The glucose clamp reveals an association between adiponectin gene polymorphisms and insulin sensitivity in obese subjects

Results concerning the association of adiponectin gene polymorphisms (single-nucleotide polymorphisms, SNPs) with obesity, type 2 diabetes (T2DM), metabolic disorders and insulin resistance have not lead to definite conclusions. The aim of our study was to investigate a possible association between the -11391G>A and -11377C>G SNPs of adiponectin gene and measure of insulin sensitivity evaluated by the hyperinsulinemic-euglycemic clamp in a group of 'uncomplicated' obese subjects (with no associated comorbidities) (n=99, mean age 35 years) with a history of obesity lasting at least 10 years. The study of uncomplicated obese subjects, free of possible confounding factors that could interfere with insulin sensitivity, such as pharmacological treatment, provides a good model to assess insulin sensitivity per se. We observed that subjects homozygous for the G allele at locus -11391 had lower M (mg/kg min)/fat-free mass (FFM) index and adiponectin levels compared to subjects with GA+AA genotypes (P=0.002 and P=0.03, respectively) and subjects carrying the -11377G variant had lower M (mg/kg min)/FFM index and adiponectin levels compared to noncarriers (P=0.003 and P=0.03, respectively). Our results imply that the two promoter SNPs, -11391G>A and -11377C>G, of the adiponectin gene are associated with a reduced insulin sensitivity evaluated by hyperinsulinemic-euglycemic clamp in obese subjects.     

The association of SNP276G>T at adiponectin gene with circulating adiponectin and insulin resistance in response to mild weight loss

OBJECTIVE: The purpose of this study was to determine whether common single nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence changes in circulating adiponectin and the features of insulin resistance in response to a weight loss intervention.Subjects:In total, 294 nondiabetic/overweight-obese Koreans participated in a clinical intervention study lasting 12 weeks involving a caloric reduction of -300kcal/day. METHODS: Plasma adiponectin, blood lipids, glucose and insulin concentrations were measured at baseline and after weight loss. Insulin resistance was estimated by homeostasis model assessment insulin resistance (HOMA-IR) derived from fasting glucose and insulin concentrations. We genotyped for three SNPs, 45T>G, 276G>T and -11377C>G. RESULTS: At baseline, HOMA-IR was significantly higher in GG homozygotes than in carriers of the T allele at SNP276G>T of the adiponectin gene (P<0.05). With regard to SNP45T>G and SNP -11377C>G, we did not find any genotype related differences in baseline levels of HOMA-IR and adiponectin. In the 45/276 haplotype test, homozygous for the TG haplotype had significantly lower concentrations of plasma adiponectin (P<0.05). After the 12-week weight loss intervention, the significant decreases in HOMA-IR (P<0.001) and increases in adiponectin (P<0.01) were observed in GG homozygotes at SNP276, which were not shown in carriers of the T allele. Furthermore, there was a significant difference in the decreases in HOMA-IR between the GG homozygotes and carriers of the T allele at SNP276 (P<0.05). Regarding SNP45T>G and SNP -11377C>G, there was no association between SNP45T>G and SNP -11377C>G and decreases in HOMA-IR. In the 45/276 haplotype test, there was a significant difference in changes of adiponectin levels among those with different haplotype combinations (P<0.05). CONCLUSION: The SNP276G>T of the ADIPOQ gene is associated with different responses of circulating adiponectin and insulin resistance to mild weight loss in overweight-obese subjects.     

福建地区2型糖尿病患者脂联素基因启动子区多态性与颈动脉内膜中层厚度有关

目的 探讨脂联素基因启动子区-11377位点单核苷酸多态性与2型糖尿病患者颈动脉内膜中层厚度(CIMT)之间的关系.方法 采用PCR-限制性片段长度多态性(RFLP)技术在504例2型糖尿病患者(CIMT正常组254例,CIMT增厚组250例)中检测脂联素基因-11377位点多态性,同时检测血脂、空腹血糖、空腹胰岛素及血清脂联素水平.结果 脂联素基因-11377C→G基因型和等位基因频率在CIMT正常组与CIMT增厚组的分布有显著性差别(P相似文献   

