Plasma Leptin,Fatty Acids,and Tumor Necrosis Factor‐Receptor and Insulin Resistance in Children

Objective: To evaluate the effect of plasma leptin, nonsterified fatty acids (NEFAs), and tumor necrosis factor‐receptor 1 (TNFR1) on plasma insulin and insulin‐resistance status in children. Research Methods and Procedures: One thousand thirty‐two children (521 boys and 511 girls) were included in this study. We measured plasma insulin and leptin levels by radioimmunoassay, plasma NEFA levels by enzymatic acyl‐coenzyme A synthase—acyl‐coenzyme A oxidase spectrophotometric methods, and TNFR1 levels by enzyme‐linked immunosorbent assay. We calculated insulin resistance index (IRI) using homeostasis model assessment and calculated insulin‐resistance syndrome summary score (IRS) by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride, high‐density lipoprotein‐cholesterol (inverse), and insulin levels. Results: Overweight children had higher BP, plasma leptin, and insulin levels and higher IRI and IRS than normal‐weight children. Plasma leptin and TNFR1 were positively correlated with insulin levels, IRI, and IRS. The correlation coefficients of leptin and TNFR1 in IRI were 0.53 and 0.12, respectively, for boys and 0.25 and 0.18, respectively, for girls. In multivariate regression analyses, TNFR1 was positively associated with insulin level and IRI in girls; NEFA was positively associated only with IRS. Plasma leptin levels were significantly positively associated with insulin levels, IRI, and IRS, even after adjusting for BMI and other potential confounders. Discussion: Overweight children had higher BP, plasma insulin, and leptin levels and adverse insulin‐resistance status than normal‐weight children. Plasma leptin levels, rather than NEFA and TNFR1, may play a significant role in the development of hyperinsulinemia and insulin resistance in children.     

Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

Obesity in the Elderly and Its Relationship with Cardiovascular Risk Factors in Taiwan**

Objectives: The obese elderly are at increased risk of mortality, morbidity, and functional disability. In this study, we examined the prevalence of obesity and relationship between various anthropometric indices (AI) and cardiovascular disease (CVD) risk factors in the elderly. Research Methods and Procedures: A stratified multistage clustered sampling scheme was used in the Elderly Nutrition and Health Survey in Taiwan during 1999 to 2000. 2432 non‐institutionalized subjects (age, 72.8 ± 9.4 years; BMI, 23.6 ± 6.4 kg/m²) were recruited. The receiver operating characteristic analysis was used to compare predictive validity of CVD risk factors among various AI, including BMI, waist circumference (WC), and waist‐to‐hip ratio (WHR). Results: The prevalence of obesity was 29.0% in men and 36.8% in women by obesity criteria for Asians (BMI ≥ 25 kg/m²) and 13.3% in men and 21.0% in women by the Taiwanese definition (BMI ≥ 27 kg/m²). Odds ratios of acquiring various CVD risk factors increased significantly with increment of WC, WHR, and BMI. The areas under the curve predicting metabolic syndrome were all <0.8. The cut‐off values of WC corresponding to the highest sensitivity and the highest specificity in predicting various CVD risk factors were 86.2–88.0 cm in men and 82.0–84.0 cm in women, respectively. Discussion: Obesity was prevalent in the Taiwanese elderly. WC was related to CVD risk factors to a greater extent than BMI and WHR. However, none of them alone was a good screening tool for CVD risk factors. Therefore, how to apply AI prudently to screen elderly for CVD risk factors needs further research.     

Dietary Fat Intake and Insulin Resistance in Black and White Children

Objective: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. Research Methods and Procedures: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24‐hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above‐AMDR/within‐AMDR guidelines), and differences were analyzed by 2 × 2 analysis of covariance, adjusting for covariates. Results: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above‐AMDR compared with within‐AMDR blacks) and was not seen in whites. Discussion: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.     

