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La Riche, France

Clark S.J.,Imperial College London | Falchi M.,Imperial College London | Olsson B.,Gothenburg University | Jacobson P.,Gothenburg University | And 18 more authors.
Obesity | Year: 2012

Recent studies have reported associations of sirtuin 1 (SIRT1) single nucleotide polymorphisms (SNPs) to both obesity and BMI. This study was designed to investigate association between SIRT1 SNPs, SIRT1 gene expression and obesity. Case-control analyses were performed using 1,533 obese subjects (896 adults, BMI >40kg/m 2 and 637 children, BMI >97th percentile for age and sex) and 1,237 nonobese controls, all French Caucasians. Two SNPs (in high linkage disequilibrium (LD), r 2 = 0.96) were significantly associated with adult obesity, rs33957861 (P value = 0.003, odds ratio (OR) = 0.75, confidence interval (CI) = 0.61-0.92) and rs11599176 (P value: 0.006, OR = 0.74, CI = 0.61-0.90). Expression of SIRT1 mRNA was measured in BMI-discordant siblings from 154 Swedish families. Transcript expression was significantly correlated to BMI in the lean siblings (r 2 = 0.13, P value = 3.36 × 10 -7) and lower SIRT1 expression was associated with obesity (P value = 1.56 × 10 -35). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 × 10 -4, 6 × 10 -4, 4 × 10 -4, and 2 × 10 -3) with the rare allele associated with a lower BMI. However, no SNP was associated with SIRT1 transcript expression level. In summary, both SNPs and SIRT1 gene expression are associated with severe obesity. © 2011 The Obesity Society.


Skilton M.R.,Baker IDI Heart and Diabetes Institute | Chin-Dusting J.P.F.,Baker IDI Heart and Diabetes Institute | Dart A.M.,Baker IDI Heart and Diabetes Institute | Brazionis L.,University of Melbourne | And 6 more authors.
Atherosclerosis | Year: 2011

Objective: To determine which metabolic and cardiovascular risk factors are associated with the change in ankle brachial pressure index and incident peripheral arterial disease over 9 years, and whether these associations differ between healthy weight and overweight & obese individuals. Methods: Metabolic factors, change in ankle brachial pressure index and incidence of peripheral arterial disease (ankle brachial pressure index <0.90) over 9-years were determined in 2139 healthy weight and 1453 overweight & obese participants from the D.E.S.I.R. study. Results: Fasting glucose, insulin, HDL-cholesterol, systolic blood pressure and pulse pressure were all directly associated with the incidence of peripheral arterial disease, however BMI and the metabolic syndrome were not. There was some evidence that the associations of fasting insulin (Pheterogeneity=0.06), insulin resistance (Pheterogeneity=0.08) and β-cell function (Pheterogeneity=0.004) with change in ankle brachial pressure index, differed between healthy weight and overweight & obese subjects. Principal components analysis identified a classical metabolic syndrome cluster, and an alternative clustering of metabolic factors that was characterised by high pulse pressure, high HDL-cholesterol and low triglycerides. This alternative cluster of cardiovascular and metabolic risk factors was associated with reductions in ankle brachial pressure index and an increased incidence of peripheral arterial disease (both P<0.0001). Conclusions: Overweight & obesity do not increase the risk of developing peripheral arterial disease. We identified an alternative cluster of metabolic factors that is strongly associated with reductions in ankle brachial pressure index and an increased incidence of peripheral arterial disease. © 2011 Elsevier Ireland Ltd.


Reutens A.T.,Baker IDI Heart and Diabetes Institute | Reutens A.T.,Monash University | Bonnet F.,Rennes University Hospital Center | Bonnet F.,French Institute of Health and Medical Research | And 6 more authors.
Nephrology Dialysis Transplantation | Year: 2013

Background. Cystatin C has recently been shown to be associated with incident type 2 diabetes. This study aims to validate this association and to study the impact of baseline adiposity. Methods. We investigated the 3-year diabetes incidence in 2849 participants from the French Data of an Epidemiological Study on the Insulin Resistance syndrome study, without overt kidney disease. Odds ratios (ORs) associated with cystatin C were adjusted for classical diabetes risk factors and interactions between cystatin C and these risk factors were studied. Results. Baseline serum cystatin C was significantly associated with incident diabetes on univariate analysis (OR/1 SD of log cystatin C: 1.74; 95% confidence interval [CI] 1.33-2.28; P = 0.0001) and after adjustment for age and gender (OR 1.55; 95% CI 1.15-2.10; P = 0.0039). This association was independent of serum creatinine-derived measures of baseline renal function and independent of fasting plasma glucose and HbA1c. When body mass index (BMI), waist circumference or baseline insulin resistance index were used as covariates, there was an interaction with cystatin C level. Cystatin C was associated only with incident diabetes for people with BMI, waist circumference or insulin resistance index ≥ median value with OR (95% CIs), respectively: 1.35 (0.98-1.84, P = 0.0625); 1.39 (1.01-1.91, P = 0.0441) and 1.41 (1.02-1.94, P = 0.0398). Conclusions. Cystatin C was associated with 3-year incident diabetes but only in people with central adiposity or insulin resistance. This should be considered in further studies assessing the clinical relevance of its prognostic value. © The Author 2013.


Amar J.,Toulouse University Hospital Center | Lange C.,French Institute of Health and Medical Research | Lange C.,University Paris - Sud | Payros G.,Bio Medical Research Federative Institute of Toulouse | And 13 more authors.
PLoS ONE | Year: 2013

Aim: We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota and incident cardiovascular disease. Methods and Results: D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/μl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35-0.70) whereas Pbac (1.56, 95%CI 1.12-2.15) was directly correlated. Conclusion: Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease. © 2013 Amar et al.


Amar J.,University Paul Sabatier | Serino M.,Bio Medical Research Federative Institute of Toulouse | Serino M.,Toulouse University Hospital Center | Lange C.,French Institute of Health and Medical Research | And 25 more authors.
Diabetologia | Year: 2011

Aims/hypothesis: Evidence suggests that bacterial components in blood could play an early role in events leading to diabetes. To test this hypothesis, we studied the capacity of a broadly specific bacterial marker (16S rDNA) to predict the onset of diabetes and obesity in a general population. Methods: Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) is a longitudinal study with the primary aim of describing the history of the metabolic syndrome. The 16S rDNA concentration was measured in blood at baseline and its relationship with incident diabetes and obesity over 9 years of follow-up was assessed. In addition, in a nested case-control study in which participants later developed diabetes, bacterial phylotypes present in blood were identified by pyrosequencing of the overall 16S rDNA gene content. Results: We analysed 3,280 participants without diabetes or obesity at baseline. The 16S rDNA concentration was higher in those destined to have diabetes. No difference was observed regarding obesity. However, the 16S rDNA concentration was higher in those who had abdominal adiposity at the end of follow-up. The adjusted OR (95% CIs) for incident diabetes and for abdominal adiposity were 1.35 (1.11, 1.60), p=0.002 and 1.18 (1.03, 1.34), p=0.01, respectively. Moreover, pyrosequencing analyses showed that participants destined to have diabetes and the controls shared a core blood microbiota, mostly composed of the Proteobacteria phylum (85-90%). Conclusions/interpretation: 16S rDNA was shown to be an independent marker of the risk of diabetes. These findings are evidence for the concept that tissue bacteria are involved in the onset of diabetes in humans. © 2011 Springer-Verlag.

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