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There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypeptide (PP), an islet hormone considered a surrogate marker of parasympathetic nervous system (PNS) drive to the pancreas. To test if hyperinsulinemia in Pima Indians is due to increased vagal input to the beta-cell, we examined the effect of PNS blockade in 17 Caucasian (aged 35 +/- 8 years, body fat 23 +/- 7% [mean +/- SD]) and 17 Pima Indian males (aged 28 +/- 8 years, body fat 29 +/- 5%) with normal glucose tolerance. Each participant underwent four consecutive standardized liquid meal tests (64% carbohydrate, 22% fat, and 14% protein) during which a primed infusion of atropine was administered for 120 min at the following doses: 0, 2.5, 5, and 10 micro g. kg fat-free mass (FFM)(-1). h(-1). Areas under the curve for early (AUC(0-30 min)) and total (AUC(0-120 min)) postprandial insulin and PP secretory responses were calculated. Early postprandial insulin and PP secretory responses were higher in Pima Indians compared with those of Caucasians (both P = 0.01). Secretion of insulin and PP was inhibited by atropine (both P < 0.001). Increasing doses of atropine attenuated the ethnic difference in PP (P = 0.01) but not in early insulin secretory responses (P = 0.6), an effect that was not due to differences in gastric emptying rate (acetaminophen test) and/or circulating glucose. Similar results were observed for total secretory responses. These results confirm that compared with Caucasians, Pima Indians have an exaggerated PNS drive to pancreatic F-cells that secrete PP. However, the hyperinsulinemia of this population does not appear to be due to increased vagal input to pancreatic beta-cells.

There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes and exhibit marked hyperinsulinemia and elevated plasma levels of pancreatic polypeptide (PP), an islet hormone considered a surrogate marker of parasympathetic nervous system (PNS) drive to the pancreas. To test if hyperinsulinemia in Pima Indians is due to increased vagal input to the beta-cell, we examined the effect of PNS blockade in 17 Caucasian (aged 35 +/- 8 years, body fat 23 +/- 7% [mean +/- SD]) and 17 Pima Indian males (aged 28 +/- 8 years, body fat 29 +/- 5%) with normal glucose tolerance. Each participant underwent four consecutive standardized liquid meal tests (64% carbohydrate, 22% fat, and 14% protein) during which a primed infusion of atropine was administered for 120 min at the following doses: 0, 2.5, 5, and 10 micro g. kg fat-free mass (FFM)(-1). h(-1). Areas under the curve for early (AUC(0-30 min)) and total (AUC(0-120 min)) postprandial insulin and PP secretory responses were calculated. Early postprandial insulin and PP secretory responses were higher in Pima Indians compared with those of Caucasians (both P = 0.01). Secretion of insulin and PP was inhibited by atropine (both P < 0.001). Increasing doses of atropine attenuated the ethnic difference in PP (P = 0.01) but not in early insulin secretory responses (P = 0.6), an effect that was not due to differences in gastric emptying rate (acetaminophen test) and/or circulating glucose. Similar results were observed for total secretory responses. These results confirm that compared with Caucasians, Pima Indians have an exaggerated PNS drive to pancreatic F-cells that secrete PP. However, the hyperinsulinemia of this population does not appear to be due to increased vagal input to pancreatic beta-cells.

Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity. To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans, we examined 1) the cross-sectional association between plasma adiponectin concentration and skeletal muscle IR tyrosine phosphorylation and 2) the prospective effect of plasma adiponectin concentration at baseline on change in insulin sensitivity. Fasting plasma adiponectin concentration, body composition (hydrodensitometry or dual energy X-ray absorptiometry), insulin sensitivity (insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2 with diabetes). Group 1 (19 subjects) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR (stimulated by 100 nmol/l insulin). The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation. Group 2 (38 subjects) had follow-up measurements of insulin-stimulated glucose disposal. Cross-sectionally, plasma adiponectin concentration was positively associated with insulin-stimulated glucose disposal (r = 0.58, P < 0.0001) and negatively associated with percent body fat (r = -0.62, P < 0.0001) in the whole group. In group 1 plasma adiponectin was negatively associated with the basal (r = -0.65, P = 0.003) and positively associated with the fold increase in IR tyrosine phosphorylation (r = 0.69, P = 0.001) before and after the adjustment for percent body fat (r = -0.58, P = 0.01 and r = 0.54, P = 0.02, respectively). Longitudinally, after adjustment for age, sex, and percent body fat, low plasma adiponectin concentration at baseline was associated with a decrease in insulin sensitivity (P = 0.04). In conclusion, our cross-sectional data suggest a role of physiological concentration of fasting plasma adiponectin in the regulation of skeletal muscle IR tyrosine phosphorylation. Prospectively, low plasma adiponectin concentration at baseline precedes a decrease in insulin sensitivity. Our data indicate that adiponectin plays an important role in regulation of insulin sensitivity in humans.

