Xueyao Han

Peking University People's Hospital, Peping, Beijing, China

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Publications (23)61.97 Total impact

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    ABSTRACT: Abstract Purpose/Aim of the study: Exostosin 2 (EXT2) is involved in early pancreatic development and the regulation of insulin synthesis. In this study, we aim to evaluate the contribution of EXT2 to the genetic pathogenesis of type 2 diabetes and its related traits in the Chinese population. Materials and methods: A case-control study in a Chinese Han population was conducted that included 4766 patients with type 2 diabetes and 4596 control subjects from 14 different regions of China. Three single nucleotide polymorphism (SNP), rs3740878, rs11037909 and rs1113132, in the EXT2 gene were genotyped using the Illumina GoldenGate Genotyping assay. Results: After adjusting for sex, age and body mass index, logistic regression analysis revealed that the EXT2 gene had no association with type 2 diabetes using an additive genetic model [rs3740878 (Odds Ratio (OR) = 0.996, 95% confidence interval (CI) 0.928-1.069, p = 0.910), rs11037909 (OR = 1.003, 95%CI 0.933-1.078, p = 0.931), and rs1113132 (OR = 0.993, 95% CI 0.925-1.065, p = 0.842)]. None of these SNPs were associated with beta cell function as determined using the baseline disposition index, early phase insulin secretion and Oral Glucose Tolerance Test (OGTT) total disposition index. Conclusions: Our study suggests that the EXT2 gene might not have a major role in the development of type 2 diabetes in the Chinese population.
    Endocrine research. 09/2014;
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    ABSTRACT: Background This work aimed to compare the efficacy of dipeptidyl peptidase-IV (DPP-4) inhibitors and their impact on β-cell function in Asian and Caucasian patients with type 2 diabetes mellitus.Methods Databases were systematically searched and qualifying studies that compared DPP-4 inhibitors with other antidiabetic medications in type 2 diabetes were included.ResultsA total of 68 studies were included in the meta-analysis. Comparison of DPP-4 inhibitors with placebo in Asian patients showed a decrease in glycosylated hemoglobin (HbA1c) favoring DPP-4 inhibitors (weighted mean difference [WMD], –0.81%; 95% confidence interval [CI], –0.95% to –0.68%; p<0.001). Comparison of HbA1c changes between Asian and Caucasian patients showed a significant between-group difference of –0.18% (95% CI, –0.32% to –0.04%; p=0.011) when compared with placebo. In Asian patients, the homeostatic model assessment for β-cell function (HOMA-β) was increased with DPP-4 inhibitors compared with placebo (WMD, 7.90; 95% CI, 4.29 to 11.51; p<0.001), although to a lesser extent in Caucasian patients. Comparisons between Asian and Caucasian patients showed a significant between-group difference of –4.97 (95% CI, –9.86 to –0.09; p=0.046) compared with placebo. Body weight increase with DPP-4 inhibitors compared with placebo was comparable in Asian and Caucasian studies (WMD, 0.37 kg and 0.45 kg and 95% CI, 0.04–0.69 and 0.27–0.62, respectively).Conclusions The glucose-lowering efficacy of DPP-4 inhibitors was greater in Asian patients than in Caucasian patients, although the effect on β-cell function was inferior in Asian patients. The effect of DPP-4 inhibitors on insulin resistance and body weight in Asian patients was comparable with that observed in Caucasian patients.
