湖北汉族人2型糖尿病与代谢综合症的遗传流行病学研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
代谢综合症(Metabolic syndrome,MetS)是当今世界最重要的健康问题之一,包括腹部肥胖、高血压、高血糖和血脂异常等一系列心血管危险因素。不同种族代谢综合症的发病率差异很大。2型糖尿病(Type 2 diabetes,T2D)是一种慢性复杂多基因疾病,受遗传因素和环境因子及其互作的影响,其主要特征是胰岛素抵抗(Insulin resistance,IR)或β胰岛细胞分泌胰岛素不足导致高血糖。ENPP1/PC-1是IR、肥胖和T2D的候选基因之一。四个亚洲人群的全基因组关联研究(GWAS)报道KCNQ1基因多态性与T2D相关联。五个分别对欧洲白人和亚洲人的GWAS分析鉴定CDKAL1基因是T2D的易感基因。不同种族KCNQ1/CDKAL1多态性与T2D的关联研究结果不尽一致。本研究的目的：1)调查MetS.IR和T2D在中国湖北人群中的发病率及其相关性。2)采用病例-对照研究和Meta分析的方法,探讨湖北汉族人群ENPP1、KCNQ1和CDKAL1多态与T2D的遗传关联。
     材料和方法
     研究对象：流行病学调查在湖北宜昌的三个乡镇进行。共调查9877人,其中男4171人,女5706人,年龄23-90岁。MetS分别采用APWP-NAFLD、NCEP-ATPⅢ和IDF标准定义；采用稳态模型IR指数(HOMA-IR)及定量胰岛素敏感性指标(QUICKI)评价了8609人(男3598,女5011)的胰岛素抵性。T2D病例采用1999世界卫生组织亚洲诊断标准,高血压和肥胖按照2004世界卫生组织诊断标准定义。
     表型分析：检测的临床指标包括体重、身高、腰臀围、空腹血糖(FBG)、餐后血糖(PBG)、收缩压(SBP)、舒张压(DBP)、总胆固醇、甘油三酸酯、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、空腹胰岛素、体重指数(BMI)和腰臀围(WHR)。
     基因分型：采用PCR-RFLP方法,对646个研究对象(高血糖343人,非高血糖303人)ENPP1基因K121Q位点进行了基因分型；采用荧光定量PCR方法,对424个研究对象(T2D组223人,对照组201人)的KCNQ1基因SNP rs2237892位点进行了基因分型。
     统计分析：所有的统计分析利用SPSS11.5软件完成。采用t检验和ANOVA分析连续变量,组间不同变量的差异采用X2检验分析。Pearson's相关系数r用来衡量IR (HOMA-IR和QUICKI)与MetS之间的相关性。多元线性回归用来分析IR指数与MetS成分之间的相关性。T2D和对照组的基因型频率分别用Hardy-Weinberg平衡检验。基因型关联分析用logistic回归分析检验。以P<0.05为差异显著。
     Meta-分析：用stata 10.0软件分析各研究之间的异质性,如果有异质性,采用随机效应模型计算OR值;如果没有异质性,采用固定效应模型计算OR值,用egg's回归分析检测发表偏倚。
     结果
     1.整个人群中MetS的患病率是17.9%-15.8%,其中女性(20.1%-18.9%)显著高于男性(15.0%-11.5%)(p<0.001)。MetS最常见的成分是高血压(50.7%)、高空腹血糖(28.6%)、高甘油三脂(25.6%)和BMI>25(22.1%)。APWP-NAFLD和亚洲NCEP-ATPⅢ有很好的一致性(κ=0.891)。APWP-NAFLD、亚洲NCEP-ATPⅢ和IDF一致性也良好(k=0.642、0.739)。
     2.根据HOMA-IR(>2.7)的定义IR的患病率为15.8%,女性明显高于男性(16.7% vs.14.7%、p--0.014),而根据QUICKI(<0.33)的定义IR的患病率为12.9%,男性(12.1%)和女性(13.4%)没有差异,HOMA-IR和QUICKI之间有很好的相关性(k=0.879)。IR与代谢综合症的所有成分显著相关,多元线性回归分析显示IR与体重指数、腰围、高密度脂蛋白胆固醇、甘油三酯和高FBG相关。
     3.T2D和糖尿病前期患病率分别为2.9%(男性3.0%,女性2.8%)和6.9%(男性7.2%,女性6.8%),低于最近杨等(2010)在中国14个省市代表性样本的数据,T2D和糖尿病前期患病率随着年龄和BMI增加而增加。
     4.高血糖组ENPP1 K121Q等位基因频率比正常葡萄糖禁食组要高(10.5% vs.6.6%,p=0.013),K121Q多态与高血糖在调整年龄、性别和BMI前后均显著相关(p值分别为0.018和0.014),K121Q多态与T2D在调整年龄、性别和BMI前后也弱相关(p值分别为0.046和0.038)。不同性别的亚组分析表明XQ基因型和Q等位基因仅在女性组与T2D显著相关(XQ:OR=2.16,p=0.019;Q:OR=2.11,p=0.018),揭示湖北汉人ENPP1 K121Q多态与T2D的关联存在性别差异。
     5.在T2D病例中KCNQ1 rs2237892的C等位基因频率比对照组要高(p=0.001),等位基因C的OR值为1.65,无论是否调整年龄、性别和BMI, CC和CC+CT基因型都与T2D相关联。对15个东亚研究进行Meta分析,KCNQ1基因的多个单核苷酸多态性和T2D相关联,其中rs2237892 C, rs2237895 C, rs2237897 C和rs2074196 G的OR值分别为1.35(p<0.0001),1.27(p<0.0001),1.32(p<0.0001)和1.3(p<0.0001)。
     6.对30个符合要求的CDKAL1和T2D关联研究进行全面的Meta分析,证实CDKAL1基因与T2D相关联,rs7756992 G,rs7754840 C和rs10946398 C的OR值分别为1.15(p<0.0001),1.15 p<0.0001)和114(p<0.0001)。
     结论
     中国湖北汉人MetS发病率为17.90%-15.8%,并且女性高于男性。IR与MetS及其组分相关(15.8%-12.9%),特别是肥胖、低的高密度脂蛋白和高PBG。T2D和糖尿病前期的发病率较低,分别为2.9%和6.9%,并且随着年龄和BMI升高而升高,女性对MetS和IR更易感。
     湖北汉人特别是女性ENPP1 K121Q与高血糖易感性显著相关,有利于T2D的发展。在中国汉人和东亚人群中,KCNQ1多态与T2D相关。CDKAL多态也与T2D相关。
Metabolic syndrome (MetS) is one of the fastest growing health problems worldwide, characterized by a clustering of cardiovascular risk factors including abdominal obesity, high blood pressure, high glucose concentration, and dyslipidemia. Type 2 diabetes (T2D) is a chronic and complex, polygenic disease influenced by interaction between genetic and environmental factors. It is characterized by hyperglycemia due to insulin resistance (IR) and/or impaired insulin secretion in the pancreaticβcells. ENPP1 has been suggested as a candidate gene for IR, obesity and T2D. Recently four genome-wide association studies (GWAS) in East Asian populations reported the association of KCNQ1 variants with T2D. CDKAL1 was identified as a susceptibility gene for T2D through five subsequent GWAS in white Europeans and Asians. Several replication studies have been conducted for association between KCNQ1/CDKAL1 variants and T2D in multiple ethnic groups, but contradictory results have been reported. The aims of this study are:1) to investigate the prevalence of metabolic syndrome, insulin resistance, type 2 diabetes and to evaluate the association of insulin resistance with metabolic syndrome components in the Hubei Han Chinese population; 2) to investigate the association of polymorphisms in ENPP1, KCNQ1 and CDKAL1 with type 2 diabetes through Hubei Han Chinese case-control studies and meta-analysis.
     Material and methods
     Subjects:Epidemiological study was conducted in 3 towns in Yichang, Hubei Province. A total of 9877 subjects (4171 men and 5706 women) aged 23-90 years were recruited. MetS was defined according to the APWP-NAFLD, modified (Asian) NCEP-ATPⅢand IDF criteria. IR was assessed for 8609 subjects (3598 men and 5011 women) by both homeostasis model assessment for IR (HOMA-IR) and quantitative insulin check index (QUICKI). All T2D cases were defined according to the 1999 World Health Organization diagnostic criteria. Hypertension and obesity were defined according to the 2004 World Health Organization recommended criteria for Asians.
     Phenotyping:Clinical parameters measured and calculated for all subjects using standard methods included weight, height, waist and hip circumference, fasting blood glucose (FBG), postprandial blood glucose (PBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin, Body mass index (BMI) and waist to hip ratio (WHR).
     Genotyping:A total of 646 subjects (343 hyperglycaemic and 303 normoglycaemic subjects) were genotyped for ENPP1 K121Q using the PCR-RFLP method. Four hundred and twenty four subjects (223 T2D cases and 201 controls) were genotyped for KCNQ1 rs2237892 using the fluorescence quantitative real-time PCR SNP method.
     Statistical analysis:All statistical analyses were conducted using SPSS software (version 11.5) for Windows. The continuous variables were analysed by Student's t-test and ANOVA tests. The differences between groups for categorical variables were detected by theχ2 test. Pearson's correlation coefficient (r) was applied to investigate the correlation between IR indexes (HOMA-IR and QUICKI) and MetS components. Multivariate linear regression was applied to investigate the association between IR indexes and MetS components. The genotype frequencies in the T2D cases and controls were separately tested for Hardy-Weinberg equilibrium using theχ2 test before association analysis. The genotype-disease association analyses were performed by logistic regression analysis. Two-tailed p-values was considered to be statistically significant when p<0.05.
     Meta-analysis:Stata 10.0 software was used to evaluate the heterogeneity between studies. Pooled ORs were calculated using a random or fixed effects model according to the presence or absence the heterogeneity between studies, respectively. The conservative Egger's regression analysis was used to evaluate publication bias.
