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Mechanistic and Pre-Clinical Studies of Diabetic Cardiovascular Complications
The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) of investigators on June 7-8, 2006, in Bethesda, Maryland, on new research directions needed to understand diabetic cardiovascular complications. The WG met to (1) identify specific areas in which insight about the cardiovascular complications of diabetes is lacking, and (2) delineate the most fruitful areas for basic, pre-clinical, and clinical research. Particular attention was paid to the current status and use of pre-clinical animal models of diabetic complications.
The clinical course of type 2 diabetes mellitus (T2DM) is marked by accelerated atherosclerosis and its subsequent complications. The impact of T2DM is manifest not only in coronary disease but also in cerebrovascular and peripheral vascular disease. Factors underlying these problems clearly involve hyperglycemia but also derive from hypertension and blood disorders, including abnormalities of leukocytes, red blood cells, the coagulation system, and the interactions of all of these elements with the arterial wall. Diabetes also has direct effects on the heart, altering the structure and function of the myocardium. The interplay between diabetes and cardiovascular disease is further complicated by the fact that both hyperglycemia (at levels diagnostic of diabetes) and diabetic atherosclerotic complications are relatively late-stage events in the natural history of these pathologies. The tightly intertwined nature of T2DM and all these cardiovascular complications is especially concerning given the epidemic of obesity and diabetes evident in America and among an increasingly younger population. Members of the WG agreed that the greatest opportunities for altering the natural history of diabetes and its cardiovascular complications likely rests in the earlier stages of these pathologic processes, including investigating mechanisms involved in the development of diabetes. Studies focusing on non-glycemic factors and pathways that predict and/or promote diabetes may have particular yield.
Diabetic macrovascular complications result from dysfunctions in many physiologic processes (e.g., lipid metabolism, glucose homeostasis, energy balance, coagulation, inflammation, and renal systems), involving a diversity of disciplines such as endocrinology, cardiology, nephrology, and lipidology. Conseqeuently, the WG also noted the need for broader, novel approaches to the growing challenges of diabetic macrovascular disease and indicated areas in which NHLBI’s leadership is needed. These include the need for (1) integrated training in metabolism and cardiovascular disease for scientists and clinicians; (2) interdisciplinary approaches to unresolved scientific questions; (3) promotion of integrated consortia across institutions that can provide the individual investigator with access to resources such as imaging, biochemical resources (mass spectroscopy, ‘-omic’ approaches), data mining resources, recombinant mouse models, and collaborative opportunities for studies in animals, including large animals; and (4) attraction of investigators in unrelated fields or those who have not previously studied pathways involved in diabetic macrovascular disease.
The WG made the following prioritized recommendations:
NHLBI web site; publication in a scientific journal
Division of Heart and Vascular Diseases
Working Group Members