Serum resistin level among healthy subjects: relationship to anthropometric and metabolic parameters

Resistin is a novel adipocyte-secreted hormone that has been proposed to be the link between obesity and diabetes, although little appears to be known regarding the physiological role of resistin in human beings. We aimed to explore the relationship between serum resistin level and certain anthropometric and metabolic parameters. Seventy-one healthy subjects with a mean body mass index of 23 kg/m 2 or greater were recruited in this study. Anthropometric measurements including height, weight, body mass index, waist and hip circumferences, waist-to-hip ratio, and blood pressure were recorded. Insulin resistance was measured by homeostasis model assessment (HOMA). Fasting serum resistin, insulin and plasma glucose, lipid profiles, and uric acid levels were measured. The results revealed that serum resistin level did not correlate with any markers for adiposity, blood pressure, fasting plasma glucose, or uric acid level for either sex. Serum resistin level correlated negatively with fasting insulin level (gamma=-0.455, P=.006) and HOMA (gamma=-0.455, P=.006) in women but not in men. Serum resistin level only correlated negatively with high-density lipoprotein cholesterol (HDL-C) level in men (gamma=-0.347, P=.038); there was no correlation between serum resistin level and lipid profiles in women. Multiple linear regression analysis using the logarithm of resistin as a dependent variable revealed that only HDL-C level (beta=-.058, P=.019) was an independent significant predictor for resistin in men; however, the analysis revealed that HDL-C level (beta=-.044, P=.029) and HOMA (beta=-.719, P=.004) were independent significant predictors for resistin in women. In conclusion, resistin is not related to adiposity, blood pressure, insulin resistance, fasting plasma glucose level, and most lipid profiles. Resistin correlates negatively with HDL-C level for both sexes. The role of resistin in metabolic syndrome warrants further investigation.     

甘肃地区PRKAA2基因单核苷酸多态性与2型糖尿病及脂联素、抵抗素关系的研究

目的 探讨甘肃地区PRKAA2基因rs2746342（G／T）单核苷酸多态性与T2DM及血清脂联素（APN）、抵抗素（Resistin）的关系。方法甘肃地区T2DM患者163例和正常对照组86名,两组年龄、性别匹配,采用聚合酶链反应／DNA限制性片段长度多态性（PCR／RFLP）、酶联免疫分析（ELISA）检测其基因多态性、空腹C肽（FC-P）、APN、Resistin,同时测身高、体重、血压、BMI、空腹血糖、血脂等。结果（1）T2DM组与正常对照组的基因型和等位基因频度分布存在显著差异（P〈0．05）;（2）T2DM组各基因型T／T、G／T、G／G中Resistin、TG、TC、LDL-C、FC-P依次降低,APN、HDL-C依次增高（P〈0．05）;（3）APN水平在糖尿病超重组低于糖尿病正常体重组和对照组,Resistin水平在糖尿病超重组高于糖尿病正常体重组和对照组（P〈0．05）;（4）相关分析表明APN水平与BMI、血压负相关,与C-肽正相关（P〈0．05）,Resistin水平与BMI、血压正相关,与G肽负相关（P〈0．05）;（5）T2DM超重组较T2DM正常体重组和正常对照组TG、LDL-C水平升高（P〈0．05）,HDL-C水平降低（P〈0．05）。结论甘肃地区PRKAA2基因rs2746342（G／T）单核苷酸基因多态性可能与T2DM及胰岛素抵抗、血清APN、Re—sistin水平关联。     

Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus

Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 ± 0.15 at baseline to 0.43 ± 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (ΔI_0-30/ΔG_0-30) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = −0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in 11 healthy subjects; but neither serum total nor HMW adiponectin changed. In conclusion, serum HMW adiponectin (but not total adiponectin) decreased rapidly after glucose loading in subjects with NGT or IFG; and the decrease of HMW adiponectin may be associated with an increase of serum insulin at 30 minutes.     

