Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes.
BACKGROUND
The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and total homocysteine (tHcy) are elevated in patients at increased cardiovascular risk. Patients with type 2 diabetes (T2DM) have higher incidence of macrovascular disease than the general population. Recent reports suggest a relationship between tHcy and ADMA. To evaluate the connection between ADMA and tHcy and macrovascular disease, we determined both risk factors in T2DM patients with and without macrovascular disease.


METHODS
Plasma concentrations of ADMA and tHcy were cross-sectionally determined in 136 T2DM patients. Fifty-five patients had macrovascular disease defined by history of stroke, myocardial infarction, coronary heart disease or peripheral arterial occlusive disease. Logistic regression analysis was performed to examine the relationship between macrovascular disease and these risk factors. Potential confounders were identified by significant Spearman rank correlation coefficients.


RESULTS
In unadjusted models ADMA (per 0.1 micromol/l) and tHcy (per 5 micromol/l) were both significantly related to macrovascular disease (OR=1.63, 95% CI: 1.21-2.19 and OR=1.49, 95% CI: 1.04-2.14). In multivariate models, ADMA was significantly associated with macrovascular disease independent of l-arginine, albumin excretion rate, tHcy and glomerular filtration rate (GFR; OR=1.53, 95% CI: 1.04-2.26). The connection between tHcy and macrovascular disease was not independent of diastolic blood pressure, age, ADMA or GFR. Linear regression analyses revealed that ADMA, GFR and low-density lipoprotein cholesterol were independent predictors for tHcy.


CONCLUSIONS
ADMA is associated with macrovascular disease independent of tHcy and traditional cardiovascular risk factors in patients with T2DM.
Krzyzanowska
Katarzyna
K
Department of Internal Medicine I, Rudolfstiftung Hospital, Juchgasse 25, 1030 Vienna, Austria. katarzyna.kryzanowska@wienkav.at
Mittermayer
Friedrich
F
Krugluger
Walter
W
Schnack
Christoph
C
Hofer
Martin
M
Wolzt
Michael
M
Schernthaner
Guntram
G
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001157:Arterial Occlusive Diseases / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D007004:Hypoglycemic Agents; D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase