J Tichet

Institut inter Régional pour la SAnté, Tours, Centre, France

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Publications (195)1022.59 Total impact

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    ABSTRACT: To determine full blood count (FBC) normal reference values for adults. FBC normal values for healthy adults were defined, after establishing preanalytical conditions, in a population of 33 258 subjects, 19 612 men and 13 646 women. The values were established after excluding from this population all people having conditions liable to modify, directly or indirectly, FBC parameters. Results for values of standard parameters are provided in detail for each parameter, by sex and by age group from 16 to 69 years of age. In addition, we present FBC values from a population of 339 subjects aged over 69 years with no comorbidities. These normal values are proposed for use in everyday practice. They make it possible to distinguish, without ambiguity, a normal situation from a pathological situation. Moreover, they might be used over all mainland France.
    Journal of clinical pathology 10/2013; · 2.43 Impact Factor
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    ABSTRACT: Association between deprivation and health is well established, particularly among unemployed or fixed-term contract or temporary contract subjects. This study aimed to assess if this relationship existed as well in full-time permanent workers. Biometrical, biological, behavioural and psychosocial health risk indicators and an individual deprivation score, the Evaluation of Precarity and Inequalities in Health Examination Centres score, were recorded from January 2007 to June 2008, in 34 905 full-time permanent workers aged 18-70 years, all volunteers for a free health examination. Comparisons of the behavioural, metabolic, cardiovascular and health risk indicators between quintiles of the deprivation score with adjustments on age and socioeconomic categories were made by covariance analysis or logistic regression. For both genders, degradation of nutritional behaviours, metabolic and cardiovascular indicators and health appeared gradually with deprivation, even for deprivation score usually considered as an insignificant value. The absence of only one social support or one social network was associated with a degradation of health. Full-time permanent workers with the poorest health risk indicators had more frequent social exclusion signs. These results were independent of socioeconomic categories and age. Understanding how deprivation influences health status may lead to more effective interventions to reduce social inequalities in health. The deprivation Evaluation of Precarity and Inequalities in Health Examination Centres score is a relevant tool to detect subjects who could benefit from preventive interventions. Our findings suggest that this deprivation score should be used as a health risk indicator even in full-time permanent workers. Assessing deprivation is useful to design and evaluate specific intervention programmes.
    The European Journal of Public Health 09/2013; · 2.52 Impact Factor
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    ABSTRACT: OBJECTIVES: To study the reproducibility and validity of a French self-administered questionnaire (NAQAPNNS) evaluating the adequation of a subject with the French national nutrition and health program recommendations. METHODS: The reproducibility was estimated by weighted kappa in 48 subjects working in the administrative departments of the head office of the Institut Inter Régional pour la Santé in Tours aged from 21 to 63 years who filled the questionnaire NAQAPNNS twice with a two weeks interval. The validity was assessed in 524 hyperglycaemic subjects (fasting plasma glucose between 1.10g/l and 1.25g/l) aged from 25 to 70 years against a seven-day dietary recall using the Kruskall-Wallis test. Agreement between self-administration of the questionnaire and dietetic interview was evaluated by weighted kappa. RESULTS: The reproducibility was "good" (kappa≥0.67) except for recommendations on breads, cereals, potatoes and legumes (kappa=0.50) and sweetened foods consumption (kappa=0.54) which showed only "satisfactory" reproducibility. For each recommendation, subjects who reached it had dietary intakes closer to dietary references intakes (P<0.03). The agreement between self-administration and dietetic interview was "good" (kappa≥0.63) except for recommendations on added fats (kappa=0.41) and salt (kappa=0.50) consumption which were only "satisfactory". DISCUSSION: The NAQAPNNS questionnaire is a consistent and reproducible tool to evaluate adequation of a subject with French national nutritional recommendations. CONCLUSION: The self-administered questionnaire NAQAPNNS can be used in clinical practice or in epidemiological studies to detect subjects with a food imbalance and needing specific care.