Factors affecting the serum levels of adipokines in Korean male patients with nonalcoholic fatty liver disease

BACKGROUND/AIMS: Adipokines are associated with various metabolic disorders including insulin resistance, obesity, and dyslipidemia. Metabolic disorders have also been reported to be associated with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to determine the relationship between the serum adipokine levels and the degrees of hepatic fat infiltration in NAFLD. This study also attempted to determine the independent factors influencing the serum adipokine levels in NAFLD. METHODOLOGY: Sixty-five Korean male patients were enrolled in this study. The degree of hepatic fat infiltration was classified into the following three groups according to the ultrasonographic findings: Group I, normal liver; Group II, mild fatty liver; and Group III, moderate to severe fatty liver. The anthropometric parameters, fasting serum adipokine levels including leptin, adiponectin and resistin were measured in all subjects. The level of insulin resistance was estimated using the HOMA-IR. RESULTS: The serum leptin levels increased with increasing degree of hepatic fat infiltration (mean +/- SD: Group I, 2.052 +/- 1.071; Group II, 2.879 +/- 1.016; and Group III, 4.457 +/- 1.965 ng/mL, P < 0.001). However, the serum adiponectin and resistin levels were similar. The fasting serum insulin level was only a related factor for the changes in the serum leptin levels (P = 0.004). There were no related factors for the change in the serum adiponectin and resistin levels. CONCLUSIONS: This study suggests an indirect role for leptin in the pathogenesis of NAFLD by inducing insulin resistance, resulting in increased fasting serum insulin level.     

Increased serum resistin in elite endurance athletes with high insulin sensitivity

Aims/hypothesis Resistin is an adipokine associated with obesity and type 2 diabetes in animal models, but in humans its role remains uncertain. This study was undertaken to test whether serum resistin is related to insulin resistance and markers of low-grade inflammation in elite athletes taken as a model of extreme insulin sensitivity.Subjects materials and methods In 23 elite athletes (sprinters, middle-distance and marathon runners) and in 72 sedentary men including lean and obese individuals with NGT, and obese individuals with IGT or new-onset type 2 diabetes, we assessed insulin sensitivity using a whole-body insulin-sensitivity index (WBISI) derived from a 3-h OGTT; energy homeostasis was also assessed by means of indirect calorimetry, along with circulating adipokines and low-grade pro-inflammatory cyto-chemokines.Results Professional athletes had increased WBISIs (p<0.001) and lipid oxidation (p<0.03); they also showed higher serum resistin concentrations (p<0.001), although the pro-inflammatory chemokines were not increased in comparison with the other study groups. Resistin was independently associated only with fasting plasma NEFA. Increased resistin was detected in the middle-distance and marathon runners, but not in the sprinters when compared with the lean, young, sedentary individuals.Conclusions/interpretation Serum resistin concentration is increased in elite athletes, providing evidence against the notion that resistin levels reflect insulin resistance in humans, as seen in animal studies. Increased resistin was observed in aerobic-endurance, but not sustained-power athletes and this feature appeared to be independently associated with parameters of fatty acid metabolism.     

Resistin polymorphisms are associated with cerebrovascular disease in Finnish Type 2 diabetic patients.

AIMS: Resistin is a hormone secreted by adipocytes and it is also expressed in monocytes. Resistin has been found to increase insulin resistance, a key feature in Type 2 diabetes. The aim of this study was to investigate whether resistin polymorphisms are associated with Type 2 diabetes and its clinical characteristics. METHODS: We studied the allele and genotype frequencies of the single-nucleotide polymorphisms (SNPs)-420 (C>G), +157 (T>C) and +299 (G>A) in the resistin gene in 258 Finnish Type 2 diabetics and 494 controls. RESULTS: These three markers were in significant linkage disequilibrium with each other. No significant (P<0.05) differences in the allele or genotype frequencies were observed between the study groups. Subjects with Type 2 diabetes showed a significant association between cerebrovascular disease and the SNPs-420 (P=0.004) and +299 (P=0.007), the G-G and A-A genotypes, respectively, had the highest frequencies. SNPs-420 (P=0.000) and +299 (P=0.002) in men and SNP+157 in men (P=0.005) and in women (P=0.019) showed significant association with higher mean blood glucose. The rare allele homozygotes also had the highest mean blood glucose values. We also observed associations between at least one of the SNPs and fasting blood glucose, glycosylated haemoglobin A1 (GHbA1), low-density lipoprotein (LDL) cholesterol and systolic and diastolic blood pressure. After correction for multiple comparisons, the association between the promoter variant SNP-420 and cerebrovascular disease in both genders and the associations between mean blood glucose and SNP-420 and SNP+299 in men remained significant. CONCLUSIONS: The results suggest that resistin may play a role in atherogenesis probably through increasing insulin resistance.     

