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1.
Recent studies from our group reveal that adipose tissue (AT) in the subcutaneous abdominal region is the most important determinant of peripheral and hepatic insulin sensitivity. Because of different anatomic and physiologic characteristics of anterior and posterior subcutaneous abdominal AT, we investigated the relationship of the masses of each compartment, as determined by magnetic resonance imaging, to insulin sensitivity (using euglycemic hyperinsulinemic glucose clamp technique), and other anthropometric variables. Thirty-four healthy men with varying ranges of obesity were recruited for the study. The mass of posterior subcutaneous abdominal AT was ~1.6 times more than that of the anterior compartment, and these masses accounted for 12.9% and 8.2% of the total body fat mass, respectively. All anthropometric variables, including body mass index (BMI), waist-to-hip circumference ratio (WHR), skinfold thicknesses, and intraperitoneal AT mass were more significantly related to the posterior than the anterior subcutaneous abdominal AT mass. Compared to the anterior compartment mass, the posterior compartment mass displayed stronger relationship with insulin-mediated glucose disposal (Rd) (r=-0.44, p=0.009, and r=-0.76, p=0.0001, respectively) as well as with residual hepatic glucose output during the 40 mU.?2.min-1 insulin infusion (r=0.39, p=0.02, and r=0.53, p=0.001, respectively). After adjusting for total body fat, the Rd values showed a significant partial correlation with the posterior subcutaneous abdominal AT mass (r=-0.52, p=0.002). To conclude, posterior subcutaneous abdominal AT mass is a more important determinant of peripheral and hepatic insulin sensitivity than the anterior subcutaneous abdominal AT.  相似文献   

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South Asians have a higher prevalence of cardiovascular disease (CVD) than Europeans. Studies have identified distinct subcompartments of subcutaneous adipose tissue (SAT) that provide insight into the relationship between abdominal obesity and metabolic risk factors in different ethnic groups. Our objective was to determine the relationship between SAT compartments and fat‐free mass (FFM) between South Asian and European cohorts, and between men and women. Healthy Europeans and South Asians (n = 408) were assessed for FFM via dual energy X‐ray absorptiometry, and SAT areas by computed tomography (CT). SAT was subdivided into superficial subcutaneous abdominal adipose tissue (SSAT) and deep subcutaneous abdominal adipose tissue (DSAT). Linear regression analyses were performed using DSAT and SSAT as separate dependent variables and FFM and ethnicity as primary independent variables adjusting for age, gender, income, education, and smoking status. Results showed that South Asian men had significantly higher amounts of DSAT (median 187.65 cm2 vs. 145.15 cm2, P < 0.001), SSAT (median 92.0 cm2 vs. 76.1 cm2, P = 0.046), and body fat mass (BFM) (25.1 kg vs. 22.6 kg, P = 0.049) than European men. In a fully adjusted model, South Asians showed significantly greater DSAT at any FFM than Europeans. Women had more SSAT at any given FFM than men and less DSAT at any given FFM than men, irrespective of ethnic background. In conclusion, South Asians had more DSAT than Europeans and men had relatively more DSAT than women. These data suggest that specific fat depots are influenced by ethnicity and gender; therefore, could provide insight into the relationship between ethnicity, gender and subsequent risk for CVD.  相似文献   

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Presence of thermogenically active adipose tissue in adult humans has been inversely associated with obesity and type 2 diabetes. While it had been shown that insulin is crucial for the development of classical brown fat, its role in development and function of inducible brown-in-white (brite) adipose tissue is less clear. Here we show that insulin deficiency impaired differentiation of brite adipocytes. However, adrenergic stimulation almost fully induced the thermogenic program under these settings. Although brite differentiation of adipocytes as well as browning of white adipose tissue entailed substantially elevated glucose uptake by adipose tissue, the capacity of insulin to stimulate glucose uptake surprisingly was not higher in the brite state. Notably, in line with the insulin-independent stimulation of glucose uptake, our data revealed that brite recruitment results in induction of solute carrier family 2 (GLUT-1) expression in adipocytes and inguinal WAT. These results for the first time demonstrate that insulin signaling is neither essential for brite recruitment, nor is it improved in cells or tissues upon browning.  相似文献   

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Insulin resistance is associated with central obesity and an increased risk of cardiovascular disease. Our objective is to examine the association between abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) and insulin resistance, to determine which fat depot is a stronger correlate of insulin resistance, and to assess whether there was an interaction between SAT, VAT, and age, sex, or BMI. Participants without diabetes from the Framingham Heart Study (FHS), who underwent multidetector computed tomography to assess SAT and VAT (n = 3,093; 48% women; mean age 50.4 years; mean BMI 27.6 kg/m2), were evaluated. Insulin resistance was measured using the homeostasis model and defined as HOMAIR ≥75th percentile. Logistic regression models, adjusted for age, sex, smoking, alcohol, menopausal status, and hormone replacement therapy use, were used to assess the association between fat measures and insulin resistance. The odds ratio (OR) for insulin resistance per standard deviation increase in SAT was 2.5 (95% confidence interval (CI): 2.2–2.7; P < 0.0001), whereas the OR for insulin resistance per standard deviation increase in VAT was 3.5 (95% CI: 3.1–3.9; P < 0.0001). Overall, VAT was a stronger correlate of insulin resistance than SAT (P < 0.0001 for SAT vs. VAT comparison). After adjustment for BMI, the OR of insulin resistance for VAT was 2.2 (95% CI: 1.9–2.5; P < 0.0001). We observed an interaction between VAT and BMI for insulin (P interaction = 0.0004), proinsulin (P interaction = 0.003), and HOMAIR (P interaction = 0.003), where VAT had a stronger association in obese individuals. In conclusion, SAT and VAT are both correlates of insulin resistance; however, VAT is a stronger correlate of insulin resistance than SAT.  相似文献   

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BAUMGARTNER, RICHARD N., ROBERT R. ROSS, DEBRA L. WATERS, WILLIAM M. BROOKS, JOHN E. MORLEY, GEORGE D. MONTOYA, AND PHILIP J. GARRY. Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes Res. Objective There are few data for associations of serum leptin with body fat, fat distribution, sex hormones, or fasting insulin in elderly adults. We hypothesized that the sex difference in serum leptin concentrations would disappear after adjustment for subcutaneous, but not visceral body fat. Serum leptin would not be associated with sex hormone concentrations or serum fasting insulin after adjusting for body fat and fat distribution. Research Methods and Procedures Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured using magnetic resonance imaging in a cross-sectional sample of 56 nondiabetic, elderly men and women aged 64 years to 94 years. Serum leptin, sex hormones (testosterone and estrone), sex hormone-binding globulin, and fasting insulin were also measured. Nine women were taking hormone replacement, and five men were clinically hypogonadal. Results Leptin was significantly associated with both SAT and VAT in each sex. Adjustment for SAT reduced the sex difference in leptin by 56%, but adjustment for VAT increased the difference by 25%. Leptin was not associated with serum estrone or hormone replacement therapy in the women, but had a significant, negative association with testosterone in the men that was independent of SAT, but not VAT. Leptin was significantly associated with fasting insulin in both sexes independent of age, sex hormones, sex hormone-binding globulin, VAT and SAT. Discussion Sex difference in serum leptin is partly explained by different amounts of SAT. Studies including both men and women should adjust for SAT rather than total body fat that includes VAT. The sex difference in serum leptin is not due to estrogen, but may be partly explained by testosterone. Testosterone is negatively associated with leptin in men, but the association is confounded with VAT. Leptin is associated with fasting insulin in non-diabetic elderly men and women independent of body fat, fat distribution. or sex hormones.  相似文献   

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Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin0), the acute insulin response to glucose (AIRg), the insulin sensitivity index (SI), basal and nadir FFA (FFA0, FFAnadir), and nadir time (TIMEnadir) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA0, FFAnadir, and TIMEnadir with ethnicity, age group, insulin measures, indexes of body composition from dual‐energy X‐ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin0 and AIRg were higher among AAs vs. EAs, whereas SI was lower, independent of age group. MLR analyses indicated that FFA0 was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), SI, and insulin0. FFAnadir was best predicted by FFA0, age group, and intra‐abdominal adipose tissue (IAAT). TIMEnadir was best predicted by leg fat mass, AIRg, and SI. In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA0 among AAs was independent of insulin0 and SI. Whether lower FFA0 is associated with substrate oxidation or risk for obesity remains to be determined.  相似文献   

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Black South African women are more insulin resistant than BMI‐matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal‐weight (BMI 18–25 kg/m2) and obese (BMI > 30 kg/m2) black and white premenopausal South African women underwent the following measurements: body composition (dual‐energy X‐ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (SI, frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 ± 0.8 vs. 9.5 ± 0.8 and 3.0 ± 0.8 vs. 6.0 ± 0.8 × 10?5/min/(pmol/l), for normal‐weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. SI correlated with deep and superficial SAT in both black (R = ?0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = ?0.554, P = 0.005 and R = ?0.546, P = 0.004), but with VAT in white women only (R = ?0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.  相似文献   