A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects

OBJECTIVE: Reduced serum adiponectin levels have been found in obesity and type 2 diabetes and variations in the adiponectin gene (APM1) have been associated with type 2 diabetes and features of the metabolic syndrome in different populations. STUDY DESIGN: Here, we investigated the expression of APM1 in adipose tissue and studied the relationship between variation in APM1 expression, the APM1 G276T polymorphism, the common PPARG Pro12Ala polymorphism and clinical features of 36 morbidly obese (body mass index (BMI) 41.5 +/- 4.9 kg/m2) nondiabetic subjects. RESULTS: APM1 mRNA expression in visceral fat was correlated with serum adiponectin levels (r = 0.54, P = 0.012). In visceral, but not in subcutaneous, adipose tissue APM1 mRNA level was 38% higher among carriers of the APM1 G276T T allele (G/T and T/T) than among carriers of the G/G genotype (0.91 +/- 0.06 for G/T and T/T carriers vs 0.66 +/- 0.09 for G/G carriers, P = 0.013). Carriers of the T allele also had significantly higher body fat percent compared to G/G carriers (65 +/- 6 vs 56 +/- 10%, P = 0.011).Conclusion:Our results indicate that genetic variation in APM1 influences the expression of the gene in visceral adipose tissue and suggest a potential role for such variation in regulation of body fat accumulation in obese subjects.     

Gender-specific differences in the association of adiponectin gene polymorphisms with body mass index

OBJECTIVE: Adiponectin gene polymorphisms are associated with obesity, metabolic syndrome and type 2 diabetes (T2D). The study evaluated possible associations of +45T/G and -11391G/A adiponectin gene polymorphisms with body mass index (BMI), waist circumferences (WC), and blood pressure in diabetic and non-diabetic Iranians. METHODS: This cross-sectional study involved two groups of subjects: 243 diabetic patients and 173 non-diabetic subjects recruited from Rafsanjan city in the south-east of Iran. RESULTS: No significant association was found between +45T/G and -11391G/A adiponectin gene polymorphisms and systolic or diastolic blood pressure. However, male carriers of the TT genotype of +45T/G had a significantly higher mean BMI than male GG homozygotes (p = 0.018). Also, male carriers of the GG genotype of -11391G/A had significantly higher mean BMI than male GA or AA homozygotes (p = 0.041). Female carriers of the GG genotype of -11391G/A had significantly higher mean WC than female GA or AA homozygotes (p = 0.038). CONCLUSIONS: We observed a significantly higher BMI in women, and GA or AA carriers of -11391G/A polymorphism. Also, there was a significantly lower WC in females and GG carriers of +45T/G. These results point to a gender-specific impact of the studied genotypes on BMI and WC.     

Heritability of plasma adiponectin levels and body mass index in twins

CONTEXT: Adiponectin is suspected to exert antiatherogenic, antiinflammatory, and insulin-sensitizing effects. However, the relative importance of the genetic and environmental factors in influencing plasma adiponectin levels (ADPN) remains unclear. OBJECTIVE: The aim of the study was to investigate whether ADPN and body mass index (BMI) are genetically determined. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES: In a series of 60 pairs of healthy twins, we estimated genetic variance and heritability of ADPN and BMI using both ANOVA and path analysis methods. Twins were genotyped at two biallelic single nucleotide polymorphisms (SNPs) at the gene encoding adiponectin: the +45 T/G (on exon 2) and the -11377 G/C (on the promoter). RESULTS: A total of 30 pairs of twins were Monozygotic (MZ), and 30 were dizygotic (DZ). The mean ADPN (+/-SD) was 10.6 +/- 5.7 in MZ and 11.1 +/- 4.5 in DZ twins (nonsignificant). Three tests of heritability (within pair = 1.13, P < 0.0001; among components = 1.62, P = 0.005; and intraclass correlation 1.34, P < 0.0001) consistently showed ADPN heritability. The preferred model of a likelihood-based analysis included an additive genetic influence and an individually unique environmental influence for ADPN, accounting for 88% and 12% of ADPN variance, respectively. We found a significantly higher within-pair difference of ADPN in DZ than in MZ pairs, and in +45 T/G SNP discordant compared with concordant DZ twins, indicating a significant effect of this adiponectin gene SNP on ADPN. CONCLUSIONS: ADPN shows significant genetic variance and heritability, which is independent of BMI and partly accounted for by the +45 T/G, but not the -11377 G/C adiponectin gene SNP.     