    La Presse Médicale 03/2013; · 0.87 Impact Factor
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    ABSTRACT: Objectifs Étudier la reproductibilité et la validité d’un auto-questionnaire simple (NAQAPNNS) en langue française permettant d’évaluer l’adhésion d’un sujet aux repères du Programme National Nutrition Santé. Méthodes La reproductibilité a été évaluée à l’aide du test kappa pondéré chez 48 sujets recrutés dans les services administratifs du siège de l’Institut inter Régional pour la Santé à Tours âgés de 21 à 63 ans ayant rempli deux fois l’auto-questionnaire NAQAPNNS à deux semaines d’intervalle. La validité a été évaluée chez 524 sujets hyperglycémiques (glycémie à jeun entre 1,10 g/L et 1,25 g/L) âgés de 25 à 70 ans par rapport à la technique de l’histoire alimentaire de 7 jours à l’aide du test de Kruskall–Wallis. L’accord entre l’auto-administration du questionnaire et l’interrogatoire diététique a été évalué à l’aide du test kappa pondéré. Résultats La reproductibilité était « bonne » (kappa ≥ 0,67) pour tous les repères à l’exception de ceux portant sur la consommation de féculents (kappa = 0,50) et de produits sucrés (kappa = 0,54) pour lesquels elle était seulement « satisfaisante ». Pour chaque repère, les apports nutritionnels étaient plus proches des apports conseillés pour ceux atteignant le repère (p < 0,03). L’accord entre l’auto-administration du questionnaire et l’interrogatoire était « bon » (kappa ≥ 0,63) pour tous les repères à l’exception de ceux portant sur la consommation de matières grasses ajoutées (kappa = 0,41) et de sel (kappa = 0,50) pour lesquels il était seulement « satisfaisant ». Conclusion L’auto-questionnaire NAQAPNNS est un outil fiable permettant d’évaluer l’adhésion d’un sujet aux repères nationaux de consommation. Il peut être utilisé en pratique courante ou lors d’études épidémiologiques pour identifier les sujets ayant un déséquilibre alimentaire et nécessitant une prise en charge. Ce qui était connu•La mise en place d’une stratégie nationale d’information et d’orientation de la population vers des choix alimentaires satisfaisants (Programme National Nutrition Santé [PNNS]).•Les baromètres santé nutrition (INPES) et les enquêtes nationales (INCA, ENNS) rapportent un pourcentage d’atteinte des repères PNNS obtenu par des méthodes plus précises de quantification mais qui nécessitent un investissement (humain, matériel et financier) plus lourd.Ce qu’apporte l’article•Un auto-questionnaire simple permettant d’évaluer l’atteinte ou non de chacun des repères du PNNS.•Un logiciel complémentaire spécifique permettant la saisie du questionnaire avec édition immédiate d’un compte rendu personnalisé avec possibilité d’une évaluation statistique sur un groupe.•Un outil validé et peu onéreux utilisable en pratique courante et dans des études épidémiologiques.
    La Presse Médicale. 01/2013; 42(s 7–8):e245–e258.
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    ABSTRACT: Most of the cardiovascular risk factors strongly associated with obesity and overweight vary with age and gender. However, few reference values are available for healthy European children. Our objective was to establish pediatric reference ranges for waist circumference, systolic and diastolic blood pressures, fasting lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), glucose, and insulin. A representative sample of 1976 healthy French individuals (1004 female participants and 972 male participants) aged 7 to 20 years was used to obtain age- and gender-specific normal ranges for each of the above-listed cardiovascular risk factors, based on the Royston and Wright method. Mean waist circumference increased with age in both genders and was slightly higher in males than in females. Whereas systolic blood pressure increased gradually with age, with the increase being steeper in males than in females, no gender effect was found for diastolic blood pressure, which was therefore modeled after pooling males and females. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride values varied little with age and gender. Glucose and insulin levels revealed pubertal peaks, which were sharper in females than in males, reflecting the normal insulin resistance during puberty. These ranges can be used as references for European children to monitor cardiovascular risk factors and to plan interventions and education programs.
    PEDIATRICS 03/2012; 129(4):e1020-9. · 4.47 Impact Factor
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    ABSTRACT: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
    PLoS Genetics 03/2012; 8(3):e1002607. · 8.52 Impact Factor
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    ABSTRACT: African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
    PLoS ONE 01/2012; 7(1):e29202. · 3.53 Impact Factor
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    ABSTRACT: Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.
    Hypertension 12/2011; 59(2):248-55. · 6.87 Impact Factor
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    ABSTRACT: Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
    The American Journal of Human Genetics 11/2011; 89(6):688-700. · 11.20 Impact Factor
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    ABSTRACT: Updating Baecke physical activity questionnaire in French, validating this version named AQAP and developing software for a personalized interpretation of the results. Validation conducted on 702 consultants in health prevention centers aged 18-79 years: reliability of the questionnaire when self-administered, validity according to the energy expenditure per interview and reproducibility after two weeks (n=31). After two months, assessment of the questionnaire's impact on knowledge and behaviors in 320 young adults aged 18-29 years. The results from self- and interviewer-administered questionnaire were correlated (Kappa>0.60). Furthermore, the total physical activity index was correlated to the energy expenditure (rho=0.39, P<0.0001). The four physical activity indexes calculated from self-administrated questionnaires barely varied at the two-week interval (P ≥ 0.23, power ≥ 77%, accepted difference ± 10%). Two months later, 80% of the participants had read the interpretation software report, 55% became conscious of their physical activity level, 43% increased their physical activity level and 42% reported being aware of the relationship between physical activity and health. AQAP characteristics are satisfactory and thus this questionnaire can be used on the general population in complement of an individual or collective action to promote physical activity and in epidemiological studies for analyzing the links between individual behaviors and health.
