Ambroise Pare Hospital AP HP

Boulogne-Billancourt, France

Ambroise Pare Hospital AP HP

Boulogne-Billancourt, France

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Kengne A.P.,University of Cape Town | Kengne A.P.,University Utrecht | Kengne A.P.,The George Institute for Global Health | Czernichow S.,Ambroise Pare Hospital AP HP | And 4 more authors.
PLoS ONE | Year: 2012

Background: Both anaemia and cardiovascular disease (CVD) are common in people with diabetes. While individually both characteristics are known to raise mortality risk, their combined influence has yet to be quantified. In this pooling project, we examined the combined impact of baseline haemoglobin levels and existing CVD on all-cause and CVD mortality in people with diabetes. We draw comparison of these effects with those apparent in diabetes-free individuals. Methods/Principal Findings: A combined analyses of 7 UK population-based cohorts resulted in 26,480 study members. There were 946 participants with physician-diagnosed diabetes, 2227 with anaemia [haemoglobin<13 g/dl (men) or <12 (women)], 2592 with existing CVD (stroke, ischaemic heart disease), and 21,396 with none of the conditions. Across diabetes and anaemia subgroups, and using diabetes-free, non-anaemic participants as the referent group, the adjusted hazard ratios (HR) were 1.46 (95% CI: 1.30-1.63) for anaemia, 1.67 (1.45-1.92) for diabetes, and 2.10 (1.55-2.85) for diabetes and anaemia combined. Across combined diabetes, anaemia and CVD subgroups, and compared with non-anaemic, diabetes-free and CVD-free participants, HR (95% CI) for all-cause mortality were 1.49 (1.32-1.69) anaemia, 1.60 (1.46-1.76) for existing CVD, and 1.66 (1.39-1.97) for diabetes alone. Equivalents were 2.13 (1.48-3.07) for anaemia and diabetes, 2.68 (2.14-3.36) for diabetes and existing CVD, and 3.25 (1.88-5.62) for the three combined. Patterns were similar for CVD mortality. Conclusions/Significance: Individually, anaemia and CVD confer similar mortality risks in people with diabetes, and are excessively fatal in combination. Screening for anaemia would identify vulnerable diabetic patients whose outcomes can potentially be improved. © 2012 Kengne et al.


Valette M.,French Institute of Health and Medical Research | Bellisle F.,French Institute of Health and Medical Research | Carette C.,Ambroise Pare Hospital AP HP | Carette C.,University of Paris Descartes | And 12 more authors.
International Journal of Obesity | Year: 2013

Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity and an important contributor to polygenic obesity. MC4R mutations with partial or total loss of function, as well as the variant rs17782313 mapped near MC4R, are positively associated with obesity. MC4R is involved in the leptin-melanocortin signalling system, located in hypothalamic nuclei, that controls food intake via both anorexigenic or orexigenic signals. Impairment in this receptor might affect eating behaviours. Thus, in the case of MC4R mutation carriers, obesity could be related, at least partly, to inadequate control over eating behaviours. Many published studies address eating behaviours in MC4R mutation carriers. Most studies focus on binge eating disorder, whereas others examine various aspects of intake and motivation. Up to now, no evaluation of this literature has been performed. In this review, we examine the available literature on eating behaviours in carriers of MC4R mutations and variant rs17782313 near MC4R gene. We address binge eating disorder, bulimia nervosa, mealtime hyperphagia, snacking, psychological factors, satiety responsiveness and intake of energy and macro/micronutrient. In a small number of studies, MC4R mutations seem to impair eating behaviours or motivation, but no clear causal effects can be found in the balance of the evidence presented. Improvements in methodologies will be necessary to clarify the behavioural effects of MC4R mutations. © 2013 Macmillan Publishers Limited.