Plasma adiponectin, T94G gene polymorphism and PAI-1 in patients with and without hypertension

BACKGROUND: Reduced adiponectin level has been associated with metabolic syndrome, type 2 diabetes, coronary artery disease and gene polymorphisms, but the interrelationships of T94G genotype, plasma adiponectin and plasminogen activator inhibitor-1 (PAI-1) are less understood. PATIENTS AND METHODS: The T94G genotypes and plasma levels of adiponectin, and PAI-1 were determined in 568 Chinese patients, 212 with and 356 without hypertension, to study the possible associations of T94G genotype, plasma adiponectin, PAI-1 and blood pressure. RESULTS: Hypertensive patients showed significantly lower plasma adiponectin (9.7 +/- 11.1 vs. 11.5 +/- 10.0 microg/ml, p = 0.04) and higher PAI-1 (p < 0.001) levels but not significantly greater adiponectin TT genotype percentage (38.7 vs. 33.5%) and T allele frequency (0.620 vs. 0.585) than normotensive subjects. Plasma adiponectin was inversely related to PAI-1 activity (r = -0.09, p = 0.03) and antigen (r = -0.202, p < 0.001). Furthermore, the TT genotypic group showed significantly lower plasma adiponectin level (10.4 +/- 10.5 vs. 13.4 +/- 10.8 mug/ml, p = 0.03) and higher plasma PAI-1 activity (17.0 +/- 9.7 vs. 13.5 +/- 7.6 IU/ml, p = 0.003) and antigen (32.3 +/- 22.7 vs. 25.9 +/- 14.7 ng/ml, p = 0.01) than the GG genotypic group. Multiple linear regression analysis in all study subjects, in men and in normotensives documented an impact of adiponectin T94G genotype on plasma levels of adiponectin (p = 0.007, 0.003 and 0.03) and PAI-1 activity (p = 0.02, 0.03 and 0.04) and antigen (p = 0.03, 0.007 and 0.04) after adjustment for potential confounding factors. CONCLUSIONS: The present study demonstrated a significant correlation of the TT genotype with lower plasma adiponectin and higher plasma PAI-1 levels in a Chinese population. The contribution of this genotype seemed greater in men and normotensives. It suggested the adiponectin gene T94G polymorphism might affect the regulation of circulating adiponectin and PAI-1.     

脂联素基因单倍型与汉族人群2型糖尿病的相关性研究

目的探讨脂联素基因多态性及其单倍型与2型糖尿病（T2DM）的相关性。方法入选T2DM患者202例,糖尿病家族史阴性的非糖尿病个体（NDM）143例。采用聚合酶链反应限制性内切酶片段长度多态性（PCR—RFLP）方法对脂联素基因SNP-11391、SNP-11377、SNP-4522、SNP＋45和SNP＋331位点进行基因分型,并构建单倍型。评估以上5个多态性位点及构建的单倍型与T2DM的相关性。结果T2DM组和NDM组脂联素基因SNP-11391、SNP—11377、SNP～4522、SNP＋45和SNP＋331基因型和等位基因频率差异无统计学意义。T2DM组和NDM组SNP—11377C—SNP-4522T单倍型频率差异有统计学意义（P〈0．05）。结论脂联素基因SNP-11377C—SNP-4522T单倍型与T2DM相关,且可能增加患T2DM风险（OR=1．60,95％CI：1．09～2．35）。     