     Results
     1. The overall prevalence of MetS was 17.9%-15.8%, with a significantly higher rate among women (20.1%-18.9%) than men (15.0%-11.5%) (p<0.001). The most frequent components of MetS were high blood pressure (50.7%), high FBG (28.6%), high triglyceride (25.6%) and BMI>25 (22.1%). Very good agreement (κ=0.891) was observed between APWP-NAFLD and modified (Asia) NCEP-ATPⅢdefinitions. The agreement among APWP-NAFLD or modified (Asia) NCEP-ATPⅢand IDF definitions was substantial (κ=0.642,0.739, respectively).
     2. The overall prevalence of IR according to HOMA-IR (>2.7) definition was 15.8% with a significantly higher prevalence among women than men (16.7% vs. 14.7%,p=0.014). However, the prevalence of IR according to QUICKI definition (<0.33) was 12.9% with no difference between men (12.1%) and women (13.4%). Very good agreement (κ=0.879) between HOMA-IR and QUICKI definitions was observed. A significant correlation was found between IR and all MetS components. Multivariate linear regression analysis revealed that the BMI, waist circumference, low HDL-C, triglyceride and high FBG were significantly associated with IR.
     3. The overall prevalence of T2D and pre-diabetes were 2.9%(men 3.0% and women 2.8%) and 6.9%(men 7.2% and women 6.8%) respectively, being lower compared with Yang's report (2010) in a nationally representative sample from 14 Chinese provinces and municipalities. The prevalence rates of T2D and pre-diabetes were consistently increased with age and BMI.
     4. The K121Q polymorphism was associated with hyperglycaemia/T2D without and with adjustment for age, sex and BMI (for hyperglycaemia,p=0.018, and 0.014; for T2D,p=0.046 and 0.038, respectively). The stratified analysis results showed that the XQ genotype and Q allele were significantly associated with the T2D risk only in women subgroup (XQ:OR=2.16,p=0.019; Q:OR=2.11, p=0.018), suggesting sex-specific association of ENPP1 K121Q polymorphism with T2D in our study population.
     5. The frequency of C allele of KCNQ1 rs2237892 polymorphism in T2D cases was higher than those of controls group (p=0.001). The odds ratio for the risk allele C was 1.65. The CC and CC+CT genotypes were associated with T2D without and with adjustment for age, sex and BMI. A meta-analysis of fifteen East Asian studies of association between SNPs in KCNQ1 and T2D revealed that combined odds ratios of the rs2237892 C, rs2237895 C, rs2237897 C, rs2074196 G allele were 1.35 (p<0.0001),1.27 (p<0.0001),1.32 (p<0.0001),1.3 (p<0.0001) respectively.
     6. A global meta-analysis of thirty eligible association studies of CDKAL1 polymorphisms with T2D revealed that combined odds ratios for rs7756992 G, rs7754840 C and rs 10946398 C allele in CDKAL1 were 1.15 (p<0.0001),1.15 (p<0.0001), and 1.14 (p<0.0001) respectively.
     Conclusions
     The prevalence of MetS in Hubei Han Chinese was 17.9%-15.8%, being higher in women than in men. The prevalence of IR (15.8%-12.9%) was associated with MetS and its components, especially with obesity, low HDL-C and high PBG. The prevalence of T2D and pre-diabetes were lower (2.9%,6.9%), increasing with age and BMI. Hubei Han Chinese women were more susceptible to MetS and IR.
     The ENPP1 K121Q was significantly associated with the susceptibility for hyperglycaemia and may contribute to the development of T2D in Hubei Han Chinese, especially in women subjects. The KCNQ1 polymorphisms were associated with T2D in Han Chinese and East Asian populations. CDKAL polymorphisms were associated with T2D in global and stratified meta-analysis.
引文
Abate N, Chandalia M, Di Paola R et al. (2006) Mechanisms of disease:ectonucleotide pyrophosphatase phosphodiesterase 1 as a "gatekeeper" of insulin receptors. Nat Clin Pract Endocrinol Metab 2:694-701.
    Abate N, Chandalia M, Satija P et al. (2005) ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes. Diabetes 54:1207-1213.
    Abdul-Ghani MA, Tripathy D, DeFronzo RA (2006) Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 29:1130-1139.
    Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539-553
    Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome-a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med 23:469-480.
    Altshuler D, Hirschhorn JN, Klannemark M et al. (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76-80.
    Anonymous (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160-3167.
    Arfa I, Abid A, Malouche D et al. (2007) Familial aggregation and excess maternal transmission of type 2 diabetes in Tunisia. Postgrad Med J 83:348-351.
    Ascaso JF, Pardo S, Real JT et al. (2003) Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 26:3320-3325.
    Assman G, Guerra R, Fox G et al. (2007) Harmonizing the definition of the metabolic syndrome: Comparison of the criteria of the Adult Treatment Panel III and the International Diabetes Federation in United States American and European Populations. Am J Cardiol 99:541-548.
    Aulchenko YS, Pullen J, Kloosterman WP et al. (2007) LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition. Diabetes 56:3020-3026.
    Avnit-Sagi T, Kantorovich L, Kredo-Russo S et al. (2009) The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas. PLoS One 4:e5033.
    Babenko AP, Polak M, Cave H et al. (2006) Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med 355:456-466.
    Bacci S, Ludovico O, Prudente S et al. (2005) The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. Diabetes 54:3021-3025.
    Balasubramanyam M, Aravind S, Gokulakrishnan K et al. (2011) Impaired miR-146a expression links subclinical inflammation and insulin resistance in type 2 diabetes. Mol Cell Biochem 351:197-205.
    Balkau B, Charles MA. (1999) Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 16:442-443.
    Barbato C, Arisi I, Frizzo ME et al. (2009) Computational challenges in miRNA target predictions: To be or not to be a true target? J Biomed Biotechnol 2009:1-9.
    Barnett AH, Eff C, Leslie RD, Pyke DA (1981) Diabetes in identical twins. A study of 200 pairs. Diabetologia 20:87-93.
    Baroukh N, Ravier MA, Loder MK et al. (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem 282:19575-19588.
    Barroso I, Luan J, Middelberg RP et al. (2003) Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol 1: e20.
    Bartoov-Shifman R, Hertz R, Wang H et al. (2002) Activation of the insulin gene promoter through a direct effect of hepatocyte nuclear factor 4a. J Biol Chem 277:25914-25919
    Bastemir M, Akin F, Alkis E, Kaptanoglu B (2007) Obesity is associated with increased serum TSH level, independent of thyroid function. Swiss Med Wkly 137:431-434.
    Bartel DP (2004) MicroRNAs:genomics, biogenesis, mechanism, and function. Cell 116:281-297.
    Bento JL, Palmer ND, Mychaleckyj JC et al. (2004) Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes. Diabetes 53:3007-3012.
    Bergman RN, Van Citters GW, Mittelman SD et al. (2001) Central role of the adipocyte in the metabolic syndrome. J Investig Med 49:119-126.
    Bhatti JS, Bhatti GK, Mastana SS et al. (2010) ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes in North Indians. Mol Cell Biochem 345:249-257.
    Bingham C, Ellard S, Allen L et al. (2000) Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1 beta. Kidney Int 57: 898-907.
    Bochenski J, Placha G, Wanic K et al. (2006) New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals. Diabetes 55:2626-2630.
    Bodhini D, Radha V, Dhar M et al. (2007) The rs12255372 (G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism 56:1174-1178.
    Bodhini D, Radha V, Ghosh S et al. (2011) Association of calpain 10 gene polymorphisms with type 2 diabetes mellitus in Southern Indians. Metabolism 60:681-688.
    Bolmeson C, Esguerra JL, Salehi A et al. (2011) Differences in islet-enriched miRNAs in healthy and glucose intolerant human subjects. chem Biophys Res Commun 404:16-22.
    Bonnycastle LL, Willer CJ, Conneely KN et al. (2006) Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes 55:2534-2540.
    Borchers JR, Clem KL, Habash DL et al. (2009) Metabolic syndrome and insulin resistance in Division 1 collegiate football players. Med Sci Sports Exerc 41:2105-2110.
    Bouatia-Naji N, Bonnefond A, Cavalcanti-Proenca C et al. (2009) A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet 41: 89-94.
    Bouhaha R, Choquet H, Meyre D et al. (2010) TCF7L2 is associated with type 2 diabetes in nonobese individuals from Tunisia. Pathol Biol (Paris) 58:426-429.
    Boutayeb A, Boutayeb S (2005) The burden of non communicable diseases in developing countries. Int J Equity Health 4:2.
    Bravo-Egana V, Rosero S, Molano RD et al. (2008) Quantitative differential expression analysis reveals miR-7 as major islet microRNA. Biochem Biophys Res Commun 366:922-926.
    Caceres M, Teran CG, Rodriguez S, Medina M (2008) Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity. BMC Pediatr 8:31.
    Cai Z, Xu X, Wu X et al. (2009) Hyperuricemia and the metabolic syndrome in Hangzhou. Asia Pac J Clin Nutr 18:81-87.
    Carey DG, Jenkins AB, Campbell LV et al. (1996) Abdominal fat and insulin resistance in normal and overweight women:Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 45:633-638.
    Carr DB, Utzschneider KM, Hull RL et al. (2004) Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes 53:2087-2094.
    Cassell PG, Jackson AE, North BV et al. (2002) Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians. Diabetes 51:1622-1628.
    Cauchi.S, Meyre D, Dina C et al. (2006) Transcription factor TCF7L2 genetic study in the French population:expression in human β-cells and adipose tissue and strong association with type 2 diabetes. Diabetes 55:2903-2908.
    Cauchi S, El Achhab Y, Choquet H et al. (2007) TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups:a global meta-analysis. J Mol Med 85:777-782.
    Cauchi S, Meyre D, Durand E et al. (2008a) Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value. PLoS One 3:e2031.
    Cauchi S, Proenca C, Choquet H et al. (2008b) Analysis of novel risk loci for type 2 diabetes in a general French population:the D.E.S.I.R. study. J Mol Med 86:341-348.
    Chambers JC, Zhang W, Zabaneh D et al. (2009) Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians. Diabetes 58:2703-2708.
    Chandalia M, Grundy SM, Adams-Huet B, Abate N (2007) Ethnic differences in the frequency of ENPP1/PC1 121Q genetic variant in the Dallas heart study cohort. J Diabetes Complications 21: 143-148.
    Chandak GR, Janipalli CS, Bhaskar S et al. (2007) Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia 50:63-67.
    Chang YC, Chang TJ, Jiang YD et al. (2007) Association study of the genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the Chinese population. Diabetes 56:2631-2637.
    Chang YC, Chiu YF, Ho LL et al. (2010) TCF7L2 genetic variants and progression to diabetes in the Chinese population:pleiotropic effects on insulin secretion and insulin resistance. J Mol Med 88: 183-192.
    Chen X, Ba Y, Ma L et al. (2008) Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997-1006.
    Chen SF, Lu XF, Yan WL et al. (2007) Variations in the calpain-10 gene are associated with the risk of type 2 diabetes and hypertension in northern Han Chinese population. Chin Med J 120:2218-2223.
    Chen Y, Kittles R, Zhou J et al. (2005) Calpain-10 gene polymorphisms and type 2 diabetes in West Africans:the Africa America Diabetes Mellitus (AADM) Study. Ann Epidemiol 15:153-159.
    Chen MP, Chung FM, Chang DM et al. (2006) ENPP1 K121Q polymorphism is not related to type 2 diabetes mellitus, features of metabolic syndrome, and diabetic cardiovascular complications in a Chinese population. Rev Diabet Stud 3:21-30.
    Chen YH, Xu SJ, Bendahhou S et al. (2003) KCNQ1 gain-offunction mutation in familial atrial fibrillation. Science 299:251-254.
    Chen Z, Zhang X, Ma G et al. (2010) Association study of four variants in KCNQ1 with type 2 diabetes mellitus and premature coronary artery disease in a Chinese population. Mol Bio 37: 207-212.
    Chien KL, Lee BC, Hsu HC et al. (2008) Prevalence, agreement and classification of various metabolic syndrome criteria among ethnic Chinese:a report on the hospital-based health diagnosis of the adult population. Atherosclerosis 196:764-771.
    Cheung CY, Chan HW, Liu YL et al. (2008) Prevalence of metabolic syndrome in Chinese renal transplant recipients. Hong Kong Med J 14:379-384.
    Chidambaram M, Radha V, Mohan V (2010) Replication of recently described type 2 diabetes gene variants in a South Indian population. Metabolism 59:1760-1766.
    Chouabe C, Neyroud N, Guicheney P et al. (1997) Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J 16:5472-5479.
    Costanzo BV, Trischitta V, Di Paola R et al. (2001) The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121). Diabetes 50:831-836.
    Cox NJ (2001) Challenges in identifying genetic variation affecting susceptibility to type 2 diabetes: examples from studies of the calpain210 gene. Hum Mol Genet 10:2301-2305.
    Croall DE, DeMartino GN (1991) Calcium-activated neutral protease (calpain) system:structure, function, and regulation. Physiol Rev 71:813-847.
    Cruz M, Valladares-Salgado A, Garcia-Mena J et al. (2010) Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev 26:261-270.
    Daimon M, Oizumi T, Saitoh T et al. (2002) Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. Diabetes Res Clin Pract 56:147-152.
    Damcott CM, Pollin TI, Reinhart LJ et al. (2006) Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish:replication and evidence for a role in both insulin secretion and insulin resistance. Diabetes 55:2654-2659.
    De Silva SN, Weerasuriya N, De Alwis NM et al. (2002) Excess maternal transmission and familial aggregation of type 2 diabetes in Sri Lanka. Diabetes Res Clin Pract 58:173-177.
    De Sousa AG, Cercato C, Mancini MC, Halpern A (2008) Obesity and obstructive sleep apnea-hypopnea syndrome. Obes Rev 9:340-354.
    DECODE Study Group, Qiao Q (2006) Comparison of different definitions of the metabolic syndrome in relation to cardiovascular mortality in European men and women. Diabetologia 49: 2837-2846.
    Deeb SS, Fajas L, Nemoto M et al. (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20:284-287.
    Dehwah MAS, Shuang Z, Yan W et al. (2008) Type 2 diabetes in Han Chinese in Hubei. J Applied Sci 8:1235-1241.
    del Bosque-Plata L, Aguilar-Salinas CA, Tusie-Luna MT et al. (2004) Association of the calpain-10 gene with type 2 diabetes mellitus in a Mexican population. Mol Genet Metab 81:122-126.
    Demirci H, Yurtcu E, Ergun MA et al. (2008) Calpain 10 SNP-44 gene polymorphism affects susceptibility to type 2 diabetes mellitus and diabetic-related conditions. Genet Test 12:305-309.
    Demenais F, Kanninen T, Lindgren CM et al. (2003) A meta-analysis of four European genome screens (GIFT Consortium) shows evidence for a novel region on chromosome 17p11.2-q22 linked to type 2 diabetes. Hum Mol Genet 12:1865-1873.
    Dhanaraj E, Bhansali A, Jaggi S et al. (2009) Predictors of metabolic syndrome in Asian north Indians with newly detected type 2 diabetes. Indian J Med Res 129:506-514.
    Dina C, Meyre D, Gallina S et al. (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39:724-726
    Doll S, Paccaud F, Bovet P et al. (2002) Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries. Int J Obes Relat Metab Disord 26:48-57.
    Dong H, Maddux BA, Altomonte J, Meseck M et al. (2005) Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance. Diabetes 54: 367-372.
    Druet C, Dabbas M, Baltakse V et al. (2006) Insulin resistance and the metabolic syndrome in obese French children. Clin Endocrinol (Oxf) 64:672-678.
    Du B, Ma LM, Huang MB et al. (2010) High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells. FEBS Lett 584:811-816.
    Dupuis J, Langenberg C, Prokopenko I et al. (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42:105-116.
    Eckel RH (2007) Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD. Proc Nutr Soc 66:82-95.
    Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415-1428.
    El Achhab Y, Meyre D, Bouatia-Naji N et al. (2009) Association of the ENPP1 K121Q polymorphism with type 2 diabetes and obesity in the Moroccan population. Diabetes Metab 35: 37-42.
    El Ouaamari A, Baroukh N, Martens GA et al. (2008) miR-375 targets 3'-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes 57:2708-2717.
    Elbein SC, Chu W, Ren Q et al. (2002) Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians. J Clin Endocrinol Metab 87:650-654.
    Elbein SC, Sun J, Scroggin E et al. (2001) Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds:the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor lalpha genes. Diabetes Care 24:472-478.
    Ereqat S, Nasereddin A, Cauchi S al. (2010) Association of a common variant in TCF7L2 gene with type 2 diabetes mellitus in the Palestinian population. Acta Diabetol 47(Suppl 1):195-198.
    Ervin RB (2009) Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index:United States,2003-2006. Natl Health Stat Report (13):1-7.
    Esmaillzadeh A, Mirmiran P, Azadbakht L et al. (2006) High prevalence of the metabolic syndrome in Iranian adolescents. Obesity 14:377-382.
    Evans JC, Frayling TM, Cassell PG et al. (2001) Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom. Am J Hum Genet 69:544-552.
    Expert Panel on Metabolic Syndrome of Chinese Diabetes Society (2004) Recommendations on Metabolic Syndrome of Chinese Diabetes Society (Chinese). Chin J Diab 12:156-161
    Ezzidi I, Mtiraoui N, Cauchi S et al. (2009) Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia:a case-control study. BMC Med Genet 10:33.
    Ezzidi I, Turki A, Messaoudi S et al. (2010) Common polymorphisms of calpain-10 and the risk of type 2 diabetes in a Tunisian Arab population:a case-control study. BMC Med Genet 11:75.
    Facchini FS, Hua N, Abbasi F, Reaven GM (2001) Insulin resistance as a predictor of agerelated diseasesJ Clin Endocrinol Metab 86:3574-3578.
    Fajans SS, Bell GI, Polonsky KS (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 345:971-980.
    Fan JG, Peng YD (2007) Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies. Hepatobiliary Pancreat Dis Int 6:572-578.
    Fingerlin TE, Erdos MR, Watanabe RM et al. (2002) Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. Diabetes 51:1644-1648.
    Fisher E, Boeing H, Fritsche A et al. (2009) Whole-grain consumption and transcription factor-7-like 2 (TCF7L2) rs7903146:gene-diet interaction in modulating type 2 diabetes risk. Br J Nutr 101: 478-81.
    Florez JC, Burtt N, de Bakker PI et al. (2004) Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes 53:1360-1368.
    Florez JC, Agapakis CM, Burtt NP et al. (2005) Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people. Diabetes 54:1884-1891.
    Florez JC, Manning AK, Dupuis J et al. (2007) A 100k genome-wide association scan for diabetes and related traits in the Framingham Heart Study:replication and integration with other genome-wide datasets. Diabetes 56:3063-3074.
    Franks PW, Rolandsson O, Debenham SL et al. (2008) Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations. Diabetologia 51:458-463.
    Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8:657-662.
    Frayling TM, Timpson NJ, Weedon MN et al. (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316: 889-894.
    Frayling TM, Colhoun H, Florez JC (2008) A genetic link between type 2 diabetes and prostate cancer. Diabetologia 51:1757-1760.
    Fred RG, Bang-Berthelsen CH, Mandrup-Poulsen T et al. (2010) High glucose suppresses human islet insulin biosynthesis by inducing miR-133a leading to decreased polypyrimidine tract binding protein-expression. PLoS One 5:e10843.
    Frittitta L, Baratta R, Spampinato D et al. (2001) The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. J Clin Endocrinol Metab 86:5888-5891.
    Garant MJ, Kao WH, Brancati F et al. (2002) SNP43 of CAPN10 and the risk of type 2 diabetes in African-Americans:the atherosclerosis risk in Communities study. Diabetes 51:231-237.
    Gallagher IJ, Scheele C, Keller P et al. (2010) Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes. Genome Med 2:9.
    Gemalmaz A, Aydin S, BAfiAK O et al. (2008) Prevalence of the metabolic syndrome in a rural Turkish population:comparison and concordance of two diagnostic criteria. Turk J Med Sci 38: 159-165.
    Gibson F and Froguel P (2004) Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians. Diabetes 53:2977-2983.
    Ginsberg HN, Zhang YL, Hernandez-Ono A (2006) Metabolic syndrome:focus on dyslipidemia. Obesity (Silver Spring) 14:41S-49S.