Costantino F.,University of Paris Descartes | Costantino F.,French Institute of Health and Medical Research | Talpin A.,University of Paris Descartes | Talpin A.,French Institute of Health and Medical Research | And 18 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To estimate the prevalence of spondyloarthritis (SpA) in reference to HLA-B27 in the French population. Methods: In 1989, 20 625 employees of the French national gas and electricity company aged 35-50 years were enrolled in the GAZEL cohort. In 2010, 18 757 still active participants were screened by a questionnaire validated for the detection of SpA. Responders with available DNA were retained for further studies. Pelvic radiograph and HLA-B27 typing were performed in all the self-reported cases of SpA or psoriatic arthritis. Self-reported diagnosis was verified by a qualified rheumatologist. HLA-B27 determination was also performed in subjects without any SpA feature. Results: The target population consisted of 6556 responders with available DNA. Their male:female ratio was 3.6 and their mean age was 65.5±3.3 years. A diagnosis of SpA was confirmed in 32 of the 72 self-reported cases, 75% of them being HLA-B27 positive. Estimated SpA prevalence adjusted for sex was 0.43% (95% CI 0.26% to 0.70%). HLA-B27 positivity rate in 2466 healthy controls was 6.9% (95% CI 5.9% to 7.9%). The relative risk of SpA in HLA-B27 positive individuals was 39 (95% CI 17 to 86). Conclusions: We estimated the prevalence of SpA in the French population in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with HLA-B27 negative subjects. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.


Julia C.,University Pierre and Marie Curie | Julia C.,University of Paris 13 | Julia C.,Avicenne Hospital AP HP | Ciangura C.,University Pierre and Marie Curie | And 8 more authors.
Diabetes and Metabolism | Year: 2013

Aim: Dynamics of improvement in health-related quality of life (QoL) after bariatric surgery have never been fully assessed, and neither has the potential influence of body mass index (BMI) and comorbidity modification. The objective of this study was to investigate early and medium-term changes in QoL following Roux-en-Y gastric bypass (RYGB), and their relationship to BMI and comorbidity variations. Methods: A total of 71 obese subjects (80% women, mean age 42.1±11.2 years, mean baseline BMI 47.6±6.2kg/m2) undergoing RYGB filled in QoL questionnaires (SF-36) before and 3, 6 and 12 months after surgery. QoL was assessed using repeated-measures Anova, with associations between its changes and changes in BMI and comorbidities (diabetes, hypertension, dyslipidaemia, sleep apnoea, knee pain) assessed by mixed-effects models. Results: Physical QoL scales (physical component summary, PCS) significantly increased over time (from 38.9±9.3 to 52.6±7.9; P<0.001) as did other physical SF-36 scales (all P<0.001), whereas mental QoL summary scale did not vary significantly (from 45.7±9.5 to 48.6±11.5; P=0.072). Major changes in QoL occurred at 3 months after surgical intervention to reach values comparable to those in the general population. PCS was mostly associated with changes in either BMI or comorbidity status except for diabetes, dyslipidaemia and sleep apnoea. Conclusion: Results show that improvements in physical QoL after RYGB are observed as early as 3 months after intervention, and are independently associated with weight loss and improvements in comorbidities. © 2013.


Kengne A.P.,University of Cape Town | Kengne A.P.,University Utrecht | Kengne A.P.,George Institute for Global Health | Czernichow S.,Ambroise Pare Hospital AP HP | And 4 more authors.
Diabetes and Vascular Disease Research | Year: 2013

Aims: We assessed the associations of fibrinogen levels with cardiovascular disease (CVD) risks in people with and without diabetes, and quantified the value of adding fibrinogen to the established predictive algorithms for CVD. Methods: We used Cox models to analyse data from prospective cohorts totalling 33,091 adults (1006 with diabetes) who took part in British and Scottish general population-based health surveys. Discrimination was assessed through c-statistic. Results: During a median follow-up of 116 months, 351 deaths (119 CVD) were recorded in participants with diabetes and 4157 deaths (1167 CVD) in those without. After adjustment for age and sex, fibrinogen (per standard deviation loge) was positively associated with a 34% (26-42%) higher risk of cardiovascular disease and 30% (26.35%) greater risk all-cause mortality. These associations were log-linear, similar in people with and without diabetes (p-value for interaction ≥0.21), robust to the adjustment of additional major CVD risk factors. Adding fibrinogen to a model containing conventional CVD risk factors resulted in only modest improvement in risk prediction. Conclusions: The associations of fibrinogen with CVD and all-cause mortality are broadly similar in people with and without diabetes status. Improvement in predictive accuracy after adding fibrinogen to established risk factors is not clinically important. © The Author(s) 2012.


