Objective: To assess the contribution of fasting blood glucose and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphism on fasting serum homocysteine (tHcy) levels in patients with uncomplicated type 2 diabetes compared with healthy subjects.
Methods and results: We studied 105 type 2 diabetic patients without cardiovascular complications or diabetic nephropathy (55 males, 50 females, mean age 53+/-10 years, mean duration of diabetes 11.4+/-8 years) and 120 age- and sex-matched control subjects (65 males, 55 females, mean age 52+/-8 years). tHcy and other biochemical variables were measured. The C677T MTHFR gene polymorphism was determined by analysis of HinfI restriction fragment length polymorphism tHcy levels were significantly lower in diabetic patients compared with control subjects (7.7 +/- 2.2 vs. 11.8 +/- 4.5 micromol/l, P < 0.0001). In both patients and control subjects, homocysteinemia was higher in men than in women (8.4+/-2.6 vs. 7.3+/-2.0 micromol/l, P < 0.03, and 13.0+/-5.3 vs. 10.4+/-2.6 micromol/l, P < 0.0001, respectively). Levels were slightly higher in subjects with the mutated Val/Val genotype compared with the Ala/Val plus Ala/Ala genotypes in both diabetic patients (P < 0.02) and control subjects (P < 0.003). On simple regression analysis, tHcy was inversely related with blood glucose levels (P < 0.02) and directly with sex (P < 0.04) in diabetic patients, and with sex (P < 0.0001), age (P < 0.02), BMI (P < 0.03), systolic and diastolic blood pressure (P < 0.0004 and P < 0.0002), uric acid and creatinine (P < 0.0001 and P < 0.0003) in control subjects. On multiple regression, tHcy levels were associated with sex (P < 0.03) and glucose levels (P < 0.04) in diabetic patients, and with uric acid (P < 0.002) and MTHFR genotype (P < 0.03) in control subjects.
Conclusion: In type 2 diabetic patients without nephropathy, basal levels of tHcy were 35% lower compared with healthy controls. Chronic hyperglycemia may control tHcy by affecting its renal excretion, or accelerate hepatic trans-sulfuration secondary to insulin disorders.