Relationships between human serum resistin, inflammatory markers and insulin resistance

OBJECTIVE: Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)). SUBJECTS: A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values. RESULTS: Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45). CONCLUSIONS: Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.     

Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome

OBJECTIVE: To investigate the relationship between C-reactive protein (CRP) and various characteristics of the metabolic syndrome. DESIGN: Population-based cross-sectional study. SUBJECTS: A total of 1929 subjects undergoing a medical examination in a preventive medicine clinic (age, 50+/-10 y; 63% males). RESULTS: The proportion of subjects with CRP levels above the cut point generally used to indicate an obvious source of infection or inflammation (>10 mg/l) was 3, 7, and 15% in subjects who were normal weight, overweight, and obese, respectively. Subjects with obesity had markedly higher CRP level compared to patients without obesity regardless of whether they had the metabolic syndrome. However, there was no significant difference in CRP levels between nonobese subjects without the metabolic syndrome and subjects in whom the diagnosis of the metabolic syndrome was based on criteria other than obesity (adjusted geometric mean CRP 1.75 vs 2.08 mg/l, P=0.79). Similarly, CRP levels did not differ among obese subjects with and without the metabolic syndrome (adjusted geometric mean CRP 3.22 vs 3.49 mg/l, P=0.99). There was a linear increase in CRP levels with an increase in the number of metabolic disorders (P(trend) <0.0001), which was substantially diminished after controlling for body mass index (BMI) (P(trend)=0.1). Stepwise multivariate linear regression analysis identified BMI, triglyceride levels, HDL cholesterol levels (inversely), and fasting glucose as independently related to CRP levels. However, BMI accounted for 15% of the variability in CRP levels, whereas triglycerides, HDL cholesterol and fasting glucose levels accounted for only approximately 1% of the variability in CRP levels. CONCLUSION: Obesity is the major factor associated with elevated CRP in individuals with the metabolic syndrome. CRP levels in the range suggesting a source of infection or inflammation (>10 mg/l) are more common among obese subjects than in nonobese subjects.     

C-reactive protein and gestational diabetes: the central role of maternal obesity

Acute-phase biomarkers such as C-reactive protein (CRP) and IL-6 have emerged as predictors of incident type 2 diabetes mellitus, implicating chronic subclinical inflammation as a factor in the pathophysiology of diabetes. Gestational diabetes (GDM) identifies a population of women at high risk of subsequent type 2 diabetes mellitus, representing an early stage in the natural history of the disease. In this context, we performed a cross-sectional study to determine whether markers of subclinical inflammation are elevated in patients with GDM. We studied 180 healthy pregnant women undergoing oral glucose tolerance testing in the late second or early third trimester. Based on oral glucose tolerance testing and prepregnancy body mass index (BMI), participants were stratified into four groups: 1) normal glucose tolerance (NGT) lean (BMI, <25 kg/m(2)) (n = 65); 2) NGT overweight (n = 28); 3) impaired glucose tolerance (n = 39); and 4) GDM (n = 48). Median CRP level was highest in overweight NGT subjects (8.8 mg/liter), followed by GDM (5.5 mg/liter), impaired glucose tolerance (4.4 mg/liter), and lean NGT (4.4 mg/liter) (overall P = 0.0297). CRP was significantly correlated with prepregnancy BMI (r = 0.38, P < 0.0001), followed by fasting insulin (r = 0.27, P = 0.0002) and fasting blood glucose (r = 0.18, P = 0.016). In multivariate linear regression analysis, prepregnancy BMI emerged as the most important determinant of CRP concentration, whereas glycemic tolerance status was not a significant factor. Furthermore, the observed stepwise increase in CRP per tertile of prepregnancy BMI was not significantly attenuated by glycemic tolerance status or factors known to be associated with GDM. In summary, we demonstrate that maternal serum levels of CRP are not related to GDM but rather correlate significantly with prepregnancy obesity. An independent contribution of CRP to risk of GDM could not be confirmed. These data suggest a model in which obesity mediates a systemic inflammatory response, with possible downstream metabolic sequelae, including insulin resistance and glucose dysregulation.     

The influence of short-term fasting on serum leptin levels, and selected hormonal and metabolic parameters in morbidly obese and lean females.

The aim of our study was to compare the changes of serum leptin levels after 24-h fasting in morbidly obese and lean females and to search for hormonal and metabolic factors responsible for the changes in serum leptin levels. Fourteen morbidly obese and twelve lean females were included in the study. The blood for leptin, insulin, cortisol, blood glucose (BG), beta-OH-butyrate (beta-OH), dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) measurements was withdrawn before and after a 24-h fast. Basal body mass index (BMI), serum leptin, insulin and beta-OH levels were significantly higher in the obese compared to the lean group. The 24-h fasting decreased significantly BMI, serum leptin (by 20% in obese vs. 62% in lean subjects), insulin (by 23.3% in obese vs. 23.1% in lean subjects) and increased beta-OH (by 36% in obese vs. 1300% in lean subjects). Basal serum leptin levels correlated positively with BMI in both groups and with insulin levels in the obese group. The multiple regression analysis using delta leptin as dependent and the basal values of the rest of studied parameters as independent variables revealed that in lean subjects serum cortisol together with DHEA-S and BMI accounted for 71% of variations of the change of serum leptin levels (delta leptin = 0.31- 0.0101 cortisol + 0.0012 DHEA-S + 0.37 BMI). In obese subjects the 43.9% of variations of the change of serum leptin levels was explained by BMI together with age and DHEA-S levels (delta leptin = 36.09 + 0.35 BMI - 0.717 age- 0.008 DHEA-S). The drop of serum leptin levels after 24-h starvation is significantly blunted in obese compared to lean subjects. The reason for the difference is probably the insulin resistance possibly further modified by different DHEA-S levels.     

Innate immunity in obese asthmatic allergic and nonallergic adults

Obesity is characterized by activation of the innate immune responses and low grade systemic inflammation with increased levels of inflammatory cytokines. In the past two decades, the prevalence of both asthma and obesity has increased dramatically. The aim of the present study is to examine the relationship between innate immunity, obesity and asthma in allergic and non allergic obese persons by estimating interleukin-6 (IL-6) and C-reactive protein (CRP) levels as markers of innate immunity. The study included 2 groups of asthmatic patients; 50 obese asthmatic and 50 lean asthmatic patients. The obese asthmatic group included 25 allergic obese and 25 non-allergic obese asthmatics. Similarly the lean asthmatic group included 25 allergic and 25 non-allergic lean asthmatics. Body mass index (BMI), skin prick test, serum total IgE, peak expiratory flow rate (PEFR), interleukin-6 (IL-6) and C-reactive protein (CRP) levels were all assessed. A significant difference was found between allergic and non-allergic obese asthmatics and between allergic and non-allergic lean asthmatics as regards IgE, IL-6 and CRP (P=0.000). Comparison between allergic obese asthmatics and allergic lean asthmatics as regards BMI, IL-6 and CRP revealed high significant differences (P=0.000). In contrast no significant differences existed between them as regards IgE, PEFR (P=0.621, P=0.321 respectively). Comparison between non-allergic obese asthmatics and non-allergic lean asthmatics as regards BMI, IL-6 and CRP levels revealed highly significant differences (P=0.000). While no significant difference existed between them as regards IgE and PEFR (P=0.14, P=0.336 respectively). A significant negative correlation was found between PEFR and IgE in all groups (P=0.000) and negative correlation between PEFR and IL-6, CRP in all groups (P=0.000) except for allergic obese asthmatics group. Meanwhile, there was a significant positive correlation between BMI and IL-6 and CRP in both allergic and non-allergic obese asthmatics (P=0.000). In conclusion, obesity is associated with activation of the innate immune system leading to release of inflammatory cytokines more in non-allergic obese than allergic obese asthmatics. Control of obesity in such patients may lead to control of asthma.     

Endothelial activation and systemic inflammation in obese asthmatic children

Asthma and obesity are prevalent disorders, each with a significant impact on the public health. The causality relating obesity and asthma has not been established. The objective of this article is to investigate whether asthma could exacerbate the endothelial activation and to determine the relationship between systemic inflammation and endothelial activation in obese asthmatic children. Eighty-nine children (10-16 years old) were divided according to their diagnosis (asthma, obese nonasthmatic, and obese asthmatic children). Twenty healthy children formed the control group. Three adhesion molecules (E-selectin, sICAM-1, and sVCAM-1) and C-reactive protein (CRP) were measured in serum samples. The levels of sICAM-1 were significantly higher in obese nonasthmatic and obese asthmatic children versus control and lean asthmatic children (414.7+/-154.7, 434.9+/-181.1, 238.6+/-117.8, and 351.2+/-153.5 ng/mL, respectively). No difference was observed between obese nonasthmatic and obese asthmatic groups. No difference of the levels of CRP, E-selectin, and sVCAM-1 was found among the study groups. Correlation analysis showed that E-selectin associated significantly with body mass index (BMI), CRP and the other two adhesion molecules. CRP depended on BMI. sICAM-1 associated with CRP, BMI, and triglycerides. Correlations were verified in multiple regression analysis models in the whole study groups: CRP levels depended on sICAM-1, E-selectin, and sICAM-1 concentrations depended on BMI. Correlations were verified in asthmatic subjects: CRP depended on sICAM-1. These results confirmed the endothelial activation in obese children. Mild nonallergic asthma in our study did not exacerbate the endothelial activation in obese or lean asthmatic children. Significant association between systemic inflammation and endothelial activation was observed in asthmatic children.     

Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome

OBJECTIVE: To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1. METHODS: A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured. RESULTS: The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides. CONCLUSIONS: Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome.     

Angiogenic factors are elevated in overweight and obese individuals

BACKGROUND: Adipose tissue produces both vascular growth factors and inhibitors. Since obesity is associated with expansion of the capillary bed in regional adipose depots the balance between these factors may favor angiogenesis. OBJECTIVE: To investigate the relationship between body mass index and serum concentrations of vascular growth factors in human subjects. METHODS: Vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D, soluble VEGF receptor-2 (sVEGFr2), hepatocyte growth factor (HGF), angiopoietin-2, angiogenin and endostatin concentrations were measured in serum collected from 58 lean (24 males, 34 female, mean BMI, 22.2+/-0.3) and 42 overweight and obese (16 males and 26 females, mean BMI, 33.5+/-1.2) subjects after an overnight fast. RESULTS: Sexual dimorphism was apparent in the serum concentrations of VEGF-C, VEFG-D and angiopoietin-2 with significantly higher levels in female compared to male subject. VEGF, VEGF-C, VEGF-D, soluble VEGF receptor-2, angiopoietin-2, angiogenin and endostatin but not HGF were significantly elevated in overweight and obese subjects. Positive correlations between BMI and the serum concentrations of VEGF-C, VEGF-D, sVEGF-R2, angiopoietin-2, angiogenin and endostatin were observed even after adjustment for gender and age. CONCLUSIONS: Increased levels of vascular growth factors as well as the angiogenesis inhibitor endostatin are present in overweight and obese subjects and may contribute to previously documented increased risk of metastatic disease in obese subjects with cancer.     

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

OBJECTIVE: The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects. SUBJECTS: Lean type 2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55) were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control, CTL n = 50). RESULTS: The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR. CONCLUSION: Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.     

Effects of exercise on insulin sensitivity, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese male adolescents

