February 2017 Research Update

RESEARCH UPDATE

Update from the Diabetes Obesity Metabolism Institute (DOMI)

Andrew Stewart MD, Director of DOMI

The Diabetes Obesity Metabolism Institute (DOMI)is the principal research arm for diabetes, obesity and metabolism activities at Mount Sinai. It includes a core of 23 research faculty, who collectively garner $8Million annually in research support from the National Institutes of Health (NIH), the Juvenile Diabetes Research Foundation, the American Diabetes Association, and other funding agencies and foundations. Together with the Albert Einstein College of Medicine/Montefiore Health System, DOMI shares one of 16 Diabetes Research Center grants from the NIH. In addition to the 23 primary DOMI faculty members, there are an additional 40-50 affiliated members at Mount Sinai who work in diabetes/obesity related research. Mount Sinai has a long and proud history of diabetes research, from the discovery of the first blood tests to measure insulin which led to the 1977 Nobel Prize, to many new "firsts", some examples of which follow. You can learn much more from our website! 

Type 1 Diabetes (T1D):

• Through Carol Levy MD and David Lam MD, in Endocrinology, we have initiated New York City's largest Artificial Pancreas research program.
•  Peng Wang PhD, Rupangi Vasavada PhD, Nagesha Kondewgowda PhD and Andrew Stewart    MD have discovered the first drugs that are able to induce human beta cells to regenerate.
•  Dirk Homann MD, PhD was recruited to spearhead research program in the autoimmunity that underlies T1D.

Type 2 Diabetes (T2D):

• Daniel Donovan MD and Jeanine Albu MD lead a large and growing portfolio of T2D clinical research programs at Mount Sinai Hospital and the new Diabetes Research Center at Mount Sinai-Saint Lukes.

•  Donald Scott MD, Christoph Buettner MD, PhD, and Adolfo-Garcia-Ocaña PhD

• Derek LeRoith MD and Emily Gallagher MD comprise a leading a center exploring the link between T2D and cancer risk.

Obesity

• We have the largest bariatric surgery program in New York City, based at Mount Sinai Hospital and Mount Sinai St. Luke's.

• We have outstanding research programs in adipocyte (fat cell) metabolism, led by Susan Fried PhD, Kalypso Karastergiou MD PhD and others.

• These are coupled with internationally renowned obesity genomics programs led by Ruth Loos PhD.

Brain Control of Metabolism:

• Led by Drs. Christoph Buettner and Sarah Stanley, and in collaboration with theFriedman Brain Institute at Mount Sinai, we have one of the premier centers in the US. Researchers are showing that the brain controls not only appetite, but also metabolic rate in fat tissue, liver and muscle: the main organs that consume calories and generate heat to balance calorie intake from food. Read -more here about the Buettner lab 

Artificial Pancreas (AP) Program Update

Research continues to proceed in this exciting area! We have competed the initial testing of the Type Zero AP system and have a collaboration with Rensselaer Polytechnic Institute studying a novel new system. We anticipate the Type Zero main study will begin enrolling in the Spring of 2017. The Animas AP system study is planned to open to enrollment late spring as well. Additional studies are being finalized and more will opening over the next few months! For those of you on injections, we have not forgotten about you! Studies are planned for a support system for people on daily injections to manage their diabetes. If you have further questions about any AP studies, please call Selassie Ogyaadu, MD, MPH research coordinator at 212-241-9089.

MSDC welcomes Dr Selassie Ogyaadu

Selassie Ogyaadu, MD, MPH received her MD degree from the University of Ghana Medical School. She then worked in Primary Care and with Sickle Cell Disease for over 6 years. Having an interest in chronic disease epidemiology and a desire to promote health among chronic disease populations, she moved to New York where she obtained a Master’s in Public Health at the Icahn School of Medicine at Mount Sinai. While a student, Dr. Ogyaadu was involved in the ground breaking Type 1 Artificial Pancreas diabetes study with Dr. Carol Levyat the Mount Sinai Diabetes Center (one of only six such centers in the U.S.A.) Dr. Ogyaadu is currently the Clinical Research Coordinator at the Mount SinaiDiabetes Center continuing the important of Artificial Pancreas studies and other notable diabetes research studies.

MSDC Welcomes Ahmad Fakhoury, MS

Ahmad Fakhoury MS, graduated with a Master’s degree in Biotechnology from Columbia University and an undergraduate degree in Biology and Forensic Sciences & Technology from Virginia Commonwealth University. He completed his internship at Columbia’s Irving Cancer Center working on a pre-clinical drug “RUC 4” for treatment of thrombosis. He also worked at Oscar health (for New York State) as a patient care coordinator and gained hands on experience working with patients; he also learned how startup companies function. Ahmad recently joined the Mount Sinai Diabetes Center as a Clinical Research Coordinator where he is assisting with searching for, screening and enrolling research study participants, planning the flow and procedures for various research studies, and reporting all information to his Principal Investigator, Dr. Daniel Donovan. Ahmad is also working Antoinette Bonaccorso CRC, MD, who has made the experience of starting off at a Mount Sinai quite seamless.

