Recent treatment perspectives in lipidology

peer reviewedClinical lipidology has gained its recognition with the publication of numerous clinical trials since the 4S study in 1994. Since that time statins have fully confirmed their promises and play now a crucial role in the battle against cardiovascular diseases. The last decade has been dominated by two demonstrations that apparently are discordant: (1) the lower the cholesterol level with the pharmacological intervention, the lower the risk of cardiovascular complications, arguing for the use of very efficacious cholesterol-lowering therapies; and (2) the cardiovascular protection provided by statins is present whatever the baseline cholesterol level, supporting the concept of pleiotropic effects of statins. As a consequence, statin treatment should be prescribed and intensified according to the high individual cardiovascular risk rather than because of the cholesterol level stricto sensu. Statin therapy should be completed by the addition of ezetimibe when LDL cholesterol level remains above target values or by the addition of fenofibrate when triglyceride levels are high and/or HDL cholesterol level is low. New pharmacological approaches aiming at further improving lipid profile, especially by targeting low HDL cholesterol levels, are currently in clinical development

Therapy of Type 2 Diabetes: Between Insulin Sensitizers and Insulin Secreting Agents

peer reviewedType 2 diabetes is a complex disease characterized by a dual defect of insulin secretion and insulin sensitivity, which may vary from patient to patient, but also along the natural history of the disease in a particular patient. Besides the lifestyle changes, the treatment strategy comprises the administration of agents that promote insulin secretion and/or that improve insulin sensitivity. Drugs facilitating weight loss also improve glucose control by reducing insulin resistance. A global approach should be recommended to reduce the high cardiovascular risk of diabetic patients. The present article aims at summarizing our contribution to the development of drugs designed for the treatment of type 2 diabetes.: Le diabète de type 2 est une maladie bipolaire caractérisée par une combinaison d’un déficit insulinosécrétoire et d’une d’insulinorésistance, en proportion variable selon les patients, et, chez un même sujet, en fonction de la durée d’évolution de la maladie. Outre les mesures hygiéno-diététiques, la stratégie thérapeutique fait appel à la prescription de médicaments insulinosécrétagogues et/ou d’agents insulinosensibilisateurs. Les médicaments favorisant une perte de poids améliorent aussi le contrôle glycémique en diminuant l’insulinorésistance. Une prise en charge globale est privilégiée pour réduire la forte morbi-mortalité cardio-vasculaire associée à cette maladie. Cet article a pour but de résumer la contribution de notre service dans la mise au point et l’évaluation des médicaments développés pour le traitement du diabète de type 2

Bariatric surgery in patients with Type 2 diabetes: benefits, risks, indications and perspectives.

Obesity plays a key role in the pathophysiology of type 2 diabetes (T2DM), and weight loss is a major objective, although difficult to achieve with medical treatments. Bariatric surgery has proven its efficacy in obtaining marked and sustained weight loss, and is also associated with a significant improvement in glucose control and even diabetes remission. Roux-en-Y gastric bypass appears to be more effective in diabetic patients than the restrictive gastroplasty procedure. This may be explained not only by greater weight reduction, but also by specific hormonal changes. Indeed, increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may lead to improved beta-cell function and insulin secretion as well as reduced insulin resistance associated with weight loss. The presence of T2DM in obese individuals is a further argument to propose bariatric surgery, and even more so when diabetes is difficult to manage by medical means and other weight-related complications may occur. Bariatric surgery is associated with a better cardiovascular prognosis and reduced mortality, even though acute and long-term complications are present. The observation that surgical rerouting of nutrients triggers changes in the release of incretin hormones that, in turn, ameliorate the diabetic state in the absence of weight loss has led to the recent development of innovative surgical procedures. Thus, bariatric surgery may be said to be progressing towards so-called 'metabolic surgery', which merits further evaluation in patients with T2DM within a multidisciplinary approach that involves both surgeons and endocrinologists

No evidence for increased mortality in SDHD variant carriers compared with the general population

Germline variants in subunit D of the succinate dehydrogenase gene (SDHD variants) are associated with an increased risk of developing paragangliomas. The aim of this study was to compare mortality rates and survival in a Dutch cohort of SDHD variant carriers with those in the general population. The study was conducted at the Leiden University Medical Center, a tertiary referral center for patients with paragangliomas. Included subjects all tested positive for SDHD variants before 1 July 2012 and visited the departments of Otorhinolaryngology or Endocrinology at least once or had a diagnosed paraganglioma and a SDHD variant-positive family history. Clinical data were retrieved from medical records, information on mortality was obtained from the Municipal Personal Records Database, and mortality rates for the Dutch population were obtained from the Dutch Central Bureau of Statistics, stratified by sex, age and date. SDHD variant carriers were followed from the date of first SDHD variant-related contact until death, emigration or 12 December 2012 and the standardized mortality ratio (SMR) was calculated. Two-hundred and seventy-five SDHD variant carriers were included in the study, of which 80% carried the c.274G>T, p.(Asp92Tyr) variant, had a mean duration of follow-up of 7.6 years, yielding 2242 person-years of observation for analysis. There were 18 deaths in the SDHD variant carrier group; two were paraganglioma related. The SMR for the whole cohort was 1.07 (95% confidence interval 0.67–1.73). In conclusion, mortality in SDHD variant carriers is not substantially increased. Additional studies are required to confirm these findings