Diabetes Meeting Promises Data, Debates, and Controversies

Daniel M. Keller, PhD

September 21, 2012

September 21, 2012 — The European Association for the Study of Diabetes (EASD) 48th Annual Meeting gets underway in Berlin, Germany, next week, and will feature special lectures, new treatment guidelines, controversies, clinical trial results, and basic science topics exploring disease mechanisms, metabolomics, and micro- and macrovascular disease.

To get a preview of what to look for at the conference, Medscape Medical News spoke with the chair of the EASD local organizing committee, Andreas Pfeiffer, MD, chief of the Department of Clinical Nutrition at the German Institute of Human Nutrition Potsdam-Rehbruecke in Nuthetal, and professor of internal medicine and director of the Department of Endocrinology, Diabetes, and Nutrition at Charité Universitaetsmedizin Berlin in Germany.

Dr. Pfeiffer highlighted new treatment guidelines from the American Diabetes Association (ADA) and EASD. He noted that they rely on a more individualized approach to the patient than before, and not as much on a strict glycated hemoglobin (HbA1c) target. The emphasis will be on patient-oriented outcomes, in general stemming from micro- and macrovascular events. "It's stroke, cardiac infarction, blindness, nephropathy, neuropathy, and amputation. These are the outcomes that are the actual treatment targets," he explained, rather than the surrogate HbA1c.

Information on these end points for the newer antidiabetic agents is lacking, but trials are underway. Dr. Pfeiffer noted that results "have been quite disappointing regarding macrovascular events" in previous trials, such as the Action in Diabetes and Vascular Disease (ADVANCE) study, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, and the United Kingdom Prospective Diabetes Study (UKPDS).

The downside of using aggressive treatment to decrease HbA1c is the risk for complications associated with hypoglycemia and hypoglycemia. Patients with "hypoglycemia have higher risks for almost all outcomes, including micro- and macrovascular outcomes," Dr. Pfeiffer explained.

The new recommendations advise adapting treatment to each patient's situation. A patient's history, wishes, and willingness to make lifestyle changes, for instance, are "very much at the center of these recommendations," he noted.

He expects discussion at the meeting about how much effort there should be to normalize glucose and the dangers of hypoglycemia.

Named Lectures

Named lectures will provide expert views on major topics.

Timothy Frayling, MB, BS, from the Peninsula College of Medicine and Dentistry of the Universities of Exeter and Plymouth in the United Kingdom, will deliver the Minkowski Lecture on the interplay between human genetics and type 2 diabetes.

Giuseppe Pugliese, MD, PhD, from "La Sapienza" University of Rome in Italy, will present the Camillo Golgi Lecture on galectin-3 and the receptor for advanced glycation end products (RAGE).

Decio Eizirik, MD, PhD, from Université Libre de Bruxelles in Belgium, will present the Albert Renold Lecture, entitled Beta Cell Apoptosis in Diabetes: A Complex Road to Disaster.

There will be 2 sessions in which experts will debate current issues in diabetes care. One will focus on whether healthcare professionals should pursue a mechanical solution to type 1 diabetes using a closed-loop system or whether immunotherapy is the way to go. The other, the Michael Berger Debate, will focus on the benefits and hazards of early insulin treatment of type 2 diabetes.

Other Topics of Interest

Dr. Pfeiffer pointed out that hundreds of abstracts will be presented on the combination of glucagon-like peptide-1 (GLP-1) agonists and insulin, and that the incretin story has many new aspects. "How long and whom can you treat with incretin [to] predict treatment success and, if you can predict it, who profits from weight loss induced by incretin treatment and who does not? These are open questions that will be discussed," he said.

Another topic of discussion will be the sodium-glucose linked transporter-2 (SGLT-2) inhibitors.

Dr. Pfeiffer predicts a fair bit of discussion about the "very important" topic of cancer and diabetes. It is a debate that has been going on for some time, he said, and "raises a lot of interest."

He expects data to be presented on the metabolic indications for bariatric surgery and its effectiveness in reversing diabetes. He noted that the data from the surgical community appear to be "a little bit optimistic." Nonetheless, it is clearly effective in obese people.

Disappointments and New Directions

Results from the Outcome Reduction With Initial Glargine Intervention (ORIGIN) study, presented earlier this year at the ADA meeting, were disappointing. Neither omega-3 fatty acids nor insulin glargine reduced the rate of death from cardiovascular causes. However, ORIGIN participants were not typical diabetes patients — they were not very insulin resistant, required only low doses of insulin, and were early diabetics — so the study did not give a good picture of what insulin can do. An independent commentator will lead a discussion on this study after the main ORIGIN results and previously unpublished results are presented.

Various trials to try to prevent type 1 diabetes have been disappointing. According to Dr. Pfeiffer, none has been successful, and many have been stopped. "So far, there is very little evidence that you can really prevent type 1 diabetes in people who are antibody-positive or who are at risk or [have an] early manifestation...but we will hear the new ideas and approaches," he said.

On a more positive note, advances have been made in our understanding of the biochemistry of insulin resistance. "The metabolomic field has...identified acylcarnitines as mediators of insulin resistance, as well as certain amino acids that play a role in combination with fat," Dr. Pfeiffer noted. He pointed to evidence that inflammation, and specifically interleukin-1 (IL-1β), plays a role in diabetes. Early-phase trials of next-generation compounds are underway, and dozens of presentations will explore the role and effects of inflammation in diabetes.

As in many areas of medicine, the human microbiome is gaining attention in the diabetes field. Dr. Pfeiffer said the human data are still weak and the human microbiome is still largely unknown. However, efforts at deep sequencing are producing insights into the variety and role of bacteria, and possibly other microorganisms, and the way they influence glucose metabolism. A session will be held on the gut and tissue microbiome in the development of metabolic diseases.

Other topics to look for at the meeting include issues and concerns related to devices, the possible role of enterovirus in type 1 diabetes, and therapeutic applications of stem cells.

Dr. Pfeiffer reports being an advisor to AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, and Lilly.