The benefits of exercise on glucose metabolism, inflammation, and serum tartrate-resistant acid phosphatase 5a (TRACP 5a) protein levels in Chinese male adolescents have not been extensively analyzed. Therefore, we examined the effects of a 12-week exercise program on weight, adiposity, insulin sensitivity (IS), and inflammatory marker expression, including the novel macrophage marker TRACP 5a, in obese Chinese male adolescents. A total of 106 male adolescents were recruited from the Army Academy in Taiwan and classified as lean (body mass index [BMI], 20.9 ± 0.2 kg/m²) or obese (BMI, 27.7 ± 0.2 kg/m²). Body composition, IS, and inflammatory markers were measured in both groups at baseline and in the obese group after completion of a 12-week exercise program. Body weight, BMI, waist circumference, body fat mass and percentage, homeostasis model assessment for insulin resistance, fasting plasma glucose, fasting serum insulin, 2-hour postchallenge plasma glucose concentration, interleukin-6, C-reactive protein, and serum TRACP 5a were significantly higher in the obese group as compared with the lean group. In addition, serum TRACP 5a was positively correlated with body mass and fat indices. After completion of the exercise program, significant reductions in all anthropometric, metabolic, and inflammatory indicators, with the exception of serum TRACP 5a were observed. Although the obese participants remained obese, exercise training significantly improved IS and reduced interleukin-6 and C-reactive protein. Tartrate-resistant acid phosphatase 5a remained unaffected by exercise training, consistent with our hypothesis that it is associated with increased adipose tissue in obese individuals.     

超重及肥胖人群血清网膜素-1水平的变化

目的 探讨在南京地区人群中超重及肥胖者血清网膜素-1水平的变化及其与体重指数、腰围、脂联素之间的相关性.方法 从2008年3月至7月全国糖尿病和代谢综合征患病率及变迁调查江苏分中心的南京地区调查人群中,选取42例超重及肥胖者和55名健康对照者,分别测定体重指数、腰围、空腹胰岛素、窄腹血糖、血脂、血清网膜素-1及脂联素的水平,计算腰臀比及胰岛素抵抗指数.采用SPSS 15.0软件进行统计学分析,血清网膜素-1和各指标问的相关性分析采用Pearson相关分析法.结果 健康对照者的血清网膜素-1浓度为(0.024±0.012)μg/L,脂联素浓度为(7.7±2.4)mg/L,超重及肥胖者的血清网膜素-1浓度为(0.016±0.007)μg/L,脂联素浓度为(6.4±3.1)mg/L.结果 显示超重及肥胖者的血清网膜素-1及脂联素水平明显低于健康对照者(P<0.05),且相关分析表明血清网膜素-1与体重指数(r=-0.321,P<0.05)、腰围(r=-0.312,P<0.05)、腰臀比(r=0.243,P<0.05)及甘油三脂(r=-0.220,P<0.05)之间旱显著负相关,与脂联索(r=0.232,P<0.05)呈明显正相关.结论 超莆及肥胖者的血清网膜素-1水平较健康对照者显著下降,且血清网膜素-1浓度变化与脂联素之间呈正相关,提示网膜素水平变化可能与肥胖、胰岛素抵抗和2型糖尿病密切相关.     

Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.     

Glucose uptake and insulin action in human adipose tissue--influence of BMI, anatomical depot and body fat distribution.

