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The vast majority of patients with type 2 diabetes (T2DM) are overweight or obese. Overweight is associated with cardiovascular risk factors and an increased risk of cardio- vascular morbidity and mortality in T2DM. Weight loss delays or prevents T2DM in prediabetes, and improves glycemic control, in overt T2DM. Weight loss was also associated with a reduction in cardiovascular risk factors in several observational studies. However, the only randomized trial conducted among overweight or obese patients with T2DM (Look AHEAD) has shown the difliculty in maintaining a significant weight loss in the long term and to demonstrate a beneficial effect of weight loss on cardiovascular morbidity and mortality. Most interventional studies show a reduction of sleep apnea, improved metabolic control, pre- vention of depression, improved quality of life and greater mobility after sustained weight los6 in patients with T2DM. The substantial weight loss obtained by bariatric surgery is associa- ted with a reduction in overall cardiovascular morbidity andmortality in the long term, there- fore this option must be considered early enough in the management of obese T2DMpatients, particularly in those not responding to education and intensive monitoring. Physicians should therefore promote a sustained weight loss in all T2DM patients in order of benefit to the individual beyond the current lack of evidence on the benefits of lifestyle management in terms of cardiovascular morbidity and mortality.

[Therapeutic education and continuous glucose monitoring in insulin-treated diabetic patients]. / Education thérapeutique et mesure continue de la glycémie chez le patient diabétique insulino-traité.

The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system to improve glucose control was investigated in patients with type 1 diabetes (glucose sensor combined with a portable insulin pump--Paradigm Real Time) and in patients with type 2 diabetes poorly controlled despite insulin therapy (Guardian RT one week per month for 3 months compared to blood glucose self-monitoring). Both studies showed a reduction in glycated haemoglobin (HbA1c) levels with the glucose sensor, associated with less symptomatic hypoglycaemic episodes. Despite some technical difficulties (mainly in patients with type 2 diabetes), this approach represents a useful tool for therapeutic education. These promising results justify the initiation of larger studies evaluating glucose sensor use in well selected diabetic patients.

[Pregnancy and overweight: underestimated consequences?]. / La grossesse chez la femme obèse: des conséquences sous-estimées?

As the prevalence of obesity grows in western countries, maternal obesity is becoming an increasingly frequent high-risk obstetrical situation. Obese women have a higher incidence of pregnancy complications (gestational diabetes, hypertension, toxaemia, etc.) and of adverse fetal outcomes (macrosomia, neural tube defects, perinatal mortality). Cesarean section is more frequent in obese women, resulting in a higher risk of anaesthetic and post-operative complications. Maternofetal complications are proportional to the degree of obesity, and even moderate overweight amplifies the risk. Long-term complications include worsening of maternal obesity, maternal type 2 diabetes, and childhood obesity and metabolic disorders. Before conception, these patients should receive tailored weight-loss advice and be screened for obesity complications. Food intake during pregnancy should be tailored to achieve the minimum maternal weight gain required for normal fetal growth. Long-term follow-up is required to prevent worsening of maternal obesity after delivery, and the child's growth curve should be closely watched

[Diabetes and socio-economic deprivation. A study in a large French population]. / Diabète et précarité. Etude d'une vaste population française.

Socio-economically deprived subjects are reported to have an increased risk of diabetes and related complications. The aim of this study was to confirm this relation in a large French population. The study subjects consisted of 32,435 men and 16,378 women aged from 35 to 80 years who had a free health checkup at the IPC Center (Investigations Preventives et Cliniques, Paris-Ile de France) between January 2003 and December 2006. Socio-economic deprivation was evaluated by using the EPICES approach (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé de France). Socio-economically deprived subjects were defined as those with scores in the 5th quintile. The prevalence of diabetes among deprived men and women was respectively 6% and 7% at age 35-59 years, and 18% and 15% at age 60-80 years. The prevalence of diabetes increased with level of deprivation. Compared to the 1st quintile of the EPICES score distribution, diabetes was three to eight times more frequent in the 5th quintile. After taking into account age, the body mass index, waist circumference, and anxiety and depression, the risk that deprived subjects would be diabetic (odds ratio) was respectively 4.2 and 5.2 for men and women aged 35-39 years, and 3.5 and 2.2 for those aged 60-80 years. The following cardiovascular risk markers were significantly higher or more frequent among deprived subjects: body mass, abdominal obesity, high blood pressure and the metabolic syndrome in women; and lower HDL cholesterol, higher triglyceride levels, proteinuria, a higher heart rate and additional ECG abnormalities in both men and women. Other indicators of poor health were also more frequent among deprived subjects, including anxiety and depression, smoking (among men), elevated gamma-GT and alkaline phosphatase levels, lung vital capacity, visual disorders, and dental plaque. Finally, deprived subjects also had more limited access to health care. Thus, socio-economic status markedly influences the risk of diabetes, independently of confounding factors. Several markers of cardiovascular risk and poor health were significantly more frequent among socio-economically deprived subjects, who also had more limited access to health care.

Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.

OBJECTIVE: To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). STUDY DESIGN: Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. RESULTS: Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p < 0.001). CONCLUSION: Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.

[Treatment of insulin-dependent diabetes: new therapy by electromagnetic replacement: towards an artificial pancreas]. / Traitement du diabète insulinodépendant: nouveautés thérapeutiques par suppléance électromécanique: vers le pancréas artificiel endocrine.

The goal of treatment of diabetes mellitus is the achievement of sustained normoglycemia to prevent the complications with the lowest incidence of hypoglycemia. In the same time, it attempts to reduce the hourly and daily constraints due to multiple injections and self monitoring of glycemia. Both intermittent injections and subcutaneous route are inappropriated to extreme precision and flexibility of regulation requested to reach optimal glycemic control and the best quality of life in most diabetic people. The progress in biomaterials and micro-electronics, the availability of stable insulin solutions have permitted to implant a pump with an awaited functional autonomy for 10 years and to perfuse insulin by peritoneal way in a continuous and modulable fashion. The intra-vascular implanted enzymatic glucose sensors, using glucose-oxidase, are able to measure with good accuracy real-time blood glucose for the duration from 6 to 12 months. The combination of these two linked devices implanted in type 1 diabetic patients has given the opportunity to perform the first trials for periods of 48 hours delivering automated insulin according to glycemic variability. This most physiological restoration of insulin function is feasible and appears to represent a possibility for long term treatment of diabetics.

Use of Vildagliptin in Management of Type 2 Diabetes: Effectiveness, Treatment Persistence and Safety from the 2-Year Real-Life VILDA Study.

INTRODUCTION: There is an increasing interest for real-life data on drug use in many countries. Reimbursement authorities more and more request observational studies to assess the conditions of use of the products but also to improve knowledge about efficacy and safety in the real world and on a longer term than in clinical trials. AIM: To evaluate the effectiveness, treatment persistence and tolerability of vildagliptin in clinical practice. METHODS: This observational, 2-year prospective cohort study was conducted in France on request of the Health Authorities [Haute Autorite de Sante (HAS)]. Type 2 diabetic mellitus (T2DM) patients initiating vildagliptin (including the fixed combination vildagliptin-metformin) or treated for <6 months were recruited through a national representative sample of general practitioners (GPs) (n = 482) and diabetologists (n = 84) between March 2010 and December 2011. At inclusion and each follow-up visit at ~ 6, 12, 18 and 24 months, a questionnaire was completed by the physician collecting information on socio-demographic, clinical and biological data, treatments and adverse events. RESULTS: 1,700 patients were included: 60% were males, aged 63 ± 11 years, with diabetes duration 7 ± 6 years and body mass index (BMI) 30 ± 6 kg/m(2). 45% were obese, 70% treated for hypertension and 66% for dyslipidemia. 64% of the patients received vildagliptin in dual therapy with metformin. 82% of patients completed the 2-year follow-up. Glycosylated hemoglobin (HbA1c) decreased from a mean baseline of 7.8 ± 1.2% when vildagliptin was started, to 7.0 ± 1.1% at 6 months and remained stable thereafter over 2 years. Mean weight, glomerular filtration rate, liver enzymes, and lipid parameters were unchanged over the study period. Eight patients (0.5%), all concomitantly treated with insulin and/or sulphonylureas, reported one severe hypoglycemia and 47 (2.9%) patients reported 64 non-severe symptomatic hypoglycemia (59% occurred when patients were treated with insulin and/or sulphonylureas). At 6 months, 44.9% of vildagliptin-treated patients reached an HbA1c <7% without hypoglycemia and no weight gain, and this percentage increased to 49.7% at 24 months. Vildagliptin treatment maintenance at 2 years was 88.8% [95% CI (87.2%; 90.4%)], with 4% of patients discontinuing for adverse events. CONCLUSIONS: In everyday conditions of care, vildagliptin efficacy was in line with existing data from randomized clinical trials, sustained over 2 years, with low discontinuation rate and low hypoglycemia risk.