Comparison of Cardiovascular Risk Factors in Obese Blacks and Whites

Blacks are known to have higher blood pressure levels, a higher prevalence of hypertension, and higher body weights than whites. However, the interrelationships of these and other cardiac risk factors have not been analyzed in an obese population. We compared blood pressure (BP) and lipid levels in 174 obese blacks and 939 obese white patients who were entering a weight loss program; we also assessed the effects of weight loss on these factors. Prevalence of treated hypertension was similar in blacks and whites (28% vs. 25%, respectively). In patients not taking BP medication, black women weighed more (108 kg) than white women (102 kg) and black and white males' weights were similar (135 kg vs. 131 kg). Systolic and diastolic BP were similar in black and white women; black males had similar SBP but a significantly lower DBP than white males (83 mmHg vs. 89 mmHg, respectively). Lipid levels were similar in black and white women except black women had lower triglycerides (1.30 mmol/L) than white women (1.58 mmol/L, p<0.05); and black males compared to white males had significantly lower total cholesterol (4.76 mmol/L vs. 5.56 mmol/L), LDL-cholesterol (3.15 mmol/L vs. 3.52 mmol/L) and triglycerides (1.31 mmol/L vs. 2.17 mmol/L, p<0.05). Adult-onset obesity adversely affected a number of cardiovascular risk factors in whites, but not in blacks. Blacks lost significantly less weight (?13 kg) than whites (?19 kg). However, controlling for the difference in weight loss, blacks sustained comparable improvement in lipids and blood pressure, except for TC/HDL-C (whites improved significantly more, ?0.36 kg/m2, than blacks, 0.03 kg/m2). Thus, the impact of obesity on cardiovascular risk factors seems ameliorated in blacks com-pared to whites.     

Overweight,Waist Circumference,Age, Gender,and Insulin Resistance as Risk Factors for Hyperleptinemia

Objective: To evaluate the influence of overweight, waist circumference, age, gender, and insulin resistance as risk factors for hyperleptinemia. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 197 subjects: 59 men (21 aged <60 years and 38 aged ≥60 years) and 138 women (37 aged <60 years and 101 aged ≥60 years). The groups were stratified by overweight and normal weight. After a 12‐hour fasting period, we measured serum leptin and insulin levels with radioimmunoassay methods. We also measured serum glucose and lipid profile. The data were analyzed by means of comparative tests. A variance‐stabilizing transformation (natural logarithmic) was used to meet multiple linear regression, analysis of covariance, and logistic regression models. Results: The leptin serum levels were higher and statistically significant in young and older women than they were in men. We observed an interaction between gender and body mass index to explain the difference in leptin levels (p < 0.0001). Our study demonstrated an inverse relationship between leptin with age and high‐density lipoprotein cholesterol. In logistic regression analysis, the overweight × gender interaction and waist circumference have a statistically significant influence as independent variables on hyperleptinemia (overweight × gender odds ratio = 6.81; 95% confidence interval, 1.10 to 46.86; p < 0.05 and waist circumference odds ratio = 4.34; 95% confidence interval, 1.47 to 12.83; p = 0.001). Discussion: Women who were overweight or had a higher waist circumference (women ≥ 88 cm and men ≥ 102 cm) have a significantly higher risk of having hyperleptinemia. The increase in age as an isolated variable is not a risk factor for hyperleptinemia.     

Evidence for Genetic Factors Underlying the Insulin Resistance Syndrome in American Indians

Previous analyses of American Indians of the Strong Heart Study have demonstrated that various insulin‐resistance variables cluster, although knowledge about the genetic determination of these clusters is unknown. In an effort to explore the influences on the aggregation of insulin‐resistance phenotypes, we used principal component factor analysis to examine the clustering of these phenotypes in participants of the Strong Heart Family Study and evaluated the genetic and environmental contributions of such factors. Nine traits were chosen for principal component factor analysis: BMI, diastolic blood pressure, fasting glucose, high‐density lipoprotein‐cholesterol, natural log‐transformed insulin, natural log‐transformed triglycerides, percentage of body fat, systolic blood pressure, and waist‐to‐hip ratio. Analyses revealed three clusters: glucose/insulin/obesity, blood pressure, and dyslipidemia factors. Using a variance component approach and accounting for the effects of age, sex, center, and medication, we detected significant heritabilities (h²) for the three factors: h² = 0.67, h² = 0.33, and h² = 0.61, respectively. In multivariate analysis, no significant genetic correlations among factors were found. These results suggest that heredity explains a substantial proportion of the variability of the factors that underlie the insulin resistance syndrome in American Indians and that these factors are genetically independent.     

