PLASMA HOMOCYSTEINE IS RELATED TO ALBUMIN EXCRETION RATE IN PATIENTS WITH DIABETES-MELLITUS - A NEW LINK BETWEEN DIABETIC NEPHROPATHY AND CARDIOVASCULAR-DISEASE

The high risk of cardiovascular disease in patients with diabetes mell itus, particularly in those with nephropathy, is not completely explai ned by classical risk factors. A high plasma homocysteine concentratio n is an independent risk factor for cardiovascular disease but informa tion on its association with diabetes is limited. Fasting homocysteine concentrations were measured in the plasma of 165 diabetic pa patient s (75 with insulin-dependent [IDDM]; 90 with non-insulin-dependent dia betes [NIDDM]) and 56 non-diabetic control subjects. Other measurement s included the prevalence of diabetic complications, glycaemic control , lipid and lipoprotein levels, vitamin status and renal function test s. Patients with NIDDM had higher homocysteine levels than control sub jects, whereas IDDM patients did not (9.2 +/- 4.5 vs 7.7 +/- 2 mu mol/ l, p < 0.01; and 7.0 +/- 3 vs 7.4 +/- 2 mu mol/l, NS). Univariate corr elations and multiple regression analysis showed albumin excretion rat e to be the parameter with the strongest independent association with homocysteine. Patients with both types of diabetes and nephropathy had higher plasma homocysteine concentrations than those without nephropa thy. Increases of homocysteine in plasma were related to increases in the severity of the nephropathy. Fasting hyperhomocysteinaemia was con sidered as the mean of the plasma homocysteine for all control subject s (7.5 +/- 2.1 mu mol/l) + 2 SD (cut-off = 11.7 mu mol/l). Nephropathy was present in 80% of diabetic patients with fasting hyperhomocystein aemia. In conclusion, increases in fasting homocysteine in diabetic pa tients are associated with increased albumin excretion rate, especiall y in those with NIDDM, thus providing a potential new link between mic roalbuminuria, diabetic nephropathy and cardiovascular disease.