Role of sclerostin and dickkopf-1 in the dramatic alteration in bone mass acquisition in adolescents and young women with recent anorexia nervosa.

BACKGROUND: The nutritional deprivation of adolescent girls with anorexia nervosa (AN) reduces bone mass acquisition. A better understanding of this process would improve the medical treatment of bone alteration and its long-term consequences. OBJECTIVE: The first aim was to model the bone mass acquisition in young women with AN. The second aim was to identify the clinical and biological factors associated with bone demineralization and investigate the potential role of sclerostin and dickkopf-1 protein (DKK-1). POPULATION AND METHODS: Ninety-eight AN patients (mean age 18.2 ± 2.6 years) and 63 age-matched controls were enrolled in this study. Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry. Calciotropic hormones, bone turnover markers, sclerostin, DKK-1, and growth factors were concomitantly evaluated. RESULTS: The aBMD was significantly reduced at all bone sites in AN patients vs controls (range, -3.3% at the radius to -12.1% for total proximal femur). Bone formation markers IGF-1 and DKK-1 were significantly decreased in AN patients, whereas PTH, sclerostin, and the bone resorption markers were increased. In patients, the AN duration, amenorrhea, weight, body mass index, fat mass, and fat-free soft tissue were negatively correlated with aBMD, whereas the age of AN onset was positively correlated. Multiple regression analysis revealed that the duration of amenorrhea was the independent factor most negatively associated with aBMD at all bone sites except the radius. CONCLUSION: This case-control study demonstrated a dramatic reduction in aBMD, reinforced for the first time by our models, and indicates the need for early, systematic, and adapted bone mass monitoring. Moreover, appropriate treatment should be started early in patients with AN. Increased secretion of sclerostin suggests that it may be a target for pharmacological action.

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

Characteristics of suicide attempts in anorexia and bulimia nervosa: a case-control study.

OBJECTIVE: Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED). METHOD: Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity. RESULTS: AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4-7.9), with a higher expectation of dying (OR = 3.7,95% CI 1.1-13.5), and an increased risk of severity (OR = 3.4,95% CI 1.2-9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt. CONCLUSION: There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients' higher desire to die and their more severe and lethal attempts.

Improvement in quality of life after laparoscopic sleeve gastrectomy.

Few studies have investigated changes in health-related quality of life (HRQOL) in surgical patients who have undergone a laparoscopic sleeve gastrectomy. Prospective data were obtained from 78 consecutive patients undergoing laparoscopic sleeve gastrectomy (LSG; mean age, 42.4 years; mean body weight, 131 kg; mean body mass index (BMI), 47 kg/m(2) (24.4% of superobese patients)). Two HRQOL questionnaires were administered preoperatively and 12 months postsurgery: the generic Medical Outcomes Study Short Form-36 and the weight-specific IWQOL-Lite questionnaire. Excess weight loss at 12 months was 57.18%. No mortality was recorded. HRQOL scores revealed a significant improvement in all areas of both questionnaires. However, changes in HRQOL were not associated consistently with amount of weight loss. Laparoscopic sleeve gastrectomy is an effective and safe procedure, with positive changes in health-related quality of life as well as weight reduction. A fruitful area for future research is the investigation of long-term changes in HRQOL after LSG.

Systems medicine and integrated care to combat chronic noncommunicable diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Is decision making really impaired in eating disorders?