    Ginsberg HN, Huang LS (2000) The insulin resistance syndrome:impact on lipoprotein metabolism and atherothrombosis. J Cardiovasc Risk 7:325-31.
    Gloyn AL, Pearson ER, Antcliff JF et al. (2004) Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 350: 1838-1849.
    Gloyn AL, Weedon MN, Owen KR et al. (2003) Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes 52:568-572.
    Goldfine ID, Maddux BA, Youngren JF et al. (2008) The role of membrane glycoprotein plasma cell antigen 1/ectonucleotide pyrophosphatase phosphodiesterase 1 in the pathogenesis of insulin resistance and related abnormalities. Endocr Rev 29:62-75.
    Gonzalez-Sanchez JL, Martinez-Larrad MT, Fernandez-Perez C et al. (2003) K121Q PC-1 gene polymorphism is not associated with insulin resistance in a Spanish population. Obes Res 11: 603-605.
    Gouda HN, Sagoo GS, Harding AH et al. (2010) The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Prol2Ala gene variant and type 2 diabetes mellitus:a HuGE review and meta-analysis. Am J Epidemiol 171:645-655.
    Gouni-Berthold I, Giannakidou E, Faust M et al. (2006) The K121Q polymorphism of the plasma cell glycoprotein-1 gene is not associated with diabetes mellitus type 2 in German Caucasians. Horm Metab Res 38:524-529.
    Granjon A, Gustin MP, Rieusset J et al. (2009) The microRNA signature in response to insulin reveals its implication in the transcriptional action of insulin in human skeletal muscle and the role of a sterol regulatory element-binding protein-lc/myocyte enhancer factor 2C pathway. Diabetes 58: 2555-2564.
    Grant SF, Thorleifsson G, Reynisdottir I et al. (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320-323.
    Grarup N, Urhammer SA, Ek J et al. (2006) Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects. Diabetologia 49:2097-2104.
    Grarup N, Rose CS, Andersson EA et al. (2007) Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects:validation and extension of genome-wide association studies. Diabetes 56: 3105-3111.
    Grarup N, Andersen G, Krarup NT et al. (2008) Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes. Diabetes 57:2534-2540.
    Groenewoud MJ, Dekker JM, Fritsche A et al. (2008) Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps. Diabetologia 51:1659-1663.
    Groop L (2000) Genetics of the metabolic syndrome. Br J Nutr 83:39-48.
    Groop L, Orho-Melander M (2001) The dysmetabolic syndrome. J Intern Med 250:105-120.
    Groop LC and Tuomi T (1997) Non-insulin-dependent diabetes mellitus-a collision between thrifty genes and an affluent society. Ann Med 29:37-53.
    Groves CJ, Zeggini E, Minton J et al. (2006) Association analysis of 6736 U.K. subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. Diabetes 55:2640-2644.
    Gu DF, Reynolds K, Wu XG et al. (2005) Prevalence of the metabolic syndrome and overweight among adults in China. Lancet 365:1398-1405.
    Gu D, Reynolds K, Duan X, et al (2003) Prevalence of diabetes and impaired fasting glucose in the Chinese adult population:International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). Diabetologia 46:1190-1198.
    Gudmundsson J, Sulem P, Steinthorsdottir V et al. (2007) Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 39:977-983.
    Gusev Y (2008) Computational methods for analysis of cellular functions and pathways collectively targeted by differentially expressed microRNA. Methods 44:61.
    Hadaegh F, Zabetian A, Tohidi M et al. (2009) Prevalence of metabolic syndrome by the Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions and their association with coronary heart disease in an elderly Iranian population. Ann Acad Med Singapore 38:142-149.
    Hall JE (2003) The kidney, hypertension, and obesity. Hypertension 41:625-633.
    Hamaguchi K, Terao H, Kusuda Y et al. (2004) The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes. J Clin Endocrinol Metab 89: 1359-1364.
    Han X, Luo Y, Ren Q et al. (2010) Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in type 2 diabetes in a Chinese population. BMC Med Genet 11:81.
    Hani EH, Hager J, Philippi A et al. (1997) Mapping NIDDM susceptibility loci in French families: studies with markers in the region of NIDDM1 on chromosome 2q. Diabetes 46:1225-1226.
    Hanis CL, Boerwinkle E, Chakraborty R et al. (1996) A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet 13:161-166.
    Hansen T, Echwald SM, Hansen L et al. (1998) Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene. Diabetes 47:598-605.
    Hanson RL, Bogardus C, Duggan D et al. (2007) A search for variants associated with young-onset type 2 diabetes in American Indians in a 100k genotyping array. Diabetes 56:3045-3052.
    Hart LM, de Knijff P, Dekker JM et al. (1999) Variants in the sulphonylurea receptor gene: association of the exon 16-3t variant with type Ⅱ diabetes mellitus in Dutch Caucasians. Diabetologia 42:617-620.
    Harzallah F, Alberti H, Ben Khalifa F (2006) The metabolic syndrome in an Arab population:a first look at the new International Diabetes Federation criteria. Diabet Med 23:441-444.
    Hayashi T, Iwamoto Y, Kaku K et al. (2007) Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population. Diabetologia 50:980-984.
    Hayes MG, Pluzhnikov A, Miyake K et al. (2007) Identification of type 2 diabetes genes in Mexican Americans through genome-wide association studies. Diabetes 56:3033-3044.
    He A, Zhu L, Gupta N, Chang Y, Fang F (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol 21:2785-2794.
    He Y, Jiang B, Wang J et al. (2006) Prevalence of the metabolic syndrome and its relation to cardiovascular disease in an elderly Chinese population. J Am Coll Cardiol 47:1588-594.
    Hegele RA, Sun F, Harris SB et al. (1999) Genome-wide scanning for type 2 diabetes susceptibility in Canadian Oji-Cree, using 190 microsatellite markers. J Hum Genet 44:10-14.
    Hegele RA, Harris SB, Zinman B et al. (2001) Absence of association of type 2 diabetes with CAPN10 and PC-1 polymorphisms in Oji-Cree. Diabetes Care 24:1498-1499.
    Helgadottir A, Thorleifsson G, Manolescu A et al. (2007) A common variant on chromosome 9p21 affects risk of myocardial infarction. Science 316:1491-1493.
    Hennessy E, Clynes M, Jeppesen PB, O'Driscoll L (2010) Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells. Biochem Biophys Res Commun 396:457-462.
    Hennessy E, O'Driscoll L (2008) Molecular medicine of microRNAs:structure, function and implications for diabetes. Expert Rev Mol Med 10:e24.
    Herrera BM, Lockstone HE, Taylor JM et al. (2009) MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of type 2 diabetes. BMC Med Genomics 2:54.
    Herrera BM, Lockstone HE, Taylor JM et al. (2010) Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes. Diabetologia 53:1099-109.
    Hertel JK, Johansson S, Raeder H et al. (2008) Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia 51:971-977.
    Hildrum B, Mykletun A, Hole T et al. (2007) Age-specific prevalence of the metabolic syndrome defined by the International Diabetes Federation and the National Cholesterol Education Program:the Norwegian HUNT 2 study. BMC Public Health 7:220.
    Hinney A, Antwerpen B, Geller F et al. (2002) No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity. Mol Genet Metab 76:152-156.
    Holmkvist J, Almgren P, Lyssenko V et.al. (2008) Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. Diabetes 57:1738-1744.
    Horikawa Y, Miyake K, Yasuda K et al. (2008) Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab 93:3136-3141.
    Horikawa Y, Oda N, Cox NJ et al. (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 26:163-175.
    Horikawa Y, Oda N, Yu L et al. (2003) Genetic variations in calpain-10 gene are not a major factor in the occurrence of type 2 diabetes in Japanese. J Clin Endocrinol Metab 88:244-247.
    Horikoshi M, Hara K, Ito C et al. (2007a) A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population. Diabetologia 50:747-751.
    Horikoshi M, Hara K, Ito C et al. (2007b) Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia 50:2461-2466.
    Hu C, Wang C, Zhang R et al. (2009) Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia 52:1322-1325.
    Huang QY, Cheng MR, Ji SL (2006) Linkage and Association studies of the susceptibility genes for type 2 diabetes. Yi Chuan Xue Bao 33:573-589.
    Huang B, Qin W, Zhao B et al. (2009) MicroRNA expression profiling in diabetic GK rat model. Acta Biochim Biophys Sin (Shanghai) 41:472-477.
    Huguenin GV, Rosa G (2010) The Ala allele in the PPAR-gamma2 gene is associated with reduced risk of type 2 diabetes mellitus in Caucasians and improved insulin sensitivity in overweight subjects. Br J Nutr 104:488-497.
    Humphries SE, Gable D, Cooper JA et al. (2006) Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women. J Mol Med 84:1005-1014.
    Hwang LC, Bai CH, Chen CJ (2006) Prevalence of obesity and metabolic syndrome in Taiwan. J Formos Med Assoc 105:626-635.
    Inoue H, Ferrer J, Welling CM et al. (1996) Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians. Diabetes 45:825-831.
    Inoue H, Ferrer J, Warren-Perry M et al. (1997) Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene:identification and lack of role in Caucasian patients with NIDDM. Diabetes 46:502-507.
    Isomaa B, Almgren P, Tuomi T et al. (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683-689.
    Iwasaki N, Horikawa Y, Tsuchiya T et al. (2005) Genetic variants in the calpain-10 gene and the development of type 2 diabetes in the Japanese population. J Hum Genet 50:92-98.
    Janssens AC, Aulchenko YS, Elefante S et al. (2006) Predictive testing for complex diseases using multiple genes:fact or fiction? Gent Med 8:395-400.
    Janssens AC, van Duijn CM (2008) Genome-based prediction of common diseases:advances and prospects. Hum Mol Genet 17:R166-R173.
    Janssens AC, Moonesinghe R, Yang Q et al. (2007) The impact of genotype frequencies on the clinical validity of genomic profiling for predicting common chronic diseases. Genet Med 9: 528-535.
    Jensen DP, Urhammer SA, Eiberg H et al. (2006) Variation in CAPN10 in relation to type 2 diabetes, obesity and quantitative metabolic traits:studies in 6018 whites. Mol Genet Metab 89:360-367.