Short-term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men

Objective Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid‐lowering and anti‐atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines. Research design and methods One‐centre, randomized, parallel three‐group study in 72 healthy men [mean age 32 ± 9 years, mean body mass index (BMI) 25·7 ± 3·2 kg/m²]. Patients Seventy‐two healthy men. Each group of 24 subjects received a 14‐day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14‐day treatment period. Measurements Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Results Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high‐density lipoprotein‐cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR. Conclusions Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.     

Decreased high-molecular-weight adiponectin in gestational diabetes: implications for the pathophysiology of Type 2 diabetes.

AIMS: Low serum concentrations of the insulin-sensitizing protein adiponectin predict the development of incident Type 2 diabetes (T2DM). It has recently emerged that the anti-diabetic activity of adiponectin may be mediated by its high-molecular-weight (HMW) isoform, circulating levels of which are decreased in T2DM. The relevance of decreased HMW adiponectin to incident T2DM, however, has not been assessed. Since gestational diabetes (GDM) identifies a population of young women at high risk of future T2DM (i.e. representing an early stage in the natural history of the disease), we sought to determine if decreased HMW adiponectin is a feature of GDM. METHODS: HMW and total adiponectin were measured in 121 women at the time of oral glucose tolerance testing (OGTT) in late pregnancy, following an abnormal glucose challenge test. Based on the OGTT, there were 41 women with and 80 without GDM. RESULTS: Median HMW adiponectin concentration was lower in women with GDM (3.5 microg/ml) than in those without GDM (5.5 microg/ml) (P < 0.0001). After full adjustment for covariates, mean HMW adiponectin remained significantly lower in women with GDM compared with their peers (3.6 vs. 5.3 microg/ml, P = 0.0035). HMW adiponectin was positively associated with insulin sensitivity (IS(OGTT)) (r = 0.38, P < 0.0001) and pancreatic B-cell function [insulin secretion-sensitivity index (ISSI)] (r = 0.33, P = 0.0002) and inversely related to blood glucose levels, including area-under-the-glucose-curve during the OGTT (AUC(glucose)) (r = -0.31, P = 0.0007). On separate multiple linear regression analyses, HMW adiponectin emerged as an independent determinant of AUC(glucose), IS(OGTT) and ISSI, respectively, mirroring the relationships of total adiponectin. CONCLUSIONS: HMW adiponectin is significantly decreased in women with GDM. Deficiency of HMW adiponectin may be an early event in the natural history of T2DM.     

Resistin levels in human immunodeficiency virus-infected patients with lipoatrophy decrease in response to rosiglitazone

Resistin is a recently recognized adipocytokine thought to contribute to insulin resistance. We determined resistin levels and metabolic parameters in 24 HIV-infected men and women with lipoatrophy and hyperinsulinemia and studied the effect of 12 wk of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone (4-8 mg/d) on resistin in these subjects. Participants completed metabolic testing before and after rosiglitazone including fasting determination of resistin, adiponectin, and leptin levels, serum inflammatory markers, and hyperinsulinemic euglycemic clamp testing. Resistin concentration decreased significantly after rosiglitazone (12.17 +/- 1.15 ng/ml to 10.23 +/- 1.05 ng/ml; P = 0.02), in conjunction with significant increases in adiponectin- (P < 0.001) and insulin- stimulated glucose disposal (P = 0.004). Leptin levels, as well as TNF-alpha, did not change with rosiglitazone. In summary, among HIV-infected subjects with insulin resistance and lipoatrophy, resistin levels decreased significantly after rosiglitazone. Further investigation into the physiological role of this peroxisome proliferator-activated receptor-gamma-responsive adipocytokine in the metabolic abnormalities associated with HIV is warranted.     

Resistin is associated with the inflammation process in patients with systemic autoimmune diseases undergoing glucocorticoid therapy: comparison with leptin and adiponectin

Objectives

We investigated the role of adipokines in patients with systemic autoimmune diseases who received glucocorticoid therapy.

