title: Complement-mediated chronic inflammation is associated with diabetic microvascular complication.
abstract: BACKGROUND
  Chronic inflammation is characteristic of type 2 diabetes mellitus (T2DM). Obesity-activated adipocytes release adipocytokines, which induce the secretion of proinflammatory cytokines, resulting in vascular endothelial dysfunction and organ injury. C3a is a candidate to induce tissue inflammation.
  
  
  METHODS
  We investigated the association between diabetic microangiopathy and complement-mediated inflammation in 32 obese T2DM patients and 32 normal donors. Plasma levels of complement components and their activation intermediates were examined and related to the level of complication. An incubation study of post-prandial serum was carried out to measure the in vitro production of acylation stimulating protein (ASP/C3a desArg) by chylomicron.
  
  
  RESULTS
  Plasma levels of C3, C4, factor B, iC3b, Bb, and ASP were significantly increased in T2DM patients. Levels of C4d and membrane attack complex (C5b-9) were not significantly elevated. The activation rate of these factors indicated that only the early phase of alternative complement pathway was excessively activated. A statistical study revealed close correlation between ASP, body mass index, and highly sensitive C-reactive protein. Plasma ASP was significantly increased in the macroalbuminuric and proliferative retinopathy patient groups. An incubation study revealed that ASP was produced after the in vitro incubation of post-prandial serum from a T2DM patient with hyperchylomicronaemia.
  
  
  CONCLUSIONS
  Activation of the alternative complement pathway occurs in obese T2DM patients and is enhanced in the post-prandial hyperchylomicronic condition, which induces overproduction of ASP and C3a-mediated tissue inflammation. Therefore, complement-mediated inflammation may contribute to the acceleration of diabetic microangiopathy in addition to the development of macroangiopathy.
authors.affiliation: Department of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo, Japan. tfujita@med.nihon-u.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fujita
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Hemmi
authors.forename: Mamiko
authors.initials: M
authors.lastname: Kajiwara
authors.forename: Minako
authors.initials: M
authors.lastname: Yabuki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Fuke
authors.forename: Atsushi
authors.initials: A
authors.lastname: Satomura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
mesh_terms: D000328:Adult; D000368:Aged; D002914:Chylomicrons / Q000097:blood; D003167:Complement Activation; D003176:Complement C3; D015926:Complement C3a / Q000096:biosynthesis* / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000276:immunology*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D019518:Postprandial Period
chemical_list: C038245:C3 protein, human; D002914:Chylomicrons; D003176:Complement C3; D036341:Intercellular Signaling Peptides and Proteins; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a