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 gene polymorphism 45T>G is associated with carotid artery plaques in patients with type 2 diabetes mellitus

Adiponectin has been reported to have a wide range of antiatherogenic actions. Two common single nucleotide polymorphisms (SNPs) at the adiponectin locus (45T>G and 276G>T) have been reported to be associated with diabetes and cardiovascular diseases. The aim of this study was to examine the association between common polymorphisms of the adiponectin gene (ACDC) and carotid atherosclerosis in patients with type 2 diabetes mellitus. A total of 708 unrelated patients with type 2 diabetes mellitus were recruited. SNP45 and SNP276 ACDC were genotyped, and B-mode ultrasonography of the carotid arteries was performed to measure carotid intima-media thickness and assess the presence of carotid artery plaques (CAP). Although there was no significant difference in carotid intima-media thickness according to ACDC genotype, subjects carrying the SNP45 GG genotype had a significantly higher risk of having CAP (odds ratio, 2.468; P = .045) compared with carriers of the T allele after adjustment for possible confounding factors. This study suggests that the GG genotype at ACDC SNP45 is associated with the presence of CAP and may contribute to atherosclerosis in type 2 diabetes mellitus.     

Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes

It is likely that the C allele of the polymorphism at position −106 in the promoter of aldose reductase gene, which codes a rate-limiting enzyme of the polyol pathway, is a susceptibility allele for diabetic retinopathy in Japanese type 2 diabetic patients.     

Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes

It is likely that the C allele of the polymorphism at position 29 of the translated sequence of transforming growth factor (TGF)-β1 gene, which codes a pleiotropic cytokine expressed in a variety of cells, is a susceptibility allele for cerebral infarction in Japanese type 2 diabetic patients.     

Adiponectin levels and cardiovascular risk factors in Japanese men with type 2 diabetes

Several cardiovascular risk factors correlate with adiponectin levels. It is not known whether total homocysteine, folate and gamma-glutamyl transferase levels correlate with adiponectin. We cross-sectionally analyzed the association between adiponectin and these cardiovascular risk factors in diabetic patients. One hundred and two male inpatients with type 2 diabetes without overt nephropathy or insulin use were studied. In a regression analysis of the quartiles of adiponectin, plasma levels of adiponectin were associated positively with HDL-cholesterol and age, and inversely with body mass index and HbA1c, but not with total homocysteine, folate or gamma-glutamyl transferase. Non-traditional cardiovascular risk factors such as homocysteine and folate levels were not associated with adiponectin levels in male type 2 diabetic patients who are not subject to insulin therapy.     

Aldose reductase gene polymorphism is associated with progression of diabetic nephropathy in Japanese patients with type 1 diabetes mellitus

Aim: The objective of this study was to investigate cross-sectionally and longitudinally whether polymorphism of the (A-C)n dinucleotide repeat sequence of the aldose reductase ( AR ) gene may modulate risk for diabetic nephropathy or retinopathy in Japanese patients with type 1 diabetes.
Methods: We obtained DNA samples from 101 patients followed up after the onset of type 1 diabetes and analysed a (A-C)n dinucleotide repeat polymorphic marker in the AR gene by polymerase chain reaction (PCR) method.
Results: Ten alleles ranging from Z−10 (128 bp) to Z+8 (146 bp) in repeat number were identified. In cross-sectional studies, the prevalence of the Z+2 allele was higher than that of any other allele in patients with diabetic nephropathy (37.5% of patients in a microalbuminuria group, and 41.7% of those in a macroalbuminuria group including patients with chronic renal failure and maintenance haemodialysis treatment). Prevalence of the Z+2 allele was not increased in patients with diabetic retinopathy. In longitudinal Kaplan–Meier plots, the cumulative incidence of nephropathy was significantly associated with homozygosity for the Z+2 allele (log rank test, p = 0.031); respective prevalence of nephropathy after diabetes durations of 10 and 15 years was 42.9% and 100% in Z+2 homozygotes ( n  = 8), 17.6% and 27.4% in Z+2 heterozygotes ( n  = 44), and 6.1% and 17.4% in patients without the Z+2 allele ( n  = 49). However, occurrence of retinopathy was not influenced by the Z+2 allele (log rank test, p = 0.926).
Conclusions: Homozygosity for the Z+2 allele was associated with accelerated early progression of diabetic nephropathy in Japanese type 1 diabetic patients.     

