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If early intervention aimed at lowering blood glucose concentrations can be shown to reduce mortality, it may be justified to lower the levels of both 2-h and fasting glucose, which define diabetes.

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Forty-four non-insulin-dependent diabetics (NIDD), all with urine negative to Albustix, were studied in 1966/67. By the end of 1980, 17 had died, all but two from cardiovascular causes. All causes of mortality and time to death were significantly related in univariate analyses to age and to the overnight urinary albumin excretion rate (AER), but not to systolic and diastolic blood pressure levels or to duration of diabetes when the latter was corrected for age. Age and duration were highly correlated with each other. In multivariate analyses age and AER were independent predictors of both mortality and time to death, with AER having the greater degree of significance. Thus subclinically elevated albumin excretion rates ('microalbuminuria') indicate a substantially increased mortality risk in non-insulin-dependent diabetes.

Mortality rates from coronary heart disease and from all causes have been ascertained over ten years in three groups of people participating in the Bedford Survey--newly-diagnosed diabetics, borderline diabetics and control subjects with normal glucose tolerance. Age corrected mortality rates, from all causes and coronary heart disease, were highest in the diabetics and intermediate in the borderline diabetics and in both groups were similar in men and women. When statistical allowance was made for baseline differences in age, blood pressure and obesity, female borderline diabetics still had a significantly increased risk over their controls of death from 'all causes'. Much of the difference appeared to be due to a relative excess of deaths due to coronary heart disease. It is concluded that borderline diabetes (or impaired glucose tolerance) is associated with a relatively greater increase in mortality risk in women than men. During the 10-year follow-up of the Bedford borderline diabetics, coronary heart disease morbidity and mortality rates were similar in men and women. Age at entry to the study was the major independent and significant predictor of mortality from all causes. The level of systolic blood pressure and current cigarette smoking at baseline were statistically significant predictors only of mortality due to coronary heart disease.

A cohort of 63 Type 1 insulin-dependent diabetic patients were first characterized for overnight urinary albumin excretion rate (AER) in 1967. In 1981, seven out of eight (87%) patients with initial AER greater than or equal to 30 less than or equal to 140 micrograms/min (microalbuminuria) developed clinical proteinuria compared to only 2 out of 55 (4%) patients with initial AER less than 30 micrograms/min. The same cohort of patients was reassessed in 1990 after a total follow-up period of 23 years. The aim was to investigate the role of microalbuminuria in the prediction of total/cardiovascular mortality and the development of renal failure, in addition to clinical proteinuria. The initially microalbuminuric patients had a significantly higher risk of developing not only clinical proteinuria (relative risk 9.3, 95% C.I. 1.36 to 3.10, P less than 0.05), but also of dying from a cardiovascular cause (relative risk 2.94, 95% C.I. 1.18 to 7.34, P less than 0.05). The rate of progression to renal failure was higher but not significantly so in the microalbuminuric (2 of 8) compared to the normoalbuminuric (4 of 53) group (relative risk 3.31, 95% C.I. 0.72 to 15.24, NS). In insulin-dependent diabetic patients microalbuminuria is a powerful predictor of clinically overt diabetic renal disease as well as cardiovascular mortality.

In a 10-year prospective study of 241 people with 'borderline diabetes' (impaired glucose tolerance) identified by screening of the Bedford adult population, 36 (15%) worsened to diabetes and 128 (53%) substantially improved their glucose tolerance. The major predictor of worsening to diabetes was the level of blood glucose at baseline. This was statistically significant (p less than 0.05), independent of other factors, both for deterioration in the first and in the second five years of observation. Body mass index, a measure of adiposity, did not predict worsening to diabetes during the first five years, but was an independent and significant predictor of worsening during the second five years (p less than 0.05). The apparent effect of adiposity was complex, for it was also significantly related to improvement in glucose tolerance during the 10-year follow-up. Persons with impaired glucose tolerance are a heterogeneous group and with present knowledge the ability to predict metabolic deterioration is limited.