Andrew J. Krentz

EMPA-REG OUTCOME: cardiovascular outcome trials in diabetes come of age

Without question, the highlight of the 2015 European Association for the Study of Diabetes conference in Stockholm was the presentation – to a capacity audience – of the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG) OUTCOME trial. This was a highly fitting event for the Association, which celebrated its 50th anniversary last year, the aims of which are innovation and clinical relevance. Moreover, the study is an exceptional example of the clinical relevance of metabolic and cardiovascular interactions in patients with diabetes.

Report of the European Group for the Study of Insulin Resistance annual meeting, Dublin, 4–6th May 2017

The annual meeting of the European Group for the study of Insulin Resistance (EGIR) was held in Dublin, Ireland in May 2017. Ably organized by Dr. Mesud Hatunic, Consultant Endocrinologist at Mater Misericordiae University Hospital, the conference explored the pathophysiology and treatment of insulin resistance and extended a perspective to include aspects of clinical diabetes care including diabetic retinopathy (Dr. David Keegan, Consultant Vitreo-Retinal Surgeon, Mater University Hospital, Dublin, Ireland), monogenic forms of diabetes (Dr. Maria Byrne, Consultant in Endocrinology and Diabetes, Mater Misericordiae Hospital, Dublin, Ireland) and the impact of gastric bypass surgery (Professor Carel le Roux, Co-Director of the Metabolic Medicine Group, University College, Dublin, Ireland). The group actively welcomed the participation of members who have recently joined from the Pasteur Institute in Lille, France, including Dr. Caroline Bonner, who will co-host the Spring 2018 EGIR meeting there with Professor Francois Pattou. New members are always welcome, e-mail: egir@med.unipi.it for details.

Introduction to a special issue : Hypertension in type 2 diabetes

Welcome to this special issue of Cardiovascular Endocrinology focused on hypertension in patients with type 2 diabetes [1]. Both disorders are highly prevalent on a global basis and often cosegregate in individuals. This conjunction elevates the risk of the development and progression of long-term microvascular and macrovascular complications [2]. Hence, we believe that this is a topic worthy of in-depth consideration.

Venus and Mars: influence of sex on diabetes and cardiometabolic disease

The latest estimates for global diabetes prevalence will no doubt concentrate the thoughts of healthcare officials in many countries [1]. Global age-standardized diabetes prevalence increased from 4.3% (95% credible interval 2.4–7.0) in 1980 to 9.0% (7.2–11.1) in 2014 in men, and from 5.0% (2.9–7.9) to 7.9% (6.4–9.7) in women. Thus, over a quarter of a century, the prevalence of diabetes more than doubled in men. The increase seen in women was less pronounced at 60%. These data are consistent with other reports that support a shift from an excess prevalence in women in the earlier part of the 20th century to a consistently higher male prevalence [2,3]. The male predominance in type 2 diabetes has implications for cardiometabolic disease prevention strategies that extend to population screening. For example, in the Rancho Bernardo Study, more women than men had isolated postchallenge (oral glucose tolerance test) hyperglycaemia as the only evidence of diabetes; the incidence of diabetes was higher in men than in women, with higher fasting but lower postchallenge glucose levels compared with women [3]. The prevalence of prediabetes syndromes – that is, impaired fasting glucose and impaired glucose tolerance – also differs by sex, with impaired fasting glucose being more prevalent in men and impaired glucose tolerance being more frequent in women [4].

Hypertension in type 2 diabetes: impact of glucose-lowering medications

Hypertension often co-exists with hyperglycaemia to elevate the risk of vascular disease. The importance of treating hypertension in type 2 diabetes is well appreciated, the benefits of good glycaemic control and effective treatment of hypertension being additive. Treating hyperglyaemia on the one hand and hypertension on the other are usually considered separate strategies of a multifactorial approach to risk reduction requiring specific antihypertensive and glucose-lowering drugs. It is well appreciated that antihypertensive medications can have effects (prodiabetic, neutral, protective against diabetes, according to drug class) on blood glucose levels. Rather less attention has been paid to the effect of glucose-lowering drugs on blood pressure (BP). Positive, neutral and negative effects on BP have been reported for different classes, with some evidence of heterogeneity between individual drugs within certain classes. In this article, the effects of glucose-lowering medication on BP are reviewed. There is a paucity of head-to-head studies of the effects of glucose-lowering medications on BP. Although BP targets in type 2 diabetes continue to be debated, there is a case for more attention to be directed towards the impact of glucose-lowering drugs on BP control.

Thirteenth World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease: selected highlights, Los Angeles, California, USA, 19–21 November 2015

Dr Sanyal described how he and his colleagues have created a multiagency discussion group that brings together the Food and Drug Administration, the European Medicines Agency, and researchers to explore and clarify the regulatory process of drugs for nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) [1]. Dr Sanyal also discussed the farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic NASH (FLINT) trial of obeticholic acid, which used a ‘vanguard’ design and early termination based on interim analyses of efficacy to minimize the need for liver biopsies [1]. A 72-month study on the use of obeticholic acid in NASH is currently in progress. According to Dr Sanyal, obeticholic acid ‘could be the first drug approved for severe NASH’. However, the FLINT trial revealed safety and tolerability issues such as elevations in low-density lipoprotein-cholesterol levels and pruritis, respectively. Of note, the noninvasive FIB4 score predicted therapeutic response in this trial http://www.hepa titisc.uw.edu/page/clinical-calculators/fib-4.

Testosterone, metabolism, and cardiovascular disease

Swedish Pituitary Center, Swedish Neuroscience Institute, Seattle, Washington, Profil Institute for Clinical Research, Chula Vista, California, USA and Foundation for Diabetes Research in Older People, Diabetes Frail, UK Correspondence to Kevin C.J. Yuen, MD, FRCP(UK), Swedish Pituitary Center, Swedish Neuroscience Institute, Seattle, 550 17th Ave Suite 400, Washington 98122, USA Tel: + 1 206 320 4844; fax: + 1 206 32

Conference report: 51st European Association for the Study of Diabetes (EASD) annual meeting 2015

Five decades of progress – and counting This year 1209 abstracts were accepted out of a total of 2067 submitted. The scene for the meeting was set by the President of the European Association for the Study of Diabetes (EASD) Prof. Andrew Boulton (UK), who considered the past, present and future of aspects of diabetes care and research. Prof. Boulton revisited the early days after the formation of the EASD when a primary aim of treating diabetes was to prevent glucosuria ‘at all costs!’ (see EMPA-REGOUTCOME trial below). The audience was reminded of the pre-haemoglobin A1c, pre-insulin pump, pre-self monitoring of blood glucose era – very much within living memory of many practising clinicians – when only three classes of glucose-lowering drugs were available: sulphonylureas, biguanides (of which only metformin has survived and indeed thrived) and insulin (bovine and porcine in various formulations with different – and generally rather suboptimal – pharmacokinetics).

Conference report: European Association for the Study of Diabetes

More than 2200 abstracts were submitted for consideration at the 2014 annual conference; of these, just over 50% were accepted for presentation. Follow-up of previous EASD conferences suggests that this high rejection rate reliably predicts the subsequent publication of full research papers in high-quality diabetes journals. Of necessity, given the wide variety of topics that were covered, this personal report is highly selective.