What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?

Although obesity is often associated with insulin resistance and a cluster of metabolic disturbances, the existence of a subgroup of healthy but obese individuals has been postulated. It is unclear why some obese individuals fail to show traditional risk factors associated with the insulin resistance syndrome despite having a very high accumulation of body fat. To address this issue, we identified and studied a subgroup of metabolically normal but obese (MNO) postmenopausal women to gain insight into potential physiological factors that may protect them against the development of obesity-related comorbidities. We carefully examined the metabolic characteristics of 43 obese, sedentary postmenopausal women (mean +/- SD, 58.0 +/- 6.0 yr). Subjects were classified as MNO or as metabolically abnormal obese (MAO) based on an accepted cut-point for insulin sensitivity (measured by the hyperinsulinemic/euglycemic clamp technique). Thereafter, we determined 1) body composition (fat mass and lean body mass), 2) body fat distribution (abdominal visceral and sc adipose tissue areas, midthigh sc adipose tissue and muscle attenuation), 3) plasma lipid-lipoprotein levels, 4) plasma glucose and insulin concentrations, 5) resting blood pressure, 6) peak oxygen consumption, 7) physical activity energy expenditure, and 8) age-related onset of obesity with a questionnaire as potential modulators of differences in the risk profile. We identified 17 MNO subjects who displayed high insulin sensitivity (11.2 +/- 2.6 mg/min.kg lean body mass) and 26 MAO subjects with lower insulin sensitivity (5.7 +/- 1.1 mg/min.kg lean body mass). Despite comparable total body fatness between groups (45.2 +/- 5.3% vs. 44.8 +/- 6.6%; P: = NS), MNO individuals had 49% less visceral adipose tissue than MAO subjects (141 +/- 53 vs. 211 +/- 85 cm(2); P: < 0.01). No difference was noted between groups for abdominal sc adipose tissue (453 +/- 126 vs. 442 +/- 144 cm(2); P: = NS), total fat mass (38.1 +/- 10.6 vs. 40.0 +/- 11.8 kg), muscle attenuation (42.2 +/- 2.6 vs. 43.6 +/- 4.8 Houndsfield units), and physical activity energy expenditure (1060 +/- 323 vs. 1045 +/- 331 Cal/day). MNO subjects had lower fasting plasma glucose and insulin concentrations and lower insulin levels during the oral glucose tolerance test (P: values ranging between 0.01-0.001). No difference was observed between groups for 2-h glucose levels and glucose area during the oral glucose tolerance test. MNO subjects showed lower plasma triglycerides and higher high density lipoprotein cholesterol concentrations than MAO individuals (P: < 0.01 in both cases). Results from the questionnaire indicated that 48% of the MNO women presented an early onset of obesity (<20 yr old) compared with 29% of the MAO subjects (P: = 0.09). Stepwise regression analysis showed that visceral adipose tissue and the age-related onset of obesity explained 22% and 13%, respectively, of the variance observed in insulin sensitivity (total r(2) = 0.35; P: < 0.05 in both cases). Our results support the existence of a subgroup of obese but metabolically normal postmenopausal women who display high levels of insulin sensitivity despite having a high accumulation of body fat. This metabolically normal profile is associated with a lower accumulation of visceral adipose tissue and an earlier age-related onset of obesity.     

Effects of weight loss after bariatric surgery on epicardial fat measured using echocardiography

