Hyperhomocysteinemia in type 2 diabetes - Relationship to macroangiopathy, nephropathy, and insulin resistance

OBJECTIVE - The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance. RESEARCH DESIGN AND METHODS - Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy; and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA). RESULTS - We found that 31% of the the cohort (group I) had raised tHcy (mean +/- 1 SD) values (20.8 +/- 5.1 pmol/l), whereas 69% (group 2) had normal values (10.2 +/- 2.0 mu mol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalence of coronary artery disease was particularly higher in group 1. (46 vs. 21%, P < 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparable, although group I had lower levels of folic acid than group 2 (5.2 +/- 2.9 vs. 7.0 +/- 3.4 ng/ml, P < 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups I and 2, respectively The degree of insulin resistance was similar in groups I and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitivity) as was the assessment of beta -cell function (63 +/- 28 and 65 +/- 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016). CONCLUSIONS - Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.