OBJECTIVE: To examine and compare in vitro basal and insulin-stimulated glucose uptake in human omental and subcutaneous adipose tissue derived from lean, overweight or obese individuals, and in those with central or peripheral obesity. DESIGN: In vitro study of basal and insulin-stimulated 2-deoxyglucose uptake in human omental and subcutaneous adipose tissue explants derived from patients undergoing elective abdominal surgery. SUBJECTS: Fourteen lean (average age 47 y, average body mass index (BMI) 22 kg/m(2)), 12 overweight (average age 51 y, average BMI 27 kg/m(2)), and 15 obese subjects (average age 45 y, average BMI 39 kg/m(2)). Ten peripherally obese (average age 43 y, average WHR 0.76) and 17 centrally obese (average age 50 y, average waist-to-hip ratio (WHR) 0.92). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry), basal and insulin stimulated [(3)H]-2-deoxyglucose uptake in omental and subcutaneous adipose tissue explants. RESULTS: In adipose tissue from lean subjects transport of 2-deoxyglucose over basal was stimulated approximately two-fold by insulin. In contrast, 2-deoxyglucose transport in adipose tissue of obese or overweight subjects was not responsive to insulin. Following incubation with 100-nM insulin for 35 min, insulin-stimulated 2-deoxyglucose transport was significantly lower in both omental and subcutaneous adipose tissue of obese and overweight compared to lean subjects. Basal 2-deoxyglucose uptake was also significantly reduced in omental and subcutaneous tissue in obese compared to lean subjects. Depot-specific differences in 2-deoxyglucose uptake were also seen. Overall 2-deoxyglucose uptake was greater in omental than subcutaneous adipose tissue but this was due to increased basal levels rather than increased insulin action. The reduction in insulin-stimulated 2-deoxyglucose uptake seen in overweight and obese subjects was relatively similar in both depots. However, insulin responsive 2-deoxyglucose transport was significantly lower in the omental adipose tissue of subjects with central obesity, as compared to that of subjects with peripheral obesity. No difference in insulin induced 2-deoxyglucose transport was observed in the subcutaneous adipose tissue explants of subjects with either central or peripheral obesity. CONCLUSION: In lean individuals insulin responsiveness of omental and subcutaneous adipose tissue was similar, but basal glucose uptake was significantly higher in omental adipose tissue. Adipose tissue obtained from overweight as well as obese individuals is insulin resistant. This insulin resistance occurs at a lower BMI than previously expected and is not adipose-depot specific. However, in obese subjects with a central distribution of adiposity insulin resistance occurs at the site of omental adipose tissue, in contrast to those with peripheral obesity.     

The associations of body mass index, C-peptide and metabolic status in Chinese Type 2 diabetic patients.

BACKGROUND: Chinese Type 2 diabetic subjects are generally less obese than their Caucasian counterparts. We hypothesized that lean and obese Chinese Type 2 diabetic subjects have different metabolic and insulin secretory profiles. We compared the clinical features, C peptide and metabolic status between lean/normal weight and obese diabetic subjects. STUDY DESIGN: We conducted a cross-sectional study on 521 consecutive diabetic subjects newly referred to a Diabetes Clinic in 1996. The subjects were categorized into underweight (< 18.5 kg/m(2)), normal weight (18.5-23 kg/m(2)) and overweight (>/= 23 kg/m(2)) according to the re-defined WHO criterion for obesity in Asia Pacific Region. Metabolic and anthropometric parameters were compared between groups with different levels of obesity. RESULTS: In this cohort, 5.8, 30.6 and 63.7% of subjects were underweight, normal weight and overweight, respectively, using the 'Asian' criteria. Of these 521 subjects, 20% had fasting C-peptide less than 0.2 nmol/l, suggesting insulin deficiency. Fasting C-peptide showed linear increasing trend (P < 0.001) while HbA(1c) showed decreasing trend (P = 0.001) with BMI after adjustment for duration of disease. There were more subjects in the underweight group who were treated with insulin (41.3% vs. 13.9 and 8.2%, P < 0.001). Although homeostasis model assessment was similar amongst the three groups, systolic (P = 0.006) and diastolic blood pressure (P < 0.001) and triglyceride (P < 0.001) showed increasing, while HDL-C (P < 0.001) showed decreasing, trends across different BMI groups. The underweight patients had the lowest C-peptide and highest HbA(1c) while overweight patients had the highest C-peptide, blood pressure, triglyceride but lowest HbA(1c) levels. CONCLUSION: In Chinese Type 2 diabetic patients, lean subjects had predominant insulin deficiency and obese subjects had features of metabolic syndrome. Clinicians should have low threshold to initiate insulin therapy in lean Type 2 diabetic patients with suboptimal glycaemic control. In obese diabetic patients, aggressive control of multiple cardiovascular risks is of particular importance.     