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Objective: To compare ethnic differences in visceral adipose tissue (VAT), assessed by computed tomography, and type 2 diabetes risk among 55‐ to 80‐year‐old Filipino, African‐American, and white women without known cardiovascular disease. Research Methods and Procedures: Subjects were participants in the Rancho Bernardo Study (n = 196), the Filipino Women's Health Study (n = 181), and the Health Assessment Study of African‐American Women (n = 193). Glucose and anthropometric measurements were assessed between 1995 and 2002. Results: African‐American women had significantly higher age‐adjusted BMI (29.7 kg/m2) and waist girth (88.1 cm) compared with Filipino (BMI, 25.5 kg/m2; waist girth, 81.9 cm) or white (BMI: 26.0 kg/m2; waist girth: 80.7 cm) women. However, VAT was significantly higher among Filipino (69.1 cm3) compared with white (62.3 cm3; p = 0.037) or African‐American (57.5 cm3, p < 0.001) women. VAT correlated better with BMI (r = 0.69) and waist (r = 0.77) in whites, compared with Filipino (r = 0.42; r = 0.59) or African‐American (r = 0.50; r = 0.56) women. Age‐adjusted type 2 diabetes prevalence was significantly higher in Filipinas (32.1%) than in white (5.8%) or African‐American (12.1%) women. Filipinas had higher type 2 diabetes risk compared with African Americans [adjusted odds ratio, 2.30; 95% confidence interval (CI), 1.09 to 4.86] or whites (adjusted odds ratio, 7.51; 95% CI, 2.51 to 22.5) after adjusting for age, VAT, exercise, education, and alcohol intake. Discussion: VAT was highest among Filipinas despite similar BMI and waist circumference as whites. BMI and waist circumference were weaker estimates of VAT in Filipino and African‐American women than in whites. Type 2 diabetes prevalence was highest among Filipino women at every level of VAT, but VAT did not explain their elevated type 2 diabetes risk.  相似文献   

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Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)‐infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV‐infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV‐infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV‐infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to ?28%, P < 0.0001 in men and ?3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper‐trunk SAT, and VAT were associated with higher IMAT in HIV‐infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV+ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT.  相似文献   

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JOHANNSSON, GUDMUNDUR, CECILIA KARLSSON, LARS LÖNN, PER MÅRIN, PER BJÖRNTORP, LARS SJÖSTRÖM, BJÖRN CARLSSON, LENA M.S. CARLSSON, BENGT-ÅKE BENGTSSON. Serum leptin concentration and insulin sensitivity in men with abdominal obesity. Obes Res. 1998;6:416–421. Objective : We have examined the association between generalized adiposity, abdominal adiposity, insulin sensitivity, and serum levels of leptin in a cross-sectional study of abdominally obese men. Research Methods and Procedures : Thirty men, 48 to 66 years of age with a body mass index (BMI) of between 25 kg/m2 and 35 kg/m2 and a waist hip ratio of <0.95, were included in the study. Serum leptin concentration was measured using radioimmunoassay. Total body fat percentage was determined from total body potassium, abdominal adiposity was measured by computed tomography, and the glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp. Results : Significant correlations were found between serum leptin concentration and BMI, percentage body fat, abdominal subcutaneous adipose tissue, serum insulin, GDR, and 24-hour urinary-free Cortisol. In a multiple regression analysis, it was shown that abdominal subcutaneous adipose tissue, GDR, and BMI explained 72% of the variability of serum leptin concentration. GDR demonstrated an independent inverse correlation with serum leptin concentration. Discussion : In abdominally obese men with insulin resistance, it was demonstrated that most of the individual variability in serum leptin concentration was explained by the amount of subcutaneous abdominal adipose tissue, insulin sensitivity, and BMI.  相似文献   

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Brown adipose tissue (BAT) can be identified by 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) in adult humans. Thirteen healthy male volunteers aged 20–28 years underwent FDG‐PET after 2‐h cold exposure at 19 °C with light‐clothing and intermittently putting their legs on an ice block. When exposed to cold, 6 out of the 13 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT‐positive group), whereas the remaining seven showed no detectable uptake (BAT‐negative group). The BMI and body fat content were similar in the two groups. Under warm conditions at 27 °C, the energy expenditure of the BAT‐positive group estimated by indirect calorimetry was 1,446 ± 97 kcal/day, being comparable with that of the BAT‐negative group (1,434 ± 246 kcal/day). After cold exposure, the energy expenditure increased markedly by 410 ± 293 (P < 0.05) and slightly by 42 ± 114 kcal/day (P = 0.37) in the BAT‐positive and ‐negative groups, respectively. A positive correlation (P < 0.05) was found between the cold‐induced rise in energy expenditure and the BAT activity quantified from FDG uptake. After cold exposure, the skin temperature in the supraclavicular region close to BAT deposits dropped by 0.14 °C in the BAT‐positive group, whereas it dropped more markedly (P < 0.01) by 0.60 °C in the BAT‐negative group. The skin temperature drop in other regions apart from BAT deposits was similar in the two groups. These results suggest that BAT is involved in cold‐induced increases in whole‐body energy expenditure, and, thereby, the control of body temperature and adiposity in adult humans.  相似文献   

