Threshold values of visceral fat measures and their anthropometric alternatives for metabolic derangement in Japanese obese boys

OBJECTIVE: To determine whether the direct measure of visceral adipose tissue (VAT) by computed tomography (CT) is a superior diagnostic criterion to the anthropometric surrogates and more classical criteria of obesity. DESIGN: Cross-sectional, clinical study. Obese boys were classified according to the occurrence of abnormal values in either serum triglyceride, alanine aminotransferase or insulin level. A threshold value of each criterion for such metabolic derangement was calculated, using the analysis of receiver operating characteristic (ROC) curve. SUBJECTS: Seventy-five consecutive outpatient Japanese obese boys, ranging in age from 6 to 14 y, were studied. MEASUREMENTS: Anthropometric indices measured were height, body weight, waist girth, hip girth, triceps and subscapular skinfold thicknesses. Classical criteria for obesity used were percentage overweight (POW), body mass index (BMI) and percentage body fat. Waist girth, sagittal diameter by CT and waist-hip ratio (WHR) were evaluated as anthropometric surrogates for VAT. The areas of total abdominal fat (TAF), VAT and subcutaneous adipose tissue (SAT) were measured by CT at the level of the umbilicus. Clinical blood biochemistry was analyzed in fasting blood samples of obese boys. RESULTS: Thirty-three boys were classified into a no-complication group, and 42 into a complication group. TAF, VAT and SAT areas were closely associated with age, body size and degree of overweight and adiposity, while VAT/SAT was not. VAT area, sagittal diameter, TAF area and waist girth were closely correlated with alanine aminotransferase, insulin, TG and HDL-C. VAT/SAT, BMI, SAT area, WHR, percentage body fat and POW were less closely associated with these biochemical indices. The descending order of the values of area under the curve for the ROC curves were as follows: VAT>sagittal diameter>TAF>VAT/SAT>waist girth>BMI>WHR>percentage body fat>POW. Both VAT area and VAT/SAT gave >80% of sensitivity and specificity. Among the anthropometric indices studied, the sagittal diameter was the best surrogate of visceral fat measure. The sensitivity and specificity for the rest of the anthropometric indices were in an unsatisfactory range. The threshold values for VAT area, VAT/SAT and sagittal diameter were 58.0 cm(2), 0.276 and 19.2 cm, respectively. CONCLUSION: The threshold values for VAT area, VAT/SAT and sagittal diameter for detecting biochemical complication in Japanese obese boys were lower than the respective values reported in adults. These values can be used for classifying the obese boys into two types: those with medical problem and those without.     

Relationship between serum adiponectin and leptin concentrations and body fat distribution

The aim of this study was to investigate the relationship between adiponectin and leptin and body fat distribution. One hundred and ninety-seven women participated in this study. Subjects were grouped based on their visceral adipose tissue area (VAT). Body fat distribution was determined by computed tomography. The numbers in the subcutaneous fat dominant group (SFDG) and visceral fat dominant group (VFDG) were 79 and 118, respectively. The VFDG showed lower adiponectin levels than the SFDG (8.9+/-0.4 microg/ml versus 11.4+/-0.7 microg/ml, P=0.006), but leptin levels did not differ significantly between groups (18.8+/-1.1 ng/ml versus 17.7+/-1.8 ng/ml, P=0.111). Adiponectin levels were inversely correlated with fasting insulin, HOMA-IR, triglyceride, SBP and DBP, subcutaneous adipose tissue area (SAT) and VAT, and waist-to-hip ratio (WHR). Leptin levels were positively correlated with fasting glucose and insulin, HOMA-IR, triglyceride, SBP and DBP, VAT and SAT, and WHR (all values of P<0.05). VAT and HDL-cholesterol were independent variables of adiponectin concentrations (R(2)=0.207, P<0.0001), and SAT, fasting insulin, and HOMA-IR were independent variables of leptin concentrations (R(2)=0.498, P<0.0001) In conclusion, adiponectin and leptin concentrations, although associated with metabolic parameters, were more strongly influenced by VAT in the case of adiponectin, and by SAT in the case of leptin.     

