Diagnosis of gestational diabetes

peer reviewedGestational diabetes (GD) is a common complication of pregnancy. Its prevalence depends on the strategy used for screening and the studied population. Pregnant women with GD are at increased risk for maternal and fetal complications. The relationship between maternal blood sugar and complications is linear, without a clear threshold defining GD. Therefore, the diagnostic criteria for GD have been the subject of several controversies since many years. The choice of the one-step or two-step method, the test to be used and the cut-off levels validated to define GD are still debated. The same is true regarding a universal versus a at-risk population screening. International experts have recently proposed the use of a one-step approach with a 2-hour oral glucose tolerance test for a universal screening. The need for a better harmonization regarding the diagnosis of GD is indeed mandatory. The present article discusses both the advantages and disadvantages of the various approaches used for GD screening.Le diabète gestationnel (DG) est une complication fréquente de la grossesse. Sa prévalence varie fortement selon la stratégie de dépistage utilisée ainsi que la population étudiée. Le DG expose à un haut risque de complications, à la fois sur le plan maternel et foetal. Ces complications sont en relation directe avec l’hyperglycémie maternelle, mais cette relation est linéaire, sans valeur-seuil clairement définie. Cela explique sans doute pourquoi il est difficile d’énoncer des critères indiscutables de diagnostic du DG. De nombreuses controverses existent depuis plusieurs années dans la littérature quant aux méthodes les plus adéquates pour dépister le DG. Les questions sont relatives à l’intérêt d’une méthode en une ou deux étapes, au test à utiliser en priorité, aux valeursseuil à considérer en fonction du test retenu ainsi qu’au choix d’un dépistage universel ou uniquement ciblé sur les femmes à risque. Un groupe d’experts internationaux a proposé récemment un dépistage universel du DG avec la réalisation d’une hyperglycémie provoquée par voie orale de 2 heures. Une harmonisation des approches diagnostiques du DG est, en effet, indispensable. Cette vignette clinique discute les avantages et désavantages des différentes stratégies proposées pour dépister le DG

Long-term glycaemic control with metformin– sulphonylurea–pioglitazone triple therapy in PROactive (PROactive 17)

peer reviewedAims We assessed the long-term glycaemic effects and the safety profile of triple therapy with the addition of pioglitazone vs. placebo in patients with Type 2 diabetes treated with combined metformin–sulphonylurea therapy in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive). Methods In a post-hoc analysis, we identified patients treated with metformin plus sulphonylurea combination therapy and not receiving insulin at baseline (n = 1314). In those patients, we compared the effects of pioglitazone (force-titrated to 45 mg⁄ day, n = 654) vs. placebo (n = 660) on glycated haemoglobin (HbA1c) reduction, concomitant changes in medications and initiation of permanent insulin use (defined as daily insulin use for a period of ‡ 90 days or ongoing use at death ⁄ final visit). Results Significantly greater reductions in HbA1c and greater proportions of patients with HbA1c at target were noted with pioglitazone vs, placebo, despite a decrease in the use of other oral glucose-lowering agents. Therewas an approximate twofold increase in progression to permanent insulin use in the placebo group vs. the pioglitazone group: 31.1 vs. 16.1%, respectively, when added to combination therapy. The overall safety of themetformin–sulphonylurea–pioglitazone triple therapy was good. Conclusions Intensifying an existing dual oral therapy regimen to a triple oral regimen by adding pioglitazone to the classical metformin–sulphonylurea combination resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy. The advantages and disadvantages of adding pioglitazone instead of adding basal insulin should be assessed further

Prevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study

ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age-specific prevalence of MS and its components in the general adult population of Luxembourg, according to the most recent Joint Interim Statement (JIS) definition, by using both the high and low cut-off points to define abdominal obesity, and 2) compare and assess the degree of agreement with the Revised National Cholesterol Education Programme-Adult Treatment Panel III (R-ATPIII) and the International Diabetes Federation (IDF) definitions. METHODS: A representative stratified random sample of 1349 European subjects, aged 18-69 years, participated to ORISCAV-LUX survey. Logistic regression and odds ratios (OR) were used to study MS prevalence with respect to gender and age. The Framingham risk score (FRS) to predict the 10-year coronary heart disease (CHD) risk was calculated to compare the proportion of MS cases below or above 20%, according to both high and low waist circumference (WC) thresholds. Cohen's kappa coefficient (kappa) was utilized to measure the degree of agreement between MS definitions. RESULTS: The prevalence of the MS defined by the JIS was 28.0% and 24.7% when using the low (94/80) and the high (102/88) WC cut-off points, respectively. The prevalence was significantly higher in men than in women (OR = 2.6 and 2.3 for the low and high WC thresholds), as were all components of the MS except abdominal obesity measured by both thresholds. It also increased with age (OR values in age categories ranging from 2.7 to 28 when compared to the younger subjects for low WC and from 3.3 to 31 for the high WC cut-offs). The 10-year predicted risk of CHD by FRS did not depend on the threshold used. Globally, excellent agreement was observed between the three definitions of MS (kappa= 0.89), in particular between JIS and IDF (kappa = 0.93). Agreement was significantly higher in women than in men, and differed between age groups. CONCLUSION: Regardless of the definition used, the adult population of Luxembourg reveals a high MS prevalence. Our findings contribute to build evidence regarding the definitive construct of the MS, to help selecting the waist circumference thresholds for Europid populations, and to support the need to revise the guidelines for abdominal obesity levels

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

The future of obesity: new drugs versus lifestyle interventions.

BACKGROUND: Obesity causes serious medical complications and impairs quality of life. However, its management remains challenging. OBJECTIVE: To assist health professionals who counsel patients who are overweight or obese by discussing the possible add-on value of new drugs over lifestyle interventions. METHODS: A critical analysis is made of the available evidence of the long-term efficacy of diet and exercise and/or anti-obesity agents such as orlistat, sibutramine and rimonabant. RESULTS/CONCLUSION: Lifestyle interventions remain the cornerstone of the treatment of obesity, but adherence is poor and long-term success is modest. Pharmacological agents may be useful adjuncts for improving weight loss and maintenance, and health outcomes, and should be continued in good responders. Drug therapy and lifestyle intervention are not opponent strategies, but should probably be combined to tackle obesity

Do statins have a place for cardiovascular prevention in elderly people?

peer reviewedCardiovascular prevention should only be considered if the treatment reduces the incidence of coronary and cerebrovascular events and death. In elderly people, such treatment should also, and most importantly, help maintain a good quality of life, without increasing the risk of iatrogenic side-effects. These key-elements should be kept in mind when prescription of a statin is envisaged in the old (> 70 years) and especially the very old (> 80 years) individual. Randomised controlled trials in people above 70 years are rather rare. In the field of cardiovascular prevention, two studies provide information, on post-hoc analysis of the Heart Protection Study (HPS) with simvastatin and the PROSPER trial with pravastatin. The protection observed in the general population of HPS was also present in the subgroup of subjects aged above 70, both for coronary and cardiovascular events. The difference was less impressive in PROSPER, without any significant difference as far as the incidence of stroke was concerned. None of these two prospective trials provide specific data on individuals above 80. Interestingly, some experimental and epidemiological observations suggested that statins may prevent Alzheimer disease. However, the data from HPS and PROSPER are not convincing in this respect. Thus, results from new ongoing trials should be awaited, especially in patients with mild to moderate Alzheimer disease. Finally, it is noteworthy that low serum cholesterol level can be used as a marker of poor nutrition in very old people. Such condition is rather common, especially among institutionalised subjects, and is usually associated with a higher risk of morbidity and mortality

Efficacy and safety of Jentadueto(R) (linagliptin plus metformin).

INTRODUCTION: Metformin is the first-choice drug in the management of type 2 diabetes. However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for combined therapy with metformin. Linagliptin shares a similar pharmacodynamic (PD) profile with other gliptins, but has a unique pharmacokinetic (PK) profile characterized by negligible renal excretion. AREAS COVERED: An extensive literature search was performed to analyze the potential PK/PD interactions between linagliptin and metformin. They are not prone to PK drug-drug interactions. The two compounds may be administered together, either separately or using a fixed-dose combination (FDC) as shown by bioequivalence studies. The addition of linagliptin in patients not well controlled with metformin alone has proven its efficacy in improving glucose levels with a good safety profile. Initial co-administration of linagliptin plus metformin improves glucose control more potently than either compound separately, without hypoglycemia, weight gain or increased metformin-related gastrointestinal side effects. EXPERT OPINION: The linagliptin plus metformin combination may offer some advantages over the classical sulfonylurea-metformin combination. Even if linagliptin is safe in patients with renal impairment, the use of metformin (and thus of the linagliptin plus metformin FDC) is still controversial in this population