Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity and diabetes are epidemic in the Pima Indians of Southwest United States. Recent evidence suggests that a reduced metabolic rate may predispose the obesity and, since metabolic rate appears to be familial, this may predispose to the familial dependence of obesity. Obesity is associated with an increased risk of diabetes. Insulin resistance is associated with obesity, but is also familial, independent of obesity. In this population insulin resistance is a risk factor for the development of diabetes. Diabetes occurs when insulin secretory failure is superimposed on insulin resistance. Reduced glucose storage in muscle, regulated by glycogen synthase, is important in determining insulin resistance especially at high plasma insulin concentrations and it is possible that a specific genetic defect may be the cause of this. Obesity has its major effect on insulin action at lower plasma insulin concentrations and we propose that this may in part be due to abnormalities of insulin action induced by an increased fat-free mass with a consequent enlargement of muscle cells, a reduced capillary supply, and reduced penetration of insulin into muscle in obese subjects. We propose therefore that insulin resistance may be due to a combination of a genetic defect and obesity-induced changes in the biophysical properties of skeletal muscle. These defects, by slightly increasing the plasma glucose concentration and inducing pancreatic glucose insensitivity, may in turn lead to the development of non-insulin-dependent diabetes mellitus.
 ...
PMID:Insulin resistance in Pima Indians. A combined effect of genetic predisposition and obesity-related skeletal muscle cell hypertrophy. 313 99

As part of a continuing epidemiological study of non-insulin dependent diabetes among Pima Indians 154 subjects who had had a transient impairment of glucose tolerance were followed up for 1.2-16.9 (median 5.8) years after their glucose tolerance had returned to normal. Of these, 49 subsequently developed diabetes; 26 subsequently developed impaired glucose tolerance; and 79 had normal glucose tolerance at the last examination. The cumulative incidence of diabetes was 16% and 48% at five and 10 years of follow up respectively, compared with 3% and 8% for a control group of 1245 members of the same population. After adjustment for age, sex, body mass index, and plasma glucose concentration two hours after glucose loading the incidence of diabetes among the subjects who had had transient impaired glucose tolerance was 3.0 times that among the controls (95% confidence interval 2.1 to 4.3). Proportional hazards function analysis indicated that obesity was the most important predictor of subsequent development of diabetes. The results suggest that transient impairment of glucose tolerance indicates, at least in some subjects, a predisposition to diabetes and should not be considered clinically unimportant.
 ...
PMID:Transient impaired glucose tolerance in Pima Indians: is it important? 314 6

Pima Indian adults with normal glucose tolerance have higher plasma glucose and insulin concentrations than Caucasian adults. To estimate the age of onset of these differences, and to assess their relationship to abdominal and gluteal adipocyte size, we measured adiposity, adipocyte size, and glucose and insulin concentrations during a glucose tolerance test in lean (less than 20% body fat), prepubertal children from each race. The Pima (n = 13) and Caucasian (n = 10) groups were of similar age, percent body fat, and weight. Pima Indian children had higher fasting glucose (101 +/- 2 v 94 +/- 2 mg/dL, P = .01) and insulin (22 +/- 2 v 15 +/- 2 microU/mL, P less than .01) concentrations and larger abdominal adipocytes (0.49 +/- 0.03 v 0.37 +/- 0.04 microgram lipid/cell, P less than .05) than the Caucasian children. Postprandial glucose and insulin concentrations and gluteal adipocyte size were similar in the two races. The higher plasma glucose and insulin concentrations found in Pima adults are present in lean Pima children, and are associated with increased abdominal adipocyte size. These increases may precede the development of obesity in this racial group.
 ...
PMID:Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children. 329 74

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 less than or equal to 0.0001), percent type I fibers (r = 0.29; P less than 0.02), and percent type 2B fibers (r = -0.38; P less than 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P less than or equal to 0.0001; r = -0.47, P less than or equal to 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -0.39; P less than 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.
 ...
PMID:Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. 330 99