    Ji LN, Chen LX, Han XY, Zhu F (2002) The role of calpain10 gene polymorphism in the genetic susceptibility to type 2 diabetes in Chinese population. Chinese Journal of Diabetes 10:7-10.
    Jia WP, Pang C, Chen L et al. (2007) Epidemiological characteristics of diabetes mellitus and impaired glucose regulation in a Chinese adult population:the Shanghai Diabetes Studies, a cross-sectional 3-year follow-up study in Shanghai urban communities. Diabetologia 50:286-292.
    Joglekar MV, Parekh VS, Mehta S et al. (2007) MicroRNA profiling of developing and regenerating pancreas reveal post-transcriptional regulation of neurogenin3. Dev Biol 311:603-612.
    Joglekar MV, Joglekar VM, Hardikar AA (2009) Expression of islet-specific microRNAs during human pancreatic development. Gene Expr Patterns 9:109-113.
    Jonsson A, Isomaa B, Tuomi T et al. (2009) A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion. Diabetes 58:2409-2413.
    Kakita A, Suzuki A, Nagata M, Itoh M (2008) Association of insulin resistance indexes QUICKI and HOMA-IR with the parameters of metabolic syndrome in non-diabetes Japanese male population. Anti-Aging Med 5:82-86.
    Kang ES, Kim HJ, Nam M et al. (2006) A novel 111/121 diplotype in the Calpain-10 gene is associated with type 2 diabetes. J Hum Genet 51:629-633.
    Kanjilal S, Shanker J, Rao VS et al. (2008) Prevalence and component analysis of metabolic syndrome:an Indian atherosclerosis research study perspective. Vasc Health Risk Manag 4: 189-197.
    Kashyap SR, DeFronzo RA (2007) The insulin resistance syndrome:physiological considerations. Diab Vasc Dis Res 4:13-19.
    Katz A, Nambi SS, Mather K et al. (2000) Quantitative insulin-sensitivity check index:A simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402-2410.
    Kelliny C, Ekelund U, Bo Andersen L et al. (2009) Common genetic determinants of glucose homeostasis in healthy children:the European Youth Heart Study. Diabetes 58:2939-2945.
    Keshavarz P, Inoue H, Sakamoto Y et al. (2006) No evidence for association of the ENPP1 (PC-1) K.121Q variant with risk of type 2 diabetes in a Japanese population. J Hum Genet 51:559-566.
    Khan SH, Khan FA, Ijaz A et al. (2007) Hypertension and metabolic syndrome:impact of clustering of hypertension in subjects with metabolic syndrome. Pak Med Sci 23:903-908.
    Kifagi C, Makni K, Mnif F et al. (2008) Association of calpain-10 polymorphisms with type 2 diabetes in the Tunisian population. Diabetes Metab 34:273-278.
    King H, Rewers M (1993) Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group. Diabetes Care 16:157-177.
    Kirchhoff K, Machicao F, Haupt A et al. (2008) Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion. Diabetologia 51:597-601.
    Kissebah AH, Sonnenberg GE, Myklebust J et al. (2000) Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 97:14478-14483.
    Kloosterman WP, Lagendijk AK, Ketting RF et al. (2007) Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol 5:e203.
    Klupa T, Malecki MT, Pezzolesi M et al. (2000) Further evidence for a susceptibility locus for type 2 diabetes on chromosome 20q13.1-q13.2. Diabetes 49:2212-2216.
    Knowler WC, Williams RC, Pettitt DJ, Steinberg AG (1988) Gm3;5,13,14 and type 2 diabetes mellitus:an association in American Indians with genetic admixture. Am J Hum Genet 43:520-526.
    Knutson KL, SpiegelK, Penev P, Van Cauter E (2007) The metabolic consequences of sleep deprivation. Sleep Med Rev 11:163-178.
    Ko GT, Cockram CS, Chow CC et al. (2006) Metabolic syndrome by the International Diabetes Federation definition in Hong Kong Chinese. Diabetes Res Clin Pract 73:58-64.
    Kong L, Zhu J, Han W et al. (2011) Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes:a clinical study. Acta Diabetol 48:61-69.
    Krek A, Grun D, Poy MN et al. (2005) Combinatorial microRNA target predictions. Nat Genet 37: 495-500.
    Krishnamurthy J, Ramsey MR, Ligon KL et al. (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453-457.
    Kubaszek A, Pihlajamaki J, Karhapaa P et al. (2003) The K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with dyslipidemia. Diabetes Care 26:464-467.
    Kubaszek A, Markkanen A, Eriksson JG et al. (2004) The association of the K121Q polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth. J Clin Endocrinol Metab 89:2044-2047.
    Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33:159-174.
    Langenberg C, Pascoe L, Mari A et al. (2009) Common genetic variation in the melatonin receptor 1B gene (MTNR1B) is associated with decreased early-phase insulin response. Diabetologia 52: 1537-1542.
    Lango H, Palmer CN, Morris AD et al (2008) Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57:3129-3135.
    Lao XQ, Thomas GN, Jiang CQ et al. (2006) Association of the metabolic syndrome with vascular disease in an older Chinese population;Guangzhou Biobank Cohort Study. J Endocrinol Invest 29:989-996.
    Laposky AD, Bass J, Kohsaka A, Turek FW (2008) Sleep and circadian rhythms:key components in the regulation of energy metabolism. FEBS Lett 582:142-151.
    Laukkanen O, Pihlajamaki J, Lindstrom J et al. (2004) Common polymorphisms in the genes regulating the early insulin signaling pathway:effects on weight change and the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study. Diabetologia 47:871-877.
    Lee YH, Kang ES, Kim SH et al. (2008) Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet 53:991-998.
    Lee JM, Okumura MJ, Davis MM et al. (2006) Prevalence and determinants of insulin resistance among U.S. adolescents:a population-based study. Diabetes Care 29:2427-2432.
    Lehman DM, Hunt KJ, Leach RJ et al. (2007) Haplotypes of transcription factor 7-like 2 (TCF7L2) gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans. Diabetes 56:389-393.
    Lewis JP, Palmer ND, Ellington JB et al. (2010) Analysis of candidate genes on chromosome 20q12 13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans. Genomics 96:211-219.
    Lewis JP, Palmer ND, Hicks PJ et al. (2008) Association analysis in African Americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies. Diabetes 57:2220-2225.
    Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15-20.
    Li S, Li L, Li K et al. (2008a) Association of adipose most abundant transcript 1 gene (apM1) with type 2 diabetes mellitus in a Chinese population:a meta-analysis of case-control studies. Clin Endocrinol (Oxf) 68:885-889.
    Li JE, Liu DM, Zhang Z (2008b) Study on the relationship between the gene polymorphism of CAPN 10 and the resistance of type 2 diabetes mellitus. Tianjin Med J 36:96-98.
    Li LL, Zhang YM, Du JY et al. (2005a) The relationship between CAPN-10 gene and type 2 diabetes mellitus in Uygurs and Kazaks. Chinese Journal of Diabetes 13:118-119.
    Li LM, Rao KQ, Kong LZ et al. (2005b) A description on the Chinese national nutrition and health survey in 2002. Zhonghua Liu Xing Bing Xue Za Zhi 26:478-484.
    Li G, Hu Y, Pan X (1996) Prevalence and incidence of NIDDM in Daqing City. Chin Med J (Engl) 109:599-602.
    Li Y, Xu X, Liang Y et al. (2010a) miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein expression. Int J Clin Exp Pathol 3: 254-264.
    Li GH, Kung AW, Huang QY (2010b) Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women. Osteoporos Int 21:1009-1020.
    Li ZY, Xu GB, Xia TA (2006) Prevalence rate of metabolic syndrome and dyslipidemia in a large professional population in Beijing. Atherosclerosis 184:188-192.
    Lima NK, Abbasi F, Lamendola C, Reaven GM (2009) Prevalence of insulin resistance and related risk factors for cardiovascular disease in patients with essential hypertension. Am J Hypertens 22: 106-111.
    Lin CC, Liu CS, Lai MM et al. (2007) Metabolic syndrome in a Taiwanese metropolitan adult population. BMC Public Health 7:239.
    Lin Y, Li P, Cai L et al. (2010) Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population. BMC Med Genet 11:97.
    Lindner TH, Njolstad PR, Horikawa Y et al. (1999) A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Hum Mol Genet 8:2001-2008.
    Ling C, Groop L, Guerra SD, Lupi R (2009a) Calpain-10 expression is elevated in pancreatic islets from patients with type 2 diabetes. PLoS One 4:e6558.
    Ling HY, Ou HS, Feng SD et al. (2009b) Changes in microRNA profile and effects of miR-320 in insulin-resistant 3T3-L1 adipocytes. Clin Exp Pharmacol Physiol 36:e32-e39.
    Liu C, Wu Y, Li H et al. (2010) MTNR1B rs10830963 is associated with fasting plasma glucose, HbAlc and impaired beta-cell function in Chinese Hans from Shanghai. BMC Med Genet 11:59.
    Liu Y, Yu L, Zhang D et al. (2008) Positive association between variations in CDKAL1 and type 2 diabetes in Han Chinese individuals. Diabetologia 51:2134-2137.
    Liu Y, Zhou DZ, Zhang D et al. (2009) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China. Diabetologia 52:1315-1321.
    Liu J, Grundy SM, Wang W et al. (2006) Ethnic-specific criteria for the metabolic syndrome: evidence from China. Diabetes Care 29:1414-1416.
    Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 33:177-182.
    Lopez-Orduna E, Garcia-Mena J, Garcia-Macedo R et al. (2007) CAPN10 mRNA splicing and decay is not affected by a SNP associated with susceptibility to type 2 diabetes. Biochem Biophys Res Commun 358:831-836.
    Lorenzo C, Williams K, Hunt KJ, Haffner SM (2007) The National Cholesterol Education Program-Adult Treatment Panel Ⅲ, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care 30:8-13.
    Love-Gregory L, Wasson J, Lin J (2003) E23K single nucleotide polymorphism in the islet ATP-sensitive potassium channel gene (Kir6.2) contributes as much to the risk of type II diabetes in Caucasians as the PPARgamma Pro12Ala variant. Diabetologia 46:136-137.