    Journal of Diabetes 07/2014; · 2.94 Impact Factor
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    ABSTRACT: Microtubule interfering agents (MIAs), that can stabilise or depolymerise microtubules, are an important class of cancer chemotherapeutic drugs. They can lead to mitotic arrest and subsequent apoptosis. We demonstrate that cell cycle-dependent kinase 1 (CDK1) is important in switching cells from mitotic arrest to apoptosis during MIAs treatment. Overexpression of non-degradable cyclin B1 sustained CDK1 activation and mitotic arrest, followed by caspase-3 dependent apoptosis. CDK1 is responsible for the phosphorylation of several pro- and anti-apoptotic Bcl-2 family proteins during MIAs treatment. CDK1-mediated Bcl-2 serine 70 phosphorylation enhances its pro-apoptotic function, whereas CDK1-mediated Bad serine 128 phosphorylation promotes apoptosis. Blockage of CDK1 activity with a specific pharmacological inhibitor suppresses Mcl-1 phosphorylation, degradation and its anti-apoptotic function. Therefore, the death of cancer cells under MIAs treatment was caused by imbalance between CDK1-induced alterations in the pro-apoptotic and anti-apoptotic functions of phosphorylated Bcl-2 family proteins
    Cell Biology International 02/2014; · 1.64 Impact Factor
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    ABSTRACT: Aims To understand the relationship between serum acylcarnitine profiles and glucose tolerance status. Methods We analyzed 61 subjects who were divided into three groups based on their glucose tolerance status: normal glucose tolerance (NGT; n = 20, M/F = 9/11, mean age 48 years), pre-diabetes (Pre-DM; n = 20, M/F = 11/9, mean age 51 years), or newly diagnosed type 2 diabetes mellitus (T2DM; n = 21, M/F = 8/13, mean age 49 years). Fasting serum free carnitine and acylcarnitine concentrations were determined using isotope dilution electrospray ionization mass spectrometry coupled with high performance liquid chromatography. Results In comparison with NGT subjects, Pre-DM and type 2 diabetes subjects showed serum metabonomic changes highlighted by dysregulation of mitochondrial fatty acid combustion. Of the long-chain carnitine esters, significantly higher palmitoylcarnitine (C16), 3-OH-hexadecanoylcarnitine (C16-OH), carnitine C20, carnitine C22, and carnitine C24 concentrations (all P < 0.05) were noted in the newly diagnosed type 2 diabetes group, and even the pre-diabetes group. Conclusions This research provides further evidence of alterations in serum acylcarnitine profiles being associated with worse glucoseintolerance. The findings may suggest different degrees of involvement of dysregulated mitochondrial function and incomplete long-chain fatty acid oxidation pathways in the natural course of type 2 diabetes.
    Diabetes Research and Clinical Practice. 01/2014;
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    ABSTRACT: Objective. To investigate the associations of 25-(OH)D and β -cell function or insulin resistance or albuminuria in Chinese type 2 diabetic patients. Methods. In total, 1408 type 2 diabetic patients without vitamin D supplement were included in this retrospective study. Results. Comparison between patients with and without 25-(OH)D deficiency indicated that, compared with patients with 25-(OH)D ≥ 50 nmol/L, patients with 25-(OH)D < 50 nmol/L showed a higher level of urine albumin-creatinine ratio (ACR) (90.15 ± 10.30 mg/g versus 52.79 ± 14.97 mg/g). Multiple regression analysis indicated that 25-(OH)D was independently and negatively correlated with urine ACR (OR = 0.985, 95%CI 0.972-0.999, P = 0.03), adjusted by age, diabetic duration, HBP duration, SBP, HbA1c, creatinine, LDL-C, triglyceride, total cholesterol, and HDL-C. Compared with patients with normal level of urine ACR, patients with higher level of urine ACR showed a significant lower level of 25-(OH)D (34.49 ± 13.52 nmol/L versus 37.46 ± 13.6 nmol/L, P = 0.00). Analysis of the associations of 25-(OH)D and β -cell function or insulin resistance showed that 25-(OH)D may not correlate with β -cell function or insulin resistance. Conclusion. 25-(OH)D was independently associated with albuminuria in Chinese type 2 diabetic patients but was not associated with β -cell function or insulin resistance.