Relationship between Plasma Adiponectin Levels and Metabolic Risk Profiles in Taiwanese Children

Objective: Adiponectin, a novel adipokine with antiinflammatory and insulin‐sensitizing properties, has an important role in glucose metabolism and is negatively correlated with body fat amount in adults. The purpose of this study was to evaluate the association of plasma adiponectin level with metabolic risk profiles and insulin resistance status among Taiwanese children. Research Methods and Procedures: We enrolled 1248 children (608 boys and 640 girls) to ascertain their demographic, anthropometric, and cardiovascular risk factors distribution in Taipei. We measured plasma insulin, adiponectin, and leptin levels by radioimmunoassay (Linco Research Inc, St. Charles, MO). We calculated an insulin resistance index (IRI) using the Homeostasis Model Assessment model and also calculated an insulin resistance syndrome (IRS) summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure, serum triglyceride, high‐density lipoprotein‐cholesterol (HDL‐C) (inverse), and insulin levels. Results: In general, the boys had larger BMI, higher systolic blood pressure, serum total cholesterol, and triglyceride, and lower plasma leptin and adiponectin levels than girls. Plasma adiponectin levels were correlated negatively with BMI, leptin, insulin, IRI, and IRS summary score but positively correlated with HDL‐C in both boys and girls. In multivariate regression analyses, adiponectin was negatively associated with insulin (girls only), IRI (girls only), and IRS score, and positively associated with HDL‐C in both genders even after adjusting for age, BMI, plasma leptin level, and other potential confounders. Discussion: These data suggest that plasma adiponectin levels were negatively associated with metabolic risk profiles that may have played a protective role in the development of insulin resistance among Taiwanese school children.     

Association of Osteocalcin With Obesity,Insulin Resistance,and Cardiovascular Risk Factors in Young Adults

Low levels of osteocalcin (OCN), an osteoblast‐specific hormone, have recently been associated with insulin resistance (homeostasis model assessment‐insulin resistance (HOMA‐IR)) and obesity, particularly in older adults. The aim of this study was to determine whether low levels of OCN would be associated with insulin resistance, obesity, and greater cardiovascular (CV) risk in young adults just emerging from adolescence. Undercarboxylated OCN and carboxylated OCN levels were measured on stored serum samples (total OCN = undercarboxylated OCN + carboxylated OCN) on 137 participants (67 males) at mean age 18.6 years (range 17–22 years). Insulin resistance was measured by hyperinsulinemic—euglycemic clamp (M_lbm). Multivariable regression analyses with ln(OCN) as the independent variable were adjusted for age, sex, ethnicity, and BMI as indicated. Total OCN was inversely related to BMI, waist circumference, systolic blood pressure (SBP), interleukin (IL)‐6, and directly related to M_lbm; only SBP remained significant (with M_lbm P = 0.0560) after further adjustment for BMI. Carboxylated OCN was inversely related to BMI, waist circumference, SBP, low‐density lipoprotein cholesterol (LDL‐C), and directly related to adiponectin; SBP and adiponectin remained significant after further adjustment for BMI. There were no significant associations with undercarboxylated OCN. In summary, most associations with OCN were mediated via BMI. However, the significant associations of OCN with SBP, obesity, and adiponectin and borderline with M_lbm, suggest a potential role for OCN in the development of insulin resistance and CV risk that becomes more apparent with aging into older adulthood.     

No Decrease in Free IGF‐I with Increasing Insulin in Obesity‐Related Insulin Resistance

Objective: Different facts suggest that the insulin growth factor (IGF)/ insulin growth factor‐binding protein (IGFBP) system may be regulated by factors other than growth hormone. It has been proposed that, in healthy subjects, free IGF‐I plays a role in glucose metabolism. The role of free IGF‐I in glucose homeostasis in insulin resistance is poorly understood. This study was undertaken to evaluate the effects of acute changes in plasma glucose and insulin levels on free IGF‐I and IGFBP‐1 in obese and non‐obese subjects. Research Methods and Procedures: Nineteen lean and 24 obese subjects were investigated. A frequently sampled intravenous glucose tolerance test was performed. Free IGF‐I and IGFBP‐1 were determined at 0, 19, 22, 50, 100, and 180 minutes. Results: Basal free IGF‐I levels tended to be higher and IGFBP‐1 lower in obese than in lean subjects. IGFBP‐1 levels inversely correlated with basal insulin concentration. To determine the effects of insulin on the availability of free IGF‐I and IGFBP‐1, changes in their plasma concentrations were measured during a frequently sampled intravenous glucose tolerance test. After insulin administration, a significant suppression of free IGF‐I at 22% was observed in lean subjects. In contrast, plasma‐free IGF‐I levels remained essentially unchanged in the obese group. The differences between both groups were statistically significant at 100 minutes (p < 0.01) and 180 minutes (p < 0.05). Serum IGFBP‐1 was suppressed to a similar extent in both groups. Discussion: These data suggest that the concentrations of free IGF‐I and IGFBP‐1 are differentially regulated by obesity. Obesity‐related insulin resistance leads to unsuppressed free IGF‐I levels.     

