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Front Endocrinol (Lausanne) 2019 28;10. Epub 2019 Jan 28.

Genetics and Bioinformatics Unit, Dasman Diabetes Institute, Kuwait City, Kuwait.

Despite dedicated nation-wide efforts to raise awareness against the harmful effects of fast-food consumption and sedentary lifestyle, the Arab population continues to struggle with an increased risk for metabolic disorders. Unlike the European population, the Arab population lacks well-established genetic risk determinants for metabolic disorders, and the transferability of established risk loci to this population has not been satisfactorily demonstrated. The most recent findings have identified over 240 genetic risk loci (with ~400 independent association signals) for type 2 diabetes, but thus far only 25 risk loci (, ALX4, , COL8A1, γ, and ) have been replicated in Arab populations. Read More

Am J Med Genet B Neuropsychiatr Genet 2019 Feb 6. Epub 2019 Feb 6.

Division of Endocrinology, Diabetes, and Metabolic Disease, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.

Schizophrenia (SCZ) and major depressive disorder (MDD) in treatment-naive patients are associated with increased risk for type 2 diabetes (T2D) and metabolic syndrome (MetS). SCZ, MDD, T2D, and MetS are often comorbid and their comorbidity increases cardiovascular risk: Some risk genes are likely co-shared by them. For instance, transcription factor 7-like 2 (TCF7L2) and proteasome 26S subunit, non-ATPase 9 (PSMD9) are two genes independently reported as contributing to T2D and SCZ, and PSMD9 to MDD as well. Read More

Endocr Res 2019 Feb 5:1-7. Epub 2019 Feb 5.

a Department of Endocrinology, Diabetes and Metabolism , Rigshospitalet , Copenhagen , Denmark.

Aim: The TCF7L2 gene variant rs7903146 has the largest effect on type 2 diabetes risk reported in genome-wide association studies, however its role in adipose tissue development and function is unknown. We investigate the association between gene variant rs7903146 and metabolic parameters and examine in vitro and ex vivo gene expression of TCF7L2 in human adipose tissue and progenitor cells from two independent populations of young healthy men with increased risk of type 2 diabetes due to low birth weight (LBW).

Design: Adipose tissue biopsies were excised from 40 healthy young men with low and normal birth weights (NBW) after a control and 5-day high-fat overfeeding diet. Read More

Clin Nutr 2019 Jan 24. Epub 2019 Jan 24.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.

Background & Aims: Type 2 diabetes (T2D) is a complex metabolic disease with numerous risk factors, including a growing number of genetic susceptibility variants. The TCF7L2 gene is closely associated with an increased risk of type 2 diabetes, but the association of TCF7L2 with weight-related traits in humans is unclear. The purpose of this study was to determine if TCF7L2 variants and body mass index/waist circumference (BMI/WC) act synergistically to influence the incidence of type 2 diabetes in a Chinese population. Read More

Comput Biol Chem 2019 Jan 24;79:24-35. Epub 2019 Jan 24.

Department of Biotechnology & Bioinformatics, Yogi Vemana University, Kadapa 516003, Andhra Pradesh, India. Electronic address:

Diabetes mellitus is clinically characterized by hyperglycemia. Though many studies have been done to understand the mechanism of Type 2 Diabetes (T2D), however, the complete network of diabetes and its associated disorders through polygenic involvement is still under debate. The present study designed to re-analyze publicly available T2D related microarray raw datasets present in GEO database and T2D genes information present in GWAS catalog for screening out differentially expressed genes (DEGs) and identify key hub genes associated with T2D. Read More

Medicine (Baltimore) 2019 Feb;98(5):e14288

Department of Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, China.

Presently, data on the type 2 diabetes mellitus (T2DM) in Chinese Korean ethnicity are very scarce. This study aimed to explore the relationship between the transcription factor 7-like 2 (TCF7L2) and T2DM in Chinese Korean ethnicity population. This case-control study involved 43 T2DM Chinese Korean ethnicity patients (T2DM group) and 43 healthy Chinese Korean ethnicity normoglycemic subjects as controls (Control group). Read More

Diabetol Metab Syndr 2019 25;11:10. Epub 2019 Jan 25.

2School of Medicine, University of Sao Paulo, São Paulo, Brazil.

Background: Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity.

Objectives: To evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide. Read More

Eur J Nutr 2019 Jan 17. Epub 2019 Jan 17.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Purpose: Sweetened beverage consumption is associated with type 2 diabetes (T2D) and LADA. We investigated to what extent this association is mediated by BMI and whether it is modified by genotypes of HLA, TCF7L2 rs7903146, or FTO rs9939609.

Methods: Swedish case-control data including incident cases of LADA (n = 386) and T2D (n = 1253) with matched population-based controls (n = 1545) was used. Read More

Gynecol Endocrinol 2019 Jan 7:1-5. Epub 2019 Jan 7.

a Department of Medical Sciences, Division of Health Sciences , University of Guanajuato , León , Mexico.

Women with previous gestational diabetes mellitus (pGDM) have a high risk of developing postpartum type 2 diabetes mellitus (T2DM). This study aimed to analyze the relationship between lactation, BMI, and TCF7L2 polymorphisms in the conversion to T2DM in women with pGDM. One hundred and fifty-three women con pGDM were recruited from public hospitals of León Guanajuato México. Read More

Pol Arch Intern Med 2019 Jan 29;129(1):802-807. Epub 2018 Dec 29.

INTRODUCTION Although the coexistence of type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) may be attributed to environmental risk factors common for both diseases, a genetic background should also be considered. Data on the role of genetic factors in the development of T2DM in patients with OSA are lacking. OBJECTIVES The study was aimed to evaluate the prevalence of polymorphisms of selected genes that are known to be associated with diabetes or obesity in patients with OSA and concomitant T2DM and to assess these polymorphisms in the context of OSA severity. Read More

Front Endocrinol (Lausanne) 2018 4;9:744. Epub 2018 Dec 4.

Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg, South Africa.

Type 2 diabetes (T2D) is a leading cause of death and disability worldwide. It is a chronic metabolic disorder that develops due to an interplay of genetic, lifestyle, and environmental factors. The biological onset of the disease occurs long before clinical symptoms develop, thus the search for early diagnostic and prognostic biomarkers, which could facilitate intervention strategies to prevent or delay disease progression, has increased considerably in recent years. Read More

J Cell Mol Med 2019 Feb 23;23(2):1628-1631. Epub 2018 Nov 23.

Institute of Molecular Biology and Medicine, Bishkek, Kyrgyzstan.

The aim of this study was to ascertain the polymorphic markers profile of ADIPOQ, KCNJ11 and TCF7L2 genes in Kyrgyz population and to analyze the association of polymorphic markers and combinations of ADIPOQ gene's G276T locus, KCNJ11 gene's Glu23Lys locus and TCF7L2 gene's VS3C>T locus with type two diabetes (T2D) in Kyrgyz population. In this case-control study, 114 T2D patients 109 non-diabetic participants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Two individual polymorphisms (ADIPOQ rs1501299, KCNJ11 rs5219) were found to be associated with T2D. Read More

Diabetes Care 2018 12;41(12):2441-2443

Divisions of Human Genetics and Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA

J Diabetes 2018 Nov 19. Epub 2018 Nov 19.

Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.

Background: The aim of this meta-analysis was to determine the association of common type 1 diabetes (T1D) and type 2 diabetes (T2D) gene variants (protein tyrosine phosphatase non-receptor 22 [PTPN22] rs2476601C/T, insulin [INS] rs689A/T and transcription factor 7-like 2 [TCF7L2] rs7903146C/T) with latent autoimmune diabetes in adults (LADA).

Methods: A systematic search of electronic databases was conducted up to 2017 and data from 16 independent case-control studies for three gene variants were pooled. The pooled allele and genotype frequencies for each T1D and T2D gene variant were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Read More

Diabetes Res Clin Pract 2018 Dec 10;146:251-257. Epub 2018 Nov 10.

German Center for Diabetes Research (DZD), Neuherberg, Germany; Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; Clinical Cooperation Group Type 2 Diabetes, Helmholtz Center Munich, Neuherberg, Germany.

Aims: Gestational diabetes (GDM) is recognized as a major risk factor for the development of type 2 diabetes (T2DM) later in life. Risk allele carriers at TCF7L2 rs7903146 have increased susceptibility for both GDM and T2DM. We hypothesized that carrying TCF7L2 risk alleles would further aggravate the negative impact of a positive history for GDM on metabolic traits related to T2DM later in life. Read More

BMC Obes 2018 2;5:26. Epub 2018 Oct 2.

1Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 123 W Franklin St, Building C, Chapel Hill, NC USA.

Background: Genome-wide association studies have implicated the () gene in type 2 diabetes risk, and more recently, in decreased body mass index. Given the contrary direction of genetic effects on these two traits, it has been suggested that the observed association with body mass index may reflect either selection bias or a complex underlying biology at .

Methods: Using 9031 Hispanic/Latino adults (21-76 years) with complete weight history and genetic data from the community-based Hispanic Community Health Study/Study of Latinos (HCHS/SOL, Baseline 2008-2011), we estimated the multivariable association between the additive number of type 2 diabetes increasing-alleles at (rs7903146-T) and body mass index. Read More

Diabetes Care 2018 12 1;41(12):2480-2486. Epub 2018 Oct 1.

University of South Florida, Tampa, FL.

Objective: The type 2 diabetes-associated alleles at the locus mark a type 1 diabetes phenotype characterized by single islet autoantibody positivity as well as lower glucose and higher C-peptide measures. Here, we studied whether the locus influences progression of islet autoimmunity, from single to multiple (≥2) autoantibody positivity, in relatives of patients with type 1 diabetes.

Research Design And Methods: We evaluated 244 participants in the Type 1 Diabetes TrialNet Pathway to Prevention study with confirmed single autoantibody positivity at screening and Immunochip single nucleotide polymorphism data (47. Read More

J Coll Physicians Surg Pak 2018 Oct;28(10):794-797

Department of Biochemistry, International School, Clinical Laboratory of Over-sea Chinese Hospital, Medical School, Jinan University, 510632, China.

Objective: To determine the risk of type II diabetes (T2D) with two transcription factor 7-like 2 gene (TCF7L2) variants in the Han nationality population of Guangdong, China.

Study Design: Case control study.

Place And Duration Of Study: International School, Clinical Laboratory of Over-sea Chinese Hospital, Department of Biochemistry, Medical School, Jinan University, China, from July 2014 to June 2016. Read More

World J Diabetes 2018 Sep;9(9):157-164

Biodiversity and Genetics Department, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay.

Aim: To investigate if mutations in are associated with "atypical diabetes" in the Uruguayan population.

Methods: Healthy, nondiabetic controls ( = 133) and patients with type 2 diabetes ( = 177) were selected from among the presenting population at level-3 referral healthcare centers in Uruguay. Patients with type 2 diabetes were subgrouped according to "atypical diabetes" ( = 92) and "classical diabetes" ( = 85). Read More

PLoS One 2018 13;13(9):e0199837. Epub 2018 Sep 13.

Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.

Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and lifestyle factors. To date, the majority of genetic studies of T2D have been in populations of European and Asian descent. The focus of this study is on genetic variations underlying T2D in Qataris, a population with one of the highest incidences of T2D worldwide. Read More

J Biol Chem 2018 09;293(36):14190-14191

From the Division of Endocrinology and Metabolism and.

Of the many common genetic variants associated with type 2 diabetes, that in remains the most studied because it has the greatest effect size. However, the mechanism by which this variant alters diabetes risk remains elusive. A new study adds another layer of complexity, suggesting that the effects of TCF7L2 are context-dependent, and highlights a novel interaction that might bias a β-cell to a secretory or proliferative phenotype. Read More

J Diabetes Complications 2018 Nov 19;32(11):1076-1084. Epub 2018 Aug 19.

IRCCS SDN, Naples, Italy; Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Background: Epigenetics modulated tissue-specific gene expression during the onset of type 1 and type 2 diabetes and their complications.

Methods: We searched the PubMed recent studies about the main epigenetic tags involved in type 1 and type 2 diabetes onset and their clinical complications. PubMed studies about the epigenetic tags involved in type 1 and 2 diabetes onset was searched. Read More

J Integr Med 2018 09 1;16(5):329-334. Epub 2018 Jun 1.

Nutrition Research Center, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran; Student Research Committee, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background: Transcription factor 7-like 2 (TCF7L2)-rs7903146 polymorphism is associated with increased risk of type 2 diabetes. The response of insulin and insulin resistance to artichoke leaf extract (ALE) may be affected by TCF7L2-rs7903146 polymorphism.

Objective: This study examined the effects of ALE supplementation on metabolic parameters of the TCF7L2-rs7903146 polymorphism in patients with metabolic syndrome (MetS). Read More

Bone 2018 Dec 30;117:6-14. Epub 2018 Aug 30.

Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China; School of Basic Medical Sciences, Central South University, Changsha, Hunan 410013, China; Center of Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. Electronic address:

Aims: Clinical and epidemiological findings point to an association between type 2 diabetes (T2D) and osteoporosis. Genome-wide association studies (GWASs) have been fruitful in identifying some loci potentially associated with osteoporosis and T2D respectively. However, the total genetic variance for each of these two diseases and the shared genetic determination between them are largely unknown. Read More

J Hum Reprod Sci 2018 Apr-Jun;11(2):137-141

Department of Biomedical Sciences, School of Bio Sciences and Technology, VIT, Vellore, Tamil Nadu, India.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder occurring in premenopausal women, with a prevalence rate of 5%-7%. It has been observed in multiple number of studies the coexistence between diabetes mellitus 2 and obesity with this endocrinopathic disorder. Transcription factor 7-like 2 (TCF7L2) gene is shown to be associated with insulin secretion. Read More

Curr Diabetes Rev 2018 Jul 30. Epub 2018 Jul 30.

The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen. Denmark.

Diabetes is a multifactorial disease, caused by a complex interplay between environmental and genetic risk factors. Genetic determinants of particularly type 1 diabetes (T1D) and type 2 diabetes (T2D) have been studied extensively, whereas well-powered studies of latent autoimmune diabetes in adults (LADA) are lacking. So far available studies support a clear genetic overlap between LADA and T1D, however, with smaller effect sizes of the T1D-risk variants in LADA as compared to T1D. Read More

Genes (Basel) 2018 Jul 26;9(8). Epub 2018 Jul 26.

Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland.

Type 2 diabetes (T2D) is a complex disorder that is caused by a combination of genetic, epigenetic, and environmental factors. High-throughput approaches have opened a new avenue toward a better understanding of the molecular bases of T2D. A genome-wide association studies (GWASs) identified a group of the most common susceptibility genes for T2D (i. Read More

Metab Syndr Relat Disord 2018 Oct 11;16(8):383-389. Epub 2018 Jul 11.

Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic College of Medicine , Rochester, Minnesota.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disorder characterized by hyperglycemia occurring as a result of impaired insulin secretion and/or insulin resistance. Among the various genetic factors associated with T2DM, a common genetic variant within the transcription factor 7-like 2 locus (TCF7L2) confers the greatest genetic risk for development of the disease. However, the mechanism(s) by which TCF7L2 predisposes to diabetes remain uncertain. Read More

NPJ Syst Biol Appl 2018 3;4:25. Epub 2018 Jul 3.

11Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 USA.

Probing the dynamic control features of biological networks represents a new frontier in capturing the dysregulated pathways in complex diseases. Here, using patient samples obtained from a pancreatic islet transplantation program, we constructed a tissue-specific gene regulatory network and used the control centrality (Cc) concept to identify the high control centrality (HiCc) pathways, which might serve as key pathobiological pathways for Type 2 Diabetes (T2D). We found that HiCc pathway genes were significantly enriched with modest GWAS -values in the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) study. Read More

Hormones (Athens) 2018 Sep 3;17(3):359-365. Epub 2018 Jul 3.

Department of Endocrinology and Diabetes, Medical School, University of Ioannina, 45110, Ioannina, Greece.

Introduction: Transcription factor 7-like 2 (TCF7L2) gene variants rs12255372 and rs7903146 have been consistently shown to raise genetic risk for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the possible role of these variants in the development of impaired glucose metabolism (IGM), including impaired fasting glucose (IFG) or T2DM, in patients with metabolic syndrome (MS).

Patients And Methods: The study population consisted of 228 patients with MS who were divided into two groups. Read More

J Biol Chem 2018 09 2;293(36):14178-14189. Epub 2018 Jul 2.