    Annals of physical and rehabilitation medicine 10/2011; 54(8):478-95.
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    ABSTRACT: A reference model for converting serum growth factor and bone metabolism markers into an SD score (SDS) is required for clinical practice. We aimed to establish reference values of serum insulin-like growth factor-1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations and bone metabolism markers in French children, to generate a model for converting values into SDS for age, sex, and pubertal stage. We carried out a cross-sectional study of 1119 healthy white children ages 6-20 years. We assessed concentrations of serum IGF-1, IGFBP-3, carboxyterminal telopeptide α1 chain of type I collagen (CrossLaps), and bone alkaline phosphatase concentrations and height, weight, and pubertal stage, and used semiparametric regression to develop a model. A single regression model to calculate the SDSs with an online calculator was provided. A positive relationship was found between SDS for serum IGF-1 and IGFBP-3, IGF/IGFBP-3 mol/L ratio, and anthropometric parameters (P < 0.0001), with slightly greater effects observed for height than for body mass index (BMI). There was a negative relationship between serum CrossLaps concentration and BMI, and a positive relationship between serum CrossLaps concentration and height. A comparison of serum IGF-1 reference databases for children showed marked variation as a function of age and pubertal group; smooth changes with age and puberty were observed only in our model. This new model for the assessment of SDS reference values specific for age, sex, and pubertal stage may help to increase the diagnostic power of these parameters for the assessment of growth and bone metabolism disorders. This study also provides information about the physiological role of height and BMI for the interpretation of these parameters.
    Clinical Chemistry 08/2011; 57(10):1424-35. · 7.15 Impact Factor
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    ABSTRACT: The superiority of several immunochemical fecal occult blood tests (I-FOBT) over guaiac-based tests in colorectal cancer screening is now established. The aim of this study was to compare the analytical performance of 3 quantitative I-FOBTs. Stool samples from 10 healthy volunteers, initially I-FOBT negative, supplemented with human blood, were used to compare reproducibility and stability of measurement at varying storage temperatures (4°C, 10°C, 20°C, and 30°C) and durations before test analysis (1 to 10 days) for 3 I-FOBTs (New Hemtube/Magstream HT, OC-Auto sampling bottle3/OC-Sensor DIANA, and FOB Gold/SENTiFOB). Concentrations ranging from 0 to 350 μg Hb/g of feces were evaluated. The measurement reproducibility of OC-Sensor was superior to Magstream and far superior to FOB Gold. For all tests, variability was essentially related to sampling. Detected hemoglobin (Hb) levels were substantially lower for all tests at temperatures above 20°C. At 20°C, this loss in concentration was less important with OC-Sensor (significant 1.7% daily decrease vs. 7.4% for Magstream and 7.8% for FOB Gold). At 30°C, daily loss was 8.6% with OC-Sensor, whereas after 24 hours, only 30% of the original Hb was detected with FOB Gold, compared to 70% with Magstream. No Hb was detected on day 5 for the latter 2 tests. About reproducibility and temperature stability, OC-Sensor performed better than Magstream and far better that FOB Gold. Independently of the chosen test, the delay between sampling and test processing should be reduced, the maximal admissible delay depending on ambient temperature.
    Cancer Epidemiology Biomarkers &amp Prevention 06/2011; 20(7):1492-501. · 4.56 Impact Factor
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    ABSTRACT: Diabet. Med. 28, 440–449 (2011)AbstractObjectives  To evaluate in a general population, the relationships between dysglycaemia, insulin resistance and metabolic variables, and heart rate, heart rate recovery and heart rate variability.Methods  Four hundred and forty-seven participants in the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) study were classified according to glycaemic status over the preceding 9 years. All were free of self-reported cardiac antecedents and were not taking drugs which alter heart rate. During five consecutive periods: rest, deep breathing, recovery, rest and lying to standing, heart rate and heart rate varability were evaluated and compared by ANCOVA and trend tests across glycaemic classes. Spearman correlation coefficients quantified the relations between cardio-metabolic risk factors, heart rate and heart rate varability.Results  Heart rate differed between glycaemic groups, except during deep breathing. Between rest and deep-breathing periods, patients with diabetes had a lower increase in heart rate than others (Ptrend < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (Ptrend < 0.009). Heart rate was correlated with capillary glucose and triglycerides during the five test periods. Heart rate variability differed according to glycaemic status, especially during the recovery period. After age, sex and BMI adjustment, heart rate variability was correlated with triglycerides at two test periods. Change in heart rate between recovery and deep breathing was negatively correlated with heart rate variability at rest, (r = −0.113, P < 0.05): lower resting heart rate variability was associated with heart rate acceleration.Conclusions  Heart rate, but not heart rate variability, was associated with glycaemic status and capillary glucose. After deep breathing, heart rate recovery was altered in patients with known diabetes and was associated with reduced heart rate variability. Being overweight was a major correlate of heart rate variability.