Serum haptoglobin: a novel marker of adiposity in humans

Haptoglobin (Hp) is a glycoprotein involved in the acute phase response to inflammation. Our previous findings indicate that Hp mRNA and protein are present in the adipose tissue of rodents and that Hp gene expression is up-regulated in obese models. The aim of the present study was to establish whether Hp could be considered a marker of obesity in humans. In 312 subjects, serum Hp was correlated directly with body mass index (BMI), leptin, C-reactive protein (CRP), and age. In a multivariate stepwise regression analysis, BMI and CRP were independent determinants of serum Hp in females, with BMI having the strongest effect. CRP and age were independent determinants of serum Hp in males, although explaining only a modest percentage of the total variability. Serum Hp was positively associated with body fat, as assessed by dual-energy x-ray absorptiometry, both in female and in male groups. The level of significance improved when serum Hp was analyzed against fat mass adjusted for lean mass. Finally, Northern and Western blot analyses performed in biopsies of sc abdominal fat from 20 obese individuals showed the presence of Hp mRNA and protein in the human adipose tissue. In conclusion, serum Hp constitutes a novel marker of adiposity in humans, and the adipose tissue likely contributes to determine its levels.     

C-reactive protein is independently associated with total body fat, central fat, and insulin resistance in adult women.

OBJECTIVE: To investigate whether C-reactive protein (CRP) concentrations are influenced by body composition, insulin resistance, and body fat distribution in healthy women. DESIGN: Cross-sectional study of CRP plasma levels in adult women. SUBJECTS: A total of 201 apparently healthy normal weight, overweight, and obese women, aged 18-60 y. MEASUREMENTS: CRP plasma levels, several fatness and body fat distribution parameters (by bioimpedance analysis and anthropometry), and insulin resistance (HOMA(IR)), as calculated by homeostatic model assessment. RESULTS: CRP was positively correlated with age, body mass index (BMI), waist, fasting glucose and insulin, HOMA(IR), fat-free mass (FFM) and fat mass (FM). After multivariate analyses, age, HOMA(IR), waist and FM maintained their independent association with CRP. CONCLUSION: Our study has shown an independent relationship of central fat accumulation and insulin resistance with CRP plasma levels, thus suggesting that mild, chronic inflammation may be a further component of the metabolic syndrome and a mediator of the atherogenic profile of this syndrome.     

Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients.

OBJECTIVE: Insulin inhibition of insulin secretion has been described in normal lean subjects. In this study, we examined whether this phenomenon also occurs in the morbidly obese who often have severe peripheral insulin resistance. SUBJECTS: Twelve obese patients, normotolerant to glucose (8 F/4 M, body mass index (BMI)=54.8+/-2.5 kg/m(2), 39 y) and 16 lean control subjects (10 F/6 M, BMI=22.0+/-0.5 kg/m(2), 31 y). DESIGN AND MEASUREMENTS: An experimental study using various parameters, including an euglycemic hyperinsulinemic clamp (280 pmol/min/m(2) of body surface), an oral glucose tolerance test (OGTT), electrical bioimpedance and indirect calorimetry. RESULTS: The obese subjects were insulin resistant (M=19.8+/-1.6 vs 48.7+/-2.6 micromol/min kg FFM, P<0.0001) and hyperinsulinemic in the fasted state and after glucose ingestion. Fasting plasma C-peptide levels (obese 1425+/-131 pmol/l vs lean 550+/-63 pmol/l; P<0.0001) decreased less during the clamp in the obese groups (-16.9+/-6.9% vs -43.0+/-5.6% relative to fasting values; P=0.007). In the lean group, the C-peptide decrease during the clamp (percentage variation) was related to insulin sensitivity, M/FFM (r=0.56, P=0.03), even after adjustment for the clamp glucose variation. CONCLUSION: We conclude that, in lean subjects, insulin inhibits its own secretion, and this may be related to insulin sensibility. This response is blunted in morbidly obese patients and may have a role in the pathogenesis of fasting hyperinsulinemia in these patients.     

