My EASD 2016 highlights: From Paleolithic diets to the artificial pancreas
The 52nd annual meeting of the European Association for the Study of Diabetes (EASD) brought together clinicians and researchers from around the world to discuss and debate the latest diabetes research, from basic laboratory science through to clinical trials of new medicines and technologies.
On the opening day, Professor Mark Cooper (Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia) presented the Claude Bernard lecture on the pathophysiology of diabetes complications. Diabetic nephropathy was used as an example to show how new understanding of the processes through which hyperglycemia disrupts key cellular function – including advanced glycation end-products, antioxidant defense and hemodynamic changes – may lead to new treatments to prevent the development of complications. He also offered a novel explanation for the “legacy effect,” the long-term benefit after a period of improved glucose control seen in many trials of glucose lowering, by suggesting that epigenetic changes as a result of changes in glucose may result in reprogramming of responses; with long-term consequences that may amplify the adverse effects of even transient hyperglycemia or the benefits of good glucose control.
The optimal diet clinicians should recommend for people with type 2 diabetes remains a controversial topic with studies of the Paleolithic diet, the effects of olive oil and high and low saturated fat diets on liver fat, and the effects of high-protein diets all being discussed. Each has its advocates, advantages and disadvantages, but the clear message that weight loss is usually beneficial and that a balanced diet with plenty of vegetables, legumes, and fruit best seems to represent the dominant view.
When diet and exercise alone are not sufficient to control diabetes, drug treatment is often necessary and we are now seeing much more positive results from the latest treatments. At EASD last year, the EMPA-REG trial was presented and showed that the SGLT2 inhibitor empagliflozin reduced cardiovascular (CV) events in high-risk patients with type 2 diabetes; the most recent data from this trial, reviewed at EASD this year, also showed a reduction in adverse renal outcomes. This year we also heard an update from the results of the LEADER trial with liraglutide, which were presented at the American Diabetes Association meeting in June, confirming that it too can reduce CV events in diabetes. Semaglutide is a novel, weekly GLP-1 receptor agonist in clinical development. Results from several of the SUSTAIN studies showing its good efficacy for glucose lowering were presented; the SUSTAIN-6 study focused on CV outcomes and not only met its primary endpoint of noninferiority, but also showed an overall reduction in myocardial infarction, stroke, and CV death. As with liraglutide there was also a reduction in adverse renal events, but an increase in retinopathy. It was speculated that this might be due to the rapid reduction in glycated hemoglobin (HbA1c) seen during the first few months of the trial, but this is clearly an area to watch. Given the positive results with SGLT2 inhibitors and GLP-1 receptor agonists there is much interest in combining the two classes, and we saw the first of such trials – DURATION 8, with exenatide once weekly plus dapagliflozin, which showed greater HbA1c reduction and weight loss compared with either drug alone in patients with type 2 diabetes. It remains to be seen if this type of combination will provide additive benefit for CV and renal disease.
Finally, in the area of technology there are continual advances in both glucose-sensing technology and in the sophistication of insulin delivery devices that can use data from sensors to adjust doses. Whilst the true artificial pancreas still remains some way off, the development of implantable glucose sensors, the use of remote (tele) monitoring and the gradual improvement of algorithms to help deal with glucose excursions caused by meals and exercise presented at this meeting shows the rapid progress being made in this area. We can expect to see further progress over the next few years as the life sciences, consumer electronics, and software industries are forming partnerships that should accelerate the process of development.