Epicardial fat assessed using echocardiography is associated with abdominal visceral adipose tissue and cardiovascular risk factors. Because of its location, epicardial fat may directly affect the coronary vasculature and myocardium through local secretion of bioactive molecules. This study examines the effects of weight loss after bariatric surgery on epicardial adipose tissue in patients with severe obesity. Clinical data and echocardiograms of 23 patients with severe obesity who had echocardiograms recorded before and 8.3 +/- 3.7 months after undergoing bariatric surgery were retrospectively reviewed. Epicardial fat thickness was measured as the hypoechoic space anterior to the right ventricle in both the parasternal long- and short-axis views, and an average was obtained. At baseline, patients had increased epicardial fat compared with normal-weight controls matched for age, gender, and ethnicity (5.3 +/- 2.4 vs 3.0 +/- 1.1 mm, p <0. 001). Epicardial fat thickness was associated with the patient's initial weight in severely obese patients (r = 0.51, p = 0.011). Patients lost an average of 40 +/- 14 kg after surgery. Epicardial fat thickness decreased from 5.3 +/- 2.4 to 4.0 +/-1.6 mm (p = 0.001). Change in epicardial fat correlated with initial epicardial fat thickness measured using echocardiography (r = 0.71, p <0.001). In conclusion, epicardial fat thickness decreases in severely obese patients who have substantial weight loss after bariatric surgery. Measuring epicardial fat thickness using echocardiography may be useful to monitor visceral fat loss with weight reduction therapies.     

La grasa epicárdica se relaciona con la visceral,el síndrome metabólico y la resistencia a la insulina en mujeres menopáusicas

Introduction and objectives

Epicardial adipose tissue has been associated with several obesity-related parameters and with insulin resistance. Echocardiographic assessment of this tissue is an easy and reliable marker of cardiometabolic risk. However, there are insufficient studies on the relationship between epicardial fat and insulin resistance during the postmenopausal period, when cardiovascular risk increases in women. The objective of this study was to examine the association between epicardial adipose tissue and visceral adipose tissue, waist circumference, body mass index, and insulin resistance in postmenopausal women.

Methods

A cross sectional study was conducted in 34 postmenopausal women with and without metabolic syndrome. All participants underwent a transthoracic echocardiogram and body composition analysis.

Results

A positive correlation was observed between epicardial fat and visceral adipose tissue, body mass index, and waist circumference. The values of these correlations of epicardial fat thickness overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P < .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome than in those without this syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm ²; P = .03).

Conclusions

Epicardial fat thickness measured by echocardiography was associated with visceral adipose tissue and other obesity parameters. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome. Therefore, echocardiographic assessment of epicardial fat may be a simple and reliable marker of cardiovascular risk in postmenopausal women.Full English text available from:www.revespcardiol.org/en     

超重和肥胖成人心外膜脂肪组织和胰岛素抵抗的关系研究

目的研究超重和肥胖成人胰岛素敏感性、胰岛素抵抗及心外膜脂肪组织和胰岛素抵抗的关系。方法收集2005年3月至2005年12月在我院体检中心符合入选标准的资料210份,均具人体指标测量、空腹血生化检查和经超声测量心外膜脂肪组织厚度、腹壁脂肪厚度(SFT)等数据,根据中国肥胖工作组推荐的判定标准,分为超重肥胖组和体重正常组。采用稳态模式胰岛素抵抗指数(HOMA-IR)评价胰岛素抵抗。用SPSS 13.0软件进行统计分析。结果超重肥胖组SI显著低于体重正常组(P<0.01),FINS、HOMA-IR显著高于体重正常组(P<0.01),心外膜脂肪组织厚度明显厚于体重正常组(P<0.01);控制年龄、性别、腰围影响因素进行偏相关分析,显示心外膜脂肪组织厚度和FINS、HOMA-IR成正相关,相关系数分别为0.239、0.249,P<0.05;和SI成负相关,相关系数为0.249,P<0.05,SFT则与各个因素无相关性;逐步法多元线性回归分析显示,心外膜脂肪组织厚度和HOMA-IR呈正相关,标准化偏回归系数0.309,P<0.01,而SFT仅和BMI呈正相关。结论超重肥胖成人存在胰岛素敏感性降低、胰岛素抵抗,心外膜脂肪组织厚度和胰岛素抵抗成正相关,可能是新的心血管和代谢疾病的危险因素。     

