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 (> 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.
Anderson
Jeffrey L
JL
Cardiovascular Department, LDS Hospital, Salt Lake City, UT 84143, USA. jeffrey.anderson@intermountainmail.org
Carlquist
John F
JF
Roberts
William L
WL
Horne
Benjamin D
BD
May
Heidi T
HT
Schwarz
Elisabeth L
EL
Pasquali
Marzia
M
Nielson
Rebecca
R
Kushnir
Mark M
MM
Rockwood
Alan L
AL
Bair
Tami L
TL
Muhlestein
Joseph B
JB
D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis*; D003348:Cortisone / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011237:Predictive Value of Tests; D018570:Risk Assessment
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D003348:Cortisone; D006854:Hydrocortisone