Glucose tolerance and hyperinsulinaemia in obese women: role of adipose tissue distribution, muscle fibre characteristics and androgens

The separate independent statistical contribution of abdominal distribution of fat, hyperandrogenicity and muscle morphology to glucose intolerance and hyperinsulinaemia was analysed in 88 obese women. In univariate analyses the waist/hip circumference ratio (WHR), body fat and lean body mass were all positively associated, and SHBG levels were negatively associated with insulin and glucose values. Muscle fibre areas were positively correlated with insulin but not with glucose concentrations. Adjustment for other variables did not remove the positive association between WHR and fasting insulin and glucose concentrations. SHBG, free testosterone and type IIb fibre areas were, however, significant confounding factors in the relationship between WHR and summed insulin and glucose concentrations. We conclude that fat distribution in obese women is associated with fasting hyperglycaemia and hyperinsulinaemia, independently of androgens and muscle fibre morphology, but that reduced SHBG concentrations and increased type IIb fibre areas may partly explain increased glucose and insulin responses to an oral glucose load in abdominally obese women.     

Association of abdominal fat distribution and cardiometabolic risk factors among obese Korean adolescents

The association between abdominal fat distribution and cardiometabolic risk factors using direct measures of abdominal fat in adolescents has not been extensively researched. This study was designed to investigate the association between visceral and subcutaneous fat and cardiometabolic risk factors, in obese Korean adolescents. The study enrolled 175 adolescents (72 boys, 103 girls), from ages nine to 19 years, who were referred to the Obesity Clinic of Asan Medical Center. Body mass index (BMI) and waist circumference (WC) were measured for each study participant. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were calculated by computed tomography. Blood pressure, fasting plasma glucose, total cholesterol, triglycerides, HDL cholesterol, insulin and homeostasis model assessment (HOMA) score were measured. Systolic blood pressure, HDL cholesterol, fasting insulin and the HOMA score were significantly correlated with BMI, WC, VAT and SAT. In addition, VAT was significantly correlated with diastolic blood pressure and triglyceride levels. On multiple regression analysis, VAT was independently correlated with blood pressure, triglycerides, HDL cholesterol, fasting insulin and the HOMA score, while SAT was independently correlated with systolic blood pressure, fasting insulin and the HOMA score. This study determined that cardiovascular risk factors are closely associated with VAT, while insulin resistance is closely associated with both VAT and SAT among obese Korean adolescents.     

Decreased hepatic insulin extraction in upper body obesity: relationship to unbound androgens and sex hormone binding globulin

Hyperinsulinemia is a well-recognized entity of simple obesity. It is demonstrated that hyperinsulinemia is associated with upper body fat and fat cell hypertrophy. Androgen excess and lower levels of sex hormone binding globulin (SHBG) may produce fat cell hypertrophy and hyperinsulinemia as well. We measured serum insulin and C-peptide levels during an OGTT in two groups of obese premenopausal women to determine whether the hyperinsulinemia is due to hypersecretion or due to a diminished hepatic extraction of insulin. In this study, we found no correlation between the insulin and C-peptide levels or their ratio and the degree of obesity. However, a significant correlation was found between the waist-to-hip circumference ratio (WHR), used as an index of body fat distribution, and the areas of insulin (r = 0.55; P less than 0.001) and C-peptide (r = 0.51; P less than 0.001). SHBG and free androgen index (FAI) were also significantly related to these areas. The peripheral C-peptide/insulin molar ratio has been assumed to reflect changes in hepatic insulin extraction while the corrected C-peptide response reflects beta-cell function. WHR was negatively related to this ratio (r = -0.44; P less than 0.005) and SHBG showed a positive correlation (r = 0.34; P less than 0.05). Stepwise multiple regression analysis revealed that the 2-h insulin and C-peptide values and both curve areas can be explained up to 40-80% by sex hormones and anthropometric variables. Also the C-peptide/insulin molar ratio is dependent in a first step on WHR (r2 = 0.23; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of body fat distribution to the metabolic clearance of insulin in premenopausal women

