Hyperhomocysteinemia Following a Methionine Load in Patients with Non-insulin-dependent Diabetes Mellitus and Macrovascular Disease

In the setting of an outpatient diabetic clinic, we determined whether macrovascular disease in patients with diabetes mellitus is associated with hyperhomocysteinemia (elevated plasma homocysteine [H(e)] concentrations) following a methionine load. Methionine-load tests were performed in 18 healthy controls, 11 diabetics without vascular disease (five insulin-dependent [IDDM] and six non-insulin-dependent [NIDDM]); and 17 diabetics with vascular disease (five IDDM and 12 NIDDM). All subjects were male, and there was no significant difference in mean age among the three groups. We measured plasma H(e) concentrations before and 2, 4, 6, 8, and 24 hours after an oral methionine load. Hyperhomocysteinemia (peak plasma H(e) concentration > control mean +/- 2 SD) occurred with significantly greater frequency (seven of 18, 39%) in patients with NIDDM as compared with age-matched controls (7%), being more common in those with macrovascular disease (five of 12, 41%). The area under the curve (AUC) over 24 hours, reflecting the total period of exposure to H(e), was also elevated with greater frequency in patients with NIDDM and macrovascular disease (33%) as compared with controls (0%). We conclude that hyperhomocysteinemia is associated with macrovascular disease in a significant proportion of patients with NIDDM. Further investigation of this association may determine whether hyperhomocysteinemia contributes to the increased frequency and accelerated clinical course of vascular disease in patients with diabetes mellitus.