Hyperhomocysteinemia Increases Risk of Death, Especially in Type 2 Diabetes

Abstract

Background—A high serum total homocysteine (tHcy) concentration is a risk factor for death, but the strength of the relation in patients with type 2 (non–insulin-dependent) diabetes mellitus compared with nondiabetic subjects is not known. A cross-sectional study suggested that the association between tHcy and cardiovascular disease is stronger in diabetic than in nondiabetic subjects. We therefore prospectively investigated the combined effect of hyperhomocysteinemia and type 2 diabetes on mortality. Methods and Results—Between October 1, 1989, and December 31, 1991, serum was saved from 2484 men and women, 50 to 75 years of age, who were randomly selected from the town of Hoorn, The Netherlands. Fasting serum tHcy concentration was measured in 171 subjects who died (cases; 76 of cardiovascular disease) and in a stratified random sample of 640 survivors (control subjects). Mortality risks were calculated over 5 years of follow-up by means of logistic regression. The prevalence of hyperhomocysteinemia (tHcy >14 μmol/L) was 25.8%. After adjustment for major cardiovascular risk factors, serum albumin, and HbA_1c, the odds ratio (95% CI) for 5-year mortality was 1.56 (1.07 to 2.30) for hyperhomocysteinemia and 1.26 (1.02 to 1.55) per 5-μmol/L increment of tHcy. The odds ratio for 5-year mortality for hyperhomocysteinemia was 1.34 (0.87 to 2.06) in nondiabetic subjects and 2.51 (1.07 to 5.91) in diabetic subjects (P=0.08 for interaction). Conclusions—Hyperhomocysteinemia is related to 5-year mortality independent of other major risk factors and appears to be a stronger (1.9-fold) risk factor for mortality in type 2 diabetic patients than in nondiabetic subjects.