OBJECTIVE: Decision making has been reported to be reduced in eating disorders. However, studies are sparse and have been carried out in various selected populations. In the current study we arranged to confirm previous observations and to assess the relationship between decision making and dimensions relevant to eating disorders. METHOD: Patients suffering from anorexia nervosa (n = 49), bulimia nervosa (n = 38), and healthy controls (n = 83) were assessed using the Iowa Gambling Task (IGT). All patients were euthymic and free of psychotropic medication. Self-questionnaires (Eating Disorder Inventory-2; Gardner, 1991; and Eating Attitude Test; Garner & Garfinkel, 1979) were used to assess clinical dimensions relevant to eating disorders. RESULTS: No significant differences in IGT performance were observed between patients and healthy controls or between restrictive and purging types of anorexia nervosa. No correlations were found between IGT performance and eating disorder questionnaires. CONCLUSION: These results do not support reduced decision making in patients with eating disorders, and suggest that previously reported alterations could be related to other clinical characteristics. This should stimulate new topic-related studies designed to reach a firm conclusion.

[Patients' paths to a designated reference center for severe obesity: the example of the Montpellier Regional Hospital Center]. / Du chemin clinique du patient vers la labellisation d'un centre de référence médicochirurgical pour l'obésité sévère : l'exemple du centre hospitalier régional universitaire (CHRU) de Montpellier.

Bariatric surgery is booming in France and there is increasing interest in developing new surgical techniques. It is essential to manage such surgery in a multidisciplinary fashion: rigorous coordination is required along with adaptability to the local care available. Organization into centers of excellence is encouraged, and good communication between the hospital medicosurgical team and the private practitioners are highly recommended. Multidisciplinary meetings for therapeutic decisions are invaluable because they allow the direct exchange of information between the hospital staff and private practitioners. The selection of one member of the hospital team as liaison for each patient can facilitate the organization of postsurgical follow up Long-term follow-up of these patients is mandatory but often very difficult to maintain beyond one year. Organized coordination between hospital and private practitioners should improve this follow-up.

Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation.

In order to understand the role of the insulin receptor substrate-2 (IRS2) gene (chromosome region: 13q34) in obesity, a complex disorder associated with insulin resistance and glucose intolerance, we determined single nucleotide polymorphims (SNPs) and complex haplotypes in women with morbid obesity and a body mass index (BMI) of 41+/-0.8 kg/m2 ( n=99) compared with controls having a BMI of 23.8+/-0.1 kg/m2 ( n=92). Sequencing of unphased DNA or digestion of polymerase chain reaction fragments revealed seven SNPs, including a new C/T(-769) replacement at the 5' untranslated region. Considering four or seven SNPs, we reconstructed with the PHASE program nine or 24 haplotypes, respectively, that were well correlated into the cladogram. Logistic regression analysis with nine haplotypes in the whole sample revealed that obesity was associated with haplotype H3, with P<0.025, an odds ratio (OR) of 1.9 and a 95% confidence interval (CI) of 1.1-3.4, or pairs 3/3 ( P<0.005, OR=8.7, CI=1.9-40.1) and 3/4 ( P<0.023, OR=2.5, CI=1.1-5.6), all containing the the Gly1057Asp allelic variant of IRS2, whereas controls were associated with H5 and H6 ( P<0.02, OR=0.2, CI=0.01-0.81). Although obese H5 carriers (also containing Gly1057Asp mutation) were the most insulin resistant, haplotypes of IRS2 were poorly correlated (analysis of variance) with insulin resistance. By contrast, haplotypes H3, H4 and pairs 3/3 were consistently associated with increased 2-h glucose levels during an oral glucose tolerance test in obese individuals ( P<0.0005, 0.025 and 0.027, respectively). These data indicate that IRS2 is an influential gene in severe obesity and glucose intolerance in this population, whereas gene-based haplotypes of IRS2 have revealed heterogeneity in the behaviour of the Gly1057Asp mutation in relation to insulin resistance.

Effects of oral monosodium (L)-glutamate on insulin secretion and glucose tolerance in healthy volunteers.

AIMS: To investigate the effects of glutamate on insulin secretion and glucose tolerance in humans. METHODS: Monosodium (L)-glutamate (10 g) was given orally in a double-blind placebo-controlled cross-over study to 18 healthy volunteers, aged 19-28 years, with an oral (75 g) glucose load. RESULTS: The 75 min insulin response (AUC(0,75 min)), up to tmax of glutamate kinetics, was significantly correlated with the AUC(0,75 min) of glutamate concentrations (r=0.485, P=0.049). Glucose tolerance was not affected. CONCLUSIONS: Oral (L)-glutamate enhances glucose-induced insulin secretion in healthy volunteers in a concentration-dependent manner.