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《PLoS biology》2013,11(2)
When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet–fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.  相似文献   

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The ability of glucose, glucose-6-phosphate, and glycerol phosphate to support incorporation of 14C-palmitate into neutral lipid of adipose tissue has been studied in eight patients with maturity-onset diabetes. After two hours'' incubation glucose and glucose-6-phosphate supported incorporation rates relative to glycerol phosphate of 30% and 44% respectively in diabetic tissue, whereas the corresponding rates in paired non-diabetic controls were 93% and 95%. This failure of adipose tissue to metabolize glucose in maturity-onset diabetes might be responsible for a delay in the clearance of glucose from the blood stream. Alternatively, a defect in glucose utilization might be due to tissue changes associated with maturity-onset diabetes.  相似文献   

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Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African‐American (n = 108) and white (n = 105) women, BMI 27–30 kg/m2. Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual‐energy X‐ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)‐α, soluble tumor necrosis factor receptor (sTNFR)‐1, sTNFR‐2, C‐reactive protein (CRP), and interleukin (IL)‐6) with enzyme‐linked immunosorbent assay (ELISA). Whites had greater intra‐abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF‐α, sTNFR‐1, and sTNFR‐2 than African Americans. Greater TNF‐α in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = ?0.29 P < 0.05, and r = ?0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation.  相似文献   

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Calcium intake is reported to enhance weight loss with a preferential loss in trunk fat. Discrepant findings exist as to the effects of calcium intake on longitudinal changes in total fat mass and central fat deposition. Therefore, the purpose of this study was to determine associations between dietary calcium intake and 1‐year change in body composition and fat distribution, specifically intra‐abdominal adipose tissue (IAAT). A total of 119 healthy, premenopausal women were evaluated at baseline and 1 year later. Average dietary calcium was determined via 4‐day food records. Total fat was determined by dual‐energy X‐ray absorptiometry (DXA) and subcutaneous abdominal adipose tissue (SAAT) and IAAT by computed tomography. Over the study period, participants' reported daily calcium and energy intakes were 610.0 ± 229.9 mg and 1,623.1 ± 348.5 kcal, respectively. The mean change in weight, total fat, IAAT, and SAAT was 4.9 ± 4.4 kg, 5.3 ± 4.0 kg, 7.7 ± 19.5 cm2, and 49.3 ± 81.1 cm2, respectively. Average calcium intake was significantly, inversely associated with 1‐year change in IAAT (standardized β: ?0.23, P < 0.05) after adjusting for confounding variables. For every 100 mg/day of calcium consumed, gain in IAAT was reduced by 2.7 cm2. No significant associations were observed for average calcium intake with change in weight, total fat, or SAAT. In conclusion, dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women. Further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution.  相似文献   

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To characterize the influence of diet‐, physical activity–, and self‐esteem‐related factors on insulin resistance in 8–10‐year‐old African‐American (AA) children with BMI greater than the 85th percentile who were screened to participate in a community‐based type 2 diabetes mellitus (T2DM) prevention trial. In 165 subjects, fasting glucose‐ and insulin‐derived values for homeostasis model assessment of insulin resistance (HOMA‐IR) assessed insulin resistance. Body fatness was calculated following bioelectrical impedance analysis, and fitness was measured using laps from a 20‐m shuttle run. Child questionnaires assessed physical activity, dietary habits, and self‐esteem. Pubertal staging was assessed using serum levels of sex hormones. Parent questionnaires assessed family demographics, family health, and family food and physical activity habits. Girls had significantly higher percent body fat but similar anthropometric measures compared with boys, whereas boys spent more time in high‐intensity activities than girls. Scores for self‐perceived behavior were higher for girls than for boys; and girls desired a more slender body. Girls had significantly higher insulin resistance (HOMA‐IR), compared with boys (P < 0.01). Adjusting for age, sex, pubertal stage, socioeconomic index (SE index), and family history of diabetes, multivariate regression analysis showed that children with higher waist circumference (WC) (P < 0.001) and lower Harter's scholastic competence (SC) scale (P = 0.044) had higher insulin resistance. WC and selected self‐esteem parameters predicted insulin resistance in high‐BMI AA children. The risk of T2DM may be reduced in these children by targeting these factors.  相似文献   

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