肥胖诱发胰岛素抵抗的炎性机制

肥胖可诱发一系列慢性代谢性疾病,如2型糖尿病、血脂障碍、高血压和非酒精性脂肪肝等.这些疾病构成了当今世界人类健康的极大威胁.胰岛素抵抗是这些疾病的共有特征.胰岛素抵抗的发生与慢性低度系统炎性密切相关,涉及多条炎性信号通路的激活和胰岛素信号转导的缺陷.本文综述了肥胖、炎性与胰岛素抵抗之间的本质联系,以及肥胖诱发胰岛素抵抗的炎性机制,以期为肥胖相关疾病的防治提供重要参考.     

Overweight,Obesity, and Blood Pressure: The Effects of Modest Weight Reduction

Several large epidemiological studies have shown an association between body mass index and blood pressure in normal weight and overweight patients. Weight gain in adult life especially seems to be an important risk factor for the development of hypertension. Weight loss has been recommended for the obese hypertensive patient and has been shown to be the most effective nonpharmacological treatment approach. However, long‐term results of weight loss programs are disappointing with people often regaining most of the weight initially lost. In recent years, a modest weight loss, defined as a weight loss of 5% to 10% of baseline weight, has received increasing attention as a new treatment strategy for overweight and obese patients. A more gradual and moderate weight loss is more likely to be maintained over a longer period of time. Several studies have confirmed the blood pressure‐lowering effect of a modest weight loss in both hypertensive and nonhypertensive patients. A modest weight loss can normalize blood pressure levels even without reaching ideal weight. In patients taking antihypertensive medication, a modest weight loss has been shown to lower or even discontinue the need for antihypertensive medication. In patients with high normal blood pressure, a modest weight loss can prevent the onset of frank hypertension. The blood pressure‐lowering effect of weight loss is most likely a result of an improvement in insulin sensitivity and a decrease in sympathetic nervous system activity and occurs independent of salt restriction. In conclusion, a modest weight loss that can be maintained over a longer period of time is a valuable treatment goal in hypertensive patients.     

Physical Activity,Obesity, and Cardiovascular Risk Factors in Children. The Belgian Luxembourg Child Study II

GUILLAUME, MICHÈLE, LEIF LAPIDUS, PER BJÖRNTORP, ANDRE LAMBERT. Physical activity, obesity, and cardiovascular risk factors in children. The Belgian Luxembourg Child Study II. Physical activity was measured in relation to cardiovascular (CV) risk factors in a randomly selected population of 1028 children from Province de Luxembourg in Belgium, a mainly rural area with a high prevalence of such risk factors among adults and children. Physical activity was estimated as participation in sport activities, a major indicator of leisure-time physical activity in schoolchildren, and physical inactivity was estimated as frequency and duration of television (TV) watching. Boys participated more frequently in sport activities than girls did (p=0. 001). A majority of the children watched TV daily. After age adjustment, bodyweight (girls, p<0. 012; boys, p<0. 027) and, in boys, body mass index (BMI) (p<0. 039) were related to days per week of TV watching. No significant relationships with other CV risk factors remained after adjustments for BMI. In analyses of independent contributions of age, TV watching, and sports activity on CV risk factors, age showed highly significant relationships. In boys, TV showed relationships with BMI (P<0. 04) and (borderline) with systolic blood pressure, independent of age and sports activity, whereas the latter was significantly related to subscapular skinfold (p<0. 04) and (borderline) with triceps skinfold and cholesterol. In girls, no significant independent contributions to risk factor associations were found. The father's education was directly associated with sports activities, whereas the mother being a housewife showed negative relationships to physical activity and positive to TV watching in their children, suggesting socioeconomic influence on the activity patterns of children. Furthermore, registrations suggested less physical activity in the most rural part of the area. It is concluded that children in this mainly rural area watch TV frequently. In boys, physical inactivity, measured both as TV watching and as registrations of sports activities, contributes independently to body fat mass. In girls, no contribution or weaker contributions of physical inactivity were found. This suggests that contributory factors leading to obesity might be different in girls and boys.     

