INCREASED LEVELS OF PLASMA HOMOCYSTEINE ARE ASSOCIATED WITH NEPHROPATHY, BUT NOT SEVERE RETINOPATHY IN TYPE-1 DIABETES-MELLITUS

The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3-mu-mol l-1; mean +/- SD, p < 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6-mu-mol l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3-mu-mol l-1; n = 25), and the control subjects (11.0 +/- 3.4-mu-mol l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels > 115-mu-mol l-1 and/or an albumin:creatinine clearance ratio greater-than-or-equal-to 0.02 x 10(-3) (17.0 +/- 5.9-mu-mol l-1 n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5-mu-mol l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.