title: Asymmetrical dimethylarginine is related to renal function, chronic inflammation and macroangiopathy in patients with Type 2 diabetes and albuminuria.
abstract: OBJECTIVE
  Patients with Type 2 diabetes mellitus (T2DM) and micro- and macroalbuminuria are at increased cardiovascular risk. The endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) is increased in renal failure and could promote atherosclerosis. To determine the relationship between ADMA, renal albumin excretion rate (AER) and cardiovascular risk, we studied 103 T2DM patients.
  
  
  METHODS
  ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were determined by high-performance liquid chromatography in plasma from 36 normo-, 40 micro- and 27 macroalbuminuric patients with T2DM (age 64 +/- 11 years; 38 women) who had comparable age, sex and metabolic parameters. Forty-six patients had macrovascular disease (MVD).
  
  
  RESULTS
  ADMA was significantly increased in patients with micro- and macroalbuminuria [median 0.61 (interquartile range 0.55-0.70) micromol/l and 0.62 (0.50-0.79) micromol/l, respectively] compared with those with normoalbuminuria [0.55 (0.48-0.63) micromol/l; both P < 0.05]. SDMA was elevated in micro- and macroalbuminuria [0.57 (0.42-0.80) micromol/l and 0.64 (0.50-0.96) micromol/l] compared with normoalbuminuric subjects [0.44 (0.37-0.53) micromol/l; both P < 0.01]. Patients with increased AER and MVD had higher ADMA and SDMA compared with those without MVD (both P < 0.001). L-arginine was comparable between all groups. ADMA correlated significantly with high-sensitivity C-reactive protein (hsCRP) and glomerular filtration rate (GFR) but not with the extent of albumin excretion, body mass index, fasting glucose, HbA(1c) or plasma lipids.
  
  
  CONCLUSIONS
  Increased ADMA in T2DM patients with albuminuria is linked to cardiovascular disease and is associated with renal dysfunction and subclinical inflammation.
authors.affiliation: Department of Internal Medicine I, Rudolfstiftung Hospital, Medical University Vienna, Austria. katarzyna.krzyzanowska@wienkav.at
authors.forename: K
authors.initials: K
authors.lastname: Krzyzanowska
authors.forename: F
authors.initials: F
authors.lastname: Mittermayer
authors.forename: N
authors.initials: N
authors.lastname: Shnawa
authors.forename: M
authors.initials: M
authors.lastname: Hofer
authors.forename: J
authors.initials: J
authors.lastname: Schnabler
authors.forename: Y
authors.initials: Y
authors.lastname: Etmüller
authors.forename: S
authors.initials: S
authors.lastname: Kapiotis
authors.forename: M
authors.initials: M
authors.lastname: Wolzt
authors.forename: G
authors.initials: G
authors.lastname: Schernthaner
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000209:etiology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000652:urine; D050197:Atherosclerosis / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003925:Diabetic Angiopathies / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000652:urine; D008297:Male; D008875:Middle Aged
chemical_list: C487735:dimethylarginine; D001120:Arginine