The effects of body fat distribution on the metabolic clearance rate of insulin (MCR) and its relationship to peripheral insulin sensitivity (M/I) and androgenic activity were assessed in six nonobese and 20 obese premenopausal women with varying waist-to-hip girth ratio (WHR). As an index of androgenic activity, plasma levels of the sex hormone binding globulin (SHBG) and percentage free testosterone (%FT) were determined. The mean MCR in the obese and nonobese groups were similar (571 +/- 29 vs 578 +/- 31 ml/min/m2). Within the obese group, MCR varied between 401 and 822 ml/min/m2 and was inversely correlated with the WHR (r = -0.50, P less than 0.05). The reduction in MCR with upper body fat localization was observed at both sub- and supra-maximal plasma insulin levels. MCR correlated negatively with fasting and postglucose challenge plasma insulin levels and positively with M/I. MCR also correlated with plasma SHBG and %FT levels. We conclude that upper body fat localization is associated with diminished insulin clearance. This diminution is closely aligned with the degree of peripheral insulinemia and insulin sensitivity. The increase in androgenic activity may contribute to the aberrant insulin clearance observed in upper body obese subjects.     

Circadian variations of androstenedione, dehydroepiandrosterone sulfate and free testosterone in obese women with menstrual disturbances

OBJECTIVE: To assess the 24 h profile of androgenemia related to the androgens of both the ovarian and adrenal origin in obese women with menstrual disturbances. METHODS: The association of body mass and body fat distribution with circadian variations of selected androgens of ovarian and adrenal origin was examined in 16 obese women with menstrual disturbances (BMI between 38 and 51 kg/m2; WHR between 0.80 and 0.99) and in 16 healthy volunteers with normal body weight (BMI between 21 and 24.6 kg/m2; WHR between 0.73 and 0.76). The age range of all subjects was 29 to 40 (mean: 36.9+/-3.2 years). RESULTS: lts. Both the patients and control subjects showed a significant 24 h rhythm of androstenedione (A) and free testosterone (FT), while the circadian oscillations of dehydroepiandrosterone sulphate (DHEAS) did not differ significantly. In all obese women mean 24 h A, DHEAS and FT levels were significantly higher than those in controls. Moreover, the disturbances of DHEAS and FT secretion in the form of acrophase shift (for DHEAS from 7.37 to 3.45 h and for FT from 6.04 to 3.31 h) and the elevation of their 24 h amplitude values were observed. All obese women showed higher values of FT/A and FT/DHEAS indexes in selected clock time of day/night cycle (except those at 8.00 h for FT/A and at 5.00 h for FT/DHEAS) when compared to control group. A positive correlation was noted in all women studied between the values of BMI index, WHR ratio and mean 24 h level of androgens studied as well as FT/A and FT/ DHEAS indexes. A weaker correlation was found between body mass and body fat distribution on the one hand and fasting level of hormones studied on the other. Higher correlation between the values of WHR ratio and mean 24 h FT levels as well as FT/DHEAS indexes were obtained in obese women when compared to those of healthy subjects. CONCLUSIONS: Our findings suggest that, when assessing the androgen disturbances in obese patients, it is more useful to determine their circadian pattern than the basal level. The most reliable indicators of hyperandrogenism in obese women are: the 24 h concentration profile of FT and the value of FT/DHEAS index, not only during fasting but also after a meal at various time intervals. Circadian FT concentration and FT/DHEAS index values are essential indicators for visceral distribution of adipose tissue.     

Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause

The menopausal status is associated with an increased risk of metabolic and cardiovascular diseases. Since the post-menopausal modifications have not been clearly investigated in obese women, we evaluated the influences of menopausal status on anthropometric, hormonal and biochemical characteristics in selected groups of normal-weight and obese women. We studied 92 female outpatients: 24 normal-weight pre-menopausal (Pre-NW) [body mass index (BMI) 23.6 +/- 0.48, age 44.8 +/- 0.68], 24 normal-weight post-menopausal (Post-NW) (BMI 23.7 +/- 0.44, age 55.5 +/- 0.69), 24 obese pre-menopausal (pre-OB) (BMI 32.3 +/- 0.45, age 44.6 +/- 0.75), 20 obese post-menopausal women (Post-OB) (BMI 32.9 +/- 0.57, age 55.2 +/- 0.82). All the subjects were non smokers and free from hypertension, diabetes or impaired glucose tolerance (IGT). Anthropometric parameters, body composition, 17 beta-estradiol, LH, FSH, androstenedione, SHBG, testosterone and leptin were determined. Free androgen index (FAI) and insulin resistance index (HOMA) were calculated. In comparison with Pre-OB, Post-OB had higher values of waist circumferences (p < 0.02), while Post-NW showed no difference. Total and LDL-cholesterol were high in Post-NW women, whereas in the obese subjects they were already elevated in the premenopausal period. SHBG levels declined and FAI increased in Post-OB in comparison with Pre-OB. SHBG levels showed an inverse correlation with BMI, waist and waist-to-hip ratio (WHR), while FAI positively correlated with waist values. Serum leptin levels were higher in Post-OB than in Pre-OB, whereas they were similar in normal-weight women. The rise of leptin levels may be related to the greater abdominal fat deposition. In addition, menopausal status of uncomplicated obese women is associated with a greater abdominal fat deposition and with higher values of free androgen index, which may be considered as factors of cardiovascular risk.     

Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity

The objectives of the study were to quantify the effect of a 1-year healthy eating-physical activity/exercise lifestyle modification program on insulin sensitivity in viscerally obese men classified according to their glucose tolerance status and to evaluate the respective contributions of changes in body fat distribution vs changes in cardiorespiratory fitness (CRF) to the improvements in indices of plasma glucose/insulin homeostasis. Abdominally obese, dyslipidemic men (waist circumference ≥90 cm, triglycerides ≥1.69 mmol/L, and/or high-density lipoprotein cholesterol <1.03 mmol/L) were recruited. The 1-year intervention/evaluation was completed by 104 men. Body weight, composition, and fat distribution were assessed by dual-energy x-ray absorptiometry/computed tomography. Cardiorespiratory fitness and cardiometabolic risk profile were measured. After 1 year, insulin sensitivity improved in association with decreases in both visceral (VAT) and subcutaneous adiposity (SAT) as well as with the improvement in CRF, regardless of baseline glucose tolerance. Further analyses were performed according to changes in glucose tolerance status: improvement (group I, n = 39), no change (group N, n = 50), or worsening (group W, n = 15) after 1 year. Groups I and N improved their insulin sensitivity and their CRF, whereas group W did not, while losing less VAT than groups I and N. Multiple regressions showed that reduction in VAT was associated with an improvement in homeostasis model assessment of insulin resistance, whereas reduction in SAT was rather associated with improvement of the insulin sensitivity index of Matsuda. Changes in CRF were not independently associated with changes in indices of plasma glucose/insulin homeostasis. A 1-year lifestyle intervention improved plasma glucose/insulin homeostasis in viscerally obese men, including those with normal glucose tolerance status at baseline. Changes in SAT and VAT but not in CRF appeared to mediate these improvements.     

Critical value for the index of body fat distribution based on waist and hip circumferences and stature in obese girls

OBJECTIVE: To determine the critical value for the standard deviation score (SDS) of waist-hip ratio (WHR)/height (Ht), as an age-adjusted measure of body fat distribution, in relation to occurrence of biochemical complications in obese girls. DESIGN: Cross-sectional, clinical study. The (WHR/Ht)-SDS was calculated as described previously. Obese girls were classified into two groups according to the occurrence of abnormal values in either serum triglyceride, alanine aminotransferase or insulin level. The criteria for obesity were subjected to the receiver operating characteristic (ROC) analysis. SUBJECTS: One-hundred and twenty-four outpatient Japanese obese girls, ranging in age from 9 to 15 y. MEASUREMENTS: Height, body weight, waist girth and hip girth as anthropometric measures. Percentage overweight, waist girth, WHR and (WHR/Ht)-SDS as criteria for obesity. Clinical laboratory analysis for fasting blood samples of obese children. RESULTS: Fifty-nine girls were classified into the no complication group, and 65 girls into the complication group. Those with complications were older, more obese, and their waist girth and WHR were larger, than the girls without complications. The (WHR/Ht)-SDS was >2-fold higher and lipoprotein profile was more atherogenic in the complication group than in the no complication group. Among the four criteria of obesity, (WHR/Ht)-SDS gave the ROC curve skewed furthest into the top left corner of the diagram. Both sensitivity and specificity for (WHR/Ht)-SDS were >80% at the critical value of 2.00. The sensitivity for waist girth was as high as that for specificity for the rest of the criteria were <80%. CONCLUSION: Only (WHR/Ht)-SDS showed high enough sensitivity and specificity to predict metabolic derangement in the present obese girls. (WHR/Ht)-SDS can serve as the diagnostic criterion that classifies obesity in Japanese adolescent girls into two types.     

