Effect of metabolic control on homocysteine levels in type 2 diabetic patients: a 3-year follow-up

Objectives. Hyperhomocysteinaemia has emerged as a novel risk factor for cardiovascular disease. The determinants of total homocysteine (tHcy) levels in type 2 diabetic patients (D2p) have not been studied in detail. We examined prospectively the effect of different degrees of metabolic control on plasma tHcy in D2p with preserved kidney function. Subjects and main outcome measurements. Ninety-five D2p were studied. Clinical parameters, fasting plasma glucose, HbA(1c), serum lipids, blood urea nitrogen ( BUN) and creatinine, vitamin B-12 and folate and tHcy were measured at the baseline and after 36 months. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism was also determined. Subjects were categorized according to deltaHbA(1c) into group A (+/-1 point), B (>1 point increase) or C (>1 point decrease). Results. Total homocysteine was reduced in subjects whose HbA(1c) decreased with time, whilst patients showing a worsened metabolic control had an increased tHcy in respect to baseline. A larger response to the improved metabolic control in terms of tHcy reduction was noted in wild type patients versus those homozygous for the mutation. A multivariate analysis revealed MTHFR polymorphism and HbA(1c) as strong determinants of changes in tHcy with time. Conclusions. The findings suggest that in D2p tHcy decreases even with modest improvement of glycaemic control; moreover patients homozygous for the MTHFR C677T mutation show the largest changes in tHcy levels with concomitant changing of HbA(1c). These results define a further mechanism through which hyperglycaemia might promote cardiovascular damage in diabetic patients.