Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis

The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options

Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction

Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered

The evolving place of incretin-based therapies in type 2 diabetes

Treatment options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were first introduced in 2005. These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In adult medicine, both treatment options are attractive and more commonly used because of their action and safety profile. The incretin-based therapies stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner and carry no intrinsic risk of hypoglycaemia. GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. This review gives an overview of the mechanism of action and the substances and clinical data available

Large-scale climatic phenomena drive fluctuations in macroinvertebrate assemblages in lowland tropical streams, Costa Rica: The importance of ENSO events in determining long-term (15y) patterns

Understanding how environmental variables influence the distribution and density of organisms over relatively long temporal scales is a central question in ecology given increased climatic variability (e.g., precipitation, ENSO events). The primary goal of our study was to evaluate long-term (15y time span) patterns of climate, as well as environmental parameters in two Neotropical streams in lowland Costa Rica, to assess potential effects on aquatic macroinvertebrates. We also examined the relative effects of an 8y whole-stream P-enrichment experiment on macroinvertebrate assemblages against the backdrop of this long-term study. Climate, environmental variables and macroinvertebrate samples were measured monthly for 7y and then quarterly for an additional 8y in each stream. Temporal patterns in climatic and environmental variables showed high variability over time, without clear inter-annual or intra-annual patterns. Macroinvertebrate richness and abundance decreased with increasing discharge and was positively related to the number of days since the last high discharge event. Findings show that fluctuations in stream physicochemistry and macroinvertebrate assemblage structure are ultimately the result of large-scale climatic phenomena, such as ENSO events, while the 8y P-enrichment did not appear to affect macroinvertebrates. Our study demonstrates that Neotropical lowland streams are highly dynamic and not as stable as is commonly presumed, with high intra- and inter-annual variability in environmental parameters that change the structure and composition of freshwater macroinvertebrate assemblages.This study was financed by National Science Foundation (DEB 1122389) to Catherine M. Pringle. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

Is there an association between liraglutide use and female breast cancer in a real-world setting?

Donnie Funch,1 Kathleen Mortimer,1 Ling Li,1 Heather Norman,1 Atheline Major-Pedersen,2 Anne Helene Olsen,3 Margit S Kaltoft,4 David D Dore1,5 1Optum Epidemiology, Boston, MA, USA; 2Global Safety, Novo Nordisk A/S, Copenhagen, Denmark; 3Epidemiology, Novo Nordisk A/S, Copenhagen, Denmark; 4Global Development, Novo Nordisk A/S, Copenhagen, Denmark; 5Department of Health Services, Policy & Practice, Brown University School of Public Health, Providence, RI, USA Background: Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza®) and more recently at 3.0 mg/day for weight management (Saxenda®). During the evaluation of liraglutide for approval in weight management, a minor imbalance in the numbers of reported breast neoplasms was observed, motivating the present study. Our objective was to quantify the association between liraglutide and incidence of breast cancer (BC) among women in a real-world setting. Patients and methods: Women initiating liraglutide or other antidiabetic therapies and who were enrolled in a large US health plan (2010–2014) were included. Comparisons of BC incidence rates were made between matched cohorts of initiators of liraglutide and cohorts of initiators of exenatide, metformin, pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors separately and as two “all comparators” groupings: with or without exenatide. Women with two or more claims with BC diagnosis codes within 61days of each other were identified as possible cases, with additional confirmation by clinician review of comprehensive claims listings. Propensity score matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed via Poisson regression. A latency analysis was performed. Results: Relative risks for BC for liraglutide vs comparators from the ITT analyses ranged from 0.90 (95% CI: 0.67–1.22) for both the “all comparator” and “all comparator except exenatide” cohorts to 1.46 (95% CI: 0.96–2.22) relative to exenatide. Latency analyses excluding the first year of follow-up yielded slightly attenuated point estimates. The TOD analyses of cumulative use of liraglutide suggested no increased risk of BC. Conclusion: Neither the ITT (overall or latency analysis) nor cumulative TOD analyses suggested an elevated risk of BC among liraglutide initiators. Short length of follow-up and the potential for confounding by unmeasured factors limit the full assessment of long-term risk. Keywords: glucagon-like peptide-1 receptor agonist, type 2 diabetes, administrative claims, intention-to-treat, time-on-dru