Insulin sensitivity is correlated with subcutaneous but not visceral body fat in overweight and obese prepubertal children

AIM: Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-alpha) in prepubertal children. SUBJECTS AND METHODS: Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1-3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test. RESULTS: Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = -0.52; P < 0.01) and liver fat content (r = -0.44; P < 0.02) but not with visceral abdominal adipose tissue (VAT) (r = -0.193; P value not significant) and fat accumulation in skeletal muscle (r = -0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P < 0.01) as well as adiponectin (r = -0.53; P <0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P < 0.01; 20 and 16% of explained variance, respectively). CONCLUSIONS: In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content. Furthermore, contrary to adults, VAT and inflammation markers were not correlated with insulin sensitivity in children.     

Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes

This study examined the effects of aerobic exercise without weight loss, a hypocaloric high monounsaturated fat diet, and diet plus exercise (D+E) on total abdominal and visceral fat loss in obese postmenopausal women with type 2 diabetes. Thirty-three postmenopausal women (body mass index, 34.6 +/- 1.9 kg/m(2)) were assigned to one of three interventions: a hypocaloric high monounsaturated fat diet alone, exercise alone (EX), and D+E for 14 wk. Aerobic capacity, body composition, abdominal fat distribution (magnetic resonance imaging), glucose tolerance, and insulin sensitivity were measured pre- and postintervention. Body weight ( approximately 4.5 kg) and percent body fat ( approximately 5%) were decreased (P < 0.05) with the D and D+E intervention, whereas only percent body fat ( approximately 2.3%) decreased with EX. Total abdominal fat and sc adipose tissue (SAT) were reduced with the D and D+E interventions (P < 0.05), whereas visceral adipose tissue (VAT) decreased with the D+E and EX intervention, but not with the D intervention. EX resulted in a reduction in total abdominal fat, VAT, and SAT (P < 0.05) despite the lack of weight loss. The reductions in total abdominal fat and SAT explained 32.7% and 9.7%, respectively, of the variability in the changes in fasting glucose levels, whereas the reductions in VAT explained 15.9% of the changes in fasting insulin levels (P < 0.05). In conclusion, modest weight loss, through either D or D+E, resulted in similar improvements in total abdominal fat, SAT, and glycemic status in postmenopausal women with type 2 diabetes; however, the addition of exercise to diet is necessary for VAT loss. These data demonstrate the importance of exercise in the treatment of women with type 2 diabetes.     