From the Section of Cell Biology and Functional Genomics and Pancreatic Islet and Diabetes Consortium, Division of Diabetes, Endocrinology and Metabolism, Imperial Centre for Translational and Experimental Medicine, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom

Variants in the transcription factor-7-like 2 (/) gene, involved in Wnt signaling, are associated with type 2 diabetes. Loss of selectively from the β cell in mice has previously been shown to cause glucose intolerance and to lower β cell mass. Deletion of the tumor suppressor liver kinase B1 (LKB1/STK11) leads to β cell hyperplasia and enhanced glucose-stimulated insulin secretion, providing a convenient genetic model for increased β cell growth and function. Read More

Diabetologia 2018 08 12;61(8):1758-1768. Epub 2018 Jun 12.

Division of Intramural Population Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, 6710 Rockledge Dr, Bethesda, MD, 20817, USA.

Aims/hypothesis: Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse.

Methods: We conducted a case-control study among 2636 women with GDM and 6086 non-GDM control women from the Nurses' Health Study II and the Danish National Birth Cohort. Read More

Curr Diab Rep 2018 Jun 22;18(8):57. Epub 2018 Jun 22.

Departments of Medicine and Epidemiology and Public Health, Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, 670 West Baltimore Street, Room 4040, Baltimore, MD, 21201, USA.

Purpose Of Review: To provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D).

Recent Findings: The prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Read More

BMC Med Genet 2018 06 5;19(1):93. Epub 2018 Jun 5.

Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Several type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population. Read More

J Clin Pharm Ther 2018 Dec 26;43(6):768-774. Epub 2018 May 26.

Unidad de Investigación Médica en Bioquímica, Centro Médico Nacional Siglo XXI IMSS, Mexico City, Mexico.

What Is Known And Objective: Glibenclamide is a prescribed glucose-lowering medication for diabetes, but there are interindividual variations in the therapeutic response. In this cross-sectional study, the aim was to explore the association of genetic variants in CYP2C9, ABCC8, KCNJ11 and TCF7L2 with good glycaemic control in Mexican type 2 diabetes (T2D) treated with glibenclamide.

Methods: Patients with T2D receiving treatment with glibenclamide or glibenclamide plus metformin were included. Read More

Diabetol Metab Syndr 2018 26;10:37. Epub 2018 Apr 26.

1Laboratory of Medical Investigation LIM-18, Division of Endocrinology, School of Medicine, University of Sao Paulo, Av Dr Arnaldo, 455 room 3324, Sao Paulo, SP 01246903 Brazil.

Background: The rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim of this study was to perform a metabolic characterization of T2DM patients with and without the rs7903146 risk T allele and analyze some influences of the genotype on glucose metabolism. Read More

Int J Obes (Lond) 2018 07 12;42(7):1345-1353. Epub 2018 Mar 12.

Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates.

Background: The United Arab Emirates (UAE) is one of the countries most threatened with obesity. Here we investigated associations between hundreds of single-nucleotide polymorphisms (SNPs) and the following obesity indicators: body mass index (BMI), waist circumference (WC), and height. We also investigated the associations between obesity-related genes with type 2 diabetes mellitus (T2DM). Read More

Diabetologia 2018 07 19;61(7):1614-1622. Epub 2018 Apr 19.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Aims/hypothesis: Most type 2 diabetes-associated genetic variants identified via genome-wide association studies (GWASs) appear to act via the pancreatic islet. Observed defects in insulin secretion could result from an impact of these variants on islet development and/or the function of mature islets. Most functional studies have focused on the latter, given limitations regarding access to human fetal islet tissue. Read More

EBioMedicine 2018 Apr 30;30:295-302. Epub 2018 Mar 30.

Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Transcription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk allele of the rs7903146 in the TCF7L2 gene increases the risk of type 2 diabetes based on real-time stable isotope measurements of insulin synthesis during an Oral Glucose Tolerance Test. Read More

Cell Physiol Biochem 2018 22;46(1):335-350. Epub 2018 Mar 22.

Background/aims: The islet is an important endocrine organ to secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. Long noncoding RNAs (lncRNAs) are involved in a variety of biological functions and play key roles in many diseases, including type 2 diabetes (T2D). The aim of this study was to determine whether lncRNA-p3134 is associated with glucose metabolism and insulin signaling in pancreatic β cells. Read More

BMC Med Genet 2018 03 7;19(1):38. Epub 2018 Mar 7.

Department of Mathematics, Harbin Institute of Technology, No.92, Xidazhi Street, Nangang District, Harbin, 150001, China.

Background: Large scale association studies have found a significant association between type 2 diabetes mellitus (T2DM) and transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146. However, the quality of data varies greatly, as the studies report inconsistent results in different populations. Hence, we perform this meta-analysis to give a more convincing result. Read More

Curr Mol Med 2017 ;17(8):580-586

Department of Biotechnology, School of Life Sciences, Manipal Academy of Higher Education, Manipal- 576104, Karnataka, India.

Background: Several SNPs were identified through GWAS for their association with type 2 diabetes which has implications to pancreatic β-cell physiology.

Objective: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A, CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in response to sulfonylureas.

Method: We performed a prospective study on 209 newly diagnosed subjects; treatment naive T2D subjects were recruited. Read More

BMC Med 2018 02 20;16(1):25. Epub 2018 Feb 20.

Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Adult-onset, or type II diabetes mellitus (T2DM) has a complex genetic architecture, from hundreds of genes with low penetrance, common susceptibility variants (e.g., TCF7L2), to a set of more than ten genes that, when mutated, can cause a single-gene or Mendelian form of T2DM (e. Read More

Diabet Med 2018 05 12;35(5):602-611. Epub 2018 Mar 12.

Epidemiology and Prevention Group, Centre for Public Health Sciences, National Cancer Centre, Tokyo.

Aims: To assess the predictive ability of a genetic risk score for the incidence of Type 2 diabetes in a general Japanese population.

Methods: This prospective case-control study, nested within a Japan Public Health Centre-based prospective study, included 466 participants with incident Type 2 diabetes over a 5-year period (cases) and 1361 control participants, as well as 1463 participants with existing diabetes and 1463 control participants. Eleven susceptibility single nucleotide polymorphisms, identified through genome-wide association studies and replicated in Japanese populations, were analysed. Read More

Aging Dis 2018 Feb 1;9(1):17-30. Epub 2018 Feb 1.

1Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

is located at one of the most strongly associated type 2 diabetes loci reported to date. We previously reported that the most abundant member of a specific protein complex to bind across the presumed causal variant at this locus, rs7903146, was poly [ADP-ribose] polymerase type 1 (PARP-1). We analyzed the impact of PARP-1 inhibition on health in the setting of hyperglycemia and on glucose-stimulated GLP-1 secretion in human intestinal cells. Read More

Oncotarget 2017 Dec 6;8(67):112024-112035. Epub 2017 Dec 6.

Almazov National Medical Research Centre, Saint Petersburg, Russia.

We hypothesized that the association of certain lifestyle parameters with gestational diabetes mellitus (GDM) risk would depend on susceptibility loci. In total, 278 Russian women with GDM and 179 controls completed questionnaires about lifestyle habits (food consumption, physical activity and smoking). GDM was diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Read More

FEBS Lett 2018 02 23;592(3):422-433. Epub 2018 Jan 23.

Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. However, the functional SNPs regulating TCF7L2 expression remain unclear. Here, we show that the SNP rs7074440 is a candidate functional SNP highly linked with rs7903146. Read More

Diabetes Care 2018 03 11;41(3):554-561. Epub 2018 Jan 11.

Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA

Objective: The rs7903146 T allele in transcription factor 7 like 2 () is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of genotype before and after interventions that influence glucose physiology.

Research Design And Methods: We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after ) one dose of glipizide (5 mg) on visit 1 and ) a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days. Read More

Diabetes 2018 04 9;67(4):554-568. Epub 2018 Jan 9.

Diabetes Division, University of Texas Health Science Center, San Antonio, TX

The gene encoding for transcription factor 7-like 2 () is the strongest type 2 diabetes mellitus (T2DM) candidate gene discovered to date. The TCF7L2 protein is a key transcriptional effector of the Wnt/β-catenin signaling pathway, which is an important developmental pathway that negatively regulates adipogenesis. However, the precise role that TCF7L2 plays in the development and function of adipocytes remains largely unknown. Read More

Diabetes Metab Res Rev 2018 05 29;34(4):e2980. Epub 2018 Jan 29.

Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Jiangsu, China.

Background: The TCF7L2 (transcription factor 7 like 2) gene is strongly associated with type 2 diabetes risk. However, many people without the TCF7L2 at-risk allele develop T2D. The aim of this study was to investigate altered Tcf7l2 DNA methylation and gene expression caused by high-fat diets (HFDs). Read More