    BioMed Research International 01/2014; 2014:640909. · 2.71 Impact Factor
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    ABSTRACT: To find the associations between diabetic retinopathy and age at diagnosis, C-peptide level and thyroid-stimulating hormone (TSH) level in Chinese type 2 diabetes mellitus. 3100 hospitalized type 2 diabetic patients in Peking University People's Hospital were included in this retrospective study. Their medical history and the laboratory data were collected. All the patients received examination of diabetic retinopathy (DR) by professional ophthalmologist. Comparisons among patients with NDR, NPDR and PDR showed that with the progression of diabetic retinopathy, patients turned to have older age but younger age at diagnosis of diabetes, and have higher SBP, longer duration of diabetes, higher mean HbA1c but lower fasting and 2 hours postprandial C-peptide level. Moreover, with the progression of diabetic retinopathy, patients turned to have higher prevalence of primary hypertension, higher prevalence of peripheral vascular sclerosis, higher proportion with insulin treatment. TSH level was comparable among the three groups of patients. Association analysis showed that after adjusting for age, sex, duration of diabetes, body mass index, HbA1c, blood pressure and albuminurea creatinine ratio and insulin treatment, age at diagnosis (OR 0.888, 95%CI 0.870-0.907, p = 0.00) and postprandial C-peptide (OR 0.920, 95%CI 0.859-0.937, p = 0.00) are the independent associated factors of DR in Chinese type 2 diabetes. According to the results, postprandial C-peptide level and age at diabetes may be two independent associated factors with DR in Chinese type 2 diabetes. The lower level of postprandial C-peptide, the younger age at diagnosis, may indicate the higher prevalence of DR.
    PLoS ONE 01/2014; 9(3):e91174. · 3.53 Impact Factor
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    ABSTRACT: Objectives. The mechanism underlying the regulation of glucolipotoxicity-induced apoptosis by MAPKs was examined in INS-1 cells. Methods. The rat insulinoma cell line INS-1 was cotreated with glucose (30 mM) and palmitic acid (0.2 mM) (GLU+PA). Apoptosis was assessed by cell morphology and detection of PARP cleavage. The activation of MAPKs was examined by Western blotting using specific antibodies against the phosphorylated forms of JNK, ERK1/2, and P38. Results. (1) Live cell imaging studies showed that treatment with GLU+PA for 72 h induced significant cell death, concomitant with PARP-1 cleavage and caspase-3 activation, which peaked at 96 h of treatment. (2) Western blot analysis of the activation of MAPKs during GLU+PA-induced INS-1 cell apoptosis showed that phosphorylation of P38 increased gradually and reached a peak at 96 h, which coincided with PARP-1 cleavage. A transient increase of ERK activation was followed by a rapid decline at 96 h, whereas JNK phosphorylation status remained unchanged in response to GLU+PA. (3) Phosphorylation of insulin receptor substrate (IRS)-2 at 48 h of treatment triggered its degradation, which coincided with P38 activation. (4) Inhibition of P38, but not JNK or ERK, blocked GLU+PA-induced INS-1 cell apoptosis. Conclusions. P38 may be involved in the regulation of glucolipotoxicity-induced apoptosis through the phosphorylation of IRS-2.
    Journal of Diabetes Research 01/2014; 2014:834528. · 3.54 Impact Factor
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    ABSTRACT: The aim of this study was to investigate whether genetic variance can influence the efficacy of glibenclamide in patients with type 2 diabetes. A total of 747 patients with type 2 diabetes was enrolled from the Xiaoke Pills Clinical Trial, which is a double-blind, randomised controlled trial. All the patients had been treated with glibenclamide for 48 weeks, with strict drug dose adjustment and data collection. Treatment failure was confirmed when patients reached the criteria for terminating their participation in the study (fasting blood glucose level ≥7.0 mmol/l on two consecutive tests 4 weeks after reaching the pre-set maximal dose or maximal tolerated dose). Using this cohort, we tested 44 single-nucleotide polymorphisms (SNPs) in 27 gene regions. The genes in our study were involved in the metabolism of sulfonylureas, islet beta cell function, insulin resistance and beta cell growth and differentiation. A logistic regression model was used to evaluate the relationship between genetic variants and treatment failure over a period of 48 weeks. We found that no SNP reached the significance level of p < 0.00125 if Bonferroni correction was performed for multiple testing in the logistic regression model used in this pharmacogenetic study. Participants with the minor allele C of rs10811661 in CDKN2A/CDKN2B showed a significantly greater reduction in fasting blood glucose (TT vs TC vs CC: 9.3% (0-20.0%) vs 9.2% (0.9-20.5%) vs 12.7% (5.2-24.4%), p = 0.008) after the initial 4 weeks of treatment independent of age, sex and BMI. There was a significant difference in beta cell function among carriers of different genotypes of rs10811661. Our study demonstrated that the CDKN2A/CDKN2B gene may be nominally associated with the efficacy of glibenclamide, and that CDKN2A/CDKN2B is associated with beta cell function.
    Diabetologia 12/2013; · 6.49 Impact Factor
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    ABSTRACT: A genome-wide association study in the Chinese Han population has identified several novel genetic variants of the serine racemase (SRR) gene in type 2 diabetes. Our purpose was to systematically evaluate the contribution of SRR variants in the Chinese Han population. rs391300 and rs4523957 in SRR were genotyped respectively in the two independent populations. A meta-analysis was used to estimate the effects of SRR in 21,305 Chinese Han individuals. Associations between single-nucleotide polymorphisms and diabetes-related phenotypes were analyzed among 2,615 newly diagnosed type 2 diabetes patients and 5,029 controls. Neither rs391300 nor rs4523957 were associated with type 2 diabetes in populations. Furthermore, meta-analysis did not confirm an association between type 2 diabetes and SRR. In the controls, rs391300-A and rs4523957-G were associated with higher 30-min plasma glucose in an oral glucose tolerance test. The present study did not confirm that SRR was associated with type 2 diabetes.
    Journal of Diabetes Investigation. 11/2013;
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    ABSTRACT: Obesity and family history are the most important predictors for type 2 diabetes mellitus(T2DM) in the Chinese Han population. However, it is not known whether the genetic loci related to obesity are associated with the risk of developing T2DM in this population. The present case-control study evaluated the associations between five genetic loci for obesity and the pathogenesis of T2DM. The study included 1117 Chinese Han patients with T2DM, 1629 patients with pre-diabetes (impaired fasting glucose and impaired glucose tolerance, IFG/IGT) and 1113 control subjects residing in Beijing. Five genetic loci including rs2815752 near NEGR1, rs10938397 near GNPDA2, rs4074134 near BDNF, rs17782313 near MC4R and rs1084753 near KCTD15 were genotyped. The results showed an association between rs4074134-BDNF minor allele and T2DM irrespective of age, gender and body mass index (BMI) (OR = 0.87; 95%CI: 0.77-0.99, P = 0.04). This SNP was also associated with pre-diabetes (OR = 0.87; 95%CI: 0.77-0.97, P = 0.01) independently of age, gender and BMI. No associations were found between diabetes or pre-diabetes and any of the other SNP loci studied. Genotype-phenotype association analysis (adjusting for age and gender) showed rs4074134-BDNF to be associated with BMI, waist circumference, fasting and postprandial plasma glucose, fasting serum insulin, and HOMA-IR in subjects without T2DM. However, fasting and postprandial plasma glucose were the only significant factors after adjusting for BMI. These results suggest that the common variation of BDNF (rs4074134) is associated with T2DM independently of obesity in Chinese Han population. This variant also has an effect on plasma glucose concentration, BMI and insulin sensitivity.
    PLoS ONE 01/2013; 8(2):e56898. · 3.53 Impact Factor
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    ABSTRACT: To compare the efficacy of glycemic control and insulin secretion of alpha glucosidase inhibitors (AGI) on type 2 diabetes patients between Asian and Caucasian. The MEDLINE®, EMBASE®, CENTRAL were searched and qualified studies in Asian and Caucasian population comparing AGI treatment with placebo or other oral anti-diabetic drugs in type 2 diabetic patients were included. Totally 58 qualified studies were included. When AGI treatment was compared with placebo, a significant difference in HbA1c decline from baseline favoring AGI treatment was found in Asian (weighted mean difference (WMD), -0.50%; 95% CI, -0.66% to -0.34%) and in Caucasian a significant difference in HbA1c decline favoring AGI treatment was also found (WMD, -0.68%; 95% CI, -0.76% to -0.60%). In Asian, fasting plasma glucose was reduced with AGI treatment compared with placebo (WMD, -0.53 mmol/L; 95% CI, -0.91 to -0.14 mmol/L) and in Caucasian there was also a significant difference in FPG changes favoring AGI therapy (WMD, -0.88 mmol/L; 95% CI, -1.00 to -0.77 mmol/L). Studies in Asian showed a significant difference in fasting insulin changes favoring AGI treatment (WMD, -0.78 uU/ml; 95% CI, -0.96 to -0.59 uU/ml). While in Caucasian fasting insulin was decreased without significance with AGI treatment (WMD-1.24 uU/ml; 95% CI, -2.51 to 0.04 uU/ml). Body weight was decreased with AGI treatment in Asian (WMD, -1.00 kg; 95% CI, -1.69 to -0.31 kg) and was also decreased with AGI treatment in Caucasian (WMD, -0.73 kg; 95% CI, -1.13 to -0.33 kg). According to results from this meta-analysis, the efficacy in glucose lowering, body weight reduction and insulin secretion decreasing of AGI treatment in Asian were comparable with those in Caucasian.