不同BMI患者内脏脂肪差异性分析

目的探讨不同体质量指数（BMI）患者其内脏脂肪（VAT）含量的差异。 方法应用计算机断层扫描（CT）测量符合纳排标准的1094例于2017年1月1日至12月31日在广州医科大学附属第一医院门诊或住院患者的VAT含量、皮下脂肪（SAT）含量和腰围（WC）。根据上述患者的BMI水平将所有患者分为四组：体重过低组（BMI<18.5 kg/m²,n=56）,体重正常组（18.5 kg/m²≤BMI<24 kg/m²,n=444）,超重组（24 kg/m²≤BMI<28 kg/m²,n=253）和肥胖组（BMI≥28.0 kg/m²,n=81）。采用秩和检验方法探讨四组患者VAT、SAT和WC的差异。采用Spearman相关分析方法了解BMI分别和VAT、SAT、WC等指标间的相关关系。 结果1094例患者中数据齐全的共834例,其中患有心血管系统疾病有71例,呼吸系统疾病114例,消化系统疾病349例,泌尿系统疾病210例,生殖系统疾病19例,内分泌系统疾病29例。不同疾病种类患者在各BMI水平的VAT含量差异无统计学意义（P>0.05）。四组间的VAT、SAT和WC均存在显著的差异（P<0.01）。组间比较结果显示：SAT含量在肥胖组>超重组>体重正常组>体重过轻组（P<0.01）。VAT含量及WC两个指标的组间比较则显示,超重及肥胖组>体重正常组>体重过轻组（P<0.01）,在肥胖与超重两个组别间的比较则未发现差异的显著性（P>0.05）。Spearman相关分析结果显示,在正常体重组和超重组,BMI与VAT呈正相关关系（r分别为0.402、0.195,P<0.05）;在体重过轻组和肥胖组未发现两者的相关性（P>0.05）。BMI与SAT在正常体重组呈正相关关系（r=0.296,P<0.05）,而在其余三组则未发现（P>0.05）。BMI与WC的正相关关系体现在正常体重组和超重组（r分别为0.199、0.144,P<0.05）,而在体重过轻组和肥胖组未发现两者的相关关系（P>0.05）。 结论BMI作为肥胖程度判断的临床常用指标,与影像学肥胖的判断指标存在有限的相关关系。一定范围内的BMI水平有助于推测内脏脂肪含量,当体重过轻或肥胖达到某种程度时,BMI水平可能难以用于推测内脏脂肪的严重程度及其分布特征。     

Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones

OBJECTIVE: To correlate anthropometric, computed tomography and fat cell data from abdominal regions with the levels of serum insulin, C-peptide, leptin, tumor necrosis factor-alpha (TNF-alpha), testosterone, 17beta-estradiol, androstenedione, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SHBG). DESIGN AND METHODS: The sample consisted of 84 obese patients (29 men, 22 premenopausal women and 33 postmenopausal women) who had undergone abdominal surgery. Weight, height, percentage of body fat by skinfolds, waist, hip and thigh circumferences, sagittal and coronal diameters, visceral and subcutaneous area, serum hormones and fat cell data were studied. RESULTS AND CONCLUSIONS: Premenopausal women showed the lowest values in most abdominal distribution parameters, although, depending on the waist circumference criteria at the umbilicus level perimeter (W1) or midway between lower rib margin and iliac crest perimeter (W2), the population was classified differently, as gynoid or android. Although there were no differences in fat cell size between genders, gynoid women had smaller and more numerous fat cells than the android type. Perivisceral fat cell size was significantly smaller than subcutaneous fat cell size. In women, central obesity was significantly correlated with an increase in serum insulin, leptin, TNF-alpha, testosterone and androstenedione levels, and a decrease in 17beta-estradiol and DHEA-S, while in men significant correlations were positive with insulin and negative with testosterone and androstenedione. Fat cell size was positively correlated with serum levels of leptin, insulin, DHEA-S, androstenedione and inversely correlated with SHBG. These data indicate that hormones seem to interact not only with body fat distribution but also with fat cell size. This interaction differs between genders and between the different abdominal adipose tissue regions.     

Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents

Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.     

Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans

CONTEXT: Visfatin was recently identified as a protein highly expressed and secreted in adipose tissue with insulin-mimetic effect and is a candidate hormone to help explain the association among adipose tissue expansion, insulin resistance, and type 2 diabetes. OBJECTIVE: The objective of the study was to assess expression of visfatin in lean and obese subjects and in sc and visceral adipose tissue and moreover to explore the role of visfatin on insulin resistance in humans. DESIGN: We measured circulating visfatin and its mRNA expression in sc adipose tissue (SAT) in lean and obese subjects. Furthermore, we measured visfatin mRNA in visceral adipose (VAT) and SAT by quantitative RT-PCR. Finally, plasma visfatin and its mRNA in SAT were measured under free fatty acid-induced insulin resistance in healthy subjects. RESULTS: Plasma visfatin and its mRNA in SAT were significantly lower in obese subjects, compared with normal-weight controls. Both circulating visfatin and SAT visfatin mRNA were negatively correlated with body mass index, whereas no correlation was found with homeostasis model assessment. Significantly higher visfatin mRNA was found in VAT of obese subjects, compared with lean controls. Interestingly, visfatin mRNA in VAT was positively correlated with BMI. Elevation of free fatty acid induced a condition of insulin resistance but did not affect either circulating visfatin or its mRNA. CONCLUSIONS: Our findings show that, in human obesity, plasma visfatin is reduced, whereas visfatin mRNA is differentially regulated in SAT and VAT. Visfatin is not related to insulin resistance either as assessed by homeostasis model assessment or during lipid infusion.     