Epicardial adipose tissue thickness in type 1 diabetic patients

Insulin resistance is getting important in the course of type 1 diabetes mellitus. Visceral fat depot is associated with insulin resistance and assessment of epicardial fat thickness is a way of measuring visceral fat. The aim of the study was to measure epicardial adipose tissue (EAT) thickness and to determine its relationship with waist-hip-ratio (WHR) and estimated glucose disposal rate (eGDR) in adult type 1 diabetic patients. Thirty-six type 1 diabetic patients (aged 31±8 years; Female/Male: 22/14) and 43 age, gender and BMI matched healthy controls were included. Fasting blood glucose (FBG), hemoglobin A1c, and lipid profiles were measured. Waist-hip-ratio (WHR) was calculated. Daily insulin dose/kg of patients were recorded and eGDR of all subjects was calculated. Epicardial adipose tissue (EAT) thickness was evaluated by echocardiography. EAT thickness of the type 1 diabetic patients was significantly higher than controls (3.30±1.06 vs. 2.30±0.34 mm, P<0.0001). EAT thickness was correlated with age (P=0.05; r=0.35), WHR (P=0.003; r=0.67), daily insulin dose/kg (r=0.45, P=0.005), and eGDR (r=-0.55, P=0.0004). Multivariate analysis revealed WHR and eGDR to be related to EAT among age, WHR, daily insulin dose/kg, eGDR, FBG, and hemoglobin A1c (r2 of the model=0.64). Epicardial adipose tissue thickness is increased in type 1 diabetic patients compared to controls and is related to WHR and eGDR in this group of patients. This measurement may point to the presence of insulin resistance in type 1 diabetic patients.     

Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non‐obese men

Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.     

Glucose uptake and perfusion in subcutaneous and visceral adipose tissue during insulin stimulation in nonobese and obese humans

To elucidate the role of adipose tissue glucose uptake in whole-body metabolism, sc and visceral adipose tissue glucose uptake and perfusion were measured in 10 nonobese and 10 age-matched obese men with positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose, and [(15)O]-labeled water during normoglycemic hyperinsulinemia. Whole-body and skeletal muscle glucose uptake rates per kilogram were lower in obese than in nonobese subjects (P < 0.01). Compared with nonobese, the obese subjects had 67% lower abdominal sc and 58% lower visceral adipose tissue glucose uptake per kilogram of fat. In both groups, insulin stimulated glucose uptake per kilogram fat was significantly higher in visceral fat depots than in sc regions (P < 0.01). Both sc and visceral adipose tissue blood flow expressed per kilogram and minute was impaired in the obese subjects, compared with the nonobese (P < 0.05). Fat masses measured with magnetic resonance images were higher in obese than in nonobese individuals. If regional glucose uptake rates were expressed as per total fat mass, total glucose uptake rates per depot were similar in obese and nonobese subjects and represented 4.1% of whole-body glucose uptake in obese and 2.6% in nonobese subjects (P < 0.02 between the groups). In conclusion, insulin-stimulated glucose uptake per kilogram fat is higher in visceral than in sc adipose tissue. Glucose uptake and blood flow in adipose tissue exhibit insulin resistance in obesity, but because of the larger fat mass, adipose tissue does not seem to contribute substantially to the reduced insulin stimulated whole-body glucose uptake in obesity.     

Adipose triglyceride lipase gene expression in human visceral obesity.