Tissue insulin sensitivity and body weight in polycystic ovary syndrome

OBJECTIVE: Polycystic ovarian syndrome (PCOS) and obesity both affect insulin sensitivity. This study was designed to investigate the biochemical indices of PCOS and tissue insulin sensitivity in groups of lean and obese women with clinically equivalent degrees of the syndrome, relative to control subjects. DESIGN: A prospective study of in vivo parameters and in vitro study of adipocytes to assess insulin sensitivity. PATIENTS: Six lean and 14 overweight patients fulfilling formal diagnostic criteria for PCOS were studied. The degree of hirsutism and amenorrhoea was similar in each group. Eight control subjects were also studied. MEASUREMENTS: Endocrine and metabolic parameters were measured in lean and overweight patients with PCOS and control subjects. In vitro studies of adipocyte insulin receptor binding and adipocyte insulin action were performed. RESULTS: The mean plasma LH level was elevated in both groups of PCOS but was significantly higher in the lean group (LH levels were 25.1 +/- 3.1 and 14.5 +/- 1.6 iu/l in lean PCOS and obese PCOS, respectively (P = 0.01)). There was a strong inverse correlation between BMI and LH levels (R = - 0.70, P = 0.001). Fasting insulin levels were elevated in both lean and obese groups (11.5 +/- 2.8 and 26.8 +/- 8.1 mU/l, respectively; P = 0.068). Mean serum testosterone and serum androstenedione levels were also elevated in PCOS compared to control subjects but there was no difference between the two groups of PCOS subjects. Insulin receptor binding in amenorrhoeic subjects with PCOS was low in both lean and obese patients with PCOS but was not significantly different between the two groups (0.79 +/- 0.17% and 0.66 +/- 0.07% per 10 cm2 cell membrane, respectively). Maximally insulin-stimulated rates of 3-O-methylglucose transport were low in both groups compared to previously studied normal subjects (0.96 +/- 0.21 and 0.64 +/- 0.07 pmol per 10 cm2 membrane in lean and obese PCOS subjects, respectively; P = NS). CONCLUSIONS: Lean subjects with a given phenotypic expression of PCOS have an equivalent degree of tissue insulin resistance compared to obese PCOS subjects. This implies that the insulin resistance may be a primary feature of PCOS. If this is so, a similar clinical degree of the syndrome may be brought about by genetically determined insulin resistance in lean subjects or by insulin resistance which is secondary to obesity.     

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r=-0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA < 4 (insulin sensitive) and HOMA>9 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulin-resistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.     

Thromboxane production in morbidly obese subjects

Postmortem studies have demonstrated that morbidly obese subjects, surprisingly, have less coronary atherosclerosis than obese subjects. However, the reasons for this apparent protection from atherosclerosis are not yet clear. Thromboxane A2, a marker of platelet activation, is greater in obese subjects than in lean subjects, and this might be a clue to their increased cardiovascular risk. However, data on thromboxane A2 in morbidly obese subjects are lacking; therefore, we hypothesized that lower levels of thromboxane A2 in morbidly obese subjects might play a role in their lower atherothrombotic burden. We measured the serum levels of thromboxane B2 (TxB2), a stable metabolite of thromboxane A2, high-sensitivity C-reactive protein (hs-CRP) and leptin in 17 lean subjects (body mass index [BMI] 22.9 ± 1.6 kg/m(2)), 25 obese subjects (BMI 32.6 ± 2.4 kg/m(2)), and 23 morbidly obese subjects (BMI 48.6 ± 7.1 kg/m(2)), without insulin resistance, diabetes, or overt cardiovascular disease. The serum TxB2 levels were lower in the lean subjects than in the obese subjects (p = 0.046) and in the morbidly obese subjects than in the lean and obese subjects (p = 0.015 and p <0.001, respectively). In contrast, the hs-CRP and leptin levels were greater in the obese than in the lean subjects (hs-CRP, p <0.001; leptin, p <0.001) and in the morbidly obese subjects than in the lean subjects (p <0.001 for both). Leptin was also higher in the morbidly obese subjects than in the obese subjects (p <0.001). TxB2 negatively correlated with leptin and BMI. hs-CRP correlated with leptin, and both also correlated with waist circumference, BMI, and homeostasis model assessment of insulin-resistance. In conclusion, insulin-sensitive morbidly obese subjects had lower levels of TxB2 than the obese subjects and lean subjects, suggesting that reduced platelet activation could play a role in the paradoxical protection of morbidly obese subjects from atherosclerosis, despite the greater levels of leptin.