In summary, over the past 16 years, since the publication of Kelly West's book, epidemiological study has provided better insight into the relation of hyperglycemia and diabetic complications. Data from the WESDR demonstrate a strong consistent relationship between hyperglycemia and the incidence and progression of microvascular (diabetic retinopathy, loss of vision, and nephropathy) and macrovascular (amputation and cardiovascular disease mortality) complications in people with IDDM and NIDDM (Figs. 19 and 20). The DCCT has demonstrated that intensive insulin therapy will reduce the incidence and progression of microvascular complications in people with IDDM (22). A number of further challenges await laboratory scientists and epidemiologists regarding hyperglycemia in people with diabetes. There is a need to understand the relation of hyperglycemia to pathogenetic mechanisms that lead to the development of specific complications, to develop new methods to detect and physiologically treat hyperglycemia, and to develop better methods of primary and secondary prevention of diabetic complications in people with IDDM and NIDDM.