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Mol Genet Genomic Med 2020 Jun 24:e1361. Epub 2020 Jun 24.

Faculty of Health and Social Sciences, University of South Bohemia, České Budějovice, Czech Republic.

Background: The Czech governmental study suggests up to a 25% higher prevalence of type 2 diabetes mellitus (T2DM) in the Roma population than within the majority population. It is not known whether and to what extent these differences have a genetic background.

Methods: To analyze whether the frequencies of the alleles/genotypes of the FTO, TCF7L2, CDKN2A/2B, MAEA, TLE4, IGF2BP2, ARAP1, and KCNJ11 genes differ between the two major ethnic groups in the Czech Republic, we examined them in DNA samples from 302 Roma individuals and 298 Czech individuals. Read More

Am J Hum Biol 2020 May 23:e23434. Epub 2020 May 23.

Center of Biotechnology, Khalifa University of Science, Technology & Research, Abu Dhabi, United Arab Emirates.

Objective: Type 2 diabetes mellitus (T2DM) has a multifactorial etiology involving a complex interplay between genes and the environment. The prevalence of T2DM among the countries of the Gulf Corporation Council (GCC), including the United Arab Emirates (UAE), ranks among the top 15 in the world. A number of studies have shown an increase in T2DM risk for the "TT" genotype at the rs4506565 and rs12255372 Single Nucleotide Polymorphisms (SNP) of the TCF7L2 gene. Read More

Eur J Nutr 2020 May 22. Epub 2020 May 22.

Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.

Purpose: Red meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes.

Methods: Analyses were based on Swedish case-control data comprising incident cases of LADA (n = 465) and T2D (n = 1528) with matched, population-based controls (n = 1789; n = 1553 in genetic analyses). Read More

PLoS One 2020 7;15(5):e0230815. Epub 2020 May 7.

Department of Medicine, Harvard Medical School, Boston, MA, United States of America.

Smoking is a potentially causal behavioral risk factor for type 2 diabetes (T2D), but not all smokers develop T2D. It is unknown whether genetic factors partially explain this variation. We performed genome-environment-wide interaction studies to identify loci exhibiting potential interaction with baseline smoking status (ever vs. Read More

Int J Biol Macromol 2020 May 1;159:402-405. Epub 2020 May 1.

Department of Diabetology, M.V. Hospital for Diabetes and Prof. M. Viswanathan Diabetes Research Center (WHO Collaborating Center for Research Education and Training in Diabetes), Royapuram, Chennai, Tamil Nadu, India. Electronic address:

The greatest risk of developing type2 diabetes (T2DM) was conferred by rs7903146 SNP of Transcription factor7-like2 (TCF7L2) gene in many ethnic populations. The aim was to investigate the association of TCF7L2 (rs7903146) gene polymorphism among newly diagnosed diabetes subjects with different parental diabetes registry. A total of 171 subjects were categorized into 3 groups based on parental diabetes registry i. Read More

J Intern Med 2020 May 3. Epub 2020 May 3.

From the, Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.

The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Obesity, physical inactivity and ageing increase the risk of T2D. Epigenetic modifications can change due to environmental exposures and may thereby predispose to disease. Read More

Diabetes Metab Syndr Obes 2020 24;13:897-906. Epub 2020 Mar 24.

Department of Epidemiology, School of Health, Arak University of Medical Sciences, Arak, Iran.

Background: Type 2 diabetes mellitus (T2DM) is a serious public health issue with significantly increasing rates across the world. The genome-wide association studies (GWAS) have previously manifested involved genes that remarkably enhance the risk of T2DM. In this study, the association of common variants with T2DM risk has been identified among Iranian population from Tehran province of Iran. Read More

Saudi J Biol Sci 2020 Feb 26;27(2):736-750. Epub 2019 Dec 26.

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.

The incidence of Alzheimer's disease (AD) has risen exponentially worldwide over the past decade. A growing body of research indicates that AD is linked to diabetes mellitus (DM) and suggests that impaired insulin signaling acts as a crucial risk factor in determining the progression of this devastating disease. Many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias. Read More

JCI Insight 2020 Apr 9;5(7). Epub 2020 Apr 9.

Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic, Rochester, Minnesota, USA.

BACKGROUNDMetabolic disorders such as type 2 diabetes have been associated with a decrease in insulin pulse frequency and amplitude. We hypothesized that the T allele at rs7903146 in TCF7L2, previously associated with β cell dysfunction, would be associated with changes in these insulin pulse characteristics.METHODSTwenty-nine nondiabetic subjects (age 46 ± 2, BMI 28 ± 1 kg/m2) participated in this study. Read More

Diabetes Metab Syndr 2020 May - Jun;14(3):175-180. Epub 2020 Feb 21.

Biostatics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.

Background And Aims: Transcription factor 7 like 2 (TCF7L-2) polymorphism has been associated with adipocyte metabolism and insulin resistance. Genetic investigations of non-alcoholic fatty liver disease (NAFLD) with obesity, type 2 diabetes mellitus (T2DM) and atherosclerosis are unknown. This study was designed to investigate the association of rs7903146 (C/T) polymorphism of TCF7L-2 gene with non-alcoholic fatty liver disease (NAFLD) in Asian Indians. Read More

Afr Health Sci 2019 Sep;19(3):2484-2490

Department of Food Hygiene and Quality control, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Background: Transcription factor 7-like 2 Protein (TCF7L2) has a strong role in the pathogenesis of type 2 diabetes mellitus (T2DM). Association between rs7903146 and T2D risk reported in some of populations. Also many loci such as UBE2Z rs46522 are affecting by TCF7L2 transcription factor have been found associated with T2D. Read More

Sci Rep 2020 Feb 5;10(1):2274. Epub 2020 Feb 5.

The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

Biochem Biophys Res Commun 2020 Mar 13;523(3):658-665. Epub 2020 Jan 13.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, PR China. Electronic address:

Genome-wide association studies (GWASs) have successfully identified numerous non-coding genetic variants for type 2 diabetes (T2D), but the functional roles underlying these non-coding variants remain largely unknown. The effects of T2D GWAS lead SNPs on transcriptional factors binding motifs were firstly analyzed via JASPAR, followed by functional validations including dual-luciferase reporter assays, biotin-based DNA pull-down assays, real-time quantitative PCR, and western blotting. The results showed that GWAS SNP rs4430796 conferred T allele specific transcriptional enhancer activity via a PAX6 binding element, and upregulated the expression of HNF1B. Read More

Rev Med Chil 2019 Aug;147(8):965-976

BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

Background: Type 2 diabetes etiology has a strong genetic component. More than 20 genetic variants have been associated with diabetes and other metabolic markers. However, the polymorphism rs7903146 of the TCF7L2 gene has shown the strongest association. Read More

Elife 2019 12 12;8. Epub 2019 Dec 12.

Department of Cell and Developmental Biology, UCL, London, United Kingdom.

Tcf7l2 mediates Wnt/β-Catenin signalling during development and is implicated in cancer and type-2 diabetes. The mechanisms by which Tcf7l2 and Wnt/β-Catenin signalling elicit such a diversity of biological outcomes are poorly understood. Here, we study the function of zebrafish alternative splice variants and show that only variants that include exon five or an analogous human variant can effectively provide compensatory repressor function to restore eye formation in embryos lacking function. Read More

Arch Physiol Biochem 2019 Dec 9:1-4. Epub 2019 Dec 9.

Isfahan Medical Students Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Type-2 diabetes mellitus (T2DM) is the common endocrinopathy which characterised by insulin resistance, insufficient expression or secretion of insulin and decrement of insulin effectiveness. Although T2DM has unknown aetiology, the strongest susceptible gene in this disease is TCF7L2. Adropin peptide may have roles in T2DM pathogenesis due to several roles in glucose tolerance, decrement of insulin resistance, lipid metabolism and energy homoeostasis. Read More

Mol Cell Endocrinol 2020 02 2;502:110673. Epub 2019 Dec 2.

Lund University, Department of Clinical Sciences, Islet Pathophysiology Group, Sweden. Electronic address:

The transcription factor TCF7L2 remains the most important diabetes gene identified to date and genetic risk carriers exhibit lower insulin secretion. We show that Tcf7l2 regulates the auxiliary subunit of voltage-gated Ca channels, Cacna2d1 gene/α2δ-1 protein levels. Furthermore, suppression of α2δ-1 decreased voltage-gated Ca currents and high glucose/depolarization-evoked Ca signaling which mimicked the effect of silencing of Tcf7l2. Read More

Indian J Endocrinol Metab 2019 Sep-Oct;23(5):563-569

Alpha Hospital and Research Center, Alpha Health Foundation, Mela Anuppanady, Madurai, Tamil Nadu, India.

Background And Aims: Metabolic abnormalities in T2DM (Type 2 diabetes mellitus) include classic manifestations such as impaired insulin secretion, synthesis and peripheral insulin resistance. The intronic variants rs7903146 and rs12255372 of the TCF7L2 (transcription factor 7-like 2) gene are strongly associated with risk of incidence of T2DM and impaired β-cell functions. Studies addressing the early T2DM onset, and early insulin dependence in T2DM patients of south Tamil Nadu are still lacking, and hence the present study focuses in determining the influence of the TCF7L2 polymorphisms in the incidence and disease course in the T2DM patients of south Tamil Nadu. Read More

Diab Vasc Dis Res 2020 Jan-Feb;17(1):1479164119888475. Epub 2019 Nov 27.

Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea.

Aim: The aim of this study was to investigate the association between the transcription factor 7-like 2 gene () rs7903146 polymorphism and peripheral arterial disease in type 2 diabetes.

Methods: In total, 1818 Korean type 2 diabetes patients were enrolled from January 2013 to December 2017. Subjects were categorized into two groups according to their duration of type 2 diabetes: long (⩾10 years,  = 771) and short (<10 years,  = 1047) durations. Read More

Kidney Dis (Basel) 2019 Oct 6;5(4):220-227. Epub 2019 Mar 6.

Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.

Background: The emerging renal and cardiovascular complications of type 2 diabetes (T2DM) genetics involves differently assembled gene variants including transcription factor 7-like 2 (TCF7L2) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) polymorphisms. However, the relevance of these genes for complication prediction has not been extensively tested.

Methods: We analyzed the SNP rs7903146 variants in TCF7L2 and PPARG2 gene polymorphisms for their contribution to the incidence of chronic kidney disease (CKD) and cardiovascular complications in a prospective cohort study. Read More

Gene 2020 Mar 21;730:144259. Epub 2019 Nov 21.

Maestría en Salud Publica, Universidad México Americana del Norte, Reynosa, Tamaulipas, Mexico; Department of Epidemiology, Human Genetics & Environmental Sciences, The University of Texas Health Science Center at Houston, Brownville, TX, USA.

Mexican Maya populations have a notably high prevalence of type 2 diabetes (T2D) as a consequence of the interaction between environmental factors and a genetic component. To assess the impact of 24 single nucleotide variants (SNVs) located in 18 T2D risk genes, we conducted a family-based association evaluation in samples from Maya communities with a high incidence of the disease. A total of four hundred individuals were recruited from three Maya communities with a high T2D incidence. Read More

J Clin Endocrinol Metab 2020 May;105(5)

McKusick-Nathans Institute of the Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Context: Individuals with cystic fibrosis (CF) develop a distinct form of diabetes characterized by β-cell dysfunction and islet amyloid accumulation similar to type 2 diabetes (T2D), but generally have normal insulin sensitivity. CF-related diabetes (CFRD) risk is determined by both CFTR, the gene responsible for CF, and other genetic variants.

Objective: To identify genetic modifiers of CFRD and determine the genetic overlap with other types of diabetes. Read More

Neurogastroenterol Motil 2020 01 5;32(1):e13724. Epub 2019 Nov 5.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Nutrient-mediated release of cholecystokinin and glucagon-like peptide-1 (GLP-1) regulates gastric emptying (GE) via duodenogastric feedback mechanisms; GLP-1 also regulates postprandial insulin secretion. Some patients with functional upper gastrointestinal symptoms have impaired glucose tolerance during enteral dextrose infusion. Our hypothesis was that variants in CCK, GLP-1, and TCF7L2 (transcription factor 7-like 2 locus), which is associated with greatest genetic risk for development of type 2 diabetes mellitus, are associated with GE and independently with glucose tolerance. Read More

Int J Appl Basic Med Res 2019 Oct-Dec;9(4):221-225. Epub 2019 Oct 11.

Department of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India.

Introduction: Cardiovascular disease (CVD) is the primary cause of morbidity and premature mortality in chronic kidney disease (CKD). The transcription factor 7-like 2 () gene product TCF4 is a transcription factor that acts as a downstream effector in the canonical Wnt signaling pathway and may be important in the development of both type 2 diabetes and renal development and disease. It is, therefore, plausible that mutations in this gene could manifest themselves in reduced kidney function or kidney disease through their effects on hyperglycemia as well as independent of this mechanism. Read More

Sci Rep 2019 11 1;9(1):15818. Epub 2019 Nov 1.

The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

The association between several Single Nucleotide Polymorphisms (SNPs) within the transcription factor 7-like 2 (TCF7L2) gene and Type 2 Diabetes (T2D) as well as additional T2D-related traits is well established. Since alteration in total and regional brain volumes are consistent findings among T2D individuals, we studied the association of four T2D susceptibility SNPS within TCF7L2 (rs7901695, rs7903146, rs11196205, and rs12255372) with volumes of white matter hyperintensities (WMH), gray matter, and regional volumes of amygdala and hippocampus obtained from structural MRI among 191 T2D elderly Jewish individuals. Under recessive genetic model (controlling for age, sex and intracranial volume), we found that for all four SNPs, carriers of two copies of the T2D risk allele (homozygous genotype) had significantly smaller amygdalar volume: rs7901695- CC genotype vs. Read More

Nat Rev Endocrinol 2020 01;16(1)

Nature Reviews Endocrinology, .

Exp Clin Endocrinol Diabetes 2019 Sep 23. Epub 2019 Sep 23.

Division of Endocrinology and Diabetology, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: The single nucleotide polymorphism in TCF7L2 rs7903146 is associated with an increased risk of type 2 diabetes mellitus and gestational diabetes mellitus. Mechanisms by which this mutation acts, and its impact on the clinical course of the diseases remain unclear. Here we investigated the clinical impact of the T risk allele in women with gestational diabetes mellitus. Read More

Endocr Regul 2019 Jan;53(1):1-7

PostgraduateProgram in Biotechnology, Universidade do Vale do Taquari- Univates,Lajeado, RS, Brasil.

Objective: Genetic variants in the transcription factor 7-like 2 (TCF7L2) gene have been described as the most noteworthy ones regarding the type 2 diabetes mellitus (T2DM) liability. This work is aimed to evaluate the association between rs12255372 and rs7903146 polymorphisms and T2DM in patients with cardiovascular disease (CAD) risk.

Methods: A sample of six hundred and forty-seven patients that underwent the coronary angiography in a Cardiac Catheterization Lab was evaluated. Read More

J Nutr 2020 01;150(1):167-175

Department of Nutrition, Harvard University TH Chan School of Public Health, Boston, MA, USA.

Background: Transcription factor 7-like 2 (TCF7L2) genetic variants that predispose individuals to type 2 diabetes (T2D) show inconsistent associations with anthropometric traits. Interaction between TCF7L2 genotypes and dietary factors may help explain these observations.

Objective: We aimed to examine the potential modulation of TCF7L2-rs7903146 and rs12255372 on anthropometric markers by a Mediterranean diet (MedDiet). Read More

Mol Metab 2019 09;27S:S25-S32

University of Pennsylvania, Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, Philadelphia, PA, USA. Electronic address:

Background: Epigenetic processes control timing and level of gene expression throughout life, during development, differentiation, and aging, and are the link to adapting gene expression profiles to environmental cues. To qualify for the definition of 'epigenetic', a change to a gene's activity must be inherited through at least one mitotic division. Epigenetic mechanisms link changes in the environment to adaptions of the genome that do not rely on changes in the DNA sequence. Read More

Sci Rep 2019 09 6;9(1):12863. Epub 2019 Sep 6.

Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria.

The transcription factor 7-like 2 (TCF7L2) polymorphism rs7903146 is known to be tightly associated with an elevated risk for type 2 diabetes, whereas the molecular mechanisms remain elusive. We evaluated the metabolic profile of a total of 394 patients' serum samples with respect to their rs7903146 genotype using targeted metabolomics in a discovery (n = 154) and a validation (n = 240) study. We have identified serotonin as the top metabolite being increased in carriers of the risk allele. Read More

Obes Rev 2019 11 2;20(11):1557-1571. Epub 2019 Sep 2.

Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany.

The pathophysiological influence of gene-lifestyle interactions on the risk to develop type 2 diabetes (T2D) is currently under intensive research. This systematic review summarizes the evidence for gene-lifestyle interactions regarding T2D incidence. MEDLINE, EMBASE, and Web of Science were systematically searched until 31 January 2019 to identify publication with (a) prospective study design; (b) T2D incidence; (c) gene-diet, gene-physical activity, and gene-weight loss intervention interaction; and (d) population who are healthy or prediabetic. Read More

Diabetes 2019 10 16;68(10):1965-1974. Epub 2019 Aug 16.

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden

Type 2 diabetes (T2D) is characterized by insufficient insulin secretion and elevated glucose levels, often in combination with high levels of circulating fatty acids. Long-term exposure to high levels of glucose or fatty acids impair insulin secretion in pancreatic islets, which could partly be due to epigenetic alterations. We studied the effects of high concentrations of glucose and palmitate combined for 48 h (glucolipotoxicity) on the transcriptome, the epigenome, and cell function in human islets. Read More

Diabetes Care 2019 09 13;42(9):1624-1629. Epub 2019 Aug 13.

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

Over the past ∼15 years there has been great progress in our understanding of the genetics of both type 1 diabetes and type 2 diabetes. This has been driven principally by genome-wide association studies (GWAS) in increasingly larger sample sizes, where many distinct loci have now been reported for both traits. One of the loci that dominates these studies is the locus for type 2 diabetes. Read More

Diabetes Metab Syndr 2019 Mar - Apr;13(2):1629-1632. Epub 2019 Mar 16.

Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address:

Background: Type 2 diabetes (T2D) is a polygenic and multi-factorial complex disease, the challenge to find genetic markers that could explain the risk of development of this disease still remains unresolved. The Arab region is one among the populations with a high prevalence of T2D and a large number of studies have been carried out in exploring the genetic factors associated with T2D risk.

Aim: To summarize the recent developments in the Arab world based on the recent studies that had looked into genetic factors associated with the development of T2D in the Arab populations. Read More

Nat Commun 2019 07 19;10(1):3195. Epub 2019 Jul 19.

Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, USA.

Genome analysis of diverse human populations has contributed to the identification of novel genomic loci for diseases of major clinical and public health impact. Here, we report a genome-wide analysis of type 2 diabetes (T2D) in sub-Saharan Africans, an understudied ancestral group. We analyze ~18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana and Kenya. Read More

Diabetol Metab Syndr 2019 5;11:56. Epub 2019 Jul 5.

Department of Endocrinology, Shengzhou People's Hospital, No. 666 Dangui Road of Sanjiang Street, Shaoxing, 312400 Zhejiang China.

Background: Some genetic association studies tried to investigate potential associations of Transcription Factor 7 Like 2 () rs7903146 polymorphism with type 2 diabetes mellitus (T2DM). However, the results of these studies were not consistent. Thus, we performed the present meta-analysis to explore associations between rs7903146 polymorphism and T2DM in a larger pooled population. Read More

Curr Diabetes Rev 2020 ;16(4):370-375

Internal Medicine Department, Cairo University, Cairo, Egypt.

Background: The exact relationship between the different TCF7L2 gene polymorphisms and the development of diabetic nephropathy (DN) remains unclear.

Objective: To investigate the association of TCF7L2 rs12255372 (G/T) gene polymorphism and diabetic nephropathy (DN) in patients with type 2 diabetes (T2D).

Methods: 100 patients with T2D (50 patients without DN and 50 patients with DN) and 50 age and sex-matched healthy controls (HC) were enrolled in the study. Read More

Genomics 2020 03 6;112(2):1192-1196. Epub 2019 Jul 6.

Department of endocrinology, Affiliated Hospital of Hebei University, Baoding 071000, Hebei, China. Electronic address:

Background: Some previous studies already explored associations of Transcription Factor 7 Like 2 (TCF7L2) polymorphisms with type 2 diabetes mellitus (T2DM), with conflicting findings. Here, we aimed to better analyze the relationship between TCF7L2 polymorphisms and T2DM in a larger combined population by performing a meta-analysis.

Methods: We searched Pubmed, Embase, Web of Science and CNKI for related articles. Read More

Biochim Biophys Acta Mol Basis Dis 2019 10 27;1865(10):2753-2764. Epub 2019 Jun 27.

Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland. Electronic address:

In the setting of metabolic overload, chronic elevations of free fatty acids in blood and tissues are associated with pancreatic β-cell lipotoxicity and failure. Ultimately, obesity combined with insulin resistance increases the dysfunctional demand of β-cells and contributes to the development of type 2 diabetes. Forkhead box O1 (FoxO1) is a potent transcriptional regulator of pancreatic β-cell function and tolerance to lipid stress. Read More

Diabetes Care 2019 08 4;42(8):1357-1364. Epub 2019 Jun 4.

