indians. 305 59

Diabetes and obesity are epidemic in the Pima Indians of the Southwestern United States, and the prevalence of diabetes is increasing. The most likely link between obesity and diabetes is tissue insulin resistance. If obesity is defined as an excess of body fat, then it can only be accurately assessed by measurements of body composition and not by approximations such as body mass index or percent of ideal weight. To compare the metabolic data of individuals of varying size, an accurate measure of metabolic size is needed. Total body weight is not an appropriate means of comparing individuals since obese subjects have a greater proportion of nonmetabolizing mass (triglyceride). Body surface area shows a sex difference, and this may distort data if both sexes are present. From studies of metabolic rate we have determined that metabolic rate is directly proportional to the fat-free mass plus 18 kg, and we suggest that this weight can be equated with metabolic size. Glucose storage in skeletal muscle appears to be important in the disposal of an intravenous glucose load. Consistent with its role in glycogen storage, glycogen synthase enzyme is activated in proportion to the ability to dispose of glucose during a hyperinsulinemic, euglycemic clamp. The role of glycogen synthase is most notable at supraphysiological plasma insulin concentrations; and since glucose uptake at these insulin concentrations is highly familial independent of the degree of obesity, we suggest that there may be a specific genetic defect expressed in skeletal muscle that reduces insulin responsiveness in some subjects. The lack of correlation between 24 hour respiratory quotient measured in a metabolic chamber (a measure of the proportion of fat derived calories) and degree of obesity indicates that in obese Pima Indians insulin resistance is not due to an inhibition of glucose metabolism by free fatty acids (glucose-fatty acid-ketone cycle). Obesity is associated with an increase in fat-free mass almost kilogram- for kilogram with fat mass when compared to the lean state. A role for this increase in fat-free tissue in producing insulin resistance has been given insufficient attention in the past. With an increase in fat-free mass, muscle cells are hypertrophied and capillaries in muscle are more widely spaced. We propose that these biophysical changes in muscle mediate, at least in part, the effects of obesity to produce a reduction in insulin sensitivity and the abnormal kinetics of insulin action found in the obese.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Obesity and insulin resistance: lessons learned from the Pima Indians. 306 59


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