Reverse correlation between urine nitric oxide metabolites and insulin resistance in patients with type 2 diabetes mellitus

We studied the possible relationship between nitric oxide (NO) production a nd insulin resistance in patients with type 2 diabetes mellitus. Urine NO m etabolites (NOx) were measured as an index for NO production by HPLC combin ed with a Cd column, Griess reaction and a spectrophotometer in 403 healthy control subjects and 102 hospitalized patients with type 2 diabetes. Gluco se infusion rate (GIR) was measured as a reverse index for insulin resistan ce by euglycemic glucose clamp study using an artificial pancreas in 20 of 102 diabetic patients. Urine NOx was lower in the patients with type 2 diab etes than in healthy control subjects (mean+/-SE: 3.18+/-0.02 versus 3.25+/ -0.01 log[mu mol/gCr], p < 0.01). Urine NOx was correlated with body mass i ndex (BMI) in 102 diabetic patients (r= -0.372, p<0.001), but not related t o either age, sex, fasting plasma glucose, HbA1(c) or blood pressure. Urine NOx was correlated with GIR independent of BMI in 20 diabetic patients (r= 0.774, P<0.0001). These findings suggest that NO production is closely rela ted with insulin resistance in patients with type 2 diabetes.