Objective Dietary calcium intake, especially from dairy products, may have a protective effect against obesity. This study aimed to determine if calcium intake is associated with body weight and adiposity in Pima Indians, an obesity-prone population. Research methods and procedures Subjects were 65 Pima Indian adults (35 men/30 women, age 33[+ or -]8 years [mean[+ or -]standard deviation]) participating in a study of eating behavior and 78 Pima Indian children (36 boys/42 girls, age 10.4[+ or -]0.3 years) participating in a study of childhood obesity. Height and weight were measured, and body composition was determined by dual-energy x-ray absorptiometry. Food intake in adults was assessed using the Block 1998 Food Questionnaire; food intake in children was assessed using a 24-hour recall with parental assistance. Results In adults, mean energy intake was 3,163[+ or -]1,037 kcal/day, mean percentage of energy from fat was 41%[+ or -]7%, and calcium intake was 914[+ or -]333 mg/day. In children, mean energy intake was 1,988[+ or -]733 kcal/day, mean percentage of energy from fat was 36%[+ or -]9%, and calcium intake was 637[+ or -]352 mg/day, half the recommended daily intake for this age group. There were no significant associations between calcium intake and body weight (r=0.05, P=.71; r=0.04, P=.73), body fat (r=0.16, P=.19; r=0.12, P=.42), or body mass index (r=0.01, P=.97; r=0.04, P=.77) in either adults or children, respectively. Discussion One explanation for the lack of association between reported calcium intake and body size in Pima Indians may be that the high-fat, high-energy diet consumed by the population overwhelmed the "anti-obesigenic" effect of calcium. Conclusions We were unable to find an association between calcium intake and body size or adiposity in Pima Indian adults and children. Although the essentiality of calcium to bone health is well established, the role of calcium and dairy product intake in obesity and weight management remains uncertain. J Am Diet Assoc. 2005;105:1401-1407.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2005.06.004 Byline: Colleen A. Venti, P. Antonio Tataranni, Arline D. Salbe Abstract: Dietary calcium intake, especially from dairy products, may have a protective effect against obesity. This study aimed to determine if calcium intake is associated with body weight and adiposity in Pima Indians, an obesity-prone population.

Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity. Am J Physiol Endocrinol Metab 286: E958-E962, 2004. First published February 17, 2004; 10.1152/ajpendo.00544.2003.--Expansion of adipose tissue mass results from increased number and size of adipocyte cells. We hypothesized that subcutaneous abdominal preadipocytes in obese individuals might have an intrinsically higher propensity to differentiate into adipocytes. Thus we investigated the relationship between obesity and the level of in vitro preadipocyte differentiation in Pima Indians. Subcutaneous abdominal stromal vascular fractions containing preadipocytes were cultured from 58 nondiabetic subjects [31 M/27 F, 30 [+ or -] 6 yr, body fat 34 [+ or -] 8% by dual-energy X-ray absorptiometry (means [+ or -] SD)]. The average percentage of preadipocyte differentiation (PDIFF; cell count by microscopy) was 11 [+ or -] 11% (range 0.2-51%). PDIFF correlated negatively with percent body fat (r = -0.35, P = 0.006) and waist circumference (r = -0.45, P = 0.0004). Multiple regression analysis indicated that waist circumference (P = 0.01), sex (P = 0.01), and percent body fat (P = 0.05) were significant determinants of PDIFF. Molecular characterization of predifferentiated cultured cells was performed by real-time PCR measurements of glucocorticoid receptor-[alpha] (GR[alpha]), insulin-like growth factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]), enhancer-binding protein GATA-3, CCAAT/ enhancer-binding protein-[alpha] undifferentiated protein (CUP/AP-2[alpha], and endothelial cell-specific marker 2 (ECSM2). The mRNA concentrations of GR[alpha] correlated with PDIFF (r = 0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPAR[gamma], r = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2[alpha], r = -0.2, P = 0.1; ECSM2, r = 0.04, P = 0.7). Contrary to our hypothesis, the results may indicate a blunted in vitro differentiation potential of preadipocytes in centrally obese individuals. The lower differentiation potential of preadipocytes in the obese subjects might be due, at least partly, to decreased glucocorticoid receptor expression. Pima Indians; gene expression; glucocorticoid receptor; adipogenesis