Methods

Fifty-two patients with systemic autoimmune diseases who had started glucocorticoid therapy were prospectively enrolled. One hundred forty healthy persons were also studied as controls. Serum levels of 3 adipokines [resistin, leptin, and high molecular weight (HMW)-adiponectin] were measured with enzyme-linked immunosorbent assay kits before and at weekly intervals for 4 weeks during glucocorticoid therapy. The effects of lipopolysaccharide and dexamethasone on adipokine expression in human peripheral blood mononuclear cells (PBMCs) were also examined.

Results

The serum resistin level was significantly higher in patients than in controls before glucocorticoid therapy, and it decreased after glucocorticoid therapy. Consistent with these results, dexamethasone inhibited lipopolysaccharide-induced upregulation of resistin expression in PBMCs in vitro. Serum leptin and HMW-adiponectin levels were lower in the patients than in the controls at baseline, and both adipokine levels were increased after glucocorticoid therapy. There was a significant correlation between serum resistin and high-sensitivity C-reactive protein. However, there was no association between serum adipokines and intima-media thickness.

Conclusion

Resistin may be associated with the inflammatory process but not atherosclerosis in patients with systemic autoimmune diseases.     

High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men

Adiponectin is an adipocyte-specific secretory protein that possesses antidiabetic and antiatherosclerotic properties. Recent studies have demonstrated that the high molecular weight (HMW) multimer form is the active form of this protein. In patients with type 2 diabetes mellitus, HMW-total adiponectin ratio was reported to be a more useful marker than total adiponectin in the prediction of insulin resistance and metabolic syndrome. In the present study of healthy Japanese male subjects without any medication, we investigated the hypothesis that measuring only HMW adiponectin may be as effective as HMW-total ratio to predict insulin resistance and/or metabolic syndrome. This was a working community-based cross-sectional study of 637 male subjects aged 30 to 65 years. Total and HMW adiponectin concentrations in serum were measured by enzyme-linked immunosorbent assay using commercially available kits. Serum HMW adiponectin level was inversely correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.375, P < .0001) even after adjustment for age and body mass index (r' = -0.245, P < .0001). When we divided the study subjects into quartile groups with equal numbers of subjects, HOMA-IR in the 4 groups based on serum HMW adiponectin level was significantly different (P < .01). Metabolic syndrome score in the 4 groups based on serum HMW adiponectin level was also significantly different (P < .01). Area under the curve of receiver operator characteristic curves of HMW adiponectin (0.73) to evaluate the presence of insulin resistance (HOMA-IR >2.5) was larger than that of total adiponectin (0.68) or HMW-total ratio (0.70). Area under the curve of receiver operator characteristic curves of HMW adiponectin (0.70) to evaluate the presence of metabolic syndrome (body mass index-based modified criteria) was also larger than that of total adiponectin (0.65), but equal to that of HMW-total ratio (0.70). These results suggest that simply measuring HMW adiponectin may be as effective as HMW-total ratio to evaluate the presence of insulin resistance and metabolic syndrome, at least in nondiabetic subjects who are not receiving any medication.     

Adipokines influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis

Adipokines including leptin, adiponectin, visfatin, resistin, and interleukin (IL)-6 significantly influence energy metabolism, insulin sensitivity, and cardiovascular health. In the current study, we investigated serum levels of these adipokines in diabetic and nondiabetic patients on maintenance hemodialysis (MD) as compared with controls with a glomerular filtration rate greater than 50 mL/min. Serum leptin, adiponectin, high-molecular-weight (HMW) adiponectin, visfatin, resistin, and IL-6 were determined by enzyme-linked immunosorbent assay in control (n = 60) and MD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. Adiponectin, visfatin, resistin, and IL-6 were significantly elevated in MD patients as compared with controls. In multivariate analyses, sex and body mass index were independently correlated with serum leptin levels in both controls and MD patients. Furthermore, insulin resistance was independently and negatively associated with adiponectin and HMW adiponectin in both groups. Moreover, circulating resistin levels were independently correlated with serum visfatin concentrations in control and MD patients. However, various independent associations were only found in either controls or patients on MD. Thus, serum IL-6 levels were strongly and independently associated with C reactive protein and resistin in MD patients but not control subjects. We show that levels of various adipokines are significantly increased in MD patients. Furthermore, regulation of adipokines in vivo strongly depends on renal function. Regulation of HMW adiponectin is similar as compared with total adiponectin in the patients studied.     