2型糖尿病患者脂联素及脂联素基因启动子区多态性与白蛋白尿的相关性

目的 研究2型糖尿病患者血浆脂联素水平及脂联素基因启动子区-11377位点单核苷酸多态性(SNP)与尿白蛋白排泄率(UAER)之间的关系.方法 按1999年世界卫生组织制定的糖尿病诊断标准,自2006年4月至2009年4月选取福建医科大学附属第二医院内分泌科2型糖尿病患者403例,根据24 h UAER分为正常组(UAER<30 mg/24 h,NAU组)201例、微量白蛋白尿组(30 mg/24 h≤UAER<300 mg/24 h,MiAU组)134例和大量白蛋白尿组(UAER≥300 mg/24 h,MaAU组)68例.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测脂联素基因启动子区SNP-11377C→G多态性.同时检测血浆脂联素、血脂、血糖、空腹胰岛素、血肌酐和内生肌酐清除率.脂联素水平与临床指标的相关性采用简单相关分析和偏相关分析.结果 脂联素水平随UAER增高呈递增趋势[NAU、MiAU、MaAU组分别为6.33(0.10～24.32)mg/L,6.97(0.25～20.12)mg/L,9.38(1.88～26.99)mg/L],MaAU组显著高于NAU和MiAU组(P<0.01).脂联素水平与血浆肌酐呈正相关(r=0.212,P<0.01),与肌酐清除率呈负相关(r=-0.157,P<0.05),与稳态模型胰岛素抵抗指数(HOMA-IR)呈负相关(r=-0.215,P<0.01).脂联素基因启动子SNP-11377C→G的基因型(CC型、CG型和GG型)和等位基因频率分布在NAU组、AU组间的差异无统计学意义(P>0.05).未发现启动子区SNP-11377C→G与脂联素水平有关.结论 2型糖尿病患者血脂联素随糖尿病肾病进展白蛋白尿加重而增高.未发现福建地区2型糖尿病患者脂联素基因启动子区-11377C→G多态性与UAER明显相关.     

An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis.

The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE activity, with the D allele being associated with higher ACE levels than the I allele. Thus, chronic exposure to high levels of circulating and tissue ACE may well predispose to vascular wall thickening and atherosclerosis. However, the effect of the ACE gene on carotid atherosclerosis remains controversial. We investigated the association between ACE gene I/D polymorphism and risk factor-dependent augmentation of carotid arterial remodeling in subjects with several risk factors for atherosclerosis. We evaluated sclerotic lesions of the common carotid artery with intima-media thickness (IMT) by ultrasonography in 184 patients (mean age +/- SD, 67 +/- 14 years old) and studied whether any risk factor-gene interactions were associated with carotid atherosclerosis. Out of the 184 subjects, 71 had the ACE II genotype, 87 the ID genotype and 26 the DD genotype. There was no significant difference in IMT among the three ACE genotypes. In total subjects, multiple regression analysis showed that age, total-cholesterol (T-C), and HDL-cholesterol (HDL-C) were significantly associated with IMT. However, the association between risk factors and IMT was genotype-specific. Systolic blood pressure (SBP) and HDL-C were significantly associated with IMT in ACE D carriers (DD+ID), but not in subjects with the ACE II genotype. Similarly, T-C was significantly associated with IMT only in subjects with the ACE II genotype. A general linear model of the interaction between the ACE genotype and the conventional risk factors showed that the SBP-ACE genotype interaction were significantly associated with IMT (F = 7.915; p = 0.005). This finding further supports the idea that analysis of risk factor-gene interaction could be a useful tool for deriving specific predictive information about the development of atherosclerosis.     

Genomic structure and mutations in adipose-specific gene, adiponectin

BACKGROUND: Adiponectin is a collagen-like plasma protein specifically synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in obesity whereas it is adipose-specific. OBJECTIVE: To clarify the significance of the genetic variations in adiponectin gene on its plasma concentrations and obesity. SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects (123 men and 96 women, age: 20-83 y, BMI: 16-43 kg/m2) including 77 obese subjects (BMI>26.4 kg/m2). MEASUREMENT: Human adiponectin gene was isolated from PAC DNA pools. Mutations in the adiponectin gene were screened by direct sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin were determined by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and two introns. Within 2.1 kb of the 5'-flanking region, there were two octamer elements present in the promoter of adipsin. Two nucleotide changes were identified. One was a polymorphism (G/T) occurring in exon 2, and the other was a missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the subjects carrying G allele were low (G/G: 4.5 microg/ml; G/T: 5.9 microg/ml; and T/T: 6.3 microg/ml), but were not statistically significant. The allelic frequency between the obese and the non-obese showed no significant difference. The subject carrying R112C mutation showed markedly low concentration of plasma adiponectin. CONCLUSION: Two nucleotide changes have been identified in the adiponectin gene. G/T polymorphism in exon 2 was associated with neither plasma adiponectin concentrations nor the presence of obesity. A subject carrying missense mutation (R112C) showed markedly low plasma adiponectin concentration.     

Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, ?11377C>G, ?11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis

Aims/hypothesis

The associations between adiponectin polymorphisms and type 2 diabetes have been studied widely; however, results are inconsistent.

