Associations of plasma homocysteine concentration in subjects with type 2 diabetes mellitus

We investigated the potential relationship between hyperhomocysteinemia and the presence of coronary heart disease (CHD) and chronic complications in a consecutive series of 358 (156 men) Kuwaiti type 2 diabetic subjects. The median (2.5(th), 97.5(th) percentiles) fasting plasma concentration of total homocysteine (tHcy) in the patients was 10.2 (5.4, 19.1) mumol/l. Fasting tHcy concentration was significantly (p<0.001) higher among men [11.3 (7.1, 24.6) mumol/l compared to women [8.8 (5.3, 16.3) mumol/l]. Of the 57 patients with a history of CHD and/or electrocardiographic (ECG) evidence of CHD, 9 (16%) had hyperhomocysteinemia (tHcy greater than or equal to15 mumol/l) compared to 8.3% (25 of 301) of patients without evidence of CHD. In univariate analysis, plasma tHcy concentration was significantly (p<0.01) higher in those diabetic subjects with history of CHD and/or abnormal ECG. Although hyperhomocysteinemia was more common in patients with microalbuminuria (15%) compared to patients with normoalbuminuria (12%), there was no significant association between hyperhomocysteinemia and the degree of albuminuria. After controlling for age and sex, multiple regression analyses showed significant associations of plasma tHcy concentration with glycated hemoglobin (p<0.05), plasma concentrations of creatinine (p<0.001) and apolipoprotein-B (p<0.05), but not with smoking, neuropathy or retinopathy. It seems that the association of hyperhomocysteinemia with diabetic microvascular complications is mediated by the confounding effect of other factors like age, sex and plasma creatinine concentration. In conclusion, we have found a univariate association between hyperhomocysteinemia and CHD but not with microalbuminuria, neuropathy and retinopathy. Although routine estimation of plasma homocysteine may be useful, the association with cardiovascular disease or microvascular complications in patients with type 2 DM deserves prospective studies.