    Diabetic Medicine 03/2011; 28(4):440 - 449. · 3.24 Impact Factor
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    ABSTRACT: 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.
    Diabetologia 03/2011; 54(3):554-62. · 6.49 Impact Factor
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    ABSTRACT: To compare incidences and risk factors for diabetes using seven definitions, with combinations of pharmacological treatment, fasting plasma glucose (FPG) ≥7.0 mmol/L, and HbA(1c) ≥6.5%. Participants aged 30-65 years from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort were followed for 9 years. More men had incident diabetes as defined by FPG ≥7.0 mmol/L and/or treatment than by HbA(1c) ≥6.5% and/or treatment: 7.5% (140/1,867) and 5.3% (99/1,874), respectively (P < 0.009); for women incidences were similar: 3.2% (63/1,958) and 3.4% (66/1,954). Known risk factors predicted diabetes for almost all definitions. Among those with incident diabetes by FPG alone versus HbA(1c) alone, there were more men (78 vs. 35%), case patients were 8 years younger, and fewer were alcohol abstainers (12 vs. 35%) (all P < 0.005). A diabetes risk score discriminated well between those with and without incident diabetes for all definitions. In men, FPG definitions yielded more incident cases of diabetes than HbA(1c) definitions, in contrast with women. An FPG-derived risk score remained relevant for HbA(1c)-defined diabetes.
    Diabetes care 02/2011; 34(4):957-9. · 7.74 Impact Factor
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    ABSTRACT: High density lipoprotein-cholesterol (HDL-C) is a strong predictor of cardiovascular risk. We investigated the distribution of HDL-C in a French general population according to age, sex, and the risk factors associated with low HDL-C values. A group of 18,483 men and 22,047 women 16-79 years of age were investigated during a medical check-up. Relevant parameters were studied in three groups according to age and gender-specific percentile classes (≤5th [HDL₅] median and >95th). Gender-specific logistic regression models selected variables associated with HDL₅. Using the National Cholesterol Education Program Adult Treatment Panel III criteria (threshold: 40 mg/dL in men, 50 mg/dL in women) the prevalence of low HDL-C was 11.1% and 26.4% in men and women and it decreased with age. Mean HDL-C levels increased with age. HDL₅ was positively associated with a sedentary lifestyle and deprivation (p < 0.00001) even after adjustment on alcohol consumption and smoking. Abdominal obesity, smoking, hypertriglyceridemia, hyperleucocytosis, and low alcohol consumption were associated with HDL₅ for both genders. The prevalence of low HDL-C was similar to that observed in other Europeans but lower than in the United States. HDL₅ was associated with cardiovascular risk factors, metabolic syndrome, and social deprivation. A prevention policy to increase HDL-C levels should focus on reducing smoking and abdominal obesity, particularly in deprived subjects.
    Annals of epidemiology 02/2011; 21(2):118-27. · 2.95 Impact Factor
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    ABSTRACT: To evaluate the predictive values of hemoglobin A(1c) (HbA(1c)) and fasting plasma glucose (FPG) for retinopathy 10 years after the baseline examination. Seven hundred men and women from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) Study underwent evaluation for retinopathy using a nonmydriatic digital camera. During the preceding 9 years, 235 had diabetes mellitus (treated or FPG level of ≥126 mg/dL at least once), 227 had an impaired FPG level (110-125 mg/dL) at least once, and 238 always had glucose levels within reference limits (<110 mg/dL). Compared with those without retinopathy, the 44 participants with retinopathy at 10 years had higher baseline mean (SD) levels of FPG (130 [49] vs 106 [22] mg/dL) and HbA(1c) (6.4% [1.6%] vs 5.7% [0.7%]) (both, P < .001). The frequency of retinopathy at 10 years, standardized according to the distribution of glycemia across the entire DESIR population, was 3.6%. In our population, FPG levels of 108 and 116 mg/dL had positive predictive values of 8.4% and 14.0%, respectively, for retinopathy at 10 years; HbA(1c) levels of 6.0% and 6.5% had positive predictive values of 6.0% and 14.8%, respectively. After 10 years of follow-up, retinopathy was equally frequent in participants with impaired FPG levels and in those who became diabetic during the study (8.6% and 6.7%, respectively), lower than in those with diabetes at baseline (13.9%). Because the positive predictive values for retinopathy increase sharply from 108 mg/dL for FPG and from 6.0% for HbA(1c) levels, these thresholds are proposed to identify those at risk of retinopathy 10 years later.