    PLoS ONE 01/2013; 8(11):e79421. · 3.53 Impact Factor
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    ABSTRACT: Heterozygous loss-of-function mutations in NEUROD1 have been identified as a very rare cause of maturity-onset diabetes of the young and neonatal diabetes. Previous studies showed that a common A45T variant located in NEUROD1 was inconsistently associated with type 2 diabetes mellitus (T2DM) in different ethnic populations. This study aimed to evaluate the contribution of variant A45T in the genetic pathogenesis of T2DM. A case-control study in a Chinese Han population was conducted, which included 3,554 (1,155 males/2,399 females) patients with T2DM and 4,181 (1,798 males/2,383 females) control subjects from 13 different regions of China. The A45T variant was genotyped by the Illumina GoldenGate platform. A meta-analysis was used to estimate the effects of variant A45T in populations from different ethnic backgrounds. No association in Chinese Han subjects was confirmed in our case control study. A relationship between variant A45T and postprandial glucose was observed in the control group (β = 0.05, p = 0.002). Meta-analyses did not find an association of this polymorphism with T2DM in Chinese, Japanese, and East Asian descent, but did for European descent Caucasians (odds ratio = 1.15, 95 %CI 1.03-1.28, p = 0.01). Our study suggests the variant A45T does not play a major role in the development of T2DM in East Asian descent, and the role in European descent Caucasian needs to be confirmed.
    Endocrine 12/2012; · 3.53 Impact Factor
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    ABSTRACT: Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.
    Diabetes 09/2012; · 7.90 Impact Factor
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    ABSTRACT: The insulin receptor substrate-1 (IRS1) plays an important role in insulin signaling. A recent genome-wide association study identified rs2943641C>T as a susceptibility locus for type 2 diabetes mellitus (T2DM) in Caucasian patients. Therefore, we determined whether this common variant near IRS1 is also associated with the risk of T2DM and T2DM-related phenotypes in a Chinese Han population. A total of 2,290 unrelated Chinese Han individuals residing in Beijing were recruited in this study, including 1177 T2DM patients and 1113 subjects with normal glucose tolerance (control group). The single nucleotide polymorphism (SNP) was genotyped using a MassARRAY iPLEX system. The frequency of risk allele C was 0.929 in the control group and 0.939 in patients with T2DM. We found no association between the C allele of rs2943641 and T2DM in a recessive model [OR 1.14, 95 % confidence interval (CI) 0.89-1.45, P = 0.298], or after adjusting for sex, age, and body mass index (BMI) (OR 1.10, 95 % CI 0.85-1.43, P = 0.301). Analysis of the clinical features of the control subjects with normal glucose tolerance revealed that the 30-min plasma glucose level during a 75-g oral glucose tolerance test was significantly different between the CC and CT+TT genotypes (P = 0.017). Linear regression analysis showed that the 30-min plasma glucose levels was significantly and positively associated with the CC genotype after adjusting for sex, age, and BMI (β = 0.065, 95 % CI 0.009-0.654, P = 0.044). In addition, a potential association between this SNP and increased waist circumference (β = 1.337, 95 % CI -0.179 to 2.853, P = 0.084) was observed with adjustment for the sex and age. Our study was not able to demonstrate the association between rs2943641 near IRS1 and T2DM in a Chinese Han population. However, this SNP may be associated with postprandial hyperglycemia.
