Genetic epidemiology of diabetic complications

Diabetes, whether insulin-dependent (IDDM) or non-insulin-dependent (NIDDM), represents a major cause of morbidity and mortality in the U.S. Susceptibility to both IDDM and NIDDM has been shown to be due, in part, to genetic factors, Recent research on families in which two or more siblings have IDDM has resulted in a number of potential IDDM susceptibility genes being mapped, but extensive work remains to isolate and identify those genetic determinants, In contrast, the genetic basis for NIDDM, although more familial, has been elusive, The increased prevalence of NIDDM (even with increased risk to relatives) and the risk due to environmental risk factors has made the search for NIDDM susceptibility genes more difficult, with most success occurring for maturity-onset diabetes of the young, Although the majority of genetic research in diabetes has centered on the susceptibility of the primary endpoints (IDDM and NIDDM), the increased morbidity and mortality result from the complications associated with the diseases, Complications of diabetes involve multiple organ systems, and can be grouped into retinopathy (eye), neuropathy (nervous system), nephropathy (kidney), and cardiovascular diseases, The clinical presentation of diabetic complications occurs after a period of time following onset (diagnosis) of diabetes, This delay may be short (a few years) or long (a few decades) in duration, Not all diabetic subjects will develop a complication, although a portion will have several complications, The distribution of complications in diabetic subjects, both in number of complications and in timing of appearance of complications, has suggested that susceptibility to complications is partially controlled by genetic factors, In this article, we review the genetic epidemiology of diabetic complications, the potential for mapping complication-specific genes, and the prospects and limitations of research designed to identify these genes.