    Love-Gregory LD, Wasson J, Ma J et al. (2004) A Common polymorphism in the upstream promoter region of the hepatocyte nuclear factor-4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an ashkenazi jewish population. Diabetes 53:1134-1140.
    Lovis P, Gattesco S, Regazzi R (2008a) Regulation of the expression of components of the machinery of exocytosis of insulin-secreting cells by microRNAs. Biol Chem 389:305-312.
    Lovis P, Roggli E, Laybutt DR et al. (2008b) Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes 57:2728-2736.
    Lu B, Yang Y, Song X et al. (2006) An evaluation of the International Diabetes Federation definition of metabolic syndrome in Chinese patients older than 30 years and diagnosed with type 2 diabetes mellitus. Metabolism 55:1088-1096.
    Lu H, Buchan RJ, Cook SA (2010) MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res 86:410-420.
    Ludovico O, Pellegrini F, Di Paola R et al. (2007) Heterogeneous effect of peroxisome proliferator-activated receptor gamma2 Ala12 variant on type 2 diabetes risk. Obesity (Silver Spring) 15: 1076-1081.
    Luo TH, Zhao Y, Li G et al. (2001) A genome-wide search for type II diabetes susceptibility genes in Chinese Hans. Diabetologia 44:501-506.
    Lv K, Guo Y, Zhang Y et al. (2008) Allele-specific targeting of hsa-miR-657 to human IGF2R creates a potential mechanism underlying the association of ACAA-insertion/deletion polymorphism with type 2 diabetes. Biochem Biophys Res Commun 374:101-105.
    Lynn FC, Skewes-Cox P, Kosaka Y et al. (2007) MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes 56:2938-2945.
    Lyssenko V, Almgren P, Anevski D et al. (2005) Genetic prediction of future type 2 diabetes. PLOS Med 2:e345.
    Lyssenko V, Jonsson A, Almgren P et al. (2008) Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med 359:2220-2232.
    Lyssenko V, Nagorny CL, Erdos MR et al. (2009) Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Net Genet 41:82-88.
    Maddux BA, Goldfine ID (2000) Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit. Diabetes 49:13-19.
    Maddux BA, Chang YN, Accili D et al. (2006) Overexpression of the insulin receptor inhibitor PC-1/ENPP1 induces insulin resistance and hyperglycemia. Am J Physiol Endocrinol Metab 290: E746-E749.
    Malecki MT, Moczulski DK, Klupa T et al. (2002) Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population. Eur J Endocrinol 146:695-699.
    Marchini J, Howie B, Myers S et al. (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39:906-913.
    Marquezine GF, Pereira AC, Sousa AG et al. (2008) TCF7L2 variant genotypes and type 2 diabetes risk in Brazil:significant association, but not a significant tool for risk stratificationin the general population. BMC Med Genet 9:106.
    Matsuoka N, Patki A, Tiwari HK et al. (2006) Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults. Int J Obes (Lond) 30:233-237.
    Matthews DR, Hosker JP, Rudenski AS et al. (1985) Homeostasis model assessment:insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412-419.
    Mattoo SK, Singh SM (2010) Prevalence of metabolic syndrome in psychiatric inpatients in a tertiary care centre in north India. Indian J Med Res 131:46-52.
    McAteer JB, Prudente S, Bacci S et al. (2008) The Enpp1 K121q polymorphism is associated with type 2 diabetes in European populations:evidence from an updated meta-analysis in 42,042 subjects. Diabetes 57:1125-1130.
    McKeown NM, Meigs JB, Liu S et al. (2004) Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. Diabetes Care 27: 538-546.
    McPherson R, Pertsemlidis A, Kavaslar N et al. (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316:1488-1491.
    Meirhaeghe A, Helbecque N, Cottel D et al. (2001) Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment:a population study. Am J Med Genet 101:4-8.
    Meyre D, Bouatia-Naji N, Vatin V et al. (2007) ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study. Diabetologia 50:2090-2096.
    Meyre D, Bouatia-Naji N, Tounian A et al. (2005) Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet 37: 863-867.
    Minton JA, Hattersley AT, Owen K et al. (2002) Association studies of genetic variation in the WFS1 gene and type 2 diabetes in U.K. populations. Diabetes 51:1287-1290.
    Miyake K, Yang W, Hara K et al. (2009) Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association. J Hum Genet 54:236-241.
    Miyake K, Horikawa Y, Hara K et al. (2008) Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects. J Hum Genet 53:174-180.
    Mori Y, Otabe S, Dina C et al. (2002) Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q,15q, and 20q and identifies two new candidate Loci on 7p and 11p. Diabetes 51:1247-1255
    Morrison JA, Gruppo R, Glueck CJ et al. (2004) Populationspecific alleles:the polymorphism (K121Q) of the human glycoprotein PC-1 gene is strongly associated with race but not with insulin resistance in black and white children. Metabolism 53:465-468.
    Muntner P, Gu D, Wildman RP et al. (2005) Prevalence of physical activity among Chinese adults: results from the International Collaborative Study of Cardiovascular Disease in Asia. Am J Public Health 95:1631-1636.
    Miissig K, Staiger H, Machicao F et al. (2009) Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 58:1715-1720.
    Narkiewicz K (2006) Obesity and hypertension-the issue is more complex than we thought. Nephrol Dial Transplant 21:264-267.
    NCEP (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285:2486-2497.
    Newman B, Selby JV, King MC et al. (1987) Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia 30:763-768.
    Neyroud N, Tesson F, Denjoy I et al. (1997) A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet 15:186-189.
    Ng MC, Tam CH, Lam VK, et al. (2007) Replication and identification of novel variants at TCF7L2 associated with type 2 diabetes in Hong Kong Chinese. J Clin Endocrinol Metab 92:3733-3737.
    Ng MC, Park KS, Oh B et al. (2008) Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57:2226-2233.
    Nielsen EM, Hansen L, Carstensen B et al. (2003) The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes 52: 573-577.
    Nishigori H, Yamada S, Kohama T et al. (1998) Frameshift mutation, A263fsinsGG, in the hepatocyte nuclear factor-1β gene associated with diabetes and renal dysfunction. Diabetes 47:1354-1355.
    Nordman S, Ostenson CG, Efendic S, Gu HF (2009) Loci of TCF7L2, HHEX and IDE on chromosome 10q and the susceptibility of their genetic polymorphisms to type 2 diabetes. Exp Clin Endocrinol Diabetes 117:186-190.
    Okamoto K, Iwasaki N, Nishimura C et al. (2010) Identification of KCNJ15 as a susceptibility gene in Asian patients with type 2 diabetes mellitus. Am J Hum Genet 86:54-64.
    Omori S, Tanaka Y, Takahashi A et al. (2008) Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes 57:791-795.
    Orho-Melander M, Klannemark M, Svensson MK et al. (2002) Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. Diabetes 51:2658-2664.
    Palmer ND, Bento JL, Mychaleckyj JC et al. (2004) Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans:the insulin resistance atherosclerosis study (IRAS) family study. Diabetes 53:3013-3019.
    Palmer ND, Goodarzi MO, Langefeld CD et al. (2008) Quantitative trait analysis of type 2 diabetes susceptibility loci identified from whole genome association studies in the insulin resistance atherosclerosis family study. Diabetes 57:1093-1100.
    Pan XR, Yang WY, Li GW, Liu J (1997) Prevalence of diabetes and its risk factors in China,1994. Diabetes Care 20:1664-1669.
    Pandi-Perumal SR, Trakht I, Srinivasan V et al. (2008) Physiological effects of melatonin:role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85:335-353.
    Park YW, Zhu S, Palaniappan L et al. (2003) The metabolic syndrome:prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey,1988-1994. Arch Intern Med 163:427-436.
    Park HS, Lee SY, Kim SM et al. (2006) Prevalence of the metabolic syndrome among Korean adults according to the criteria of the International Diabetes Federation. Diabetes Care 29:933-934.
    Parker A, Meyer J, Lewitzky S et al. (2001) A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11. Diabetes 50:675-680.
    Pascoe L, Tura A, Patel SK et al. (2007) Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic β-cell function. Diabetes 56: 3101-3104.
    Patel YM, Lane MD (1999) Role of calpain in adipocyte differentiation. Proc Natl Acad Sci USA 96: 1279-1284.
    Permutt MA, Wasson JC, Suarez BK et al. (2001) A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population. Diabetes 50:681-685.
    Peschke E, Stumpf I, Bazwinsky I et al. (2007) Melatonin and type 2 diabetes-a possible link? J Pineal Res 42:350-358.
    Peschke E (2008) Melatonin, endocrine pancreas and diabetes. J Pineal Res 44:26-40.
    Peterfy M, Phan J, Xu P (2001) Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nat Genet 27:121-124.
    Pizzuti A, Frittitta L, Argiolas A et al. (1999) A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes 48:1881-1884.
    Plaisance V, Abderrahmani A, Perret-Menoud V et al. (2006) MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem 281: 26932-26942.
    Pongchaiyakul C, Nguyen TV, Wanothayaroj E et al. (2007) Prevalence of metabolic syndrome and its relationship to weight in the Thai population. J Med Assoc Thai 90:459-467.
    Poulsen P, Kyvik KO, Vaag A (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance-a populationbased twin study. Diabetologia 42:139-145.
    Prokopenko I, Langenberg C, Florez JC et al. (2009) Variants in MTNR1B influence fasting glucose levels. Nat Genet 41:77-81.
    Prudente S, Chandalia M, Morini E et al. (2007) The Q121/Q121 genotype of ENPP1/PC-1 is associated with lower BMI in nondiabetic whites. Obesity (Silver Spring) 15:1-4.
    Poy MN, Spranger M, Stoffel M (2007) microRNAs and the regulation of glucose and lipid metabolism. Diabetes Obes Metab (Suppl 2) 9:67-73.
    Poy MN, Eliasson L, Krutzfeldt J et al. (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226-230.
    Poy MN, Hausser J, Trajkovski M et al. (2009) miR-375 maintains normal pancreatic {alpha}-and {beta}-cell mass. Proc Natl Acad Sci USA 106:5813-5828.
    Pulizzi N, Lyssenko V, Jonsson A et al. (2009) Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes. Diabetologia 52:825-829
    Qi L, Cornelis MC, Kraft P, Stanya KJ et al. (2010) Genetic variants at 2q24 are associated with susceptibility to type 2 diabetes. Hum Mol Genet 19:2706-2715.
