Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes

Atherosclerosis. 2006 Nov;189(1):236-40. doi: 10.1016/j.atherosclerosis.2005.12.007. Epub 2006 Jan 18.


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.

Subjects and 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.

Conclusion: ADMA is associated with macrovascular disease independent of tHcy and traditional cardiovascular risk factors in patients with T2DM.

MeSH terms

  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arterial Occlusive Diseases / blood*
  • Arterial Occlusive Diseases / complications
  • Arterial Occlusive Diseases / epidemiology
  • Biomarkers / blood
  • Chromatography, High Pressure Liquid
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Follow-Up Studies
  • Homocysteine / blood*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Prognosis
  • Risk Factors
  • Severity of Illness Index


  • Biomarkers
  • Hypoglycemic Agents
  • Homocysteine
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase