Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study

We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. the GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.Societe Francophone du Diabete (SFD - Alfediam)Association Diabete Risque Vasculaire (ADRV), FranceCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INSERMCNAMTSLillyNovartis PharmaSanofi-AventisINSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante)Association Diabete Risque VasculaireFederation Francaise de CardiologieLa Fondation de FranceALFEDIAMONIVINSArdix MedicalBayer DiagnosticsBecton DickinsonCardionicsMerck SanteNovo NordiskPierre FabreRocheTopconUniv Paris 07, INSERM, Res Unit 695, F-75018 Paris, FranceFed Univ Hlth Sci Porto Alegre, Postgradut Program Hlth Sci, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilAssistance Publ Hop Paris Cochin Hosp, Dept Immunol & Diabetol, Paris, FranceUniv Paris 05, UFR Med, Paris, FranceUniv Paris 07, UFR Med, Paris, FranceAssistance Publ Hop Paris Bichat Hosp, Dept Endocrinol Diabetol & Nutr, Paris, FranceInst Inter Reg Sante IRSA, La Riche, FranceINSERM, U1018, CESP, Ctr Res Epidemiol & Populat Hlth, Villejuif, FranceUniv Paris 11, UMRS 1018, Villejuif, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilCAPES: 1798-09-0Web of Scienc

The common-866G > A variant in the promoter of UCP2 is associated with decreased risk of coronary artery disease in type 2 diabetic men

OBJECTIVE-Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (-866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects.RESEARCH DESIGN and METHODS-We studied 3,122 subjects from the 6-year prospective Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied.RESULTS-We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80-0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered-myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death-contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25-0.89]; P = 0.02 for a recessive model).CONCLUSIONS-The A allele of the -866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.INSERM, Fac Med Xavier Bichat, U695, F-75018 Paris, FranceCochin Hosp, AP HP, Dept Immunol & Diabetol, Paris, FranceUniv São Paulo, Lab Cellular & Mol Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilFed Fac Fdn Med Sci Porto Alegre, Post Grad Program Med Sci, Porto Alegre, RS, BrazilHop La Pitie Salpetriere, Dept Cardiol, AP HP, Paris, FranceUniv Paris 07, Paris, FranceUniv Paris 05, Paris, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilWeb of Scienc

Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study

<p>Abstract</p> <p>Background</p> <p>Fatty liver is known to be linked with insulin resistance, alcohol intake, diabetes and obesity. Biopsy and even scan-assessed fatty liver are not always feasible in clinical practice. This report evaluates the predictive ability of two recently published markers of fatty liver: the Fatty Liver Index (FLI) and the NAFLD fatty liver score (NAFLD-FLS), for 9-year incident diabetes, in the French general-population cohort: Data from an Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R).</p> <p>Methods</p> <p>At baseline, there were 1861 men and 1950 women, non-diabetic, aged 30 to 65 years. Over the follow-up, 203 incident diabetes cases (140 men, 63 women) were identified by diabetes-treatment or fasting plasma glucose ≥ 7.0 mmol/l. The FLI includes: BMI, waist circumference, triglycerides and gamma glutamyl transferase, and the NAFLD-FLS: the metabolic syndrome, diabetes, insulin, alanine aminotransferase, and asparate aminotransferase. Logistic regression was used to determine the odds ratios for incident diabetes associated with categories of the fatty liver indices.</p> <p>Results</p> <p>In comparison to those with a FLI < 20, the age-adjusted odds ratio (95% confidence interval) for diabetes for a FLI ≥ 70 was 9.33 (5.05-17.25) for men and 36.72 (17.12-78.76) for women; these were attenuated to 3.43 (1.61-7.28) and 11.05 (4.09 29.81), after adjusting on baseline glucose, insulin, hypertension, alcohol intake, physical activity, smoking and family antecedents of diabetes; odds ratios increased to 4.71 (1.68-13.16) and 22.77 (6.78-76.44) in those without an excessive alcohol intake. The NAFLD-FLS also predicted incident diabetes, but with odds ratios much lower in women, similar in men.</p> <p>Conclusions</p> <p>These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes. Physicians should screen for diabetes in patients with fatty liver.</p

SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe

Aims: To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe. Methods and results: SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively. Conclusion: SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe

SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe

Aims: To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe. Methods and results: SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively. Conclusion: SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe

Variations des taux des lipoproteines plasmatiques chez l'homme: effets de facteurs nutritionnels et genetiques

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : TD 20306 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Polymorphism of the 5-HT2A receptor gene and food intakes in children and adolescents: the Stanislas Family Study.

International audienc

Abstract 3459: Human Atrial Natriuretic Peptide (ANP) Gene Is Associated With Metabolic Syndrome In The French Population

Background: ANP is important in hemodynamics, but also in lipolysis, particularly in overweight. Its plasmatic concentration is related to number of metabolic syndrome components. Its gene, NPPA, was considered as a candidate for susceptibility to metabolic disorders. Aims-Methods: We assessed the effect of 3 Hapmap-tagged haplotypes-defining NPPA SNPs, G664A (rs5063), 708C&gt;T (rs5064) and 2238T&gt;C (rs5065) on metabolic parameters levels and metabolic syndrome and their interaction with overweight in a cohort study included 2,576 men and 2,636 women from the general population, followed for 9 years. Results: In the whole population, there was a significant effect of the 708C&gt;T SNP on waist girth (CC: 83.5 ± 0.1cm, CT: 83.1 ± 0.2 and TT: 81.2 ± 0.9, p=0.04) and HDL-C (CC: 1.63 ± 0.01 mM CT: 1.63 ± 0.01 and TT: 1.77 ± 0.03, p=0.04). The 708C&gt;T SNP interacted with overweight on triglycerides (TG) and waist girth (p=0.002 and p=0.03 respectively for interaction) and in overweight subjects, was associated with TG (CC: 1.51 ± 0.03mM, CT: 1.37 ± 0.07 and TT: 1.13 ± 0.31, p=0.009) and waist girth (CC: 93.1 ± 0.2cm, CT: 92.1 ± 0.4 and TT: 89.1 ± 1.8, p=0.009). The 2238T&gt;C SNP interacted with overweight on waist girth (p=0.08 for interaction) and in overweight subjects, was associated with waist girth (TT: 93.1 ± 0.2cm, TC: 92.4 ± 0.3 and CC: 91.1 ± 0.9, p=0.03). The overweight 708TT carriers and 2238CC carriers had a lower risk of metabolic syndrome (MS) during the 9-year follow-up (rare allele OR=0.74, p=0.043 and 0.75, p=0.017 respectively). No association was found with 664G&gt;A. Haplotype GTC (carrying the minor allele of 708C&gt;T) was significantly associated with lower waist girth level (p=0.007) and TG (p=0.02) in overweight subjects, and with a lower risk of developing MS during follow-up (p=0.02) in overweight subjects. Conclusion: NPPA tagged SNPs and haplotypes are associated with cardiovascular risk in the general French population through association with lipids, waist girth levels and with incidence of MS in particular in overweight subjects.</jats:p