    Endocrine 05/2012; · 3.53 Impact Factor
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    ABSTRACT: To investigate the daily insulin doses and the ratio of basal insulin to total daily insulin in Chinese type 2 diabetic patients who received basal bolus insulin therapy. Totally 2480 patients prescribed with pre-meal bolus insulin and bedtime basal insulin were included. The mean daily insulin doses was 38.22 ± 14.92 IU/day, the mean daily insulin doses per weight was 0.58 ± 0.22 IU/kg, the mean bolus insulin dose was 0.44 ± 0.17 IU/kg and the mean basal insulin dose was 0.13 ± 0.08 IU/kg. The mean basal/total daily insulin ratio (BD/TDD) was 0.23 ± 0.08. In most patients (47.94%), the BD/TDD was between 0.20 and 0.30. Diabetic duration, BMI, HbA1c, fasting and postprandial blood glucose level were positively associated with daily insulin dose, while age was negatively associated with daily insulin dose. Diabetic duration, BMI, HbA1c, fasting blood glucose level, and using metformin were positively associated with BD/TDD ratio, while age, postprandial C peptide, postprandial blood glucose level and CRE level were negatively associated with BD/TDD ratio. The daily insulin doses of intensive treatment in Chinese type 2 diabetic patients was 38.22 IU/day, the mean daily insulin doses per weight was 0.58 IU/kg, mean BD/TDD ratio was 0.23.
    PLoS ONE 01/2012; 7(6):e38962. · 3.53 Impact Factor
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    ABSTRACT: A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results. The main aim of this work was to evaluate more precisely the genetic influence of KCNJ11 on T2DM in East Asian populations by means of a meta-analysis. We identified 20 articles for qualitative analysis and 16 were eligible for quantitative analysis (meta-analysis) by database searching up to May 2010. The association was assessed under different genetic models, and the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The allelic and genotypic contrast demonstrated that the association between KCNJ11 and T2DM was significant for rs5210. However, not all results for rs5215 and rs5218 showed significant associations. For rs5219, the combined ORs (95% CIs) for allelic contrast, dominant and recessive models contrast (with allelic frequency and genotypic distribution data) were 1.139 (1.093-1.188), 1.177 (1.099-1.259) and 1.207 (1.094-1.332), respectively (random effect model). The analysis on the most completely adjusted ORs (95% CIs) by the covariates of rs5219 all presented significant associations under different genetic models. Population-stratified analysis (Korean, Japanese and Chinese) and sensitivity analysis verified the significant results. Cumulative meta-analysis including publication time and sample size illustrated the exaggerated genetic effect in the earliest studies. Heterogeneity and publication bias were assessed. Our study verified that single nucleotide polymorphisms (SNPs) of KCNJ11 gene were significantly associated with the risk of T2DM in East Asian populations.
    Molecular Biology Reports 05/2011; 39(1):645-59. · 2.51 Impact Factor
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    ABSTRACT: Recently, several genome-wide and candidate gene association studies have identified many novel genetic loci for type 2 diabetes (T2D); among these genes, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 are the most important. We aimed to determine the effects of these genetic loci associated with T2D in the Chinese Han population of China. Single-nucleotide polymorphisms (SNPs) in or near CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 genes were genotyped in a case-control Chinese Han sample living in Beijing, China involving 1024 patients with T2D and 1005 control subjects. In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 x 10(-4)) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index. Not only did an association between WFS1-rs6446482 and early-onset T2D exist in the subgroup analysis, but TCF2-rs7501939 and WFS1-rs6446482 were also confirmed to confer risk for T2D in this meta-analysis. Moreover, the relationship between FTO-rs8050136 and body mass index, together with the effect of CDKAL1-rs10946398 on beta cell function, was also observed in the control individuals. Our findings support the important contribution of these genetic loci to susceptibility for T2D in the Chinese Han population in Beijing of China.