In comparison to subcutaneous (SC) fat, visceral adipose tissue is more sensitive to catecholamine-induced lipolysis and less sensitive to the antilipolytic effects of insulin. Variation in the expression of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been reported. We therefore hypothesized that expression of adipose triglyceride lipase (ATGL) is different in visceral and SC depot and investigated whether ATGL mRNA expression is related to obesity, fat distribution and insulin sensitivity. ATGL, LPL, and HSL mRNA expression was measured in 85 paired samples of omental and subcutaneous adipose tissue in normal glucose tolerant lean and obese individuals. In addition, we included a subgroup of obese (BMI >30 kg/m2) individuals with either impaired or preserved insulin sensitivity determined by euglycemic-hyperinsulinemic clamps. ATGL mRNA levels are significantly decreased in insulin resistant obese subjects. Independently of body fat mass, omental ATGL mRNA correlates with fasting insulin concentration, glucose uptake during the steady state of the clamp and HSL mRNA expression. In obese, but not in lean subjects, LPL and HSL mRNA expression was significantly higher in omental compared to SC fat. In both depots, HSL mRNA was significantly lower in obese individuals. Visceral HSL mRNA expression is closely related to adipocyte size and fasting plasma insulin concentrations, whereas visceral fat area significantly predicts visceral LPL mRNA expression. ATGL mRNA expression is not significantly different between omental and SC fat. HSL, but not ATGL mRNA expression is closely related to individual and regional differences in adipocyte size. Impaired insulin sensitivity was associated with decreased ATGL and HSL mRNA expression, independently of body fat mass and fat distribution.     

Relationship between hormone replacement therapy use with body fat distribution and insulin sensitivity in obese postmenopausal women.

The aim of this study was to compare the effect of hormone replacement therapy (HRT) on insulin resistance and central adiposity in obese postmenopausal women. Forty-five obese postmenopausal women (16 HRT users and 29 nonusers), with a mean age of 56.6 +/- 5.3 years and duration of current, continuous HRT use of 4.7 +/- 2.9 years, were included in the study. Subjects were studied using oral glucose tolerance tests, euglycemic clamping, dual photon x-ray absorptiometry, computed tomography, doubly labeled water, and treadmill testing. Insulin sensitivity, total fat, visceral fat, subcutaneous abdominal fat, thigh muscle attenuation, daily physical activity energy expenditure, peak oxygen consumption (Vo(2)) were measured. HRT users had lower body weight (88.0 +/- 11.0 v 98.2 +/- 15.0 kg, P =.05), lower body mass index (33.1 +/- 3.5 v 36.8 +/- 5.2 kg/m(2), P =.05), lower fat mass (38.3 +/- 7.3 v 44.1 +/- 10 kg, P =.05), less visceral adipose tissue (157 +/- 47 v 211 +/- 81 cm(2); P =.05), and higher peak Vo(2) (21.1 +/- 4.6 v 17.6 +/- 2.2 mL/kg/min, P =.001) than nonusers. After adjustment for total fat, we noted a trend for decreased visceral adipose tissue in HRT users (P =.09). After adjustment for peak Vo(2), the decreased visceral adipose tissue persisted in HRT users (P <.01). Insulin sensitivity per kilogram of lean body mass did not differ between HRT users (0.51 +/- 0.22 mmol/kg/min) and nonusers (0.49 +/- 0.22 mmol/kg/min). It was concluded that obese postmenopausal women using HRT have a more favorable body composition and fat distribution pattern than nonusers. Although visceral adipose tissue is decreased in HRT users, insulin sensitivity does not differ between HRT users and nonusers.     

Relationship between visceral fat,steroid hormones and insulin sensitivity in premenopausal obese women