    Qi Q, Li H, Loos RJ et al. (2009) Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Hum Mol Genet 18:3508-3515.
    Raman R, Gupta A, Pal SS et al. (2010) Prevalence of metabolic syndrome and its influence on microvascular complications in the Indian population with type 2 diabetes mellitus. Sankara nethralaya diabetic retinopathy epidemiology and molecular genetic study (SN-DREAMS, report 14). Diabetol Metab Syndr 2:67.
    Rampersaud E, Damcott CM, Fu M et al. (2007) Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the old order Amish:Evidence for replication from diabetes-related quantitative traits and from independent populations. Diabetes 56:3053-3062.
    Ramracheya RD, Muller DS, Squires PE et al. (2008) Function and expression of melatonin receptors on human pancreatic islets. J Pineal Res 44:273-279.
    Rasmussen SK, Urhammer SA, Berglund L et al. (2002) Variants within the calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to type 2 diabetes, insulin resistance, and impaired acute insulin secretion among Scandinavian Caucasians. Diabetes 51:3561-3567.
    Rathmann W, Haastert B, Icks A et al. (2006) Prevalence of the Metabolic Syndrome in the elderly population according to IDF, WHO, and NCEP definitions and associations with C-reactive protein. Diabetes Care 29:461.
    Reaven GM (1995) Pathophysiology of insulin resistance in human disease. Physiol Rev 75:473-486.
    Reiling E, van't Riet E, Groenewoud MJ et al. (2009) Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk. Diabetologia 52:1866-1870.
    Rees SD, Bellary S, Britten AC et al. (2008) Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population. BMC Med Genet 9:8.
    Reppert SM, Godson C, Mahle CD et al. (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain:the Mellb melatonin receptor. Proc Natl Acad Sci USA 92:8734-8738.
    Reynisdottir I, Thorleifsson G, Benediktsson R et al. (2003) Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2. Am J Hum Genet 73:323-335.
    Reynolds K, Gu D, Whelton PK et al. (2007) Prevalence and risk factors of overweight and obesity in China. Obesity (Silver Spring) 15:10-18.
    Rhee J, Inoue Y, Yoon JC et al (2003) Regulation of hepatic fasting response by PPARg coactivator-la (PGC-1):requirement for hepatocyte nuclear factor 4a in gluconeogenesis. Proc Natl Acad Sci USA 100:4012-4017
    Rhodes CJ, White MF (2002) Molecular insights into insulin action and secretion. Eur J Clin Invest 32:3-13.
    Ridderstrale M, Groop L (2009) Genetic dissection of type 2 diabetes. Mol Cell Endocrinol 297:10-17.
    Roggli E, Britan A, Gattesco S et al. (2010) Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells. Diabetes 59:978-986.
    Rong R, Hanson RL, Ortiz D et al. (2009) Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes 58:478-488.
    Rudovich N, Pivovarova O, Fisher E et al. (2009) Polymorphisms within insulin-degrading enzyme (IDE) gene determine insulin metabolism and risk of type 2 diabetes. J Mol Med 87:1145-1151.
    Rung J, Cauchi S, Albrechtsen A et al. (2009) Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 41:1110-1115.
    Ronn T, Wen J, Yang Z, Lu B et al. (2009) A common variant in MTNR1B, encoding melatonin receptor 1B, is associated with type 2 diabetes and fasting plasma glucose in Han Chinese individuals. Diabetologia 52:830-833.
    Ruchat SM, Elks CE, Loos RJ et al. (2009) Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies. Acta Diabetol 46:217-226.
    Ryu HS, Park SY, Ma D et al. (2011) The induction of MicroRNA targeting IRS-1 is involved in the development of insulin resistance under conditions of mitochondrial dysfunction in hepatocytes. PLoS One 6:e17343.
    Sakamoto Y, Inoue H,Keshavarz P et al. (2007) SNPs. in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population. J Hum Genet.52:781-793.
    Sakura H, Wat N, Horton V et al. (1996) Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel:no association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro. Diabetologia 39:1233-1236.
    Salonen JT, Uimari P, Aalto JM et al. (2007) Type 2 diabetes whole-genome association study in four populations:the DiaGen consortium. Am J Hum Genet 81:338-345.
    Sandhu MS, Weedon MN, Fawcett KA J et al. (2007) Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 39:951-953.
    Sanghera DK, Ortega L, Han S et al. (2008) Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs:PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Medical Genetics 9:1-9.
    Sanghera DK, Been L, Ortega L al. (2009) Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. J Hum Genet 54:162-168.
    Santos AC, Barros H (2007) Impact of metabolic syndrome definitions on prevalence estimates:a study in a Portuguese community. Diab Vasc Dis Res 4:320-327.
    Saxena R, Gianniny L, Burtt NP et al. (2006) Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 55:2890-2895.
    Saxena R, Voight BF, Lyssenko V et al. (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331-1336.
    Saxena R, Hivert MF, Langenberg C et al. (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42:142-148.
    Saez ME, Gonzalez-Sanchez JL, Ramirez-Lorca R et al. (2008) The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PLoS One 3:e2953.
    Schwanstecher C, Meyer U, Schwanstecher M (2002) K (IR) 6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K (+) channels. Diabetes 51:875-879.
    Scott LJ, Mohlke KL, Bonnycastle LL et al. (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341-1345.
    Scott LJ, Bonnycastle LL, Willer CJ et al. (2006) Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 55:2649-2653.
    Serjeantson SW, Owerbach D, Zimmet P et al. (1983) Genetics of diabetes in Nauru:effects of foreign admixture, HLA antigens and the insulin-gene linked polymorphism. Diabetologia 25: 13-17.
    Sharifi F, Mousavinasab SN, Saeini M, Dinmohammadi M (2009) Prevalence of metabolic syndrome in an adult urban population of the west of Iran. Exp Diabetes Res.2009:136501.
    Shima Y, Nakanishi K, Odawara M et al. (2003) Association of the SNP-19 genotype 22 in the calpain-10 gene with elevated body mass index and hemoglobin Alc levels in Japanese. Clin Chim Acta 336:89-96.
    Shimomura I, Hammer RE, Ikemoto S (1999) Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401:73-76.
    Shu XO, Long J, Cai Q et al. (2010) Identification of new genetic risk variants for type 2 diabetes. PLoS Genet 6 pii:e1001127.
    Shulman GI (2000) Cellular mechanisms of insulin resistance. J Clin Invest 106:171-176.
    Silander K, Mohlke KL, Scott LJ et al. (2004) Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141-1149.
    Singh RB, Bajaj S, Niaz MA et al. (1998) Prevalence of type 2 diabetes mellitus and risk of hypertension and coronary artery disease in rural and urban population with low rates of obesity. Int J Cardiol 66:65-72.
    Sladek R, Rocheleau G, Rung J et al. (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881-885.
    Son le NT, Kunii D, Hung NT et al. (2005) The metabolic syndrome:prevalence and risk factors in the urban population of Ho Chi Minh City. Diabetes Res Clin Pract 67:243-250.
    Sookoian S, Gemma C, Pirola CJ (2010) Influence of hepatocyte nuclear factor 4alpha (HNF4alpha) gene variants on the risk of type 2 diabetes:a meta-analysis in 49,577 individuals. Mol Genet Metab 99:80-89.
    Sowers JR, Frohlich ED (2004) Insulin and insulin resistance:impact on blood pressure and cardiovascular disease. Med Clin North Am 88:63-82.
    Sowers JR, Epstein M, Frohlich ED (2001) Diabetes, hypertension, and cardiovascular disease:an update. Hypertension 37:1053-1059
    Spars(?) T, Bonnefond A, Andersson E et al. (2009) G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release:studies involving 19,605 Europeans. Diabetes 58:1450-1456.
    Staiger H, Machicao F, Stefan N et al. (2007) Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function. PLoS One 2:e832.
    Staiger H, Stancakova A, Zilinskaite J et al. (2008) A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations:results from the EUGENE2 study. Diabetes 57:514-517.
    Stancakova A, Pihlajamaki J, Kuusisto J et al. (2008) Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. J Clin Endocrinol Metab 93: 1924-1930.
    Stancakova A, Kuulasmaa T, Paananen J et al. (2009) Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes 58:2129-2136.
    Steinthorsdottir V, Thorleifsson G, Reynisdottir I et al. (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39:770-775.
    Stevens RJ, Coleman RL, Adler AI et al. (2004) Risk factors for myocardial infarction case fatality and stroke case fatality in type 2 diabetes:UKPDS 66. Diabetes Care 27:201-207.
    Stolerman ES, Manning AK, McAteer JB et al. (2008) Haplotype structure of the ENPP1 gene and nominal association of the K121Q polymorphism with glycemic traits in the Framingham Heart Study. Diabetes 57:1971-1977.
    Sun HX, Zhang KX, Du WN et al. (2002) Single nucleotide polymorphisms in CAPN10 gene of Chinese people and its correlation with type 2 diabetes mellitus in Han people of northern China. Biomed Environ Sci 15:75-82.
    Sun LL, Jiang BG, Li WT et al. (2011) MicroRNA-15a positively regulates insulin synthesis by inhibiting uncoupling protein-2 expression. Diabetes Res Clin Pract 91:94-100.
    Surana SP, Shah DB, Gala K (2008) Prevalence of metabolic syndrome in an urban Indian diabetic population using the NCEP ATP Ⅲ guidelines. J Assoc Physicians India 56:865-868.
    Suviolahti E, Reue K, Cantor RM et al. (2006) Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism. Hum Mol Genet 15:377-386.
    Tabara Y, Osawa H, Kawamoto R et al. (2009) Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes 58:493-498.
    Tabassum R, Mahajan A, Chauhan G et al. (2010) Evaluation of DOK5 as a susceptibility gene for type 2 diabetes and obesity in North Indian population. BMC Med Genet 11:35.
    Takeuchi F, Serizawa M, Yamamoto K et al. (2009) Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes 58:1690-1699.
    Tam CH, Ho JS, Wang Y et al. (2010) Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects. PLoS One 5:e11428.
    Tan JT, Nurbaya S, Gardner D et al. (2009) Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function:A study of 3734 subjects comprising three ethnicities living in Singapore. Diabetes 58:1445-1449.
    Tang X, Muniappan L, Tang G, Ozcan S (2009) Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. RNA 15:287-293.
    Tanyolac S, Mahley RW, Hodoglugil U, Goldfine ID (2008) Gender differences in the relationship of ENPP1/PC-1 variants to obesity in a Turkish population. Obesity (Silver Spring) 16:2468-2471.
    Taskinen MR (2003) Diabetic dyslipidaemia:from basic research to clinical practice. Diabetologia 46: 733-749.
    Teo YY, Sim X, Ong RT et al. (2009) Singapore Genome Variation Project:a haplotype map of three Southeast Asian populations. Genome Res 19:2154-2162.
    Thomas G, Jacobs KB, Yeager M, Kraft P et al. (2008) Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet 40:310-315.
    Thorsby PM, Midthjell K, Gjerlaugsen N et al. (2009) Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study-the HUNT study. Scand J Clin Lab Invest 69:282-287.
    Tong Y, Lin Y, Zhang Y et al. (2009) Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus:a large Human Genome Epidemiology (HuGE) review and meta-analysis. BMC Med Genet 10:1-25.
    Tsai HJ, Sun G, Weeks DE et al. (2001) Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans:no evidence of association. Am J Hum Genet 69:1236-1244.
    Tsai FJ, Yang CF, Chen CC et al. (2010) A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet 6:e1000847.
    Tsuchiya T, Schwarz PE, Bosque-Plata LD et al. (2006) Association of the calpain-10 gene with type 2 diabetes in Europeans:results of pooled and meta-analyses. Mol Genet Metab 89:174-184.
    Ubeda M, Rukstalis JM, Habener JF (2006) Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity. J Biol Chem 281:28858-28864.
    Ullrich S, Su J, Ranta F, Wittekindt OH et al. (2005) Effects of I(Ks) channel inhibitors in insulin-secreting INS-1 cells. Pflugers Arch 451:428-436.
    Unoki H, Takahashi A, Kawaguchi T et al. (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40:1098-1102.
    Vaag A, Henriksen JE, Madsbad S et al. (1995) Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulindependent diabetes mellitus. J Clin Invest 95:690-698.
    van den Ouweland JM, Lemkes HH, Trembath RC et al. (1994) Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes 43:746-751.
    van Hoek M, Dehghan A, Witteman JC et al. (2008) Predicting type 2 diabetes based on polymorphisms from genome wide association studies:a population-based study. Diabetes 57: 3122-3128.
    van Tilburg JH, SandkuijI LA, Strengman E et al. (2003) A genome-wide scan in type 2 diabetes mellitus provides independent replication of a susceptibility locus on 18p11 and suggests the existence of novel Loci on 2q12 and 19q13. J Clin Endocrinol Metab 88:2223-2230.
    Vaxillaire M, Veslot J, Dina C et al. (2008) Impact of common type 2 diabetes risk polymorphisms in the DESIR prospective study. Diabetes 57:244-254.
    Vionnet N, Hani EH, Dupont S et al. (2000) Genomewide search for type 2 diabetes-susceptibility genes in French whites:evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet 67:1470-1480.
    Voight BF, Scott LJ, Steinthorsdottir V et al. (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42:579-589.
    Wan C, Zhang T, Wang B et al. (2006) Obesity risk associated with the K121Q polymorphism of the glycoprotein PC-1 gene. Diabetes Obes Metab 8:703-708.
    Wang CC, Goalstone ML, Draznin B (2004) Molecular mechanisms of insulin resistance that impact cardiovacsular biology. Diabetes 53:2735-2740.
    Wang Y, Mi J, Shan XY et al. (2007) Is China facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in China. Int J Obes (Lond) 31:177-188.
    Wang F, Han XY, Ren Q et al. (2009) Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population. Chin Med J (Engl) 22:2477-2482.
    Warth R, Garcia Alzamora M, Kim JK et al. (2002) The role of KCNQ1/KCNE1 K(+) channels in intestine and pancreas:lessons from the KCNE1 knockout mouse. Pflugers Arch 443:822-828.
    Weedon MN, McCarthy MI, Hitman G et al. (2006) Combining information from common type 2 diabetes risk polymorphisms improves disease prediction. PLOS Med 3:e374.
    Weedon MN, Schwarz PE, Horikawa Y et al. (2003) Meta-analysis and a large association study confirm a role for calpain-10 variation in type 2 diabetes susceptibility. Am J Hum Genet 73: 1208-1212.
    Wei FY, Nagashima K, Ohshima T et al. (2005) Cdk5-dependent regulation of glucose-stimulated insulin secretion. Nat Med 11:1104-1108.
    Wen J, Ronn T, Olsson A et al. (2010) Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort. PLoS One 5:e9153.
    Wild S, Roglic G, Green A et al. (2004) Global prevalence of diabetes:estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047-53.
    Willer CJ, Bonnycastle LL, Conneely KN et al. (2007) Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes 56:256-264.
    Winckler W, Weedon MN, Graham RR et al. (2007) Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes 56:685-693.
    World Health Organization Expert Consultation (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:157-163.
    Wray NR, Goddard ME, Visscher PM (2007) Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res 17:1520-1528.
    Wu Y, Li H, Loos RJ et al. (2008) Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes 57:2834-2842.
    Wu B, Takahashi J, Fu M et al. (2005) Variants of calpain-10 gene and its association with type 2 diabetes mellitus in a Chinese population. Diabetes Res Clin Pract 68:155-161.
    Xia HQ, Pan Y, Peng J, Lu GX (2011) Over-expression of miR375 reduces glucose-induced insulin secretion in Nit-1 cells. Mol Biol Rep 38:3061-3065.
    Xiang KS, Fang QC, Zheng TS et al. (2001) The impact of calpain-10 gene combined-SNP variation on type 2 diabetes mellitus and its related metabolic traits. Chin J Med Genet 18:426-430.
    Xu WH, Ruan XN, Fu XJ (2010) Prevalence of the metabolic syndrome in Pudong New Area of Shanghai using three proposed definitions among Chinese adults. BMC Public Health 10:246.
    Yamauchi T, Hara K, Maeda S et al. (2010) A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nat Genet 42:864-868.
    Yan Y, North KE, Ballantyne CM et al. (2009) Transcription factor 7-like 2 (TCF7L2) polymorphism and context-specific risk of type 2 diabetes in African American and Caucasian adults:the Atherosclerosis Risk in Communities study. Diabetes 58:285-289.
    Yang Q, Khoury MJ, Botto L et al. (2003) Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes. Am J Hum Genet 72:636-649.
    Yang FY, Wahlqvist ML, Lee MS (2008) Body mass index (BMI) as a major factor in the incidence of the metabolic syndrome and its constituents in unaffected Taiwanese from 1998 to 2002. Asia Pac J Clin Nutr 17:339-351.
    Yang W, Lu J, Weng J et al. (2010) Prevalence of diabetes among men and women in China. N Engl J Med 362:1090-1101.
    Yasuda K, Miyake K, Horikawa Y et al. (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40:1092-1097.
    Yeni-Komshian H, Carantoni M, Abbasi F, Reaven GM (2000) Relationship between several surrogate estimates of insulin resistance and quantification of insulin mediated glucose disposal in 490 healthy nondiabetic volunteers. Diabetes Care 23:171-175.
    Yip J, Facchini FS, Reaven GM (1998) Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 83:2773-2776.
    Yokoi N, Kanamori M, Horikawa Y et al. (2006) Association studies of variants in the genes involved in pancreatic β-cell function in type 2 diabetes in Japanese subjects. Diabetes 55:2379-2386.
    Yoon YS, Lee ES, Park C et al. (2007) The new definition of metabolic syndrome by the international diabetes federation is less likely to identify metabolically abnormal but non-obese individuals than the definition by the revised national cholesterol education program:the Korea NHANES study. Int J Obes (Lond) 31:528-534.
    Yu L, Zhang YH, Liu YY et al. (2009) Comparison of three diagnosis criteria for metabolic syndrome in Mongolian people of agricultural and pastoral regions. J Endocrinol Invest 32:420-425.
    Zacharova J, Chiasson JL, Laakso M; STOP-NIDDM Study Group (2005) The common polymorphisms (single nucleotide polymorphism [SNP]+45 and SNP+276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes:the STOP-NIDDM trial. Diabetes 54:893-899.
    zalez-Sanchez JL, Martinez-Larrad MT, Zabena C et al. (2008) Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population. Diabetologia 51:1993-1997.
    Zeggini E, Weedon MN, Lindgren CM et al. (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336-1341.
    Zeggini E, Scott LJ, Saxena R et al. (2008) Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40: 638-645.
    Zhang C, Qi L, Hunter DJ, Meigs JB et al. (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men. Diabetes 55:2645-2648.
    Zhang J, Chen LL, Li HG (2004) Relationship between Calpain-10 Gene Polymorphism and Insulin Resistance Phenotypes in Chinese. J Huazhong Univ Sci Technolog Med Sci 24:452-455.
    Zhao T, Liu Z, Zhang D et al. (2011) The ENPP1 K121Q polymorphism is not associated with type 2 diabetes or obesity in the Chinese Han population. J Hum Genet 56:12-16.
    Zhou J, Young TL (2005) Evaluation of lipin 2 as a candidate gene for autosomal dominant 1 high-grade myopia. Gene 352:10-19.
    Zhou JB, Yang JK, Zhao L, Xin Z (2010) Variants in KCNQ1, AP3S1, MAN2A1, and ALDH7A1 and the risk of type 2 diabetes in the Chinese Northern Han population:a case-control study and meta-analysis. Med Sci Monit 16:BR179-183.
    Zhou D, Zhang D, Liu Y et al. (2009) The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population. J Hum Genet 54:433-435.
    Zhu Q, Yamagata K, Miura A et al. (2003) T130I mutation in HNF-4alpha gene is a loss-of-function mutation in hepatocytes and is associated with late-onset type 2 diabetes mellitus in Japanese subjects. Diabetologia 46:567-573.
    Zouali H, Hani EH, Philippi A et al. (1997) A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene. Hum Mol Genet 6:1401-1408.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址：北京市海淀区学院路29号 邮编：100083

电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700