Transmission of Type 2 diabetes to sons and daughters: the D.E.S.I.R. cohort.

AIMS: To document the family transmission of Type 2 diabetes to men and women. METHOD: The French D.E.S.I.R. cohort followed men and women over 9 years, with 3-yearly testing for incident Type 2 diabetes. First- and/or second-degree family histories of diabetes were available for 2187 men and 2282 women. Age-adjusted hazard ratios were estimated for various family members and groupings of family members, as well as for a genetic diabetes risk score, based on 65 diabetes-associated loci. RESULTS: Over 9 years, 136 men and 63 women had incident Type 2 diabetes. The hazard ratios for diabetes associated with having a first-degree family member with diabetes (parents, siblings, children) differed between men [1.21 (95% CI 0.80, 1.85)] and women [3.02 (95% CI 1.83, 4.99); Pinteraction =0.006]. The genetic risk score was predictive of diabetes in both men and women, with similar hazard ratios 1.10 (95% CI 1.06, 1.15) and 1.08 (95% CI 1.02, 1.14) respectively, for each additional at-risk allele. In women, the risk associated with having a family member with diabetes persisted after adjusting for the genetic score. CONCLUSION: Women with a family history of diabetes (paternal or maternal) were at risk of developing Type 2 diabetes and this risk was independent of a genetic score; in contrast, for men, there was no association. Diabetes screening and prevention may need to more specifically target women with diabetes in their family, but further studies are required as the number of people with diabetes in this study was small.

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population.

AIM: Adiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population. METHODS: Two polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n=5212) and people with T2D in the DIABHYCAR study (n=3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n=230), and in controls who remained normoglycaemic (n=226) throughout. RESULTS: In a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04-1.18; P=0.001) and 0.92 (95% CI: 0.87-0.98; P=0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P=0.03) and HbA1c (P=0.006), and lower plasma adiponectin levels (P=0.03) in the D.E.S.I.R. PARTICIPANTS: Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P=0.03), HbA1c (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA1c, FLI and adiponectin levels persisted after adjusting for BMI. CONCLUSION: CDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.

Evaluating physical activity: the AQAP questionnaire and its interpretation software.

OBJECTIVES: Updating Baecke physical activity questionnaire in French, validating this version named AQAP and developing software for a personalized interpretation of the results. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Influence of blood glucose on heart rate and cardiac autonomic function. The DESIR study.

OBJECTIVES: 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 (P(trend) < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (P(trend) < 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.

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.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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.

Risk factors for incident type 2 diabetes in individuals with a BMI of <27 kg/m2: the role of gamma-glutamyltransferase. Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR).

AIMS/HYPOTHESIS: Risk factors for incident type 2 diabetes, in particular, hepatic markers, have rarely been studied in leaner individuals. We aimed to identify the metabolic and hepatic markers associated with incident diabetes in men and women with a BMI of <27 kg/m(2) and to compare them with those in individuals with a BMI of >or=27 kg/m(2). METHODS: Risk factors for 9 year incident diabetes were compared in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. Comparisons were made between the 2,947 participants with a BMI of <27 kg/m(2) and the 879 with a BMI of >or=27 kg/m(2). RESULTS: There were 92 incident cases of diabetes in individuals with a BMI of <27 kg/m(2) and 111 in those with a BMI of >or=27 kg/m(2). Among those who were not markedly overweight, classical biological markers were associated with 9 year incident diabetes, glycaemia being the strongest predictor. gamma-Glutamyltransferase (GGT), either considered as a continuous variable or at levels >or=20 U/l, was associated with incident diabetes, with a stronger effect in the BMI <27 kg/m(2) group: OR 1.59 (95% CI 1.29-1.97, p < 0.001) in comparison with OR 1.07 (95% CI 0.82-1.38, p = 0.63) for those with a BMI of >or=27 kg/m(2) (results after adjustment for alcohol intake, alanine aminotransferase, waist circumference and the HOMA insulin resistance index). CONCLUSIONS/INTERPRETATION: In individuals with a BMI of <27 kg/m(2), GGT was the strongest predictor of diabetes after fasting hyperglycaemia. This association with incident diabetes remained after adjustment for conventional markers of insulin resistance, suggesting potential interactions between GGT, enhanced hepatic neoglucogenesis and/or early alterations of insulin secretion.