Abstract: Objectives. The relationships between visceral fat distribution, steroid hormones and peripheral insulin sensitivity were studied. Setting. All subjects were hospitalized in the Institute of Internal Medicine of the University of Verona, Italy. Subjects. Nineteen fertile obese women were studied with ages ranging from 18 to 53 years and body mass indexes ranging from 27.3 to 48.4. Intervention. Body fat distribution was evaluated by waist-to-hip circumference ratio and by computed tomography. The insulin tolerance test was used to evaluate peripheral insulin sensitivity. Glucose, insulin and C-peptide were measured in fasting conditions and during glucose load; total and free plasma testosterone and urinary cortisol excretion were also determined. Results. Significant correlations emerged between visceral adipose tissue and fasting glucose, insulin, and C-peptide. but not between visceral adipose tissue and total testosterone, free testosterone or urinary cortisol excretion. A negative correlation emerged between visceral adipose tissue and insulin sensitivity (r = ?0.70; P < 0.01). No significant correlations were found between insulin sensitivity and age, body weight, body mass index, total adipose tissue, subcutaneous adipose tissue or waist-to-hip ratio. Total testosterone correlated with body weight, subcutaneous adipose tissue and total adipose tissue. Free testosterone and urinary cortisol excretion correlated positively with body weight, and negatively with age. No correlation was found between insulin sensitivity and total testosterone, free testosterone or urinary cortisol excretion. The correlation between visceral adipose tissue and insulin sensitivity remained significant even after adjusting for both age and the body mass index. Conclusions. Our study shows that visceral fat is more closely associated with aberrations of insulin sensitivity than with obesity itself. Total testosterone, free testosterone and urinary cortisol excretion in our subjects do not seem to be associated with such aberrations.     

Insulin resistance early in adulthood in subjects born with intrauterine growth retardation

In a case-control study that investigated the effect of intrauterine growth retardation (IUGR) on glucose homeostasis, 20-yr-old adults born with IUGR were shown to be hyperinsulinemic in an oral glucose tolerance test, suggestive of insulin resistance. The aim of this study was to ascertain the decreased insulin sensitivity in young IUGR-born adults compared to that in controls. We studied 26 IUGR-born subjects and 25 controls, aged 25 yr. Insulin sensitivity was assessed by peripheral glucose uptake and monitoring free fatty acid (FFA) concentrations under euglycemic hyperinsulinemic clamp. The percent body fat was significantly higher in the IUGR group (27.2 +/- 7.6% vs. 22.0 +/- 7.3%; P = 0.02), contrasting with comparable body mass index in both groups. Insulin-stimulated glucose uptake was significantly lower in IUGR-born subjects than in controls (6.7 +/- 2.9 vs. 8.0 +/- 1.9 mg/kg fat-free mass x min; P = 0.05), and the difference remained significant after adjustment for body mass index, total body fat, or waist to hip ratio. In IUGR-born subjects, insulin-stimulated FFA suppression correlated significantly with peripheral glucose uptake (r2 = 0.23; P = 0.02). First phase insulin release in the iv glucose tolerance test, adjusted for insulin sensitivity, did not significantly differ between IUGR and control groups (442 +/- 284 vs. 391 +/- 209 pmol/L; P = 0.86). In conclusion, IUGR subjects have decreased insulin-stimulated glucose uptake as early as 25 yr of age without major impairment of insulin secretion. Low glucose uptake is associated with a lesser degree of FFA suppression in adipose tissue, which suggests a role of adipose tissue at an early stage of insulin resistance in these subjects.     

Relation of body fat distribution in men and degree of coronary narrowings in coronary artery disease.

This study evaluates the relation between body fat distribution and severity of coronary artery disease (CAD). The study sample comprised 33 patients with angiographically demonstrated CAD and 10 angiographically normal control subjects. Body fat distribution was estimated by computed tomography and degree of coronary narrowings by angiographic score. Body weight, body mass index and total and subcutaneous abdominal adipose tissue areas showed no statistical differences in the 2 groups; visceral abdominal adipose tissue area and the visceral to subcutaneous abdominal adipose tissue area ratio were significantly higher in patients with CAD (p < 0.05). There was a significant correlation between visceral fat and triglycerides, apoprotein B and sum of glucose and insulin during glucose oral tolerance test. Sum of insulin during glucose oral tolerance test, visceral abdominal adipose tissue area and visceral/subcutaneous abdominal adipose tissue area ratio correlated significantly with severity of CAD, as evaluated by coronary score in all subjects and in CAD patients alone. Stepwise multiple regression analysis using the coronary score as the dependent variable and anthropometric and metabolic parameters as independent variables shows that in all subjects and in CAD patients alone, visceral/subcutaneous abdominal adipose-tissue area ratio entered the regression first and the sum of insulin during glucose oral tolerance test second. The results suggest that visceral abdominal adipose tissue area and visceral to subcutaneous abdominal adipose tissue area ratio may be cardiovascular risk factors.     

