The comparative risk of cardiovascular deaths in type 2 diabetes is much higher than the appearance of end-stage renal disease even if diabetes is diagnosed at age 55, the peak age of diagnosis in the U.S., and remains poorly controlled throughout. Studies of glycemic control and macrovascular complication are limited by the complex interaction of multiple risk factors. However, correlations between glycemic levels and cardiovascular morbidity are detectable, even in non-diabetic person in epidemiological and cross-sectional studies.One study shows a linear correlation for non-diabetic fasting glycemic level in men, while in non-diabetic women, there is a threshold at130 mg/dl. In an elderly population(mean age 75) comprising survivors of the original Framingham cohort, there is a strong correlation in non-diabetic HbA levels with cardiovascular disease in women; a weak correlation is also reported for men. A separate report of casual non-diabetic blood glucose determination, also from the Framingham study. Shows a correlation with cardiovascular disease only in women. However,in men, correlations between high non-diabetic glycemic levels and coronary disease have been shown to be equal to or more than in women in several surveys. In any case,once the diagnosis of diabetes is established, the incidence of cardiovascular disease is much higher in either sex. Twice as much or more, than that of simple impaired glucose tolerance. In a recent report. Diabetic patients with history of MI have a 45%, 7-years incidence rate of MI and those without a previous MI have a 20.2% rate. Duration of diabetes, corrected for . age, correlates independently with C V mortality, both fatal and non-fatal MI, and PVD, suggesting a cumulative effect of the metabolic abnormalities of diabetes on CV disease In a large Japanese study, fasting glucose over 200 mg/dl positively correlated with mortality In type 2 diabetic patients with clinically manifested arteriosclerosis, impaired glycemic control correlates with risk of recurrent MI, and amputation for gangrene Several reports associated severity of hyperglycemia in type 2DM and CV morbidity and mortality.

The epidemiological evidence might simply indicate that more severe the diabetes, more severe the CV complications. The only completed randomized long-term trial in adult onset diabetes prior to the UKPDS, the University Group Diabetes Program (UGDP) was inconclusive, and the subsequent trials have failed to demonstrate the beneficial effects of glycemic control on CV complications. At the time of the UGDP, monitoring techniques were inefficient. and the design included several different treatment groups. most with sub-optimal doses of pharmacological agent.

It should be noted that the older age of type 2 patients, and their more prevalent atherosclerotic risk foctor, might partially explain their macrovascular morbidity. On the other hand, prospective and retrospective studies in type 2 diabetics demonstrate similar excess of complications over the general population after statistical correction for those risk factors. A large department of veterans Affairs cooperative study to prospectively evaluate the effect of intensive glycemic control on the appearance of cardiovascular events in type 2 diabetics who failed to respond to oral agents alone has been initiated in the United States.