Plasma resistin levels are associated with insulin resistance in older Japanese men from a rural village

Abstract Background: The role of resistin in the pathophysiology of insulin resistance in human is controversial and different in men and women. Thus, the discrepancy among previous reports may be resolved by gender-specific analysis of a large number of participants. Methods: From a single community, we recruited 746 men (mean age, 60±14 years) and 1033 women (63±12 years) during their annual health examination. We investigated whether plasma resistin levels are associated with insulin resistance evaluated by homeostasis of model assessment of insulin resistance (HOMA-IR) according to gender. Results: Resistin levels were significantly correlated with HOMA-IR in men, but not in women. Analysis of covariance showed that two regression lines were significantly different (F=9.941, P=0.002). Multiple linear regression analyses for resistin showed that the resistin levels (β=0.124, P<0.001) were independently and significantly associated with HOMA-IR as well as body mass index (BMI), alcohol consumption, smoking status, uric acid, γ-glutamyltransferase (GGT), and high molecular weight (HMW) adiponectin only in men and not in women. The interaction between gender and resistin level (F=11.50, P<0.001) was also a significant and independent determinant for HOMA-IR as well as gender, BMI, alcohol consumption, smoking status, uric acid, GGT, HMW adiponectin, and resistin. Conclusions: These results suggest that plasma resistin levels are associated with insulin resistance in older Japanese men.     

Serum adipokine profiles in Kawasaki disease

Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.     

Serum adiponectin and resistin: Correlation with metabolic syndrome and its associated criteria among temiar subtribe in Malaysia

Background and objectivesMetabolic syndrome (MetS) is characterized as a cluster of metabolic disorder including increased blood pressure, elevated blood glucose level, high cholesterol level and visceral fat obesity. Polypeptide hormones such as adiponectin and resistin play a significant role in glucose and lipids metabolism, liver and pancreas function. This study aimed to investigate the relationship between serum adiponectin and resistin with MetS criteria among Temiar subtribe in Kuala Betis.Materials and methodsThis cross sectional study involved 123 subjects from Temiar subtribe in Kuala Betis, Gua Musang, Kelantan. MetS criteria were measured according to standard protocol by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guideline. Anthropometric and biochemical measurements were performed including serum adiponectin and resistin for every study subjects.ResultsSerum adiponectin was significantly lower in MetS subjects (7.98 ± 5.65 ng/ml) but serum resistin was found to be significantly higher in MetS subjects (11.22 ± 6.34 ng/ml) compared to non-MetS subjects with p < 0.001 and p = 0.002 respectively. Serum adiponectin was negatively correlated with most of the cardio-metabolic risk factors; BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, triglyceride and total cholesterol. Serum resistin was found to be positively correlated with BMI, waist circumference, fasting blood glucose and total cholesterol.ConclusionThe difference in serum adiponectin and resistin level among MetS individuals indicated the potential of serum adiponectin and resistin to be used as a biomarker for the diagnosis of MetS among Temiar subtribe.     

Distribution and determinants of adiponectin, resistin and ghrelin in a randomly selected healthy population

OBJECTIVE: Adiponectin, resistin, ghrelin and the IGF-I system seem to play an important role in the regulation of body composition throughout life, but the mechanisms are not well understood. The aim of our study was to analyse the distribution among sexes and all decades of the adult life of adiponectin, resistin and ghrelin and their relationship with anthropometric, body composition parameters and the IGF-I system. SUBJECTS: One hundred and thirty-four men and 127 healthy women were included in the study. MEASUREMENTS: Plasma concentration of adiponectin, resistin, ghrelin, total IGF-I, free IGF-I and IGFBP-3 were determined in all subjects. Body composition was evaluated by bioelectrical impedance. RESULTS: Resistin and ghrelin were not affected by age. Plasma adiponectin correlated negatively with age, body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), fat mass (FM) and body fat (BF) in men. Adiponectin correlated negatively with WHR and positively with free IGF-I in women. Resistin correlated positively with BMI and WC only in men, and ghrelin correlated positively with WC, BMI and FM and negatively with free IGF-I in men. In multiple regression analysis adiponectin remained associated with WHR (beta=-0.19, P=0.01) in women. Resistin was positively associated with BMI (beta=0.30, P=0.003) in women and ghrelin was negatively related to free IGF-I (beta=-0.158, P=0.019) in men. CONCLUSIONS: Plasma adiponectin declines with age and is negatively associated with FM in men. Our data suggest the existence of a positive correlation of adiponectin and the IGF-I axis in women and of an inverse relationship between ghrelin and the IGF-I system in men.     

Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction

OBJECTIVE: Resistin is an adipokine that has been suggested to be correlated with markers of inflammation and to be predictive of coronary atherosclerosis and type II diabetes in humans. A common single nucleotide polymorphism (SNP) (-420C/G) in the promoter of resistin is associated with increased resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of the -420C/G polymorphism with metabolic syndrome, obesity, myocardial infarction and kidney disease. DESIGN AND RESULTS: First we studied 1542 subjects from the PLIC study (a population based cohort). GG carriers showed an higher prevalence of obesity and metabolic syndrome as well as increased plasma triglycerides levels, BMI, systolic and diastolic blood pressure and cardiovascular risk according to Framingham algorithm (P < 0.05 for all). Next we investigated the presence of the -420C/G resistin polymorphism in a case-control study that included 300 subject with myocardial infarction and 300 age and sex matched controls and then we studied the role of the -420C/G SNP in 88 patients with mild to moderate renal dysfunction. No statistically significant differences in allele frequencies between the PLIC study, the myocardial infarction (MI) cases and the subjects with renal dysfunction were observed. Pro-inflammatory gene expression profiling of peripheral blood mononuclear cells failed to detect any difference between wild type subjects and carriers of the rare allele. CONCLUSION: Our data suggest that the presence of the -420C/G SNP of the resistin gene is associated with increased obesity and metabolic syndrome, although it is not different in subjects at high cardiovascular risk such as patients with myocardial infarction or patients with renal dysfunction compared with controls.     

Maternal serum adiponectin and infant birthweight: the role of adiponectin isoform distribution

OBJECTIVE: Adiponectin is an insulin-sensitizing protein that circulates in oligomeric complexes, including trimers, hexamers and high-molecular-weight (HMW) multimers. In pregnant women, conflicting associations have been reported between maternal serum levels of total adiponectin (i.e. reflecting all isoforms) and infant birthweight. As the HMW complex has recently been proposed as the primary mediator of metabolic bioactivity, we hypothesized that differences in isoform distribution may underlie these conflicting reports. Therefore, we evaluated the relationship between maternal adiponectin isoforms and infant birthweight. DESIGN/PATIENTS/MEASUREMENTS: HMW and total adiponectin, as well as the ratio of HMW to total adiponectin (ratio known as S(A)), were measured in healthy pregnant Caucasian women (n = 58) undergoing an oral glucose tolerance test (OGTT), following an abnormal glucose challenge test. RESULTS: On univariate analysis adjusted for neonate gender and length of gestation, birthweight was positively correlated with weight gain in pregnancy (r = 0.29, P = 0.031) and inversely associated with the IS(OGTT) index of insulin sensitivity (r = -0.27, P = 0.041), total adiponectin (r = -0.31, P = 0.021), HMW adiponectin (r = -0.34, P = 0.0093) and S(A) (r = -0.34, P = 0.011). On multiple linear regression analyses, however, total adiponectin was not related to birthweight. By contrast, HMW adiponectin was related at borderline significance (t = -1.87, P = 0.068), while S(A) emerged as an independent negative determinant of infant birthweight (t = -2.46, P = 0.0175). Adjusted mean neonatal birthweight was significantly higher in the infants of women comprising the lowest tertile of S(A) compared to women in the highest tertile of S(A) (3684 vs. 3424 g, P = 0.0375). CONCLUSIONS: The proportion of maternal serum adiponectin in HMW form (S(A)) is independently and inversely associated with infant birthweight. Thus, adiponectin isoform distribution, rather than total adiponectin concentration, may be a correlate of foetal size.     

Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients

BACKGROUND/AIMS: Insulin resistance is a well-known phenomenon in uremia. Resistin, a recently discovered insulin inhibitor secreted by adipocytes, is associated with obesity and insulin resistance in mice. Adiponectin, also secreted by adipocytes, is known to reduce insulin resistance in humans. The aim of the present study was to address the hypothesis that changes in resistin or adiponectin serum levels may relate to body composition and to insulin resistance in patients with end-stage renal disease. METHODS: In a cross-sectional study, 33 non-diabetic patients (24 males and 9 females, mean age 61.5+/-15.8 years) with end-stage renal disease on chronic hemodialysis (treatment duration 41+/-31 months) that lacked signs of infection were enrolled. The control group consisted of 33, matched for age, sex and body mass index (BMI), healthy volunteers (22 males, 11 females, mean age 62.6+/-12.1 years). BMI (kg/m(2)) was calculated from body weight and height. Body fat (%) was measured by means of bioelectrical impedance. Blood samples were taken always in the morning after a 12-hour fasting period before and after the hemodialysis session. Resistin and adiponectin serum concentrations were measured by enzyme immunoassays and insulin by an electrochemiluminescence immunoassay. The post-treatment values were corrected regarding the hemoconcentration. The homeostasis model assessment index (HOMA-R) was calculated as an estimate of insulin resistance from the fasting glucose and insulin serum levels. RESULTS: Pre-treatment resistin serum levels were significantly increased in hemodialysis patients compared to healthy controls (19.2+/-6.2 vs. 3.9+/-1.8 ng/ml; p<0.001). Hemodialysis did not alter resistin levels, as pre- and post-treatment levels were not different when corrected for hemoconcentration (19.2+/-6.2 vs. 18.7+/-5.0 ng/ml; p=0.54). Adiponectin levels were also increased in hemodialysis patients compared to healthy controls (25.4+/-21.5 vs. 10.5+/-5.9 microg/ml; p<0.001). A significant inverse correlation was observed between the serum adiponectin levels before the hemodialysis session on the one hand and the BMI (r=-0.527, p=0.002), the HOMA-R (r=-0.378, p<0.05) and the fasting insulin levels (r=-0.397, p<0.05) on the other. However, no significant correlation was observed between serum resistin levels on the one hand versus HOMA-R index (3.2+/-3.9 mmol.microIU/ml; r=-0.098, p=0.59), insulin levels (13.3+/-14.4 mU/l; r=-0.073, p=0.69), glucose levels (89+/-13 mg/dl; r=-0.049, p=0.78), BMI (25.6+/-3.7 kg/m(2); r=-0.041, p=0.82) and body fat content (26.4+/-8.4%; r=-0.018, p=0.94) on the other hand. CONCLUSION: Resistin serum levels are significantly elevated in non-diabetic patients with end-stage renal disease that are treated by hemodialysis. The hemodialysis procedure does not affect the resistin levels. Along with previous observations in patients with renal insufficiency in the pre-dialysis stage, our findings implicate an important role of the kidney in resistin elimination. However, increased resistin serum levels in hemodialysis patients are not related to reduced insulin sensitivity encountered in uremia.     

Serum resistin is positively correlated with the accumulation of metabolic syndrome factors in type 2 diabetes

Objective Resistin, secreted from adipocytes, causes insulin resistance in rodents. We reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at ?420 increases type 2 diabetes (T2DM) susceptibility by enhancing promoter activity. We also showed that serum resistin was positively correlated with G at SNP‐420, the duration of T2DM, and HbA1c in T2DM. The aim of this study was to determine the relation between serum resistin and factors related to the metabolic syndrome (MetS) in T2DM. Design, patients and measurements We analysed 238 Japanese T2DM subjects (124 males and 114 females, age 60·2 ± 11·3 years, body mass index (BMI) 24·1 ± 3·9) whose overnight fasting sera were available. Serum resistin was measured using ELISA. Results Serum resistin was higher in subjects with either obesity (P = 0·041), low HDL (P = 0·004), high triglycerides (TG) (P = 0·019), hypertension (HT) (P = 0·001) or atherosclerosis (P = 0·012). Simple regression analysis revealed that serum resistin was correlated with lower HDL, TG and high‐sensitivity C‐reactive protein (hsCRP). Multiple regression analysis (or logistic regression analysis for HT), adjusted for age, gender, BMI and the duration of T2DM, revealed that serum resistin was correlated with lower HDL (P = 0·008), TG (P = 0·041), HT (P = 0·031) and hsCRP (P = 0·004). Serum resistin was positively correlated with the number of MetS factors, independent of age, gender and the duration of T2DM (P < 0·001). Adjustment by either thiazolidinedione (TZD) treatment or hsCRP had no effects on these findings. Conclusions Serum resistin was positively correlated with the accumulation of MetS factors in T2DM.