The Insulin Tolerance Test in Morbidly Obese Patients Undergoing Bariatric Surgery

Objective: To assess the effect of massive weight loss in relation to insulin resistance and its correlation to changes in glycemic homeostasis and lipid profile in severely obese patients. Research Methods and Procedures: A prospective clinical intervention study was carried out with 31 morbidly obese women (body mass index: 54.2 ± 8.8 kg/m²) divided into three groups according to their glucose tolerance test: 14 normal, 8 impaired glucose tolerance, and 9 type 2 diabetes. All subjects underwent an insulin tolerance test with intravenous bolus of 0.1 U insulin/kg body weight before silastic ring vertical gastroplasty Roux‐en‐Y gastric bypass surgery, and again at 2, 4, 6, and 12 months postoperatively. Fasting plasma glucose, hemoglobin A1c, and lipid profile were also evaluated. Results: A reduction of 68 ± 15% in initial excess body weight was evident within 1 year. Along with weight loss, the following statistically significant changes were found: an increase in the insulin‐sensitivity index (Kitt) and a decrease in fasting plasma glucose and hemoglobin A1c, most notably in the type 2 diabetes group. An overall improvement in lipid profile was observed in all three groups. Discussion: Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Significant correlations were found between insulin resistance and metabolic improvements. Weight loss after bariatric surgery induced an improvement in metabolic fitness, related to the reduction in insulin resistance over a range of glucose tolerance statuses from normal to diabetic.     

胰岛素信号通路、炎症信号通路与泛素-蛋白酶体系统的交互作用

胰岛素抵抗是肥胖和2型糖尿病的主要表征。胰岛素信号通路根据是否需要胰岛素受体底物（insulin receptor substrate, IRS）介导可分为IRS介导和非IRS介导的信号通路,其中以IRS介导的信号通路为主。肥胖可增强炎性细胞因子表达并活化IKKβ/NF κB和JNK等炎症信号通路,抑制IRS酪氨酸磷酸化,从而阻止胰岛素的信号转导,降低胰岛素的敏感性,表现为胰岛素抵抗。泛素 蛋白酶体系统作为机体蛋白降解的主要途径,与胰岛素和炎症信号通路联系密切,一方面胰岛素信号通路的阻断可活化泛素依赖的蛋白降解,另一方面,泛素依赖的蛋白降解系统也可直接降解胰岛素和炎症信号通路的关键蛋白,影响胰岛素的作用。本文拟综述肥胖时,胰岛素信号通路、炎症相关信号通路和泛素 蛋白酶体系统之间的交互作用,在分子水平上探讨胰岛素抵抗的发生机制。     

Relation of Leptin to Insulin Resistance Syndrome in Children

Objectives: To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children. Research Methods and Procedures: Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11‐ to 14‐year‐old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (M_lbm). Children were divided by median BMI (boys = 20.5 kg/m²; girls = 21.4 kg/m²) into below‐median (thin) and above‐median (heavy) groups. Correlation coefficients between log‐leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race. Results: BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, M_lbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and M_lbm in heavy children and with insulin in thin children. Discussion: Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long‐term consequences in the development of the obesity‐insulin resistance‐related cardiovascular risk profile.     

Impact of Obesity and Body Fat Distribution on Cardiovascular Risk Factors in Hong Kong Chinese

Objective: Body fat distribution has been reported to differentially contribute to the development of cardiovascular risk. We report the relative associations between general and central obesity and risk factors in 2893 Chinese subjects recruited from the Hong Kong population. Research Methods and Procedures: Anthropometric parameters [waist circumference (WC) and BMI], surrogate measures of insulin resistance (fasting plasma glucose and insulin, oral glucose tolerance test, 2 hours glucose and insulin), fasting lipids (total, low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol, and triglycerides) and systolic and diastolic blood pressure were measured. General obesity was classified as BMI ≥25.0 kg/m² and central obesity as a WC ≥80 or ≥90 cm in women and men, respectively. Results: A total of 39.2% of the population was found to be obese. Obesity per se increased the levels of the risk factors, but central adiposity contributed to a greater extent to adverse high‐density lipoprotein‐cholesterol, triglyceride, and insulin resistance levels. There was a continuous relationship between increasing obesity, both general and central, and cardiovascular risk, with lowest risk associated with the lowest indices of obesity. In the 1759 nonobese subjects divided into quartiles of BMI or WC, the levels of the cardiovascular risk factors still significantly increased with increasing quartiles of adiposity. Discussion: Central adiposity appears to contribute to a greater extent than general adiposity to the development of cardiovascular risk in this population. The relationship between obesity parameters and risk is a continuum, with risk factors significantly increasing even at levels usually considered nonobese. These observations support the proposed redefinition of overweight and obesity in Asian populations using lower cut‐off points.     