Sex hormone-binding globulin predicts the incidence of hyperglycemia in women: interactions with adiponectin levels.

OBJECTIVE: Previous evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG and adiponectin levels in the development of dysglycemia. DESIGN: We used a nested case-control design in the large prospective study, Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). We studied 227 men and women who were normoglycemic at baseline but hyperglycemic at 3 years (glycemia > or = 6.1 mmol/l or type 2 diabetes). They were matched for sex, age, and body mass index with 227 subjects who remained normoglycemic at 3 years. RESULTS: At baseline, the concentration of SHBG was significantly lower in women who subsequently developed hyperglycemia than in those who remained normoglycemic, with no difference for men. In multiple regression, SHBG at baseline was as an independent determinant of plasma adiponectin levels, in both women (P<0.0001) and men (P=0.002). In multivariate conditional logistic regression taking into account physical activity and changes in waist circumference over the follow-up, plasma SHBG remained significantly associated with the development of hyperglycemia in women but not in men. These associations persisted after adjustment for fasting insulinemia, high fasting glucose, and adiponectin levels. CONCLUSIONS: These findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes.

Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location.

We investigated variations in sensitivity of an immunochemical (I-FOBT) and a guaiac (G-FOBT) faecal occult blood test according to type and location of lesions in an average-risk 50- to 74-year-old population. Screening for colorectal cancer by both non-rehydrated Haemoccult II G-FOBT and Magstream I-FOBT was proposed to a sample of 20 322 subjects. Of the 1615 subjects with at least one positive test, colonoscopy results were available for 1277. A total of 43 invasive cancers and 270 high-risk adenomas were detected. The gain in sensitivity associated with the I-FOBT was calculated using the ratio of sensitivities (RSN) according to type and location of lesions, and amount of bleeding. The gain in sensitivity by using I-FOBT increased from invasive cancers (RSN=1.48 (1.16-4.59)) to high-risk adenomas (RSN=3.32 (2.70-4.07)), and was inversely related to the amount of bleeding. Among cancers, the gain in sensitivity was confined to rectal cancer (RSN=2.09 (1.36-3.20)) and concerned good prognosis cancers, because they involve less bleeding. Among high-risk adenomas, the gain in sensitivity was similar whatever the location. This study suggests that the gain in sensitivity by using an I-FOBT instead of a G-FOBT greatly depends on the location of lesions and the amount of bleeding. Concerning cancer, the gain seems to be confined to rectal cancer.

Prevalence of overweight in 6- to 15-year-old children in central/western France from 1996 to 2006: trends toward stabilization.

OBJECTIVE: The prevalence of overweight in children has markedly increased over the past few decades in France, as in all Western countries. We sought to describe the yearly prevalence of childhood overweight from 1996 to 2006 and to assess whether a shift in trends could be observed dating from the time the Nutrition and Health National Program (PNNS) was set up in France in 2001, in particular according to gender, age and family economic status. DESIGN: We used annual overweight prevalence of standardized 6- to 15-year-old populations (total=26 600) with weight and height measured at health examination centers in the central/western part of France between 1996 and 2006. Regression slopes of overweight prevalence were evaluated between 1996 and 2006, and specifically between 1996 and 2001, and 2001 and 2006. The annual prevalence and estimated slopes were compared in subgroups, taking into account gender, age and economic status of the family. RESULTS: The prevalence increased between 1996 (11.5%) and 1998 (14.8%) and was stable between 1998 and 2006 (15.2%). According to linear regression, the overall trend in prevalence of overweight children between 1996 and 2006 was stable (slope=0.19, P=0.08). Similarly, the prevalence of overweight increased between 1996 and 1998 in boys and girls, in 6-10 year olds, in 11-15 year olds and in non-disadvantaged children, and remained stable thereafter. The prevalence of overweight in the disadvantaged group increased between 1996 (12.8%) and 2001 (18.9%) (slope=1.16, P=0.004) and was stable between 2001 and 2006 (18.2%) (slope=0.09, P=0.78). CONCLUSION: The results of this study reveal a stable prevalence of overweight since 1998 in most groups studied, and since 2001 in the disadvantaged group.

