Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: Markers for diabetes and cardiovascular risk?

Background Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired fasting glucose (110-125), or diabetic (>= 126) status. Methods High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoossay for C-peptide. Results Asymmetric dimethylarginine levels were positively associated with glycemic category (P <.001). Quartiles 2 to 4 ADMA also conferred increased risk of death/Ml independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P =.002). Cortisol/Cortisone ratios (P =.013) and C-pepticle (P =.047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/Ml (adjusted hazard ratio, 0.48,P <.001), whereas C-peptide did not predict outcomes. Conclusions Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.