GENETIC EPIDEMIOLOGY OF DIABETIC COMPLICATIONS

Diabetes, whether insulin-dependent (IDDM) or non-insulin-dependent (N IDDM), 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 pa rt, to genetic factors, Recent research on families in which two or mo re siblings have IDDM has resulted in a number of potential IDDM susce ptibility genes being mapped, but extensive work remains to isolate an d identify those genetic determinants, In contrast, the genetic basis for NIDDM, although more familial, has been elusive, The increased pre valence of NIDDM (even with increased risk to relatives) and the risk due to environmental risk factors has made the search for NIDDM suscep tibility genes more difficult, with most success occurring for maturit y-onset diabetes of the young, Although the majority of genetic resear ch in diabetes has centered on the susceptibility of the primary endpo ints (IDDM and NIDDM), the increased morbidity and mortality result fr om the complications associated with the diseases, Complications of di abetes involve multiple organ systems, and can be grouped into retinop athy (eye), neuropathy (nervous system), nephropathy (kidney), and car diovascular diseases, The clinical presentation of diabetic complicati ons occurs after a period of time following onset (diagnosis) of diabe tes, This delay may be short (a few years) or long (a few decades) in duration, Not all diabetic subjects will develop a complication, altho ugh a portion will have several complications, The distribution of com plications in diabetic subjects, both in number of complications and i n timing of appearance of complications, has suggested that susceptibi lity to complications is partially controlled by genetic factors, In t his article, we review the genetic epidemiology of diabetic complicati ons, the potential for mapping complication-specific genes, and the pr ospects and limitations of research designed to identify these genes.