Platelet FcgammaRIIA expression is associated with the alpha2 integrin C807T gene polymorphism in type 2 diabetes

"Patelet" FcgammaRIIA is stably overexpressed in type 2 diabetes and may also play a role in collagen-mediated platelet activation. Platelet surface integrin a(2)ss(1)-collagen interaction is an early step associated with platelet adhesion and activation and plays an important role in arterial thrombosis. The objective of this study was to characterize the relationship in diabetes and non-diabetes platelets between FcgammaRIIA expression and a polymorphism associated with arterial thrombotic events, polymorphism C807T on the gene encoding a(2)ss(1). Platelet flow cytometry and allele-specific PCR revealed a significant correlation in type 2 diabetes between low platelet FcgammaRIIA expression and the 807TT genotype that is associated with increased platelet a(2)ss(1) receptor density. We conclude that uni- or bi-directional modulation of surface expression may exist between the platelet FcgammaRIIA receptor and a a(2)ss(1) thrombogenic polymorphism that could play a role in platelet sensitivity to collagen in type 2 diabetes.     

Cholesteryl ester transfer protein polymorphism associated with macroangiopathy in Japanese patients with type 2 diabetes

A polymorphism in the gene for cholesteryl ester transfer protein (CETP) has been reported to be associated with serum cholesterol levels and risk for atherosclerotic vascular diseases, and to clarify the relationship between the gene polymorphism for CETP and macroangiopathy in diabetes mellitus, a cross-sectional study was performed. The subjects of the study were182 Japanese (age: 59.6+/-8.6 years) with type 2 diabetes and no signs of renal dysfunction, 24 of whom had macroangiopathy, and 158 of whom did not. The genotype of the subjects for the TaqIB polymorphism of CETP in intron one was analyzed by using polymerase chain reaction - restriction fragment length polymorphism. Serum CETP levels were significantly higher in the B1/B1 genotype than in the other genotypes (P<0.05). The serum CETP levels were correlated with the serum LDL cholesterol levels (P<0.01), but not with the HDL cholesterol levels. Macroangiopathy was more frequently observed in subjects with the B1/B1 genotype than in the other genotypes (odds ratio=2.953, 95% confidence interval=1.250-6.977, P=0.0136). Logistic regression analysis revealed that the CETP genotype was independently associated with macroangiopathy. The exact mechanism underlying the association remains unknown, but differences in serum CETP levels may be involved.     

Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus

This study aims to investigate the relationship between the circulating level of homocysteine and body adiposity in Japanese patients with type 2 diabetes mellitus. We measured the body mass index (BMI), waist and hip circumferences, visceral and subcutaneous adiposities, visceral/subcutaneous (V/S) adiposity ratio, and insulin resistance as assessed by the Homeostasis Model Assessment (HOMA) index in patients with hyperhomocysteinemia. The study group consisted of 17 Japanese patients with type 2 diabetes and hyperhomocysteinemia (age: 62+/-10 years, mean+/-S.D.), and the control group consisted of 24 age-matched type 2 diabetes patients with normohomocysteinemia (60+/-11 years). The visceral adiposity, HOMA index, and V/S ratio were significantly higher in the hyperhomocysteinemia group than in the normohomocysteinemia group (P<0.05). In contrast, the BMI, hip circumference, and subcutaneous adiposity were similar between the two groups (P>0.1). Furthermore, multiple regression analysis showed that hyperhomocysteinemia was closely related to insulin resistance and visceral adiposity. Our results indicate that the presence of hyperhomocysteinemia in our population of Japanese patients with type 2 diabetes-associated insulin resistance was associated with increased visceral but not subcutaneous adiposity.     

Methylenetetrahydrofolate reductase gene polymorphism in patients with type 2 diabetes

Hyperhomocysteinemia is recognised as a risk factor of ischaemic heart disease and vascular complications of arterial hypertension. Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is associated with hyperhomocysteinaemia. The aim of the study was the assessment of an association of the above polymorphism with type 2 diabetes with special attention to myocardial infarction and arterial hypertension accompanying diabetes. The study group consisted of 172 type 2 diabetics. 172 control subjects with normal glucose tolerance were age and sex matched to patients with diabetes. C677T polymorphism in MTHFR gene locus was detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. CT and TT genotypes were found more often among diabetics (OR 1.83, 95% CI 1.16-2.89; p < 0.01). This finding may be secondary to the excess of T allele bearers among diabetics with myocardial infarction when compared to diabetics without infarction and to control group. Upon obtained results the potential role of genotypes CT and TT as risk factors of myocardial infarction among patients with type 2 diabetes could not be excluded (OR 2.33, 95% CI 0.93-5.8; p = 0.07). Genotypes containing T allele are not associated with diabetes type 2 and concomitant arterial hypertension (OR 1.45, 95% CI 0.89-2.57; p = 0.14). A confirmation in further studies is needed for the presented findings.     

