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.

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.

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.

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.

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.

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 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.

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.

[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.

[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.

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.

[Larger waist circumference is a predictive factor for the occurrence of microalbuminuria in a non-diabetic population]. / Un tour de taille élevé est un facteur prédictif de survenue d'une microalbuminurie dans une population non diabétique.

Obesity and insulin resistance are directly associated with the presence of microalbuminuria. However, the prospective relationship between abdominal adiposity and the occurrence of micro-albuminuria has been little studied in a non-diabetic population. From the DESIR cohort, we examined whether waist circumference was associated with the incidence of micro-albuminuria at 6 years (D6). The study evaluated 2738 non-diabetic subjects without micro-albuminuria at inclusion who were then followed prospectively. At 6 years, 254 individuals (9.3%) had developed pathological micro-albuminuria (> or =20 mg/l) measured at micturation. In both sexes, the incidence of micro-albuminuria was associated with increased waist circumference and blood pressure, but not with blood glucose levels, lipid parameters or body mass index. Subjects with a higher waist circumference at inclusion were at a higher risk of having micro-albuminuria at 6 years compared to those with a normal waist circumference. Logical regression analysis showed that waist circumference as a continuous value, or greater than 94 cm for males and 88 cm for females, were predictive factors for the incidence of micro-albuminuria, after adjustment for age, hypertension, ACE inhibitor usage, fibrinogen, and blood glucose level. Abdominal adiposity is thus linked in both sexes to the development of microalbuminuria, which underlines the importance of measuring waist circumference when assessing risk factors for renal lesions in non-diabetic hypertensives.

Immunogenetic determinants and prediction of IDDM in French schoolchildren.

Islet cell antibodies (ICAs) are predictive markers of the disease in first-degree relatives of patients with insulin-dependent diabetes mellitus (IDDM). The large majority of newly diagnosed cases, however, will develop in children with no family history of diabetes. In France, the risk for development of IDDM up to the age of 20 years is 60 times higher in first-degree relatives than in the general population. The aim of this study was to test whether data collected in the first-degree relatives of IDDM patients could be transferred to children for the prediction of overt diabetes. A large population-based cohort of French school-aged children (n = 13,380; ages 6-17 years) were screened for ICAs, and results were compared with those of 1,185 first-degree relatives of IDDM patients. ICA prevalence rates were significantly different in the two populations (5.5% vs. 1.5%; P < 0.0001), with a significantly higher proportion of high ICA titers in first-degree relatives (37%) than in schoolchildren (14%) (P = 0.0005). ICA titers remained remarkably stable in children over 4 years. Insulin autoantibodies (IAAs) were found in 3.4 and 15.4% of ICA+ children and first-degree relatives, respectively. Susceptibility alleles at the human leukocyte antigen (HLA)-DQB1 locus were observed significantly more frequently in children in whom ICA titers > or = 20 Juvenile Diabetes Foundation units (JDF U) were found on two separate occasions (67%) than in ICA- children (52%) (P = 0.05). Five subjects developed overt diabetes during follow-up. ICA titers of > 20 JDF U were found in all of them on the first sample and at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphisms of the receptor of advanced glycation endproducts (RAGE) and the development of nephropathy in type 1 diabetic patients.

OBJECTIVES: We investigated the association of the RAGE (Receptor for Advanced Glycation End products) exon3 gene polymorphisms with stages of nephropathy in type 1 diabetes. METHODS: The RAGE exon 3 genotype was assessed by Denaturing Gradient Gel Electrophoresis (DGGE) procedure in 487 type 1 diabetic patients with proliferative retinopathy subdivided into four groups according to their level of renal involvement and in 351 control subjects (GENEDIAB study). RESULTS: We reported here three main low frequency dimorphisms, previously submitted to data banks, Gly82Ser, Val89 CTC/CTG, and Arg77Cys. The genotype distribution of these polymorphisms was not statistically different in type 1 diabetic patients compared to healthy controls (p=0.37). Among the three described polymorphisms, only the RAGE Gly82Ser genotype frequency was significantly increased in the group with advanced nephropathy (11%) defined by a chronic renal failure compared to the three others groups: no nephropathy, 5%; incipient (microalbuminuria) 5%; established (macroalbuminuria), 2%) (P=0.04). The 82 Ser allele was identified as an independent risk marker for the stage of advanced nephropathy: adjusted odds ratio 3.17(95% CI 1,32-7,85, p=0.008). CONCLUSION: These data suggest that the 82 Ser allele of the RAGE gene is a risk allele for developing advanced nephropathy. This suggests that some RAGE gene polymorphisms may be associated with progression to diabetic advanced nephropathy in Caucasian type 1 diabetic patients.

Superiority of radiobinding assay over ELISA for detection of IAAs in newly diagnosed type I diabetic children.

OBJECTIVE: Liquid- or solid-phase assays have been used for insulin autoantibody (IAA) determination, and the method of IAA measurement has not been standardized. RESEARCH DESIGN AND METHODS: IAAs were determined by radiobinding assay (RBA) and enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children. RESULTS: Positivity for IAA by RBA (greater than or equal to nondiabetic mean + 3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic children, respectively. Prevalence of IAA by RBA was significantly higher in the youngest age-group (63% between 0-4 yr). Positivity for IAA by ELISA was 1 of 178 (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively. Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5 of 58 (8.6%) in diabetic children. CONCLUSIONS: We conclude that RBA is more appropriate than ELISA for IAA detection at the onset of the disease. In addition, because available data suggest that IAAs detected by RBA only are high-affinity antibodies, it is tempting to speculate that IAAs reflect a mature immune reaction against endogenous insulin.

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

High blood pressure and associated cardiovascular risk factors in France.

OBJECTIVE: To estimate, with respect to age and gender, the prevalence of high blood pressure (BP) in treated and non-treated subjects and its association with other cardiovascular risk factors. DESIGN: A cross-sectional study. SETTING: Healthcare centres in the centre of France. PARTICIPANTS: All subjects (n = 61,108) who had a free health check-up, between February 1995 and September 1996. MAIN OUTCOME MEASURES: High BP (systolic blood pressure (SBP) > 140 mmHg, diastolic blood pressure (DBP) > 90 mmHg or antihypertensive therapy); diabetes (fasting glucose plasma concentration > 1.26 g/l or antidiabetic therapy); hypercholesterolaemia (total cholesterol > 2 g/l or lipid-lowering therapy); hypertriglyceridaemia (fasting triglycerides plasma concentration > 2 g/l or triglyceridaemia-lowering therapy); overweight (body mass index >or= 25 kg/m2); abdominal fat distribution (waist to hip ratio > 0.9 in males and > 0.8 in females). RESULTS: Prevalence of high BP was 37.7% in males and 22.2% in females. BP was normalized in 29.7% of treated males and 44.1% of treated females. High BP was associated with at least another cardiovascular risk factor in 83.8% of the males and 76.7% of the females with high BP. Hypercholesterolaemia was the most frequently associated risk factor. Except smoking, the prevalence of each cardiovascular risk factor was shown to increase with the severity of hypertension. Two or more other cardiovascular risk factors were present in 22.9% of the males and 9.8% of the females with high BP. CONCLUSIONS: Rate of high BP, even in treated subjects, is high. More than three out of four subjects with high BP have at least one other cardiovascular risk factor.

Gene polymorphisms of the renin-angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study. Projet d'Etude des Gènes de l'Hypertension Artérielle Sévère à modérée Essentielle.

OBJECTIVE: To investigate a possible involvement of polymorphisms of the renin-angiotensin system in predisposition to moderate and severe hypertension and their relationship to parental histories of myocardial infarction and stroke. METHODS: Hypertensive cases (453 men, 326 women) were patients followed up by general practitioners for established hypertension. Inclusion criteria were an age of onset of hypertension < or = 60 years and a diastolic blood pressure > or = 105 mmHg without antihypertensive medication or > or = 100 mmHg under treatment. Normotensive controls were selected from population-based samples (362 men) and during a preventative medicine visit (170 women). Polymorphisms of the angiotensinogen gene (AGT M235T and T174M), the angiotensin I converting enzyme gene (ACE I/D), and the angiotensin II type 1 receptor gene (AGT1R A1166C) were investigated. RESULTS: The AGTT235 allele prevalence was higher among male hypertensive cases than it was among controls (0.46 versus 0.40, P = 0.01) and a similar trend was observed with female cases whose hypertension had been diagnosed before they were aged 45 years (0.44 versus 0.38, P = 0.20). The AGT1R C1166 allele prevalence was higher among female hypertensives than it was among controls (0.30 versus 0.23, P = 0.03) but no such difference was observed for men. The AGT T174M and ACE I/D polymorphisms were not associated with hypertension. Hypertensive patients reporting a parental history of myocardial infarction before age 60 years had a higher prevalence of the ACE D allele than did those without such a parental history (0.68 versus 0.56, P = 0.01). The ACE D allele prevalence was also greater among patients reporting a parental history of stroke incidence before age 65 years (0.66 versus 0.57, P = 0.05). CONCLUSIONS: These results support the hypothesis that the AGT gene plays a role in predisposition to hypertension and that the ACE gene plays a role in predisposition to acute ischemic events.