title: Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia.
abstract: BACKGROUND
  Diabetic nephropathy, especially when advanced, is associated with high prevalence of atherosclerotic cardiovascular disease in which inflammation and coagulation may play pathogenic roles. We investigated the relationships between diabetic nephropathy and coagulation, fibrinolysis, or inflammation in patients with Type 2 diabetes.
  
  
  METHODS
  We evaluated markers of inflammation and coagulation in 105 Type 2 diabetic patients with various grades of nephropathy and 49 healthy control subjects, in association with plasma total homocysteine (tHcy) measurements.
  
  
  RESULTS
  Plasma tHcy concentrations were significantly higher in diabetic patients than in controls (8.96 +/- 3.04 vs. 6.92 +/- 1.36 micromol/l, P < 0.0001). Plasma concentrations of interleukin (IL)-6 were significantly higher in diabetic patients than in control subjects (P < 0.0001). In diabetic patients, plasma tHcy correlated positively with urinary albumin, fibrinogen, IL-6 and plasmin-alpha2-antiplasmin complex (PAP), while plasma tHcy correlated negatively with creatinine clearance (Ccr) and protein C activity. After adjustment for Ccr, IL-6 and protein C activity were significantly associated with plasma tHcy. Plasma tHcy concentrations were significantly higher in patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria, as were plasma concentrations of fibrinogen, prothrombin F1+2, and interleukin-6.
  
  
  CONCLUSIONS
  Diabetic nephropathy is associated with elevated markers for both coagulation and inflammation. High plasma homocysteine may be a link between diabetic nephropathy and both chronic inflammation and hypercoagulability, increasing cardiovascular risk.
authors.affiliation: Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. yaso@dokkyomed.ac.jp
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Aso
authors.forename: Noboru
authors.initials: N
authors.lastname: Yoshida
authors.forename: Ki-ichi
authors.initials: K
authors.lastname: Okumura
authors.forename: Sadao
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Rika
authors.initials: R
authors.lastname: Matsutomo
authors.forename: Kohzo
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Inukai
mesh_terms: D000419:Albuminuria / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001777:Blood Coagulation; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood* / Q000209:etiology / Q000276:immunology; D005260:Female; D005340:Fibrinogen / Q000652:urine; D005341:Fibrinolysin / Q000652:urine; D005342:Fibrinolysis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D007249:Inflammation / Q000209:etiology; D015850:Interleukin-6 / Q000097:blood / Q000652:urine; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000652:urine
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D011486:Protein C; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D006710:Homocysteine; D005340:Fibrinogen; D003404:Creatinine; D005341:Fibrinolysin