Common genetic variation near MC4R is associated with eating behaviour patterns in European populations.

Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.

Influence of gender and body composition on hydration and body water spaces.

BACKGROUND & AIMS: Hydration disorders are frequent in clinical practice and can be a life threatening issue in frail patients. Mild dehydration (1-2% loss of body weight) appears to impair cognitive and muscular performance. There is, however, no infallible indicator of correct hydration, and of hydration disorders. This study aim at describing total body water (TBW), extra-cellular water (ECW) and intracellular water (ICW) in a cohort of healthy subjects varying in age, gender and body composition. Two indicators of cellular hydration (TBW over fat free mass, and ICW over fat free mass) were studied. METHODS: The study cohort was made of 944 men and 874 women (mean age 42.7+/-13.1 yrs, BMI 24.3+/-3.5 kg/m(2)). All were volunteers for a preventive health examination. TBW, ECW, ICW were measured with bioelectrical impedance analysis. Body composition was assessed with the 3-compartment model. RESULTS: Values for TBW, ECW, and ICW differed with gender and with BMI categories (lean, overweight, and obese). The ratio of TBW over weight decreased with increasing BMI and was lower in women than in men. ECW (as a proportion of TBW) increased with BMI. The ratio of TBW over fat free mass decreased in obese subjects. The ratio of ICW over fat free mass was normally distributed, and decreased with BMI, more so in women than in men. CONCLUSIONS: This study provides reference values for body water spaces in healthy adults that are negatively correlated with BMI. Women and obese people display indicators of cellular dehydration, and are more at risk of dehydration.

Strong association of common variants in the CDKN2A/CDKN2B region with type 2 diabetes in French Europids.

AIMS/HYPOTHESIS: Genome-wide association studies (GWASs) recently identified common variants in the CDKN2A/CDKN2B region on chromosome 9p as being strongly associated with type 2 diabetes. Since these association signals were not picked up by the French-Canadian GWAS, we sought to replicate these findings in the French Europid population and to further characterise the susceptibility variants at this novel locus. METHODS: We genotyped 20 single nucleotide polymorphisms (SNPs) spanning the CDKN2A/CDKN2B locus in our type 2 diabetes case-control cohort. The association between CDKN2A/CDKN2B SNPs and quantitative metabolic traits was also examined in the normoglycaemic participants comprising the control cohort. RESULTS: We report replication of the strong association of rs10811661 with type 2 diabetes found in the GWASs (P= 3.8 X 10(-7); OR 1.43 [95% CI 1.24-1.64]). The other CDKN2A/CDKN2B susceptibility variant, rs564398, did not attain statistical significance (p = 0.053; OR 1.11 [95% CI 1.00-1.24]) in the present study. We also obtained several additional nominal association signals (p < 0.05) at the CDKN2A/CDKN2B locus; however, only the rs3218018 result (p = 0.002) survived Bonferroni correction for multiple testing (adjusted p = 0.04). CONCLUSIONS/INTERPRETATION: Our comprehensive association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant rs10811661 and type 2 diabetes in the French population. Further genetic and functional studies are required to identify the aetiological variants at this locus and determine the cellular and physiological mechanisms by which they act to modulate type 2 diabetes susceptibility.

Prevalence of sarcopenia in the French senior population.