High concentrations of nonesterified fatty acids (NEFA) are a risk factor for developing type 2 diabetes in Pima Indians. In vitro and in vivo, chronic elevation of NEFA decreases glucose-stimulated insulin secretion. We hypothesized that high fasting plasma NEFA would increase the risk of type 2 diabetes by inducing a worsening of glucose-stimulated insulin secretion in Pima Indians. To test this hypothesis, fasting plasma NEFA concentrations, body composition, insulin action (M), acute insulin response (AIR, 25-g IVGTT), and glucose tolerance (75-g OGTT) were measured in 151 Pima Indians [107 normal glucose tolerant (NGT), 44 impaired glucose tolerant (IGT)] at the initial visit. These subjects, participants in ongoing studies of the pathogenesis of obesity and type 2 diabetes, had follow-up measurements of body composition, glucose tolerance, M, and AIR. In NGT individuals, cross-sectionally, high fasting plasma NEFA concentrations at the initial visit were negatively associated with AIR after adjustment for age, sex, percent body fat, and M (P = 0.03). Longitudinally, high fasting plasma NEFA concentrations at the initial visit were not associated with change in AIR. In individuals with IGT, cross-sectionally, high fasting plasma NEFA concentrations at the initial visit were not associated with AIR. Longitudinally, high fasting plasma NEFA concentrations at the initial visit were associated with a decrease in AIR before (P < 0.0001) and after adjustment for sex, age at follow-up, time of follow-up, change in percent body fat and insulin sensitivity, and AIR at the initial visit (P = 0.0006). In conclusion, findings in people with NGT indicate that fasting plasma NEFA concentrations are not a primary etiologic factor for [beta]-cell failure. However, in subjects who have progressed to a state of IGT, chronically elevated NEFA seem to have a deleterious effect on insulin-secretory capacity. [beta]-cell; insulin secretion; insulin sensitivity; diabetes; oral and intravenous glucose tolerance tests; normal glucose tolerance; impaired glucose tolerance

Objective. To assess the effect of energy expenditure, including resting metabolic rate (RMR), total energy expenditure (TEE), and activity energy expenditure (AEE), as well as substrate oxidation (respiratory quotient [RQ]), on the development of obesity in a large cohort of Native American children with a high propensity for obesity. Methods. During the summer months of 1992 to 1995 and again 5 years later, 138 (65 boys and 73 girls) 5-year-old Pima Indian children were studied. At baseline and follow-up, height and weight were measured; body composition was assessed with the use of [sup.18]O dilution; RMR and RQ were assessed with the use of indirect calorimetry; TEE was measured with the use of the doubly-labeled water method; and AEE was calculated (TEE--[RMR + 0.1 x TEE]). In addition, an activity questionnaire was used to assess participation in sporting activities as well as television viewing during the previous year. Linear regression models were used to assess the effects of the baseline variables on the development of obesity. Results. Pima Indian children were markedly overweight at both 5 and 10 years of age. Cross-sectionally, percentage of body fat and body weight at 5 and 10 years of age were negatively correlated with sports participation and positively correlated with television viewing. Most important, there was a marked change in the correlation between body size and activity between 5 and 10 years of age: at age 5 years, weight was positively correlated with AEE and PAL, but at age 10 years, the correlation with AEE was lost and that with PAL was negative. However, prospectively, none of the variables measured at baseline was a predictor of percentage of body fat at age 10 years after adjustment for percentage of body fat at age 5 years. Conclusions. At age 5 years, obesity is associated with decreased participation in sports and increased television viewing but not with a decreased PAL. At age 10 years, obesity is associated with decreased participation in sports, increased television viewing, and a decreased PAL, suggesting that a decrease in PAL in free-living conditions seems to follow, not precede, the development of obesity. Pediatrics 2002;110:307-314; childhood obesity, growth and development, energy metabolism, physical activity, Pima Indians., ABBREVIATIONS. RQ, respiratory quotient; DEXA, dual-energy x-ray absorptiometry; TEE, total energy expenditure; RMR, resting metabolic rate; AEE, activity energy expenditure; PAL, physical activity level; BMI, body mass index. The prevalence [...]

Objective. To assess the effects of body weight, body composition, parental obesity, and metabolic variables on the development of obesity in a large cohort of 5-year-old Native American children with a high propensity for obesity. Methods. During the summer months of 1992 to 1995 and again 5 years later, 138 (65 boys and 73 girls) 5-year-old Pima Indian children were studied. Height; weight; body composition; parental obesity; and fasting plasma insulin, glucose, and leptin concentrations were determined at baseline and follow-up. Linear regression models were used to assess the effect of the baseline variables on the development of obesity. Results. At both 5 and 10 years of age, Pima Indian children were heavier and fatter than an age- and gender-matched reference population. All anthropometric and metabolic variables tracked strongly from 5 to 10 years of age (r [greater than or equal to] 0.70). The most significant determinant of percentage of body fat at 10 years of age was percentage of body fat at 5 years of age ([R.sup.2] = 0.53). The combined effect of high maternal body mass index, elevated fasting plasma leptin concentrations, and low fasting plasma insulin concentrations at baseline explained an additional 4% of the total variance in adiposity at follow-up. Conclusions. Although parental obesity and metabolic variables such as insulinemia and leptinemia at baseline account for a small percentage of the variance in adiposity at follow-up, early childhood obesity is the dominant predictor of obesity 5 years later. These results suggest that strategies to prevent childhood obesity must be initiated at a very early age. Pediatrics 2002;110:299-306; childhood obesity, growth and development, parent-child relationship, overweight tracking, Pima Indians., ABBREVIATIONS. BMI, body mass index; DEXA, dual-energy x-ray absorptiometry. Widespread reports indicate that the prevalence of obesity among children and adolescents has been increasing in recent years, (1,2) just as [...]