Methods

We searched electronic literature databases and reference lists of relevant articles. A fixed or random effects model was used on the basis of heterogeneity. Sub-group and meta-regression analyses were conducted to explore the sources of heterogeneity.

Results

There were no statistically significant associations between +45T>G (rs2241766), +276G>T (rs1501299), ?11391G>A (rs17300539) and type 2 diabetes risk. However, for ?11377C>G (rs266729), the pooled OR (95% CI) for G vs C allele was 1.07 (1.03?C1.11, p?=?0.001). Subgroup analysis by study design revealed that ?11377C>G (rs266729) dominant model (CG+GG vs CC, p?=?0.0008) and G vs C allele (p?=?0.0004) might be associated with type 2 diabetes risk in population-based case?Ccontrol studies. After stratification by ethnicity, we found that ?11377C>G (rs266729) dominant model (CG+GG vs CC, p?=?0.004) and G vs C allele (p?=?0.001) might be associated with type 2 diabetes risk in white individuals. In individuals with a family history of diabetes, the presence of ?11391G>A (rs17300539) dominant model (GA+AA vs GG) and A vs G allele might be associated with increased risk of type 2 diabetes.

Conclusions/interpretation

The presence of +45T>G (rs2241766), +276G>T (rs1501299) and ?11391G>A (rs17300539) do not appear to influence the development of type 2 diabetes. However, G vs C allele of ?11377C>G (rs266729) might be a risk factor for type 2 diabetes.     

Decreased plasma adiponectin is associated with insulin resistance and HDL cholesterol in overweight subjects

The purpose of this study was to investigate plasma adiponectin concentration and its relation with metabolic parameters in overweight and normal weight subjects. The study was carried out in 46 overweight subjects (20 male, 26 female; mean age 39.4 +/- 10.2 years) and 48 (19 male, 29 female; mean age 36.1 +/- 10.6 years) sex- and age-matched normal weight subjects. Anthropometric measurements were recorded and adiponectin, glucose, insulin, lipid profile, total homocysteine (tHcy) and fibrinogen levels were measured. The insulin resistance index was assessed by homeostasis model assessment for insulin resistance (HOMA-IR). Plasma mean adiponectin concentrations of the overweight subjects were significantly lower than those of normal weight subjects (15.0 +/- 4.2 vs 17.3 +/- 5.6 ng/ml) (P<0.05). In overweight subjects, adiponectin levels negatively correlated with body weight (r = -0.35, P<0.001), body mass index (BMI) (r = -0.28, P<0.006), systolic blood pressure (r = -0.21, P<0.04), fasting insulin (r = -0.19, P<0.01) and HOMA-IR (r = -0.20, P<0.01) and positively with high-density lipoprotein cholesterol (HDL-C) (r = 0.27, P<0.009). Overweight subjects with low HDL-C levels had significantly decreased plasma adiponectin levels compared to those with high HDL-C levels (P<0.05). Multiple regression analysis revealed that BMI, HOMA-IR and HDL-C explained 12%, 20% and 15% variance of the adiponectin concentrations. These findings may suggest that circulating adiponectin is associated with insulin resistance and HDL-C levels independent from BMI in overweight subjects.     

Human adipose tissue cannabinoid receptor 1 gene expression is not related to fat cell function or adiponectin level

CONTEXT: The cannabinoid receptor 1 gene (CNR1) is implicated in adipocyte function. OBJECTIVE: We investigated human adipose tissue CNR1 mRNA in relation to obesity, clinical and metabolic variables, adipocyte function, and adiponectin (ADIPOQ) levels. METHODS: We assessed sc fat biopsies from 96 obese and nonobese subjects and omental fat biopsies from 82 obese and nonobese subjects. RESULTS: The sc and omental adipose CNR1 gene expression were similar in obese and nonobese subjects. No association between either sc or omental adipose CNR1 mRNA levels and body mass index, waist circumference, plasma levels of glucose and insulin, lipids, or blood pressure was found. The sc and omental maximal adrenergic lipolytic activation as well as lipolytic adrenoceptor sensitivity were not related to CNR1 gene expression. Lipogenesis in sc adipocytes also showed no association with CNR1 mRNA levels. Finally, no relation was found between adipose CNR1 gene expression and ADIPOQ mRNA, adipose tissue adiponectin secretion, or circulating adiponectin. CONCLUSION: We found no association of human adipose tissue CNR1 mRNA expression with measures of body fat, metabolic parameters, fat cell function, or ADIPOQ expression. These data do not suggest a major role of human adipose CNR1 in fat cell function or metabolic disease development.     

