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Hôpital-Camfrout, France

Verges B.,French Institute of Health and Medical Research | Renard E.,Diabete
Diabetes and Metabolism | Year: 2011

Aim: Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family: in the presence of elevated blood glucose, it stimulates insulin secretion and inhibits glucagon production. In addition, GLP-1 slows gastric emptying. GLP-1 secretion has also been reported to potentially affect patients with type 2 diabetes (T2DM) compared with non-diabetics and, as enzymatic inactivation by dipeptidyl peptidase-4 (DPP-4) shortens the GLP-1 half-life to a few minutes, GLP-1 receptor agonists such as exenatide twice daily (BID) and liraglutide have been developed, and have become part of the management of patients with T2DM. This review focuses on the potential beneficial effects of these compounds beyond those associated with improvements in blood glucose control and weight loss, including changes in the cardiovascular and central nervous systems. Methods: This was a state-of-the-art review of the literature to evaluate the relationships between GLP-1, GLP-1 receptor agonists, weight and the cardiovascular system. Results: GLP-1 receptor agonists improve glucose control and do not significantly increase the risk of hypoglycaemia. Also, this new class of antidiabetic drugs was shown to favour weight loss. Mechanisms may involve central action, direct action by reduction of food intake and probably indirect action through slowing of gastric emptying. The relative importance of each activity remains unclear. Weight loss may improve cardiovascular outcomes in patients with T2DM, although GLP-1 receptor agonists may have other direct and indirect effects on the cardiovascular system. Reductions in myocardial infarct size and improvements in cardiac function have been seen in animal models. Beneficial changes in cardiac function were also demonstrated in patients with myocardial infarcts or heart failure. Indirect effects could involve a reduction in blood pressure and potential effects on oxidation. However, the mechanisms involved in the pleiotropic effects of GLP-1 receptor agonists have yet to be completely elucidated and require further study. Conclusion: These compounds may play an important role in the treatment of patients with T2DM as their potential effects go beyond glucose-lowering (weight loss, potential improvement of cardiovascular risk factors). However, to better understand their place in the management of T2DM, further experimental and clinical prospective studies are required. © 2011 Elsevier Masson SAS. Source

Many observational and meta-analysis studies suggested a decreased risk of cancer in patients treated with metformin. However multiple biases have been related to these studies which are known to increase downward the effect of the drug, thus making metformin seems to be protective when in fact it may have less or no effect. Large randomized studies on diabetes treatment did not confirm any protective effect for metformin. The potential effect of sulfonylureas and glinides on cancer risk and mortality has been suggested in several observational studies mainly showing an increased risk for colorectal and pancreatic cancers. The randomized trials ADOPT and RECORD did not find such an exaggerated risk. Two meta-analysis have given divergent results with regard to cancer risk. The first one showing an increased risk for cancer in users of sulfonylureas with or without insulin compared to non users. The second metaanalysis found no risk when users of sulfonylureas without insulin were compared to others patients. A cohort study in the French National Healthcare Insurance Database between 2003 and 2010 suggested a two-fold risk of cancer in patients more exposed to sulfonylureas. It appears difficult to know whether cancer risk excess is due to sulfonylureas itself or to associated insulin treatment, or yet explained by the lower risk seen in control group treated with metformin. According to the results of observational studies, two meta-analysis found a higher risk for any cancer in insulin users. French National Healthcare Insurance Database likewise suggested a two-fold increased risk of cancer in patients highly exposed to insulin. Main criticism pointed out these studies have potential biases as insulin-treated patients have a diabetes with a longer duration and more severe comorbidities (among them cancer). The initial warning on insulin glargine appeared to be erased whereas it remains necessary to have more long term safety studies. In diabetics with high risk or antecedents for cancer, epidemiological, clinical trials and experimental data converge for first promoting combining and reinforcing therapies against insulin resistance. © 2014 - Elsevier Masson SAS. Source

Maimoun L.,Montpellier University | Maimoun L.,French Institute of Health and Medical Research | Guillaume S.,French Institute of Health and Medical Research | Lefebvre P.,Diabete | And 15 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

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 aimwasto identify the clinical and biological factors associated with boned emineralization 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 agematched 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 a BMD, 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 a BMD at all bone sites except the radius. Conclusion: This case-control study demonstrated a dramatic reduction in a BMD, 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. Copyright © 2014 by the Endocrine Society. Source

Maimoun L.,Montpellier University Hospital Center | Maimoun L.,Montpellier University | Guillaume S.,French Institute of Health and Medical Research | Lefebvre P.,Diabete | And 11 more authors.
Hormone and Metabolic Research | Year: 2015

Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies. © Georg Thieme Verlag KG Stuttgart. New York. Source

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