An update from the Buettner Lab

The interests and goals of Dr. Christoph Buettner’s laboratory are to study the regulation of metabolism through the central nervous system. Laboratory researchers employ integrated physiology approaches to understand a role of the brain in regulating metabolism throughout the body (orchestrating organ crosstalk such as nutrient flux between adipose tissue and the liver and its relevance in regulating insulin action). It turns out that the brain controls

metabolism and diseases that affect the brain such as Alzheimer’s and other psychiatric diseases, alcohol consumption and stress impair the ability of the brain to control metabolism. In obesity and diabetes, the ability of the brain to process important signals from the periphery such as sensing hormones and nutrients are similarly impaired. The Buettner laboratory tries to understand how the brain achieves this control and how to restore metabolic control by the brain. The group has found that the brain controls inflammation by

controlling lipid metabolism.

A commonly used approach in the Buettner laboratory is to study nutrient partitioning using

metabolic tracers during clamps in rodents that allow the simultaneous assessment of lipid, glucose and amino acid fluxes. These physiological study techniques are complemented by transcriptional, proteomic and metabolomic techniques to arrive at a molecular understanding of how the brain controls nutrient fluxes in peripheral organs such as liver and adipose tissue. The Buettner lab has established that hypothalamic leptin and insulin signaling play important roles in the regulation of adipose tissue lipolysis and lipogenesis. Further, our results obtained to date indicate that hypothalamic insulin and leptin play important roles in regulating hepatic glucose production, VLDL (very low density lipoprotein) secretion, amino acid metabolism and systemic inflammation. In obesity and diabetes, hypothalamic insulin action is impaired, in part through increased endocannabinoid tone in the brain, resulting in dysregulated

nutrient partitioning and a pro-inflammatory state.

Research Highlights from the Diabetes Obesity and Metabolism Institute (DOMI)

• Dr.Andrew Stewart, MD, the Irene and Dr. Arthur M. Fishberg Professor of Medicine and Director of Mount Sinai’s Diabetes, Obesity and Metabolism Institute led a team of scientists who discovered a novel mechanism that regulates the replication of insulin-producing beta cells in the pancreas. Their findings provide novel working models describing the control of cell cycle progression in the human beta cell. These discoveries offer new insights into possible therapeutic approaches to stimulate the regeneration of pancreatic beta cells in patients with type 1 and type 2 diabetes. To find out more about this discovery, click here.

• In a study published in Cell Metabolism, Christoph Buettner, MD, PhD, Associate Professor of Medicine, and Neuroscience and colleagues recently  reported that that impairment in insulin action in the brain may be one of the earliest defects that occurs in obese patients who eventually develop diabetes. To find out more about this discovery, click here.

• In a study published in the Journal of Autoimmunity, Dr. Yaron Tomer (Chief of the Division of Endocrinology, Diabetes and Bone Disease) and colleagues recently reported that epigenetic changes, which are changes in the way genes work when they are not mutated, play a key role in the development of type 1 diabetes. To find out more about this discovery, click here.

Diabetes Clinical Research Corner Update

Mount Sinai is dedicated to diabetes research.  Below are research studies that are currently underway, recruiting, or completed.  If you are interested in becoming a research volunteer reach out to Camilla Levister, NP at 212-241-5177 or our research coordinator at 212 241-9089:

• PERL (Prevention of Early Renal Loss in Diabetes): This is an exciting and landmark National Institutes of Health-sponsored study to explore if a pill that has commonly been used for other conditions can prevent the progression of kidney damage caused by type 1 diabetes.  .   Recruitment ends October 31^st.You can learn more by going to www.perl-study.org

• Artificial Pancreas Program:  If you are interested in participating in future Artificial Pancreas Studies, contact Camilla Levister, NP at 212-241-5177.

• TrialNet, Pathway to Prevention:  This is a study jointly funded by ADA, JDRF, NIDDK and others, being conducted at 18 Clinical Centers in 8 countries and studies those at increased risk for type 1 diabetes.  If you are 1-45 years old and the 1^st degree relative of a person with type 1 diabetes, you may be eligible to participate.  Second degree relatives (cousins, uncles, nieces, nephews, half siblings, or grandparents) of someone with type 1 diabetes between the ages of 1 and 20 years old may also be eligible.  This study is currently recruiting.  Contact our research coordinator for further information at 212 241-9089.

• Victoza (liraglutide) use in type 1 diabetes:  This study explored the efficacy of liraglutide in patients with type 1 diabetes in improving glycemic control, reducing total daily insulin requirements, and body weight loss.  This study is currently completed and we look forward to hearing about the results when the data from all sites is fully analyzed. 

• Faster acting insulin aspart (FIAsp):  This study is currently completed.  FIAsp is a new and faster formation of insulin aspart, a type of rapid acting insulin.  This trial explored the efficacy of FIAsp in diabetes management as measured by hemoglobin A1c and finger stick glucose values after meals.  We look forward to the results of data analysis for this multisite study. 

• Sotogaflozin use in type 1 diabetes: This is a study assessing the benefits of an SGLT 1/SGLT 2 inhibitor as adjunctive therapy in the management of type 1 diabetes; this study will likely be opening mid September 2015. 

Additional studies will soon be starting for type 1 and type 2 diabetes.  Please call 212 241-5177 or 212 241-9089 if you would like to additional information regarding current or  upcoming studies.