University of Miami, Miami, FL.

Current efforts to prevent progression from islet autoimmunity to type 1 diabetes largely focus on immunomodulatory approaches. However, emerging data suggest that the development of diabetes in islet autoantibody-positive individuals may also involve factors such as obesity and genetic variants associated with type 2 diabetes, and the influence of these factors increases with age at diagnosis. Although these factors have been linked with metabolic outcomes, particularly through their impact on β-cell function and insulin sensitivity, growing evidence suggests that they might also interact with the immune system to amplify the autoimmune response. Read More

J Clin Endocrinol Metab 2019 10;104(10):4815-4826

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

Objective: We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

Methods: We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Read More

Sci Rep 2019 05 23;9(1):7785. Epub 2019 May 23.

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.

Impaired insulin secretion from pancreatic islets is a hallmark of type 2 diabetes (T2D). Altered chromatin structure may contribute to the disease. We therefore studied the impact of T2D on open chromatin in human pancreatic islets. Read More

Endocr Metab Immune Disord Drug Targets 2019 ;19(6):719-731

Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Type 2 Diabetes Mellitus (T2DM) is a worldwide disorder as the most important challenges of health-care systems. Controlling the normal glycaemia greatly profit long-term prognosis and gives explanation for early, effective, constant, and safe intervention.

Material And Methods: Finding the main genetic and epigenetic profile of T2DM and the exact molecular targets of T2DM medications can shed light on its personalized management. Read More

Diabetes Metab 2020 Jun 20;46(3):243-247. Epub 2019 May 20.

Intensive Care Unit, CHU de Lille, 59000 Lille, France; Medical School, université de Lille, 59000 Lille, France; PRESAGE Simulation Center, université de Lille, 59000 Lille, France; UMR 1190 Inserm Translational research in diabetes, 59000 Lille, France; EGID European Genomics Institute for Diabetes, CHU de Lille, 59000 Lille, France. Electronic address:

Objective: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU.

Methods: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. Read More

J Diabetes Res 2019 14;2019:3618103. Epub 2019 Apr 14.

Department of Epidemiology, Shanxi Medical University School of Public Health, Taiyuan 030001, China.

Gestational diabetes mellitus (GDM) is a growing public health concern for many reasons, and its etiology remains unclear. Due to the similarity of its pathophysiology with type 2 diabetes (T2DM), we evaluated the relationship between published T2DM susceptibility genes and the risk of GDM. A total of 303 SNPs from genes including , , , , , , and and the risk of GDM were examined in a nested case-control study with 321 GDM cases and 316 controls. Read More

PLoS One 2019 13;14(5):e0216627. Epub 2019 May 13.

General Surgery Unit, Hospital das Clínicas, Federal University of Pernambuco, Recife, PE, Brazil.

Objective: To assess the influence of bariatric surgery on transcription factor 7-like 2 (TCF7L2) expression and its association with body mass index (BMI) and Type 2 diabetes mellitus (T2DM).

Methods: Prospective study performed between 2016 and 2018, where 26 obese patients undergoing bariatric surgery were divided into two subgroups: diabetics and non-diabetics. The RNAs were extracted from peripheral blood samples that were obtained from each patient in two different moments: before surgery and after 12 months of follow-up. Read More

Bosn J Basic Med Sci 2019 Nov 8;19(4):368-374. Epub 2019 Nov 8.

Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. Read More

Diabetologia 2019 07 2;62(7):1204-1211. Epub 2019 May 2.

Department of Diabetes and Endocrinology, University of KwaZulu-Natal, Durban, 4013, South Africa.

Aims/hypothesis: Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic analysis in African populations.

Methods: We conducted two type 2 diabetes genome-wide association studies in 4347 Africans from South Africa, Nigeria, Ghana and Kenya and meta-analysed both studies together. Read More

J Nutr 2019 06;149(6):915-922

Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.

Background: The transcription factor 7-like 2 (TCF7L2) gene confers one of the strongest genetic predispositions to type 2 diabetes, but diabetes development can be modified by diet.

Objective: The aim of our study was to evaluate postprandial metabolic alterations in healthy men with a high genetic risk of diabetes, after two meals with varying macronutrient content.

Methods: The study was conducted in 21 homozygous nondiabetic men carrying the high-risk (HR, n = 8, age: 31. Read More