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

Anderson JL, Carlquist JF, Roberts WL, Horne BD, May HT, Schwarz EL, Pasquali M, Nielson R, Kushnir MM, Rockwood AL, Bair TL, Muhlestein JB,

Cardiovascular Department, LDS Hospital, Salt Lake City, UT 84143, USA. jeffrey.anderson@intermountainmail.org

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 (> or = 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 immunoassay 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/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (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.

Published 18 December 2006 in Am Heart J, 153(1): 67-73.
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Diabetes Research Today Archive:

Volume 1 (2004)
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Diabetes Books

The New Glucose Revolution for Diabetes: The Definitive Guide to Managing Diabetes and Prediabetes Using the Glycemic Index (Marlowe Diabetes Library)

The New Glucose Revolution for Diabetes: The Definitive Guide to Managing Diabetes and Prediabetes Using the Glycemic Index (Marlowe Diabetes Library)