Effect of obesity and body fat distribution on sex hormones and insulin in men

To investigate the relationship between body fat distribution, sex hormones, and hyperinsulinemia in male obesity, we examined 52 obese men (body mass index [BMI], 35.0 +/- 6.1, mean +/- SD) and 20 normal-weight controls. Their waist to hip circumference ratio (WHR), which was used as an index of fat distribution, was 0.985 +/- 0.052 and 0.913 +/- 0.061 (P less than .005), respectively. Compared with controls, obese men presented significantly lower levels of total (357 +/- 132 v 498 +/- 142 ng/dL; P less than .005) and free testosterone (14.2 +/- 2.9 v 17.1 +/- 2.6 pg/mL; P less than .05) and sex hormone-binding globulin (SHBG; 41.7 +/- 31.9 v 66.2 +/- 18.6 nmol/L; P less than .001) without any significant difference on the other sex steroid or on gonadotropin concentrations. Fasting and glucose-stimulated insulin and C-peptide levels were significantly higher in obese than in controls, and in obese with the WHR value greater than 0.97 (corresponding to the distribution median) than in those with WHR lower or equal to 0.97. BMI was negatively correlated with testosterone (P less than .005), free testosterone (P less than .01), and SHBG (P less than .001) and positively with fasting (P less than .001) and glucose-stimulated (P less than .005) C-peptide concentrations, whereas no relationship was found between these variables and WHR values. On the contrary, WHR was significantly correlated with fasting and post-glucose insulin levels (P less than .05), but not with those of sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sex hormones and adipose tissue distribution in premenopausal cigarette smokers.

Androgen dominance is associated with android (abdominal) adiposity and increased health risk. Cigarette smoking has an anti-estrogenic effect in women and recent evidence has linked cigarette smoking with abdominally-localized adipose tissue. The relationship between cigarette smoking, endogenous sex steroid levels and adipose tissue distribution in women has not been examined. We assessed anthropometric indicators of fat distribution and serum levels of estradiol, testosterone and sex hormone-binding globulin (SHBG) in 56 women aged 20-35 years (27 cigarette smokers and 29 non-smokers). Free estradiol and testosterone were estimated. Endocrine and anthropometric variables were adjusted for overall fatness. Cigarette smokers had significantly higher mean serum levels of SHBG than non-smokers (63.38 nmol/l and 57.85 nmol/l, respectively; P less than 0.01); there were no differences in serum estradiol, testosterone or estimated free levels of these sex steroids. Cigarette smokers had a more android distribution of adipose tissue: significantly greater waist-to-hip ratio (WHR) (P less than 0.01), greater waist-to-thigh ratio (WTR) (P less than 0.02) and smaller thigh girth (P less than 0.05). Waist and umbilical girths were greater in cigarette smokers (P less than 0.0002), but there was no difference in the sum of central skinfold thicknesses (abdominal, iliac crest and supra-spinale). A significant interaction (P less than 0.05) of cigarette smoking with serum testosterone levels was observed in effects on WHR; the relative impact of serum testosterone upon abdominal adiposity was greater in cigarette smokers than in non-smokers. The results suggest that in premenopausal women, cigarette smoking promotes android adiposity by increasing abdominal fat deposition and decreasing femoral fat deposition via interactive effects with sex steroids. The results also suggest an effect of cigarette smoking on serum SHBG, independent of effects on androgen/estrogen balance.     

