ADMA is a correlate of insulin resistance in early-stage diabetes independent of hs-CRP and body adiposity

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 μmol/L; p < 0.001) and hs-CRP (3.0 ± 2.1 vs 1.3 ± 1.0 mg/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.