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CIDE Scholars Visits page 2 Trending on Twitter page 3 Etzwiler Scholars pages 3 & 4 WHAT’S NEW IN DIABETES June–July 2016 Select Scholars from CIDE Program Visit IDC and Mayo Clinic International Diabetes Center (IDC) and Mayo Clinic hosted two groups of China Initiative for Diabetes Excellence (CIDE) Scholars June 20–24 and June 27–July 1, 2016. During their week at IDC, each group learned about new diabetes medications, treatments, and technologies. The Scholars also saw the power of team management of diabetes by observing IDC staff working with patients. In addition, Scholars traveled to various community sites to learn more about diabetes management in action. Community activities included traveling to HealthPartners to learn about using electronic medical records for clinical decision support, touring Methodist Hospital and learning about hospital diabetes management, touring the YMCA and learning about the Y’s diabetes prevention program, touring a supermarket and learning about label reading and carbohydrate counting, and touring Melrose Center and learning about eating disorders and diabetes. Scholars also had the opportunity wear a continuous glucose monitor (CGM) for the week. Those who participated watched their glucose numbers change as they ate various meals, exercised, and slept. At the end of the week, Scholars received their own ambulatory glucose profile (AGP) report to review and understand. This activity helped the Scholars empathize with their patients who have diabetes. continued on page 2 The Latest Research On … The Positive Effects of SGLT2 Inhibitors and GLP-1 Agonists on Cardiovascular Outcomes in People with Type 2 Diabetes The American Diabetes Association’s 76th Scientific Sessions was held from June 10 to 14, 2016, in New Orleans, Louisiana. A main theme at this annual conference was recent data from 2 studies1,2 that showed the positive effects of SGLT2 inhibitors and GLP-1 agonists to improve cardiovascular (CV) outcomes and lower CV risk in patients with type 2 diabetes who either had established cardiovascular disease (CVD) or were considered at very high risk for CVD. The EMPA-REG Outcome study examined the effects of the SGLT2 inhibitor empagliflozin, as compared with placebo, on CV morbidity and mortality in people with type 2 diabetes at high risk for CV events. The results showed a clinically significant reduction in myocardial infarction (MI), stroke, and CV mortality: 14% reduction overall, 38% reduction on CV mortality, and 32% reduction in all-cause mortality. The number needed to treat was 39 for 3 years to prevent one CV death. These benefits align with the benefits of other established therapies in diabetes, including statins and ACE Inhibitors. Most notable, protective effects were seen within the first 3 months of taking empagliflozin and continued throughout the duration of the study. How did empagliflozin reduce the risk of CV problems so quickly? Ele Ferrannini, a professor of internal medicine at University of Pisa, Italy, presented his hypothesis at the conference.3 Ferrannini hypothesized that in the EMPA-REG Outcome study, participants who took the SGLT2 inhibitor better avoided a CV event because their body tissues could better withstand ischemia. Why? A side effect of SGLT2 inhibitors is a slightly higher glucagon level, leading to enhanced lipolysis and a rise in free fatty acids, which in turn lead to low-level ketone production. For people with type 2 diabetes at risk for CV disease, perhaps low-level ketone production is beneficial because these ketones can get into many body tissues—including the heart—easily and enter into the energy-producing Krebs cycle. In addition, the diuretic action of SGLT2 inhibitors increases the hematocrit that enhances the potential for oxygen delivery to the heart. The diuresis that accompanies SGLT2 inhibition also results in a modest reduction in blood pressure, which has the potential for cardioprotection. Another major presentation at the conference described the results of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, which analyzed the long-term effects of the GLP-1 agonist liraglutide on CV outcomes and other clinically important events. continued on page 2 The Latest Research On … (continued from page 1) Like the results of the EMPA-REG Outcome study, the results of the LEADER trial showed a significant reduction in CV events: 13% reduction overall and 22% reduction in CV mortality. The number needed to treat was 66 to prevent one CV event. Protective effects were seen within 9 to 12 months of taking liraglutide. Treatment with liraglutide did not increase the risk of pancreatitis or C-cell tumors, conditions that have been associated with liraglutide, as indicated on the package insert. The exact mechanism of liraglutide that produces these cardioprotective effects is currently unknown. The beneficial effects of liraglutide (such as weight loss, lowered blood pressure, improved lipid panel, lowered glucose level without hypoglycemia, and reduced inflammation) may likely underlie the cardioprotection that was demonstrated in the LEADER trial. The diabetes community eagerly awaits the results of other trials that focus on the safety of SGLT2 inhibitors and GLP-1 agonists on CV outcomes. The results will help determine whether these effects are due to the class of medication or whether something inherent in the individual medication caused these effects. The results will also help determine the placement of these medications in glucose lowering algorithms. References 1. B. Zinman, C. Wanner, J. M. Lachin et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. NEJM 2015; 373:2117–28. 