OBJECTIVE: To determine the plasma concentration of total homocysteine (tHcy), a recognized risk factor for vascular disease, in patients with type 1 diabetes and to examine the relationships with age, sex, duration of diabetes, microvascular complications and neuropathy, and folic acid concentration. RESEARCH DESIGN AND METHODS: Plasma tHcy and folic acid concentrations were measured in a randomly selected cohort of type 1 diabetic patients (n = 119), well characterized as regards microvascular complications, and in a matched control group (n = 51). RESULTS: Plasma tHcy was higher in male than in female control subjects (geometric mean [95% CI]: 9.3 [8.0-10.9] vs. 6.1 [5.2-7.2] micromol/l, P < 0.001), as previously described, but there was no sex difference in diabetic patients. Plasma tHcy significantly correlated with age in patients (r = 0.348, P < 0.01) but not in control subjects (r = 0.007, P = 0.96). Male patients without microvascular complications had lower plasma tHcy concentrations than did male control subjects (6.2 [5.1-7.5] vs. 9.3 [8.0-10.9] micromol/l, P < 0.001), but values in female patients without complications were similar to those of female control subjects. Plasma folic acid concentration was higher in diabetic patients than in control subjects. The expected negative association between plasma tHcy and folic acid was stronger in control subjects than in patients. CONCLUSIONS: Subnormal tHcy concentrations in male patients, the absence of a sex difference, and the positive association with age indicate that homocysteine metabolism differs between type 1 diabetic patients and control subjects. Homocysteine is unlikely to be of pathogenic significance in patients, particularly male subjects, with early microvascular disease and/or neuropathy.

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