INTRODUCTION: A muscle mass normalized for height2 (MMI) or for body weight (SMI) below 2SD under the mean for a young population defines sarcopenia. This study aimed at setting the cutoffs and the prevalence of sarcopenia in the French elderly population. Another objective was to compare the results obtained with SMI and MMI. METHODS: Muscle mass was assessed by bioelectrical impedance analysis in 782 healthy adults (< 40 years) to determine skeletal mass index (SMI, muscle mass*100/weight) and muscle mass index (MMI, muscle mass/height2). Prevalence was estimated in 888 middle aged (40-59 years) and 218 seniors (60-78 years). All were healthy people. RESULTS: For women mean-2SD were 6.2 kg/m2 (MMI) and 26.6% (SMI); for men limits were 8.6 kg/m2 (MMI) and 34.4% (SMI). In middle aged persons a small number of them were identified as sarcopenic. In healthy seniors, 2.8% of women and 3.6% of men were sarcopenic (MMI). The prevalence was 23.6% in women and 12.5% in men with SMI. MMI and SMI identified different sarcopenic populations, leaner subjects for MMI while fatter subjects for SMI. CONCLUSION: Cutoff values for the French population were defined. Prevalence of sarcopenia was different from that in the US population.

Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids.

AIMS/HYPOTHESIS: In the present study, we sought to examine the evidence that LMNA variants are associated with type 2 diabetes and quantitative metabolic traits in French Europid individuals. METHODS: We genotyped 24 single nucleotide polymorphisms (SNPs) spanning the LMNA gene in 3,093 case-control participants. The association between LMNA SNPs and quantitative metabolic traits was also examined in the 1,674 normoglycaemic adults who made up the control cohort. RESULTS: SNP rs505058, a synonymous SNP (D446D) in exon 7, showed nominal evidence of association with type 2 diabetes [p = 0.003, odds ratio (OR) 1.30 (95% CI 1.09-1.56)] in French Europids. A meta-analysis of available rs505058 genotype data from 7,819 participants provided support for a modest association of rs505058 with type 2 diabetes [p = 0.003, OR 1.19 (95% CI 1.06-1.35)]. We found no evidence (p = 0.91) that the tag SNP rs4641 is associated with type 2 diabetes. However, a meta-analysis of all available rs4641 genotype data in a total of 15,591 participants produced borderline evidence of association [p = 0.054, OR 1.05 (95% CI 1.00-1.11)]. SNP rs6669212, in the 3' untranslated region of LMNA, exhibited suggestive associations with WHR (p = 0.013), fasting serum levels of total cholesterol (p = 0.023) and triacylglycerol (p = 0.015). We emphasise that these quantitative trait associations are not corrected for multiple testing. CONCLUSIONS/INTERPRETATION: The available data do not support a major effect of common LMNA variation on type 2 diabetes susceptibility in northern Europeans. Further large-scale studies are required to conclusively establish the extent to which LMNA variants have an impact on quantitative metabolic traits.

[Ten-year incidence of high blood pressure in the general population: influence of clinical parameters, and implication for screening strategies]. / Incidence à 10 ans de l'HTA dans la population générale: rôle des paramètres démographiques et cliniques, et implication pour la surveillance des normotendus.

BACKGROUND: International guidelines recommend to modulate the periodicity of hypertension screening according to the initial level of blood pressure (BP). The aim of our study was to evaluate other factors that could be useful to optimise the screening for hypertension. METHODS: 9777 normotensive volunteers (4151 men, 5626 women) aged 16 to 68, studied at a 10 year interval during systematic health check ups (standardised questionnaire, clinical examination, biological tests) were included. We determined the 10-year incidence of high BP (systolic BP >or=140 mmHg and/or diastolic BP >or=90 mmHg and/or anti-hypertensive treatment). The role of potential risk factors for hypertension was assessed. RESULTS: The 10 year incidence of high BP was 19.9%. It was associated with the initial level of BP (OR=2.02 and 1.81 per +10 mmHg of systolic and diastolic BP, respectively, p<0.0001). Initial age and BMI were strongly associated with the incidence of a high BP (OR=1.88 / + 10 years and 1.18 / + 1 kg/m2, p<0.0001) after adjustment for the initial systolic BP. In men, a low reported physical activity level, alcohol consumption, and current smoking were independent risk factors (Table1). [table: see text] CONCLUSION: These results suggest that the recommendations for the screening of hypertension should not be based solely on the initial level of BP.

ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study.

AIMS/HYPOTHESIS: We assessed the predictive value of ectonucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1) SNPs with regard to the risk of developing obesity and/or type 2 diabetes in a large French general population. METHODS: We genotyped the ENPP1 SNPs K121Q (rs1044498), IVS20delT-11 (rs1799774) and A/G+1044TGA (rs7754561) in 5,153 middle-aged participants of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. RESULTS: At baseline, the K121Q polymorphism was not associated either with BMI (p = 0.98) or with class I obesity (odds ratio [OR] 0.99, p = 0.81), but showed a borderline association with class II obesity (OR 1.65, p = 0.02). The K121Q variant was not associated with any trait during the 9-year follow-up. Pooled analyses both at baseline and at follow-up failed to show any association with hyperglycaemia (OR 1.08, p = 0.28) or type 2 diabetes (OR 1.15, p = 0.38). However, we did show an association of the Q121 allele with the risk of hyperglycaemia (OR 1.45, p = 0.001; n = 265) and type 2 diabetes (OR 1.65, p = 0.01; n = 103) in participants reporting a family history of type 2 diabetes. These results did not remain significant after a Bonferroni correction. The IVS20delT-11 and A/G+1044TGA polymorphisms and the three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA [QdelTG]) were not associated with any trait, either at baseline or at follow-up. CONCLUSIONS/INTERPRETATION: In a general French population we did not find an association of the QdelTG risk haplotype with adult obesity and type 2 diabetes. We detected nominal evidence of association between the K121Q polymorphism and both severe adult obesity at baseline and the risk of hyperglycaemia or type 2 diabetes in participants with a family history of type 2 diabetes in pooled analyses both at baseline and follow-up.

Prevalence of diabetic retinopathy in children and adolescents with type-1 diabetes attending summer camps in France.

OBJECTIVE: To evaluate, using fundus photography, the prevalence of diabetic retinopathy (DR) in young diabetic subjects attending summer camps run by the Aide aux Jeunes Diabétiques Association (Aid to Young Diabetics). RESEARCH DESIGN AND METHODS: Five hundred and four children and adolescents (250 boys and 254 girls), with type 1 diabetes mellitus, aged 10-18 years (mean:13+/-2), were screened for DR using non mydriatic photography, during their stay in a holiday camp. Demographic and clinical data recorded on subjects' arrival in the camp included date of birth, height, weight, treatment, blood pressure, and duration of diabetes. HbA(1c) was determined with a DCA 2000 kit. RESULTS: Mean diabetes duration was 4.8+/-3.4 years and mean HbA(1c) was 8.5+/-1.3%. Mild non proliferative DR was diagnosed in 23 children (4.6%). Compared to subjects without DR, those with DR were significantly older (P<10(-3)), had a longer duration of diabetes (P=0.001), higher systolic blood pressure (P=0.04), and had higher (but not significantly so) HbA(1c) (P=0.15). After adjustment for age, only longer duration remained significantly associated with DR (P=0.01). CONCLUSION: The prevalence of DR in these young patients was low compared to that reported in previous studies. The decrease may be due to modern diabetes care with multiple insulin injections. However, early detection of DR in adolescents, especially in their late teens, remains important, because it allows the identification of patients at high risk of progression towards severe stages of DR.

Confirmation of associations between ion channel gene SNPs and QTc interval duration in healthy subjects.