Early hypertension is associated with reduced regional cardiac function, insulin resistance, epicardial, and visceral fat

Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47+/-1 years; body mass index: 28.4+/-0.6 kg m(-2); mean+/-SEM) included 13 with normal blood pressure (BP: 113+/-5/67+/-2 mm Hg), 13 with prehypertension (BP: 130+/-1/76+/-2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150+/-2/94+/-2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from -17.0+/-0.5% in normal blood pressure to -15.2+/-0.7% in prehypertension to -13.6+/-0.8% in those newly diagnosed with essential hypertension; P=0.004). Reduced circumferential strain was significantly associated with raised BP independent of age (r=0.41; P=0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function.     

原发性高血压患者体脂分布与胰岛素抵抗的关系

采用放射免疫分析法测定21例原发性高血压(EH)伴肥胖者,19例单纯性肥胖及16例正常体重者的空腹及口服75g葡萄糖耐量试验(OGTT)的血清胰岛素(INS)和C肽(CP)浓度.以腰臀围比(WHR)作为估计腹型肥胖的指标;以胰岛素敏感性指数(ISI)作为胰岛素抵抗(IR)指标.结果显示,在总体脂相似的情况下,EH伴肥胖者腹部脂肪蓄积较多,循环胰岛素清除率下降明显.提示EH伴肥胖患者较单纯性肥胖者有更严重的IR和高胰岛素血症(HI).EH患者的IR不但与总体脂增多有关,而且与体脂分布关系密切.     

RARRES2, encoding the novel adipokine chemerin, is a genetic determinant of disproportionate regional body fat distribution: a comparative magnetic resonance imaging study

Visceral fat mass is a strong and independent predictor of obesity-related disorders. To date, little is known about the genetic determinants of regional body fat distribution in humans. As candidates of regional fat distribution, we investigated the fat mass- and obesity-associated gene, the peroxisome proliferator-activated receptor-δ gene, and the retinoic acid receptor responder 2 (RARRES2) gene. We studied whether genetic variation within these genes contributes to the development of disproportionate visceral obesity and obesity-related traits, such as insulin resistance and β-cell dysfunction. We genotyped 337 subjects with an increased risk for type 2 diabetes mellitus for tagging single nucleotide polymorphisms (SNPs) in the 3 genes and performed association analyses with anthropometric data and parameters of insulin sensitivity and β-cell function. All subjects underwent an oral glucose tolerance test; a subset was additionally characterized by a hyperinsulinemic-euglycemic clamp. Body fat distribution was assessed by nuclear magnetic resonance imaging. The fat mass- and obesity-associated gene SNP rs8050136 was nominally associated with body mass index (P = .0130), but not with body fat distribution, after appropriate adjustment. Magnetic resonance imaging-quantified visceral fat mass was significantly associated with RARRES2 SNP rs17173608 and nominally associated with RARRES2 SNP rs10278590 in nonobese subjects (P = .0002 and P = .0423, respectively), with carriers of the minor alleles displaying lower visceral adipose tissue mass. Besides, the minor allele of SNP rs17173608 was nominally associated with a lower waist-to-hip ratio (P = .0295). In obese subjects, these associations were not detected. No associations were found between the peroxisome proliferator-activated receptor-δ gene and measures of whole-body adiposity and of body fat distribution. All SNPs were associated neither with insulin sensitivity nor with insulin secretion. Common genetic variation within RARRES2 is associated with increased visceral fat mass in nonobese subjects. In generalized obesity, this genetic effect may be masked by the close association between whole-body obesity and visceral fat mass.     