    Archives of ophthalmology 02/2011; 129(2):188-95. · 3.86 Impact Factor
  • Nature Genetics 01/2011; 43(4):388. · 35.21 Impact Factor
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    ABSTRACT: Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 x 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery, and follow-up data identified SNPs significantly associated with BP at p < 8.56 x 10(-7) at four further loci (NPR3, FIFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
    American Journal of Human Genetics. 01/2011; 89(6):688-700.
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    ABSTRACT: Systolic and diastolic blood pressure (SBP; DBP) increase with age, but after 45 years of age, the yearly change in DBP (ΔDBP) tends to be smaller in comparison with the yearly change in SBP (ΔSBP), which increases with age. The effect of the metabolic syndrome (MetS) on this yearly change has never been explored. In a 9-year longitudinal cohort Data from an Epidemiologic Study on the Insulin Resistance syndrome (DESIR) study, we examined 1308 men and 1325 women, aged 30–65 years, who had never been treated for hypertension. SBP and DBP were measured at four examinations 3 years apart, and pulse pressure (PP) and yearly changes (ΔSBP, ΔDBP and ΔPP) were calculated. SBP and PP increased with age to a higher degree in patients with the MetS. In men and women with the MetS, DBP remained nearly constant, but in those without the MetS, DBP increased. After adjusting for baseline values, ΔSBP and ΔPP increased by 0.5 mm Hg per year for every additional 10 years from baseline. These correlations with age were similar for men and women, and the yearly change was always higher than in those with the MetS. In contrast, ΔDBP increased very slowly until 50 years of age and then decreased similarly for those with and without the MetS. The increase in PP with age, a marker of vascular aging, was determined to begin earlier in the present study than has been shown in the past, and the MetS amplified this effect. This new aspect of the MetS might modify clinical management leading to earlier drug treatment, particularly in regard to both endothelial dysfunction and increased arterial stiffness.Keywords: aging; arterial stiffening; blood pressure; epidemiology; metabolic syndrome
    Hypertension Research 10/2010; 34(1):91-97. · 2.79 Impact Factor

Publication Stats

5k Citations
1,022.59 Total Impact Points

Institutions

  • 1978–2013
    • Institut inter Régional pour la SAnté
      Tours, Centre, France
  • 2012
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
  • 2011
    • Assistance Publique – Hôpitaux de Paris
      • Department of Ophthalmology
      Paris, Ile-de-France, France
  • 2008–2010
    • Université René Descartes - Paris 5
      • Faculté de Médecine
      Paris, Ile-de-France, France
    • Institut de Biologie de Lille
      Lille, Nord-Pas-de-Calais, France
  • 2004–2010
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1995–2010
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2009
    • McGill University
      Montréal, Quebec, Canada
    • Steno Diabetes Center
      Gjentofte, Capital Region, Denmark
    • Institut de France
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Caen
      Caen, Lower Normandy, France
  • 2008–2009
    • Institut Pasteur de Lille
      Lille, Nord-Pas-de-Calais, France
    • Imperial College London
      Londinium, England, United Kingdom
  • 1995–2009
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2000–2008
    • University of Tours
      Tours, Centre, France
  • 2007
    • Centre Hospitalier Universitaire d'Angers
      • Département de pneumologie
      Angers, Pays de la Loire, France
    • Hôpital Lariboisière - Fernand-Widal (Hôpitaux Universitaires Sant-Louis, Lariboisière, Fernand-Widal)
      Lutetia Parisorum, Île-de-France, France
  • 2006
    • CHU de Lyon - Hôpital Femme-Mère-Enfant
      Lyons, Rhône-Alpes, France
  • 2005
    • Centre Hospitalier Universitaire de Poitiers
      Poitiers, Poitou-Charentes, France
  • 2000–2002
    • Centre Hospitalier Universitaire de Tours
      Tours, Centre, France
  • 2001
    • University of Angers
      Angers, Pays de la Loire, France
  • 1994
    • Centre Hospitalier Universitaire Rouen
      Rouen, Upper Normandy, France
  • 1992
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France