Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative retinopathy, and severe macroangiopathy suggests a common cause of albuminuria and the severe renal and extrarenal complications associated with it. Enzymes involved in the metabolism of anionic components of the extracellular matrix (e.g. heparan sulphate proteoglycan) vulnerable to hyperglycaemia, seem to constitute the primary cause of albuminuria and the associated complications. Genetic polymorphism of such enzymes is possibly the main reason for variation in susceptibility.

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Fifty-nine Type 1 (insulin-dependent) diabetic patients with (group I) and 59 patients without nephropathy (group II) pair-matched according to sex (30 males and 29 females), age (33 years, range 15-48) and diabetes duration (19 years, range 6-42) were followed for a period of 10 years from about 5 years before to 5 years after onset of proteinuria. The cumulative incidence of coronary heart disease was estimated, and blood pressure and serum cholesterol were followed. Within six years after onset of proteinuria the cumulative incidence of coronary heart disease was increased eight-fold in group I (40%) compared with group II (5%), (p less than 0.001). Blood pressure was higher in group I compared with group II from before onset of proteinuria (135/86 +/- 17/9 mmHg vs 129/80 +/- 15/8 mmHg, p less than 0.001), and serum cholesterol elevated from onset of proteinuria in group I (6.3 +/- 1.2 mmol/l) vs. group II (5.5 +/- 1.0 mmol/l), (p less than 0.005). Patients in group I who developed coronary heart disease had similar age (36 years, range 21-51, vs 38 years, range 21-53), sex (50% males vs. 52% males), smoking frequency (50% vs 49%), diabetes duration (22 years, range 9-39, vs 24 years, range 10-42) and serum creatinine (110 mumol/l, range 69-284, vs 108 mumol, range 72-1024) compared with patients not developing coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

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