Bretault M.,Ambroise Pare Hospital | Boillot A.,Rothschild | Boillot A.,University Paris Diderot | Muzard L.,Ambroise Pare Hospital | And 19 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Objectives: Craniopharyngiomas are rare low-grade tumors located in the hypothalamic and/or pituitary region. Hypothalamic involvement and treatment resulting in hypothalamic damage are known to lead to development of "hypothalamic obesity" (HyOb) in 50% of cases. The management of HyOb, associated with eating disorders and rapid comorbidities, is an important issue. Bariatric surgery is the most effective therapy for weight loss in patients with severe exogenous obesity. The aim of this systematic review and meta-analysis was to determine the 12-month outcome of bariatric surgery for HyOb due to craniopharyngioma treatment. Methods and Results: Relevant studies were identified by searches of the MEDLINE and EMBASE databases until January 2013. A total of 21 cases were included: 6 with adjustable gastric banding, 8 with sleeve gastrectomy, 6 with Roux-en-Y gastric bypass, and 1 with biliopancreatic diversion. After data pooling, mean weight difference was -20.9 kg after 6 months (95% confidence interval [CI], -35.4, -6.3) and -15.1 kg after 12 months (95% CI, -31.7, +1.4). The maximal mean weight loss was achieved by the gastric bypass group: -31.0 kg (95% CI, -77.5, +15.5) and -3.7 kg (95% CI, -80.7, +13.3) after 6 and 12 months, respectively. Conclusions: In this largest ever published study on the effect of bariatric surgery on obesity after craniopharyngioma treatment, we observed an important weight loss after 1 year of follow-up. Larger studies are warranted to establish appropriate selection criteria and the best surgical technique to perform bariatric surgery. Copyright © 2013 by The Endocrine Society.


Mejean C.,University Utrecht | Droomers M.,University of Amsterdam | Droomers M.,National Institute of Public Health and the Environment RIVM | Van Der Schouw Y.T.,University Utrecht | And 9 more authors.
International Journal of Cardiology | Year: 2013

Background The role of differences in diet on the relationship between socioeconomic factors and cardiovascular diseases remains unclear. We studied the contribution of diet and other lifestyle factors to the explanation of socioeconomic inequalities in cardiovascular diseases. Methods We prospectively examined the incidence of coronary heart disease (CHD) and stroke events amongst 33,106 adults of the EPIC-NL cohort. Education and employment status indicated socioeconomic status. We used Cox proportional models to estimate hazard ratios ((HR (95% confidence intervals)) for the association of socioeconomic factors with CHD and stroke and the contribution of diet and lifestyle. Results During 12 years of follow-up, 1617 cases of CHD and 531 cases of stroke occurred. The risks of CHD and stroke were higher in lowest (HR = 1.98 (1.67;2.35); HR = 1.55 (1.15;2.10)) and lower (HR = 1.50 (1.29;1.75); HR = 1.42 (1.08;1.86)) educated groups than in the highest. Unemployed and retired subjects more often suffered from CHD (HR = 1.37 (1.19;1.58); HR = 1.20 (1.05;1.37), respectively), but not from stroke, than the employed. Diet and lifestyle, mainly smoking and alcohol, explained more than 70% of the educational differences in CHD and stroke and 65% of employment status variation in CHD. Diet explained more than other lifestyle factors of educational and employment status differences in CHD and stroke (36% to 67% vs. 9% to 27%). Conclusion The socioeconomic distribution of diet, smoking and alcohol consumption largely explained the inequalities in CHD and stroke in the Netherlands. These findings need to be considered when developing policies to reduce socioeconomic inequalities in cardiovascular diseases. © 2013 Elsevier Ireland Ltd © 2013 Published by Elsevier Ireland Ltd.