Severe insulin resistance contrasting with mild anthropometric changes in the adipose tissue of HIV-infected children with lipohypertrophy

BACKGROUND: The HIV-associated lipodystrophic syndrome (HIV-LDS) combines redistribution of fat mass with insulin resistance and hyperlipidemia. We have previously reported that HIV-LDS prevails in children in a comparable pattern as in adults. The metabolic activity itself of the lipodystrophic adipose tissue in HIV infection has been poorly studied. AIM AND METHODS: To assess in situ the insulin sensitivity of the lipohypertrophic subcutaneous abdominal adipose tissue using the microdialysis technique in HIV-infected children. Insulin sensitivity, assessed by the inhibition of glycerol release, was measured in the abdominal subcutaneous adipose tissue during a standard oral glucose tolerance test (OGTT) in six HIV-infected children under multi-therapy with abdominal lipohypertrophy (supra-iliac skinfold thickness >97th percentile) (HIV/LH+), in six obese children (obese group) and in eight HIV-infected children without lipodystrophy (HIV/LH-). RESULTS: Glucose tolerance was normal in all subjects. Mean insulin areas under the curve (IAUC) were significantly higher in the obese and HIV/LH+ groups than in HIV/LH- (8769+/-5429, 8161+/-4552 and 3618+/-2222 mU min l(-1), respectively; P=0.04 for the three groups comparison by the Kruskal-Wallis test), reflecting insulin resistance in the two former groups independent of a significant difference in percentage fat mass (37.2+/-4.7, 22.8+/-10.9 and 20.7+/-7.1%, respectively; P= 0.006). The crude inhibition of glycerol release, expressed as the relative change in dialysate glycerol concentration between baseline and 120 min, was not statistically different between the three groups (14% in obese, -38+/-14% in HIV/LH+ and -51+/-17% in HIV/LH- groups; P=0.3). The inhibition of glycerol release with respect to the circulating insulin level (expressed by IAUC) was similar in HIV/LH+ and obese groups (-6+/-5 x 10(-3) and -7+/-5 x 10(-3) l mU(-1) min(-1), respectively, P=0.4 for two-groups comparison by the U-Mann-Whitney test) and four-fold less than in the HIV/LH- group (-24+/-25 x 10(-3) l mU(-1) min(-1); P=0.02). CONCLUSION: These data argue in favor of insulin resistance in the adipose tissue of lipohypertrophies associated with HIV infection.     

Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects

Early reports suggested that resistin is associated with obesity and insulin resistance in rodents. However, subsequent studies have not supported these findings. To our knowledge, the present study is the first assessment in human subjects of serum resistin and insulin sensitivity by the insulin clamp technique. Thirty-eight nonobese subjects [age, 23 +/- 4 yr; body mass index (BMI), 25.4 +/- 4.3 kg/m(2)], 12 obese subjects (age, 54 +/- 8 yr; BMI, 33.0 +/- 2.5 kg/m(2)), and 22 obese subjects with type 2 diabetes (age, 59 +/- 7 yr; BMI, 34.0 +/- 2.4 kg/m(2)) were studied. Serum resistin concentrations were not different among nonobese (4.1 +/- 1.7 ng/ml), obese (4.2 +/- 1.6 ng/ml), and obese diabetic subjects (3.7 +/- 1.2 ng/ml), and were not significantly correlated to glucose disposal rate during a hyperinsulinemic glucose clamp across groups. Serum resistin was, however, inversely related to insulin sensitivity in nonobese subjects only (r = -0.35; P = 0.05), although this association was lost after adjusting for percent body fat. Serum resistin was not related to percent fat, BMI, or fat cell size. A strong correlation was observed between serum resistin and resistin mRNA expression from abdominal sc adipose tissue in a separate group of obese subjects (r = 0.62; P < 0.01; n = 56). Although the exact function of resistin is unknown, we demonstrated only a weak relationship between resistin and insulin sensitivity in nonobese subjects, indicating that resistin is unlikely to be a major link between obesity and insulin resistance in humans.     

Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women

Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = -0.22), or physical activity energy expenditure (r = -0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a lower glucose disposal per kg lean body mass compared to those with low visceral adipose tissue levels (0.44 +/- 0.14 vs. 0.66 +/- 0.28 mmol/kg x min; P < 0.05). Visceral adipose tissue is an important and independent predictor of glucose disposal, whereas markers of skeletal muscle fat content or physical activity exhibit little association in obese postmenopausal women.     

Unremitting embolus from cardiac myxoma at circumflex artery trifurcation

In this study we sought to evaluate whether increase in echocardiographic epicardial fat thickness, index of cardiac and visceral adiposity, is associated with impaired fasting glucose (IFG). Epicardial fat thickness and fasting plasma glucose (FPG) were measured in 115 consecutive non-diabetic Caucasian subjects [65 men, 50 women, median age of 42 years (range 30-64 years), median body mass index (BMI) of 27 kg/m(2) (range 22-33 kg/m(2)), who underwent routine transthoracic echocardiogram. Study subjects were designated as having normal fasting glucose (NFG) with FPG<100 mg/dl; and IFG with FPG (100 and <126 mg/dl). Epicardial fat thickness was significantly higher in IFG than NFG subjects (8+/-3 vs 6+/-2 mm; 7.1+/-4 vs 5.8+/-3 mm, p<0.001 for both and respectively in men and women. Epicardial fat thickness was significantly correlated with FPG (r=0.60, p<0.001). Our data indicate for the first time that higher epicardial fat thickness is associated with IFG in non-diabetic men and women. Echocardiographic epicardial fat measurement may be an additional tool for diabetes-related cardiac risk stratification.     

Visceral fat in hypertension: influence on insulin resistance and beta-cell function

Preferential visceral adipose tissue (VAT) deposition has been associated with the presence of insulin resistance in obese and diabetic subjects. The independent association of VAT accumulation with hypertension and its impact on insulin sensitivity and beta-cell function have not been assessed. We measured VAT and subcutaneous fat depots by multiscan MRI in 13 nondiabetic men with newly detected, untreated essential hypertension (blood pressure=151+/-2/94+/-2 mm Hg, age=47+/-2 years, body mass index [BMI]=28.4+/-0.7 kg x m(-2)) and 26 age-matched and BMI-matched normotensive men (blood pressure=123+/-1/69+/-2 mm Hg). Insulin secretion was measured by deconvolution of C-peptide data obtained during an oral glucose tolerance test, and dynamic indices of beta-cell function were calculated by mathematical modeling. For a similar fat mass in the scanned abdominal region (4.8+/-0.3 versus 3.9+/-0.3 kg, hypertensive subjects versus controls, P=0.06), hypertensive subjects had 60% more VAT than controls (1.6+/-0.2 versus 1.0+/-0.1 kg, P=0.003). Intrathoracic fat also was expanded in patients versus controls (45+/-5 versus 28+/-3 cm2, P=0.005). Insulin sensitivity was reduced (10.7+/-0.7 versus 12.9+/-0.4 mL x min(-1) x kg(ffm)(-1), P=0.006), and total insulin output was proportionally increased (64 [21] versus 45 [24] nmol x m(-2). h, median [interquartile range], P=0.01), but dynamic indices of beta-cell function (glucose sensitivity, rate sensitivity, and potentiation) were similar in the 2 groups. Abdominal VAT, insulin resistance, and blood pressure were quantitatively interrelated (rho's of 0.39 to 0.47, P<0.02 or less). In newly found, untreated men with essential hypertension, fat is preferentially accumulated intraabdominally and intrathoracically. Such visceral adiposity is quantitatively related to both height of blood pressure and severity of insulin resistance, but has no impact on the dynamics of beta-cell function.