Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes - 5-year follow-up of the Hoorn study

Background-A high serum total homocysteine (tHcy) concentration is a risk f actor fur 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 betwe en tHcy and cardiovascular disease is stronger in diabetic than in nondiabe tic subjects. We therefore prospectively investigated the combined effect o f hyperhomocysteinemia and type 2 diabetes on mortality. Methods and Results-Between October 1, 1989, and December 31, 1991, serum w as 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 concen tration was measured in 171 subjects who died (cases; 76 of cardiovascular disease) and in a stratified random sample of 640 survivors (control subjec ts). Mortality risks were calculated over 5 years of follow-up by means of logistic regression. The prevalence of hyperhomocysteinemia (tHcy >14 mu mo l/L) was 25.8%. After adjustment For major cardiovascular risk factors, ser um 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-m u mol/L increment of tHcy, The odds ratio for 5-year mortality for hyperhom ocysteinemia 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 f actor for mortality in type 2 diabetic patients than in nondiabetic subject s.