Predicting abdominal adipose tissue among women with familial partial lipodystrophy

The objective of the study was to determine correlations between magnetic resonance imaging (MRI) measures of truncal adiposity (trunk fat percentage [TrF %_MRI], visceral adipose tissue [VAT], and subcutaneous abdominal adipose tissue [SAT]), simple clinical measures (body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]), and bioelectrical impedance analysis (BIA)-derived measures (total fat percentage [TF %] and TrF %_BIA) in female patients with familial partial lipodystrophy (FPLD). Our secondary aim was to generate and cross-validate predictive equations for VAT and SAT using these simple clinical and BIA-derived variables. Measures of truncal adiposity were measured using 1.5-T MRI (VAT, SAT, and TrF %_MRI) and Tanita (Tokyo, Japan) 8-electrode body composition analyzer BC-418 (TrF %_BIA) in 13 female FPLD patients. Pearson correlation coefficients were determined among the various adiposity parameters (BMI, WC, WHR, SAT, VAT, TrF %_MRI, TrF %_BIA, and TF %). Equations to estimate VAT and SAT were determined among 6 of the 13 FPLD subjects using multilinear regression analysis, and the best equations were then cross-validated in the remaining 7 subjects. Variables entered into the model included age, BMI, WC, WHR, TrF %_BIA, and TF %. The TrF %_MRI showed moderate correlation (r = 0.647, P = .02) with the TrF %_BIA, but the discrepancy between the 2 variables increased with increasing truncal adiposity. The strongest correlate for TrF %_MRI was BMI (r = 0.886, P < .0001). Visceral adipose tissue was poorly associated with simple clinical measures of BMI, WC, and WHR, but was inversely correlated with TF %, TrF %_BIA, and SAT. The TF % was the strongest correlate for both SAT and VAT. Thus, the best regression equation for VAT included age, BMI, WC, and TF % (R² = 1.0), whereas that for SAT only included TF % (R² = 0.75). The corresponding standard error of the estimate for the predictive equations was approximately 0.03 % and 18.5 % of the mean value of VAT and SAT, respectively. In the cross-validation study, differences between predicted and observed values of SAT were larger than those of VAT. We conclude that, among female FPLD patients, (1) no simple clinical anthropometric measure correlates well with VAT, whereas BMI correlates well with SAT; (2) BIA measure of TF % most strongly correlated with both VAT and SAT; and (3) based on the cross-validation study, VAT but not SAT could be more reliably estimated using the regression equations derived.     

Differences in the redox status of human visceral and subcutaneous adipose tissues – relationships to obesity and metabolic risk

ObjectiveMetabolic homeostasis depends on adipocyte metabolic responses/processes, most of which are redox-regulated. Besides, visceral and subcutaneous adipose tissues (VAT and SAT, respectively) differ metabolically and in their contribution to metabolic complications, but their redox characteristics in humans are still unknown. To understand the molecular mechanisms of metabolic syndrome development, we analysed the redox characteristics of VAT and SAT in groups with various body weights and metabolic risks.Material and MethodsFifty premenopausal women were classified according to body mass index into normal-weight and obese groups, and these groups were further sub-classified into metabolically healthy and metabolically obese (“at risk”) based on the homeostasis model assessment of insulin resistance (HOMA-IR) index and the triglyceride, total-, LDL- and HDL-cholesterol levels. Antioxidant components, NADPH oxidase protein and 4-hydroxynonenal (4-HNE) levels were analysed in VAT and SAT.ResultsCompared with the SAT, the VAT showed a higher basal level of glutathione (GSH) and GSH-dependent enzyme activities. Compared with the metabolically healthy normal-weight controls, the obese groups of women showed lower GSH levels in both depots. However, in these groups, additional prooxidative changes (increased NADPH oxidase and 4-HNE and decreased levels of SOD and/or CAT) were observed only in VAT.ConclusionsBecause of the critical role of thiol-redox homeostasis in lipogenesis, interdepot-differences in the GSH-dependent antioxidant part may be connected to the higher metabolic activity found in VAT. Analogously, the lower GSH levels that occur during obesity and the corresponding additional redox imbalance may be signs of VAT metabolic dysfunction that underlie the subsequent metabolic impairment.