Non-insulin-dependent diabetes mellitus (NIDDM) is a genetic disorder characterized by two major pathogenic processes: reduced insulin action and a relative or absolute decrease in plasma insulin concentrations. We studied 116 nondiabetic siblings from 45 families to determine if in vivo insulin action showed any aggregation among siblings. Subjects were Pima Indians from the Gila River Indian Community in Arizona who, as a group, have the highest reported incidence and prevalence of NIDDM in the world. In vivo insulin action was determined by the euglycemic-clamp technique at two rates of insulin infusion in each subject with resulting mean plasma insulin concentrations of 119 and 1938 microU/ml. After adjustment for age, sex, and degree of obesity, there was significant aggregation among siblings of in vivo insulin action at the high insulin infusion rate (P less than or equal to .0001). Family membership independently accounted for approximately 34% of the variance in this measure of insulin action. Glucose uptake at the lower insulin infusion rate also showed familial aggregation (P less than .01), with family membership independently accounting for approximately 15% of the variance of this measurement. We conclude that in vivo insulin action is a familial characteristic. The familial component of insulin action occurs in addition to the effects of obesity, age, and sex on insulin action. Therefore it is not sufficient to simply know that an individual is lean or obese to predict his/her in vivo insulin resistance, because it must also be known whether he/she is from an insulin-resistant or insulin-sensitive family.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:In vivo insulin action is familial characteristic in nondiabetic Pima Indians. 331 55

To evaluate mechanisms of diabetes-induced changes in very-low-density lipoprotein (VLDL), VLDL triglyceride (TG) and VLDL apolipoprotein B (apoB) metabolism were studied in 12 obese Pima Indian control subjects and in 15 Pima Indian obese non-insulin-dependent diabetics. Eleven of the diabetics were restudied after reduction of hyperglycemia with oral sulfonylurea therapy. In addition, adipose, muscle, and postheparin lipoprotein lipase and postheparin hepatic lipase activities were measured in all subjects. Obese diabetics as compared with obese controls showed a trend toward increased production of VLDL TG (46 +/- 4 vs. 35 +/- 6 g/day, P = .10) but not of VLDL apoB (1595 +/- 106 vs. 1597 +/- 164 mg/day, NS); production of VLDL TG declined to control levels (33 +/- 4 g/day, P less than .05) during therapy, whereas there was no change in production of VLDL apoB. Diabetics had a clearance defect for VLDL, indicated by significantly lower fractional catabolic rates for both VLDL TG (10.6 +/- .9 vs. 13.1 +/- .9 pools/day, P less than .05) and VLDL apoB (5.6 +/- .4 vs. 7.5 +/- 0.7, P less than .05) as compared with controls; fractional catabolic rates increased after therapy (to 13.3 +/- 1.5, P less than .05, and 6.7 +/- .4, P less than .05, respectively). In the diabetics, this decrease in clearance was accompanied by a lower adipose lipoprotein lipase (.30 +/- .09 vs. .92 +/- .25 mumol X g-1 X h-1, P less than .01), which increased during therapy (to .61 +/- .17, P less than .05). Hepatic lipase also decreased significantly after therapy (27.4 +/- 3.6 to 26.4 +/- 3.2, P less than .01). Composition of VLDL in diabetics was also abnormal, indicated by a higher TG/apoB ratio (14.7 +/- .6 vs. 11.7 +/- .8, P less than .01); this ratio fell during therapy (to 12.5 +/- .8, P less than .05). The data indicate there are multiple abnormalities in structure and metabolism of VLDL in non-insulin-dependent diabetics. Control of hyperglycemia with sulfonylureas has the capability of reversing some of these abnormalities.
 ...
PMID:Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism. Studies before and after sulfonylurea therapy. 353 Aug 55

The relationships of birth weight and maternal diabetes to the development of obesity were examined at 5-19 yr of age in the offspring of Pima Indian women. At each age, offspring of diabetic women, even those who were of normal birth weight, had a higher mean weight relative to height than offspring of nondiabetic and prediabetic women. Birth weight was predictive of relative weight in 5- to 9- and 10- to 14-yr-old offspring of nondiabetic women but not in the oldest group. In contrast, for offspring of prediabetic and diabetic women, birth weight was not predictive of subsequent obesity at any age studied. Offspring of diabetic women were heavier than offspring of nondiabetic and prediabetic women regardless of birth weight. Thus, maternal diabetes was important in predicting body size in the offspring even after accounting for the effects of the birth weight and maternal body size.
 ...
PMID:Obesity in offspring of diabetic Pima Indian women despite normal birth weight. 356 64

