Complications Prevention Research Strategy
Despite significant advances in blood sugar (blood glucose) level monitoring and insulin therapy, people with diabetes still spend significant portions of the day with too high levels of blood glucose, placing them at risk for the development of diabetes complications. The landmark Diabetes Control and Complications (DCCT) trial in 1993 and the subsequent Epidemiology of Interventions and complications (EDIC) follow-up study report that less than 50% of patients in the United States are achieving target A1C values. Since the conclusion of the DCCT, longitudinal evaluation of other clinical cohorts has reported increasing adoption of tight glucose control practices and a changed landscape in the rates of progression of diabetic complications. However, maintenance of normal blood glucose levels is currently unattainable with today’s tools. Thus, unfortunately within their lifetime, people with diabetes remain at risk for developing diabetes complications.
JDRF is committed to developing new approaches that will help patients resist and reverse diabetic complications. JDRF is exploring two different general approaches: exploit candidate targets and pathways and identify novel targets and pathways based on understanding the genetic basis of resistance to high glucose-induced complications in humans. Significant research over the last two decades, including JDRF-funded research, has revealed changes in multiple biological pathways triggered by high blood glucose levels related to complications. Certain pathways appear to be pivotal and upstream to subsequent signaling known to promote multiple complications, we believe these candidate targets/pathways would allow intervention at the earliest stages of high blood glucose level-induced cellular damage and lend themselves to drug discovery.
To identify novel targets and pathways based on understanding the genetic basis of resistance to high blood glucose level-induced complications, JDRF will exploit the genetics of individuals with long-standing established type 1 diabetes who have remained free of complications despite poor blood glucose control and high blood glucose levels. The Joslin 50-Year Medalists and similar cohorts are clinical research studies of individuals with long duration of type 1 diabetes (>50 years) and include many individuals who have remained free of diabetic complications. Studies of this unique and valuable population and other groups that have not developed complications after decades of type 1 diabetes, may uncover essential factors that afford protection from the adverse effects of high blood sugar levels that can then be applied to drug discovery and to the development of measurement tools to predict risk or stage the progression of diabetic complications.
Complications Prevention and Treatment Research: Top Priority Areas for Fiscal Year 2013
- Identification and validation of factors conferring resistance and susceptibility to complications.
- Prognostic and predictive biomarkers in diabetic eye and kidney disease.