Monnet D.,University of Paris Descartes | Kadi A.,University of Paris Descartes | Izac B.,University of Paris Descartes | Lebrun N.,University of Paris Descartes | And 7 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spondyloarthritis. Particular attention was devoted to genotype-phenotype correlations. Methods Seven single-nucleotide polymorphisms (SNP) and a variable number tandem repeat located in the IL-1 gene cluster were genotyped in 185 independent spondyloarthritis trios. Family-based association test (FBAT) was computed using the FBAT software. Analysis was carried in spondyloarthritis as a whole and also in AS. A case-control replication study was performed for four of the SNP, in an independent sample of 414 spondyloarthritis and 264 controls. A combined analysis of both studies was performed. Results The SNP rs2856836 in IL1A was significantly associated with spondyloarthritis (p=0.009) and AS (p=0.010) in the family study. The case-control study revealed an association between another IL1A variant (rs1894399) and AS (p=0.035), and between IL1F10.3 (rs3811058) and spondyloarthritis (p=0.041). By combining family and case-control studies an association between AS and IL1A was confirmed (rs1894399, p=0.024), whereas non-AS was more significantly associated with IL1F10.3 (p=0.0043). Family-based and case-control studies revealed significant association between the two most frequent haplotypes combining the four SNP of the replication study and both spondyloarthritis (p=0.0054 and p=0.038) and AS phenotypes (p=0.018 and 0.0036). Conclusion This study is the first to demonstrate an association between several polymorphisms located in the IL-1 gene cluster and spondyloarthritis as a whole. The IL1A locus was strongly associated with AS phenotype, whereas IL1F10 was associated with non-AS.


PubMed | French Atomic Energy Commission, University Paris Diderot and Ambroise Pare Hospital AP HP
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2016

Spondyloarthritis (SpA) is a chronic inflammatory disorder with high heritability but with complex genetics. Apart from HLA-B27, most of the underlying genetic components remain to be identified. We conducted a whole-genome high-density non-parametric linkage analysis to identify new genetic factors of susceptibility to SpA.914 subjects including 462 with SpA from 143 multiplex families were genotyped using Affymetrix 250K microarrays. After quality control, 189368 single nucleotide polymorphisms (SNPs) were kept for further analyses. Both non-parametric and parametric linkage analyses were performed using Merlin software. Association was tested with Unphased.Non-parametric linkage analysis identified two regions significantly linked to SpA: the major histocompatibility complex (LODmax=24.77) and a new 13q13 locus (LODmax=5.03). Additionally, eight loci achieved suggestive LOD scores, including the previously identified SPA2 locus at 9q33 (LODmax=3.51). Parametric analysis supported a codominant model in 13q13 with a maximum heterogeneity LOD, HLOD score of 3.084 (=0.28). Identification of meiotic recombination events around the 13q13 linkage peak in affected subjects from the 43 best-linked families allowed us to map the disease interval between 38.753 and 40.040Mb. Family-based association analysis of the SNPs inside this interval in the best-linked families identified a SNP near FREM2 (rs1945502) which reached a p value close to statistical significance (corrected p=0.08).We report here for the first time a significant linkage between 13q13 and SpA. Identification of susceptibility factor inside this chromosomal region through targeted sequencing in linked families is underway.


PubMed | University of Versailles, University of Paris Descartes and Ambroise Pare Hospital AP HP
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2015

To estimate the prevalence of spondyloarthritis (SpA) in reference to HLA-B27 in the French population.In 1989, 20625 employees of the French national gas and electricity company aged 35-50years were enrolled in the GAZEL cohort. In 2010, 18 757 still active participants were screened by a questionnaire validated for the detection of SpA. Responders with available DNA were retained for further studies. Pelvic radiograph and HLA-B27 typing were performed in all the self-reported cases of SpA or psoriatic arthritis. Self-reported diagnosis was verified by a qualified rheumatologist. HLA-B27 determination was also performed in subjects without any SpA feature.The target population consisted of 6556 responders with available DNA. Their male:female ratio was 3.6 and their mean age was 65.53.3years. A diagnosis of SpA was confirmed in 32 of the 72 self-reported cases, 75% of them being HLA-B27 positive. Estimated SpA prevalence adjusted for sex was 0.43% (95% CI 0.26% to 0.70%). HLA-B27 positivity rate in 2466 healthy controls was 6.9% (95% CI 5.9% to 7.9%). The relative risk of SpA in HLA-B27 positive individuals was 39 (95% CI 17 to 86).We estimated the prevalence of SpA in the French population in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with HLA-B27 negative subjects.

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