To investigate the reasons for the lack of sex differences in high density lipoproteins (HDL) observed in population studies of the Pima Indians, we selected 18 lean (9 men, 9 women, body mass index (BMI) less than 27) and 22 obese (12 men, 10 women, BMI greater than 27) Pima Indians for an inpatient study of HDL composition. We measured lipase activities and steroid hormone concentrations, both of which have previously been implicated in the control of HDL. The lean women had higher concentrations of HDL and HDL2 than did either the obese women or the lean or obese men. Lean women had significantly lower hepatic lipase activities and significantly higher concentrations of estradiol compared to obese women. Lean women also had different HDL2 composition, as indicated by the molar ratio of HDL2 cholesterol/A-I. Significant negative correlations between HDL and obesity measured by either BMI or percent body fat were observed in both sexes, but the slope of the relationship was steeper in women. Significant negative associations were observed between HDL or HDL2 concentrations and hepatic lipase in both sexes, and there were significant positive associations between HDL2 and plasma estradiol in women. The data suggest that obesity in this population has a stronger negative influence on HDL concentrations in women, possibly through changes in estradiol and hepatic lipase activities. Since there are so few lean women in the Pima population, the net result is that HDL levels in women in the population as a whole do not differ from those of men.
 ...
PMID:Lack of sex differences in high density lipoproteins in Pima Indians. Studies of obesity, lipase activities, and steroid hormones. 359 76

We have examined the relationship of free fatty acid (FFA) turnover and lipid oxidation rates in vivo to the size of body triglyceride stores and compared these findings with the in vitro lipolytic rates of isolated abdominal fat cells. The studies were performed in 20 Pima Indian women 18 to 35 years of age, both lean and obese. FFA turnover rate was measured using a 1-14C-palmitate infusion, lipid oxidation rate by indirect calorimetry using a ventilated hood, body composition by underwater weighing with correction for residual lung volume, and fat cell lipolytic rates in vitro by published methods. Both FFA turnover and lipid oxidation rates, expressed per kg of body fat, decreased with increasing degree of obesity (as measured by percent body fat) (r = -0.90, and r = -0.75, P less than or equal to 0.0001, respectively). In contrast, the rate of lipolysis determined in vitro, expressed per kg of fat, increased with increasing degree of obesity (r = 0.58, P less than 0.01). A ratio of FFA turnover/lipolysis, which directly compares these in vivo and in vitro measurements, decreased significantly with increases in the degree of obesity (r = -0.81, P less than or equal to 0.0001). Furthermore, there were no positive correlations between the measures of in vivo FFA metabolism and in vitro lipolysis when both were expressed per fat mass, per fat cell number, or per fat cell surface area. The in vivo data also demonstrated that lipid oxidation could only account for 50% of the FFA disappearance rate. While lipid oxidation rate adjusted to the metabolic size increased with increasing plasma FFA concentration (r = 0.75, P less than 0.0003), the nonoxidative component of the FFA turnover failed to increase with increases in plasma FFA concentration (P = 0.5). We conclude that FFA is not available in vivo in proportion to the size of the triglyceride stores. The reason for this is not due to an inability of fat cells to release their stored triglyceride as assessed in vitro. Hence, in vitro measurements of fat cell lipolysis cannot be used to directly predict in vivo FFA metabolism. The large nonoxidative FFA disposal is likely to be important in the regulation of plasma FFA concentrations.
 ...
PMID:Free fatty acid metabolism and obesity in man: in vivo in vitro comparisons. 371 12

To assess whether thermogenesis or sympathetic nervous system (SNS) function might differ between lean and obese human subjects, studies of thermic and sympathetic responses to standard stimuli were undertaken in Pima Indians, an ethnic group with a high prevalence of obesity. Plasma levels of norepinephrine (NE) and energy expenditure at rest and in response to feeding, exercise, and graded infusions of NE were compared in five lean and five obese Indians during a period of weight maintenance (WM), after 3 weeks of overfeeding (OF) and, in the obese, also after 6 weeks of underfeeding (UF). Basal energy expenditure, when adjusted for fat free mass, was equivalent during WM and increased 3% with OF (P less than 0.01) in both groups. Thermic responses to exercise or a test meal did not differ in lean and obese and did not change with OF, while thermic responses to NE infusion fell during OF to a greater degree in obese than lean (P less than 0.05). A similar pattern (decreased effect in obese with OF) was also noted in the glycemic response to infused NE (P less than 0.05). Although not quantitatively different in lean and obese, the plasma NE concentration appeared to vary more in response to feeding or dietary alteration in the obese than lean, a finding that may reflect lower plasma clearance of NE in the obese. These studies, therefore, raise the possibility that overfeeding in obese Pima Indians may limit the contribution of sympathetically mediated thermogenesis to energy expenditure, though the implications of this for body weight regulation are speculative.
 ...
PMID:Effect of diet on energy expenditure and plasma norepinephrine in lean and obese Pima Indians. 378 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>