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Mar 18, 2009
The Beta Cell Function Symposium was held on April 15-16, 2009 in Washington DC at the Capital Hilton. - April 15: Dinner/Meeting 6-10 p.m.
- April 16: Meeting 8- 4:30 p.m.
Objectives included: 1) How we assess beta cell function today. 2) What the most appropriate tests might be for a specific application? and 3) What arethe factors that influence beta cell function? For more information: http://guest.cvent.com/EVENTS/Info/Summary.aspx?e=dc82798b-60bd-459b-8e46-a65dabe367e2 This symposium was organized by The Metabolic Disorders Steering Committee of The Biomarkers Consortium. The complete agenda and related presentations are available below. AGENDA Organized by: The Beta Cell Function Working Group under the aegis of the Metabolic Disorders Steering Committee of The Biomarkers Consortium, a public private partnership managed by the Foundation for the NIH. www.biomarkersconsortium.org Executive Summary:It is relatively easy to acutely measure beta cell function. Stimulated or unstimulated insulin, c-peptide, and proinsulin form the core measures that allow us to quantify beta cell function as well as place these responses in the context of relative insulin sensitivity. The challenge is the inability to predict the decay of insulin secretory capacity over longer periods of time. The lack of predictive ability has ramifications for several clinical and drug development scenarios. That is why this meeting is going to focus on addressing the following key questions: 1. Among the current methods of assessing beta cell function in humans, what is considered to be the “gold standard”? a. What are the current methods, and what are the strengths and weaknesses of each method? b. How is normal beta cell function defined with each of the methods? c. What is the intra and inter-person variability of the methods? What are the factors affecting variability? d. What methods are in development that may become available during the next 5 to 10 years? 2. In patients with type 2 diabetes mellitus, what methods and parameters are predictive of longer-term change in insulin secretory function? This is critical for estimating how long a patient may be able to be managed on this new therapy versus requiring additional glucose-lowering therapies. 3. In patients with impaired glucose tolerance, what method and factors will predict the decline in insulin secretion that will catapult the patient’s classification from IGT type 2 diabetes mellitus? This has relevance to the design and success of diabetes prevention programs. 4. How soon can changes in these measures be reliably detected? Is it possible to do so within 3-6 months of the therapy (or shorter)? 5. What evidence would be needed to definitively demonstrate a beneficial effect on beta cell function (beyond glycemic control)?
Besides the established methods for assessment of beta cell function, are there any emerging circulating beta-cells markers that may predict long term sustained beta-cell function? 6. Deciphering these problems has important implications for the development of new therapies. If a long and large study is required to address these questions, then sponsors will be less likely to pursue them in this context. The objectives of this meeting are to review: a) how we assess beta cell function today, b) what the most appropriate tests might be for a specific application (clinical, regulatory, etc.), and c) the factors that influence beta cell function. As an outcome of the meeting, we hope to identify the steps necessary to address the above and any other important issues. Day I 6:00 pm Dinner 6:30 pm Welcome and introductions (5 min.) – Dr. Vassileva, MDSC Scientific Program Manager 6:35 pm The Biomarkers Consortium Overview and the Key Questions To Be Addressed (25 min.) - Dr. Staten, NIDDK/NIH, MDSC Co-chair and Dr. Carlsson, Astra Zeneca, MDSC Co-chair 7:00 pm The challenges in the BCF field and implications for industry (40 min) – Niels Porksen, Lilly and David Kelley, Merck. 7:40 pm A historical perspective: the developments within the field of beta cell mass and function that span the last 20 years (25 min.) - Dr. Gordon Weir, Joslin Diabetes Center, Harvard Medical School 8:05 pm - The present state of the art in measuring beta cell function: comparison of current methods, definition of the gold standard and remaining gaps - IV Challenge (30 min.) - Dr. Adrian Vella, Mayo Clinic - Oral Challenge (30 min.) - Dr. Jerry P. Palmer, VA Puget Sound Health Care System 9:05 pm Heterogeneity in functional beta cell mass (25 min) – Dr. Danny Pipeleers, Diabetes Research Center, Brussels Free University (VUB), Belgium 9:30 pm Beta cell mass: what do we know about its relationship to secretion, an overview of islet transplantation (25 min) – Dr. Paul Robertson, Pacific Northwest Diabetes Research Institute 9:55 pm Adjourn Day II 8:00 am Breakfast 8:30 am Summary of Day I and the overall goals of the meeting (10 min.) - Dr. Jarema Kochan, Roche, Beta Cell Function Working Group Chair 8:40am Review of animal data correlating function and mass: what data, if any, are there showing the magnitude of difference in islet mass that can be discerned by measuring beta cell function? (25 min) – Dr. Jack Leahy, University of Vermont 9:05 am What are the effects of other organs, tissues and systems (e.g. liver, gut, CNS) on beta cells? (25 min) – Dr. Rohit Kulkarni, Joslin Diabetes Center, Harvard Medical School 9: 30 am Imaging: what does it bring in addition to the functional measurements and what would it take to bring the technology to use in humans – a general overview of the field? (25 min) – Dr. Anna Moore, Harvard Medical School 9:55 am The role of genetics (25 min) – Dr. Mark McCarthy, Oxford University, England 10:20 am Can proteomics or metabolomics be used as key tools? Are there additional technologies that should be considered? (25 min) – Dr. Christopher Newgard, Duke University 10:45am Coffee Break (10 minutes) 10:55 am Minimal Model of Assessment of Beta Cell Function from IV and Oral Tests (30 min) – Dr. Claudio Cobelli, University of Padova, Italy 11:25 am Testing individuals with different stages of the disease: effects of rising glucose levels on differences in insulin secretion. (25 min) – Dr. Adrian Vella, Mayo Clinic 11:50 am Are there individual differences and effects on the burst of insulin secretion on liver metabolism? (25 min) – Dr. Alexey Matveyenko, UCLA 12:15 pm The role of gut peptides (GLP-1, GIP, PYY, others) on beta cells (20 min.) – Dr. Allison Goldfine, Joslin Diabetes Center, Harvard Medical School 12:35 pm Lunch 1:05 pm Areas of overlapping interest with IMI (25 min) – Dr. Alan Edgar, Roche 1:30 pm Potential new paths: where we want to go next (a panel discussion) The consortium goals and perspective will be initially restated by Dr. Jarema Kochan, Roche, MDSC member and chair of the Beta Cell Function Working Group. The panel will have representatives from academia (Dr. Ian Sweet, University of Washington), government (Dr. Ilan Irony, CDER/FDA, Dr. Bruce Schneider and Dr. Malcolm Moos, CBER/FDA and Dr. David Harlan, NIDDK/NIH), nonprofit organizations (Dr. Robert Goldstein, JDRF) and industry (Dr. David Moller, Lilly). Dr. Staten from NIDDK/NIH to moderate the discussion.One of the issues to be discussed is the need for a database (what should be included in it, how the information should be structured, what the database would be used for and the funding needs to develop, launch and maintain it). 3:30 pm Summary of the discussions of Day 1 and Day 2: Perspectives (Drs. Cobelli, Goldfine, Robertson and Vella) 4:10 pm Break (attendees of the open session will leave at this time) 4:30 pm Generating a consensus statement (closed session) – David Kelley, moderator - drafting an outline (30 min) - selecting the action items and deadlines, listing the key people to continue being involved (20 min) - listing which professional societies should be asked to endorse the consensus statement once prepared (5 min) 5:25 pm Closing remarks and next steps (Drs. Staten and Carlsson) 5:30 pm Adjourn |