    BMC Medical Genetics 01/2010; 11:81. · 2.54 Impact Factor
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    ABSTRACT: To identify risk factors associated with the presence of diabetes. A diabetes survey was conducted in 2801 citizens aged 35-79 years living in 10 communities in Beijing, China. Participants were recruited by residents committees. 75g oral glucose tolerance test was performed to define diabetes according to the WHO 1999 criteria. Logistic regression analysis was used to estimate odds ratios (OR) for diabetes. The prevalence of diabetes and impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was 24.2% and 20.4% in men, respectively and 19.4% and 19.0% in women, respectively. The multivariate adjusted OR (95% CI) corresponding to a one standard deviation increase in age (year) was 1.52 (1.25,1.86), waist circumference (cm) 1.35 (1.12,1.63), serum triglycerides (mmol/L) 1.29 (1.09,1.54) and high density lipoprotein cholesterol (mmol/L) 0.74 (0.61,0.91) in men and 2.03 (1.77,2.33), 1.21 (1.06,1.38), 1.34 (1.21,1.49), 0.74 (0.66,0.84) in women, respectively. For diabetes family history they were 2.46 (1.66,3.65) in men and 2.39 (1.84,3.10) in women, and for hypertension 1.14 (0.77,1.68) in men and 1.54 (1.18,2.01) in women. There were no significant associations between the presence of diabetes and occupation, education level, household income, leisure time physical activities, current smoking and drinking status. Age, diabetes family history, obesity, dyslipidemia and hypertension were all associated with the presence of diabetes in this study population.
    Diabetes research and clinical practice 12/2009; 86(3):233-8. · 2.74 Impact Factor
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    ABSTRACT: Understanding the metabolic basis of glucose intolerances and insulin resistance is essential to facilitate early diagnosis, satisfactory therapies and personalized treatments of type 2 diabetes (T2DM). Here, we analyzed the serum metabolic variations from 231 human participants with normal glucose tolerance (NGT, n = 80, M/F = 34/46, mean age 53 +/- 10 years), impaired glucose regulation (IGR, n = 77, M/F = 33/44, mean age 51 +/- 10 years) and T2DM (n = 74, M/F = 32/42, mean age 51 +/- 9 years) to establish the relationship between the serum metabolite compositions and the development of diabetes. By using the proton nuclear magnetic resonance spectroscopy in conjunction with the multivariate data analysis, we found that the development of both glucose intolerances and insulin resistances are closely correlated with the progressive changes of human serum metabonome. Compared with NGT subjects, the IGR and T2DM participants showed clear dysfunctions of choline metabolism, glucose metabolism, lipid and amino acid metabolisms, and disruptions of TCA cycle. The insulin resistance statuses were closely associated with the serum metabonomic changes in terms of glucose, fatty acid and protein/amino acid metabolisms. We also found greater metabonomic heterogeneity among the populations with T2DM and high insulin resistance status. These findings provide useful information to bridge the gaps in our understandings to the metabolic alterations associated with the progression of glucose intolerances and insulin resistance status.
    Journal of Proteome Research 09/2009; 8(11):5188-95. · 5.06 Impact Factor
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    ABSTRACT: To evaluate the effect of TCF7L2 on genetic susceptibility of type 2 diabetes (T2DM) in East Asian population by using the meta-analysis. Search all the publications about the association between TCF7L2 and T2DM in East Asian population from PubMed, CNKI and abstracts of major diabetes conferences. Perform the meta-analysis of all the validated studies and evaluate the association between rs7903146 T allele, rs12255372 T allele, rs11196205 C allele, rs290487 C allele and rs11196218 G allele of TCF7L2 and the risk of T2DM. Eleven studies from nine eligible papers and one unpublished study of ours were included in the meta-analysis. Ten eligible studies were analyzed for rs7903146, five were analyzed for rs12255372 and rs11196205, and three were analyzed for rs290487 and rs11196218. We found that four SNPs (rs7903146, rs12255372, rs11196205, rs290487) in TCF7L2 were significantly associated with T2DM in East Asian populations. The rs11196218 also showed a marginal association. The estimated population-attributable risk (PAR) associated with analyzed SNPs ranged from 2% to 7%. SNPs in TCF7L2 were strongly associated with the risk of T2DM in East Asian population. But the contribution of its genetic variants to the epidemic of type 2 diabetes in East Asian was relatively low.
    Diabetes research and clinical practice 06/2009; 85(2):139-46. · 2.74 Impact Factor