Population-based association studies have identified several polymorphic variants in genes encoding ion channel subunits associated with the electrocardiographic heart-rate-corrected QT (QTc) length in healthy populations of Caucasian origin (KCNH2 rs1,805,123 (K897 T) and rs3,815,459, SCN5A rs1,805,126 (D1,819D), 1,141-3 C>A, rs1,805,124 (H558R), and IVS24+116 G>A, KCNQ1 rs757,092, KCNE1 IVS2-128 G>A and rs1,805,127 (G38S), and KCNE2 rs2,234,916 (T8A)). However, few of these results have been replicated in independent populations. We tested the association of SNPs KCNQ1 rs757,092, KCNH2 rs3,815,459, SCN5A IVS24+116 G>A, KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 with QTc length in two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2,008 healthy subjects. All polymorphisms were in Hardy-Weinberg equilibrium in both groups. The minor allele SCN5A IVS24+116 A was more frequent in the group of subjects with the shortest QTc, whereas the minor alleles KCNQ1 rs757,092 G and KCNH2 rs3,815,459 A were more frequent in the group with the longest QTc. There was no significant difference for KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 between the two groups. Haplotype analysis showed a twofold increased risk of QTc lengthening for carriers of the haplotype, combining alleles C and A of the two common KCNE1 SNPs, IVS2-129 C>T (rs2,236,609) and rs1,805,127 (G38S), respectively. In conclusion, our study confirms the reported associations between QTc length and KCNQ1 rs757,092 and KCNH2 rs3,815,459.

[Prevalence of symptoms of sleep apnea syndrome. Study of a French middle-aged population]. / Prévalence des symptômes du syndrome d'apnées du sommeil. Etude dans une population française d'âge moyen.

OBJECTIVE: To study the prevalence of symptoms of sleep apnoea syndrome (SAS) in a large French middle-aged population and to establish what proportion have symptoms that justify further investigation with a sleep study. METHODS: We performed a cross-sectional study of 2,195 men and 2,247 women, 33 to 69 year old (DESIR. cohort) recording responses to a self-administered "sleep" questionnaire and a general questionnaire including socio-economic characteristics and lifestyle factors. RESULTS: The prevalence of symptoms in men and women were respectively: snoring frequently (28%, 14%), frequent daytime sleepiness (14%, 18%) and frequent apnoeas (5%, 2%). Overall, 8.5% of men and 6.3% of women reported a pattern of symptoms suggestive of OSA, as they snored and had daytime sleepiness and/or apnoeas. This pattern was associated, for both sexes, with age, body mass index and after adjustment on these two factors, to a mediocre self-reported health status and treatment with benzodiazepines or other sedatives. For men only, the OSA pattern of symptoms was also associated with, hypertension, alcohol consumption and smoking. CONCLUSION: Snoring, daytime hypersomnolence and witnessed apnoeas are symptoms frequently observed in the general population. Subjects with a combination of these abnormalities suggesting a high probability of sleep apnoea syndrome and in whom a sleep study is warranted represent 7.5% of the adult population.

Five-year predictive factors of type 2 diabetes in men with impaired fasting glucose.

AIM: The outcome of 743 French men (age 20-60) with impaired fasting glucose (IFG) [blood glucose 6.1-6.9 mmol/l] at T1 was evaluated 5 years later, at T2. METHODS: Personal and family medical history, smoking, nutritional habits, physical activity, blood pressure, body mass index (BMI) and waist girth, fasting biological data were collected at T1 and T2. Predictive factors for developing diabetes were compared between those who returned to normal fasting glucose and those who had diabetes, before and after adjustment for age, BMI, glucose and triglyceride (TG) levels. RESULTS: At T2, 44%, 39%, 17% were classified as normal fasting plasma glucose (FPG), IFG or diabetic, respectively. Odd ratios for diabetes were 4.2 for men with a family history of diabetes (FHD), 3.4 if BMI > or = 25 kg/m(2), 2.9 if waist girth > or = 90 cm, 2.8 if TG > or = 2 mmol/l and 1.9 if no daily dairy products were eaten. Still significant after adjustment for age, BMI, glucose and TG levels were: FHD (P=0.001), no daily dairy products (P=0.001), high alcohol intake (P=0.02) and low physical activity (P = 0.02). CONCLUSION: No daily dairy products, high alcohol intake and low physical activity were independent predictive factors of a 5-year onset of diabetes after adjusting for BMI, FHD, triglyceride and glucose levels at baseline. For a better prevention of diabetes, these findings give clues for behaviour modifications as soon as IFG is detected.