2. S. P. Marso, G. H. Daniels, K. Brown-Frandsen et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. NEJM 2016; published online 2016 June 13. 3. E. Ferrannini, M. Mark, E. Mayoux. CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis. Diabetes Care 2016 Jul; 39(7):1108–114. CIDE Group 3 at IDC June 20–June 24, 2016 (with a few IDC faculty and staff) Select Scholars...continued from page 1 At Mayo Clinic, the Scholars toured research units, laboratories, and other Mayo facilities. The groups also observed diabetes patient visits with Mayo medical staff and attended lectures on current diabetes-related topics from Mayo Clinic faculty. These visits culminate the 5-year CIDE program, which involved training 500 endocrinologists in China. It has been IDC’s pleasure to partner with Mayo Clinic faculty to lead this comprehensive, cutting-edge program. We plan to continue to work with these recently trained physicians in China in a new capacity in the near future. The CIDE program was made possible as the result of generous financial support from Sanofi China through an unrestricted educational grant. With Sanofi China’s support and partnership, IDC has been able to further its vision of providing advanced diabetes medical education to improve the lives of people with diabetes throughout the world. See below for photos of the Scholars’ visits. CIDE Group 4 at IDC June 27–July 1, 2016 (with a few IDC faculty and staff) Page 2 IDC hosts week-long program for 2016 Etzwiler Scholars From April 25 through April 29, 2016, IDC hosted a stimulating and exciting program for the Class of 2016 Etzwiler Scholars. The program featured such diverse topics as an update on new therapies, management of kidney disease in diabetes, technology-based research, nutrition around the world, contemporary issues in diabetes management, and new diabetes pumps and patches. We enjoyed hosting the Etzwiler Scholars Class of 2016 at IDC for this challenging and inspiring program! Class of 2016 Etzwiler Scholars at IDC April 25–29, 2016 Back row: Akshay Jain, MD–Canada; Mohammed Hassan Zeitoun, MD, PhD– Egypt; Professor Richard Bergenstal–IDC; Gregg Simonson, PhD–IDC; Andrew Lansdown, MD–United Kingdom; Krishnan Swaminathan, MD–India Front row: Nevena Yankova Chakarova, MD, PhD–Bulgaria; Ines Khochtali, MD– Tunisia; Dina Melnik–IDC; Jane Norstrom–IDC Note: Class of 2016 Etzwiler Scholar Hemant Makan, MD–South Africa will attend Trending on Twitter the Etzwiler Scholars program at IDC in spring 2017. CGM Monitor, HbA1c Assay Set for FDA Advisory Review Israeli company develops insulin pills to treat diabetes Iron intake in women with gestational diabetes and the risk of type 2 diabetes Ideas for newsletter topics? Contact Jane Norstrom or Gregg Simonson Page 3 Meet Two 2016 Etzwiler Scholars Dr. Nevena Chakarova obtained her master’s degree in medicine from Medical University of Sofia, Bulgaria. She started postgraduate studies at the University Hospital of Endocrinology and Gerontology, Medical University of Sofia. The title of her dissertation was “Cardiovascular risk in prediabetic states—impaired fasting glucose and impaired glucose tolerance.” After obtaining her PhD, she continued working as assistant professor and chief assistant professor at Bulgaria’s only specialized department of diabetology at University Hospital of Endocrinology and Gerontology. Since 2010, Dr. Chakarova has specialized in endocrinology. Nevena Chakarova MD, PhD Chief Assistant Professor University Hospital of Endocrinology Medical University of Sofia Sofia, Bulgaria Dr. Chakarova’s clinical work includes management of patients with type 1 diabetes and patients with type 2 diabetes in the hospital setting as well as screening and prevention of individuals at risk for diabetes in the ambulatory setting. As an assistant professor, she trains medical students and participates in university lecture courses and in national scientific conferences. Her main interests are diabetes prevention, management of high-risk individuals, management of cardiovascular risk factors, treatment of type 1 diabetes, and continuous subcutaneous insulin infusion therapy. Dr. Krishnan Swaminathan is a consultant endocrinologist at Kovai Medical Center and Hospital (KMCH), Coimbatore, India. He is also president of the KMCH Research Foundation, a not-for-profit research organization whose aim to improve health care research in India. Krishnan Swaminathan MD Consultant Endocrinologist President of the KMCH Research Foundation Kovai Medical Center and Hospital Coimbatore, India Dr. Swaminathan completed his undergraduate medical education from Madras Medical College, Madras, India, and received specialist training in diabetes and endocrinology from renowned institutions in the United Kingdom, including Guy’s Hospital and St. Thomas’ Hospital, London; Addenbrooke’s Hospital, Cambridge; and Ninewells Hospital, Dundee. He attained Membership of the Royal Colleges of Physicians of the United Kingdom in 1999, was awarded Fellowship of the Royal College of Physicians of Edinburgh in 2009, and completed his research MD degree in diabetes and cardiovascular disease. He has been credited with nearly 50 publications in peer-reviewed international journals. Currently, Dr. Swaminathan is pursuing a PhD from the Indian Institute of Technology–Madras, focusing on environmental endocrine disruptors and diabetes. His other research interests include gestational diabetes, type 1 diabetes, and diabetic complications. Dr. Swaminathan founded aTTiTude, a club for children with type 1 diabetes. He is the founding trustee of Idhayangal, a registered charity that funds various charitable causes, especially those for poor children in India. Page 4