脂联素基因3224C/T多态性与男性高血压患者发生糖代谢异常相关性研究

目的:探讨脂联素基因3’非编码区(UTR)3224C/T多态性与中国上海地区男性高血压患者发生糖代谢异常的关系。方法:研究对象共729例,其中男性高血压伴糖耐量异常(IGT)患者359例,男性高血压伴糖耐量正常(NGT)患者370例。采用基质辅助激光解吸附电离飞行时间质谱(MALDI-TOF)检测技术鉴定脂联素基因3224C/T多态性。同步进行口服葡萄糖耐量试验(OGTT)及胰岛素释放实验。结果:脂联素基因3224C/T多态等位基因频率和基因型分布,在IGT和NGT2组间分布有显著差异(均P     

Fluctuations in HbA1c are associated with a higher incidence of cardiovascular disease in Japanese patients with type 2 diabetes

Aims/Introduction: To reveal whether visit‐to‐visit variability in HbA1c is associated with higher risk of cardiovascular disease (CVD) in patients with type 2 diabetes. Materials and Methods: The study was conducted on 689 Japanese patients with type 2 diabetes [295 women, 394 men; mean (±standard deviations (SD)) age 65 ± 11 years]. Variability in HbA1c was evaluated as the intrapersonal SD of serial measurements of HbA1c during the follow‐up period for at least 12 months. Patients were divided into quartiles according to the SD of HbA1c, and the primary endpoint was defined as incident CVD. Cox’s proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: During a median follow‐up period of 3.3 years (range 1.0–6.3 years), 26 ± 14 measurements of HbA1c were obtained per patient and 61 episodes of incident CVD were recorded. The 5‐year cumulative incidence of CVD in patients across the first, second, third, and fourth quartiles of SD in HbA1c was 4.9, 8.7, 17.1, and 26.2%, respectively (P < 0.001, log‐rank test). Multivariate Cox regression analysis revealed that the incidence of CVD was significantly higher in patients in the fourth quartile of SD in HbA1c compared with those in the first quartile (HR 3.38; 95% CI 1.07–10.63; P = 0.039), independent of mean HbA1c and other traditional cardiovascular risk factors. Conclusions: Variability of HbA1c may be a potent predictor of incident CVD in Japanese patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00155.x, 2011)     

Endothelial nitric oxide synthase Glu298Asp (G894T) gene polymorphism in coronary artery disease patients with type 2 diabetes mellitus

AimsEndothelial dysfunction is thought to be a significant risk factor for cardiovascular disease. This study determined the role of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism and intergenotypic variation of plasma nitric oxide (NO) levels in coronary artery disease (CAD) patients with type 2 diabetes mellitus (DM).MethodsThis case–control study included 28 documented CAD patients with type 2 DM and 32 non-diabetic patients with CAD. Fifty healthy volunteers without any major cardiovascular risk factors served as controls. NO was estimated by modified Griess method. The eNOS gene polymorphism was studied by amplifying DNA by PCR and digesting with BanII restriction enzyme. Restriction fragment length polymorphism was studied by using a gel documentation system.ResultsThe genotype frequencies for Glu298Asp (GT) genotype were 10.71% in diabetic CAD patients, 28.1% in non-diabetic CAD patients and 12% in controls. The T allele frequency was higher in the non-diabetic CAD group (14%) as compared with the diabetic CAD (5.4%) and control group (6%). NO level was significantly lower in non-diabetic CAD patients (10.25 mmol/L) but not in diabetic CAD patients (13.89 mmol/L) as compared to controls (16.78 mmol/L).ConclusionGlu298Asp polymorphism is not the mediator of increased incidence of CAD in diabetic patients.     

Haplotype combination of Calpain-10 gene polymorphism is associated with metabolic syndrome in type 2 diabetes

Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, -19, and -63 of the Calpain-10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes in many populations. The aim of this study was to examine the association of the CAPN10 polymorphism with metabolic syndrome in patients with type 2 diabetes in Korea. Overall, 382 patients with type 2 diabetes were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, -19, and -63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of components of metabolic syndrome was determined. Two hundred and sixty-five (69.4%) patients had metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (odd ratio (OR)=2.334, P=0.010). Patients with the 111/121 haplotype combination had a significantly high risk of metabolic syndrome (OR=1.927, P=0.042). The results of this study suggest that a novel 111/121 haplotype combination created by the CAPN10 SNP-43, -19, and -63 increases the susceptibility to the metabolic syndrome in patients with type 2 diabetes.     

