Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes

OBJECTIVE - To assess the impacts of insulin resistance and renal function on plasma total homocysteine (tHey) levels in patients with type 2 diabetes with a wide range of nephropathy. RESEARCH DESIGN AND METHODS - Plasma tHey levels were measures using the enzyme immunoassay method in 75 patients with type 2 diabetes and compared with those in 54 healthy control subjects. Insulin sensitivity indexes were assessed in patients with type 2 diabetes by hyperinsulinemic-euglycemic clamp using artificial pancreas. RESULTS - Plasma tHey levels and their log-transformed values (log tHey) were significantly higher in all patients with diabetes than in control subjects (tHey, 12.0 +/- 0.7 [SE] vs. 8.7 +/- 0.3 mu mol/l, P < 0.0001; log tHey, 1.040 +/- 0.021 vs. 0.920 +/- 0.016 <mu>mol/l, P < 0.0001). Plasma tHey levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHey correlated with insulin sensitivity. indexes (r = -0.319, P = 0.005) as well as creatinine clearance (r = 0.634. P < 0.0001) in all patients with diabetes. Multiple regression analyses showed that insulin sensitivity indexes (<beta> = -0.245) as well as creatinine clearance were independent contributors to log tHey in all patients with diabetes (R-2 = 0.750, P < 0.0001). For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin sensitivity indexes were also shown to be a significant contributor to log tHey (P = -0.438, R-2 = 0.561, P < 0.001). CONCLUSION - Insulin resistance and renal function are independent determinants of tHey levels in patients with type 2 diabetes.