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

OBJECTIVE - The aim of this study was to determine the distribution of plas ma 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., m acroangiopathy microalbuminuria, macroproteinuria, decreased creatinine cle arance, hypertension, retinopathy; and neuropathy) was recorded alongside a n assessment of insulin resistance by the homeostasis model assessment (HOM A). RESULTS - We found that 31% of the the cohort (group I) had raised tHcy (me an +/- 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 high er in group 1 than in group 2 subjects (70 vs. 42%, P < 0.01); the prevalen ce of coronary artery disease was particularly higher in group 1. (46 vs. 2 1%, P < 0.02). The prevalence of impaired renal function, evidenced by decr eased creatinine clearance, was higher in group 1 (32 vs. 10%, P < 0.005). Other clinical and biological characteristics of both groups were comparabl e, 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 microalbu minuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups I and 2, respectively The degree of insulin resistance was s imilar in groups I and 2 (46 +/- 21 and 42 +/- 20% of HOMA-insulin sensitiv ity) 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 pla sma 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 f rom creatinine clearance indexes and is not associated with different degre es of insulin resistance.