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Plasma homocysteine is not increased in microalbuminuric patients with type 2 diabetes without clinical cardiovascular disease.

Although mild hyperhomocysteinemia (MHH) has been considered as an independent risk factor for cardiovascular disease (CVD) (1,2), some investigators have cast doubts about this statement (2–4). Subjects with type 2 diabetes and microalbuminuria (MA) are particularly at risk of developing CVD. In these subjects, there is some controversy as to whether total plasma homocysteine (tHcy) levels are increased (5–7) or not (8–11). Usually, these studies, which include subjects with and without CVD, do not take into account this variable when analyzing their results. It is well known that there is a positive relationship between the presence of CVD and MA (12). In addition, CVD itself is associated with MHH (1,2). We hypothezised that studies that found an increase in tHcy levels in subjects with MA did not take into account the presence of a preexisting CVD as a confounding variable. Therefore, as subjects with type 2 diabetes and MA have a higher prevalence of preexisisting CVD, higher values of tHcy could be expected as a result of CVD and not because of MA.

To test this hypothesis, we studied 93 subjects with type 2 diabetes (55 with normoalbuminuria and 38 with MA) and 86 nondiabetic control subjects matched for age and sex, all of whom were recruited at a primary care center. The exclusion criteria were: age 85 years, serum creatinine >1.4 mg/dl, uncontrolled hypertension (systolic >160 mmHg and/or diastolic >95 mmHg), congestive heart failure, major invalidating disease, pregnancy, …