Determinants of early atherosclerosis in obese children and adolescents

CONTEXT: Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity. OBJECTIVE: The aim of the study was to investigate determinants of increased carotid intima-media thickness (IMT), an early marker of atherosclerosis, in obese children. DESIGN: A total of 104 obese children [age, 12.7 +/- 0.2 yr; body mass index (BMI)-z-score, 2.8 +/- 0.7] underwent an oral glucose tolerance test. Fasting levels of glucose, insulin, C-reactive protein and adhesion molecules (sICAM, sVCAM, sE-selectin), lipid profile, adiponectin, and resistin were determined. IMT was measured by ultrasound. Insulin resistance was estimated by the homeostatic model assessment index. Baseline measurements of blood parameters were obtained from 93 nonobese children (age, 13.0 +/- 0.2 yr; BMI-z-score, -0.2 +/- 0.9), and IMT was measured in 23 other control children with similar characteristics. RESULTS: Univariate analysis showed a significant positive correlation between IMT and relative BMI, the degree of systolic hypertension, fasting insulin levels, homeostatic model assessment-R index, and resistin concentrations, whereas an inverse correlation with adiponectin levels was found. No correlation was obtained between IMT and classical CV risk factors such as positive familial history of type 2 diabetes or precocious CV disease, visceral obesity, or the lipid profile. C-reactive protein and adhesion molecule levels were not associated with IMT in our obese population. When controlled for sex, Tanner stage, and relative BMI, only adiponectin levels remained an independent determinant of IMT. CONCLUSION: Adiponectin more than conventional CV risk factors and inflammation status may be related to early atherosclerosis in obese children.     

Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients

Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.     

Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients

A single-nucleotide polymorphism (SNP) G276T in the adiponectin gene has been associated with lower plasma adiponectin levels and insulin resistance, which are related to the prevalence of type 2 diabetes or diabetic complications of macroangiopathy. We performed a case-control study to examine whether the SNP276 of the adiponectin gene was also related to early diabetic nephropathy. SNP276 was examined with genomic DNA obtained from 108 type 2 diabetic patients with microalbuminuria (urinary albumin creatinine ratio [ACR] between 30 mg/g x Cr and 300 mg/g x Cr; case subjects), and 208 patients with normoalbuminuria (ACR < 30 mg/g x Cr; control subjects). The genotype distribution and G allele frequency of SNP276 in the case subjects (0.71) did not significantly differ from the control subjects (0.69). There were no differences among the genotypes of the adiponectin gene regarding age, duration of diabetes, body mass index (BMI), hemoglobin A(1c) (HbA(1c)), serum lipids, serum creatinine, and plasma adiponectin levels. These data suggest that SNP276 of the adiponectin gene is not an independent risk factor for incipient diabetic nephropathy in Japanese type 2 diabetic patients.     

Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism

OBJECTIVE: Adiponectin, an adipose tissue-derived hormone, has been reported to have anti-inflammatory and anti-atherogenic effects. The physiological effect of adiponectin on the metabolic changes and its relation with cardiovascular risk factors in thyroid dysfunction states is still not clear. The aim of the study was to evaluate plasma adiponectin level and its relation to cardiovascular risk factors in patients with thyroid dysfunction. PATIENTS AND MEASUREMENTS: Sixty-seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age- and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C-reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all subjects. Insulin sensitivity was determined using the Homeostasis Model Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid, hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels correlated negatively with body mass index (BMI) and HOMA-IR index and positively with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a significant correlation between adiponectin and CRP levels in both hypothyroid and hyperthyroid groups. In all groups, adiponectin levels did not correlate with age, systolic blood pressure, diastolic blood pressure and thyroid hormones. Multiple regression analysis revealed BMI and HDL-C levels to be the most important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma adiponectin levels are associated with BMI and HDL-C levels in patients with hypothyroidism and hyperthyroidism. But there is not a direct relation of adiponectin with thyroid hormones in these patients.