Linkage Analysis of Factors Underlying Insulin Resistance: Strong Heart Family Study

In previous work in non‐diabetic participants of the Strong Heart Family Study, we identified three heritable principal components of nine insulin resistance (IR) phenotypes: 1) a glucose/insulin/obesity factor, 2) a blood pressure factor, and 3) a dyslipidemia factor. To localize quantitative trait loci (QTL) potentially influencing these factors, we conducted a genome scan of factor scores in Strong Heart Family Study participants. Approximately 599 men and women, ≥18 years of age, in 32 extended families at three centers (in Arizona, Oklahoma, and North and South Dakota), were examined between 1997 and 1999. We used variance components linkage analysis to identify QTLs for the IR factors. With age, sex, and study center as covariates, we detected linkage of the glucose/insulin/obesity factor to chromosome 4 (robust logarithm of the odds (LOD) = 2.2), the dyslipidemia factor to chromosome 12 (robust LOD = 2.7), and the blood pressure factor to chromosome 1 (robust LOD = 1.6). The peak linkage signals identified for these IR factors support several positive findings from other studies and occur in regions harboring interesting candidate genes. The corroboration of existing QTLs will bring us closer to the identification of the functional genes that predispose to IR.     

线粒体自噬影响胰岛素抵抗的作用及机制

胰岛素抵抗（IR）是诱发许多代谢疾病的关键因素,包括代谢综合征、非酒精性脂肪性肝病、动脉粥样硬化和2型糖尿病（T2DM）。随着相关代谢疾病日益增多,寻找新的治疗靶点迫在眉睫。线粒体自噬是一种选择性自噬,其通过清除受损和功能失调的线粒体以维持正常线粒体功能和能量代谢。研究发现,线粒体自噬在代谢疾病中有积极作用,线粒体自噬受到各种信号通路与信号分子调控而改善代谢疾病,如AMPK/ULK1、PINK1/Parkin信号通路以及BNIP3/Nix和FUNDC1等信号分子。本文阐述了线粒体自噬在胰岛素抵抗中的作用及调控机制,综述了近年的相关研究进展。     

Waist Circumference and Cardiovascular Risk Factors in Prepubertal Children

Objective: Intra‐abdominal fat has been identified as being the most clinically relevant type of fat in humans. Therefore, an assessment of body‐fat distribution could possibly identify subjects with the highest risk of adverse lipid profile and hypertension. Few data on the relationship between body‐fat distribution and cardiovascular risk factors are available in children, especially before puberty. Research Methods and Procedures: This cross‐sectional study was undertaken to explore the relationship between anthropometric variables, lipid concentrations, and blood pressure (BP) in a sample of 818 prepubertal children (ages 3 to 11 years) and to assess the clinical relevance of waist circumference in identifying prepubertal children with higher cardiovascular risk. Height, weight, triceps and subscapular skinfolds, waist circumference, and BP were measured. Plasma levels for triacylglycerol, total cholesterol, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) were determined. Results: Females were fatter than males (5.8 [3.5] vs. 4.8 [3.3] kg of fat mass; p < 0.01). Males had higher HDL cholesterol and ApoA1/ApoB plasma concentrations than females (p < 0.001 and p < 0.01, respectively). Waist circumference had a higher correlation with systolic and diastolic BP (r = 0.40 and 0.29, respectively; p < 0.001) than triceps (r = 0.35 and 0.21, respectively; p < 0.001) and subscapular (r = 0.28 and 0.16, respectively; p < 0.001) skinfolds and relative body weight (0.33 and 0.23, respectively; p < 0.001). Multivariate linear model analysis showed that ApoA1/ApoB, HDL cholesterol, total cholesterol/HDL cholesterol, and systolic as well as diastolic BP were significantly associated with waist circumference and triceps and subscapular skinfolds, independently of age, gender, and body mass index. Discussion: Waist circumference as well as subscapular and triceps skinfolds may be helpful parameters in identifying prepubertal children with an adverse blood‐lipids profile and hypertension. However, waist circumference, which is easy to measure and more easily reproducible than skinfolds, may be considered in clinical practice. Children with a waist circumference greater than the 90th percentile are more likely to have multiple risk factors than children with a waist circumference that is less than or equal to the 90th percentile.