Objectives: It has been shown that insulin resistance is associated with a state of chronic low-grade inflammation. Furthermore, depletion of nitric oxide (NO) or ineffectiveness of NO-mediated vasodilator mechanisms are associated with arterial stiffness and progression of insulin resistance to type-2 diabetes. In this study, we decided to evaluate the association between asymmetric dimethylarginine ([ADMA], an endogenous NO synthase inhibitor), high-sensitivity C-reactive protein ([hs-CRP]; a marker of chronic inflammation) and insulin resistance in early-stage type-2 diabetes.
Methods: A total of 40 diabetic patients and 40 age-, sex- and body mass index (BMI)-matched healthy adult volunteers were recruited in this case-control study. Diabetic patients were recently diagnosed and did not have a history of any diabetes-related complications. Fasting blood samples were obtained and fasting plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, creatinine, insulin, ADMA and hs-CRP were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was also calculated.
Results: ADMA (0.9+/-0.2 vs 0.7+/-0.2 micromol/L; p<0.001) and hs-CRP (3.0+/-2.1 vs 1.3+/-1.0mg/L; p<0.001) were significantly higher in diabetic participants vs healthy controls. Age- and sex-adjusted ADMA values were significantly (p<0.05) correlated with hs-CRP (r=0.279) and HOMA-IR (r=0.288) in diabetic patients. These associations were not significant in healthy controls. The association between ADMA and HOMA-IR in diabetic patients remained significant (r=0.255; p<0.05), after adjustment for BMI, waist circumference, serum lipids, and hs-CRP. In multivariate regression analysis, ADMA and hs-CRP were independently correlated with diabetes.
Conclusion: In early-stage type-2 diabetic patients, ADMA is an independent predictor of insulin resistance. Our results could possibly point to an independent mechanism for contribution of ADMA in development of insulin resistance.
Copyright 2010 Elsevier Masson SAS. All rights reserved.