脂联素基因多态性与2型糖尿病的相关性

脂联素是新近发现由脂肪组织特异性分泌的蛋白质,由人类脂联素基因(APM-1/ACDC/ADIPOQ)编码.目前许多研究表明脂联素基因多态性与2型糖尿病和胰岛素抵抗相关,且受遗传背景和环境因素影响,不同群体研究结果之间存在差异.同时,脂联素基因多态性与2型糖尿病的治疗和干预也存在相关性.     

Diabetic retinopathy is associated with visceral fat accumulation in Japanese type 2 diabetes mellitus patients

The presence of diabetic retinopathy (DR) and increased of visceral fat accumulation (VFA) are associated with high mortality in type 2 diabetes mellitus patients. This preliminary study was therefore designed to test the hypothesis that DR is associated with insulin resistance and VFA in type 2 diabetes mellitus patients without insulin treatment. A total of 102 type 2 diabetes mellitus patients were divided into 2 groups: DR group (age, 60 ± 6 years [mean ± SD]; n = 31) and no diabetic retinopathy (NDR) group (59 ± 5 years, n = 71). The level of blood glucose was assessed by fasting plasma glucose, fasting immunoreactive insulin, homeostasis model assessment index, and hemoglobin A_1c. The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The body mass index and waist circumference were higher in the DR group than in the NDR group (P < .001 and P < .0005, respectively). Plasma levels of triglyceride were higher, whereas high-density lipoprotein cholesterol was lower, in the DR group than in the NDR group (P < .005 and P < .0001, respectively). Fasting plasma glucose (P < .0005), insulin concentrations (P < .0001), homeostasis model assessment index (P < .0001), and VFA (P < .0001) levels were higher in the DR group than in the NDR group. Multivariate logistic analysis revealed that DR was independently predicted by high VFA and insulin resistance. The results of this preliminary study indicate that the presence of DR was associated with high VFA and insulin resistance in Japanese patients with type 2 diabetes mellitus.     

The endothelial dysfunction in patients with type 2 diabetes mellitus is associated with IL-6 gene promoter polymorphism in Chinese population

The purpose of this study is to examine the effects of IL-6 gene promoter -174G/C and -572G/C polymorphism on endothelial function of Chinese T2DM and normal glucose regulation (NGR) subjects. 512 newly diagnosed T2DM patients and 483 NGR subjects were recruited and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed for the IL-6 gene promoter -174G/C and -572G/C polymorphism. Flow-mediated dilation (FMD) was measured as a non-invasive indicator for endothelial function. The results show that the C allele and CC genotype at -174 of IL-6 gene promoter region was extremely rare in both T2DM and NGR groups; genotypes' and alleles' frequency at -572 of IL-6 gene promoter region is of no difference between T2DM and NGR groups; within T2DM group, higher plasma IL-6 concentration and lower FMD was found in patients with -572 GC (2.36 ± 0.69, 4.23 ± 3.82%) or GG (2.32 ± 0.74, 4.24 ± 3.67%) genotype, compared with patients with CC (2.15 ± 0.62, 5.28 ± 3.94%) genotype. The conclusion of the study is that in comparison with patients of CC genotype, the T2DM patients of -572 GC or GG genotype may have more aggravated endothelial dysfunction (ED) and be at higher risk for coronary artery disease (CAD).     

Serum resistin level is associated with insulin sensitivity in Japanese patients with type 2 diabetes mellitus

Impaired insulin secretion and decreased insulin sensitivity are the main pathophysiologic features responsible for development of hyperglycemia in type 2 diabetes mellitus. Insulin resistance is often associated with increased adipose tissue mass. To examine which variables influence insulin sensitivity, we compared metabolic parameters, serum resistin, leptin, and adiponectin concentrations to the insulin sensitivity, obtained by frequently sampled intravenous glucose tolerance test using the minimal model analysis, in 113 Japanese patients with type 2 diabetes mellitus. Duration of diabetes, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistance index, and serum resistin concentration were significantly higher in the insulin-resistant subgroup compared with the insulin-sensitive subgroup and correlated with insulin sensitivity. Stepwise regression analysis also identified these parameters as independent regulators of insulin sensitivity. The present study reconfirmed that fasting insulin level or homeostasis model assessment of insulin resistance would be a surrogate measure of insulin resistance and demonstrated that insulin resistance increases progressively after the onset of overt diabetes and that the serum resistin level is associated with insulin sensitivity, suggesting that resistin plays an important role in the development of insulin resistance in Japanese patients with type 2 diabetes mellitus.