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 (tHcy) levels in patients with type 2 diabetes with a wide range of nephropathy. RESEARCH DESIGN AND METHODS—Plasma tHcy levels were measured 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 tHcy levels and their log-transformed values (log tHcy) were significantly higher in all patients with diabetes than in control subjects (tHcy, 12.0 ± 0.7 [SE] vs. 8.7 ± 0.3 μmol/l, P < 0.0001; log tHcy, 1.040 ± 0.021 vs. 0.920 ± 0.016 μmol/l, P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHcy 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 (β = –0.245) as well as creatinine clearance were independent contributors to log tHcy in all patients with diabetes (R2 = 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 tHcy (β = –0.438, R2 = 0.561, P < 0.001). CONCLUSION—Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.