title: Serum CXCL1 concentrations are elevated in type 1 diabetes mellitus, possibly reflecting activity of anti-islet autoimmune activity.
abstract: BACKGROUND
  Identification of unique inflammatory markers may facilitate prediction of type 1 diabetes mellitus (T1DM). We previously compared transcript profiles of bone marrow-derived dendritic cells from non-obese diabetic mice with those from non-obese non-diabetic mice and found that bone marrow-derived dendritic cells' expressions of inflammatory mediators, including chemokine (C-X-C motif) ligand 1 (CXCL1), were three to five times higher in 4-week-old female non-obese diabetic mice than in non-obese non-diabetic mice. In humans, microarray analysis results have suggested this chemokine be a biomarker representing active anti-islet autoimmunity. We investigated whether serum CXCL1 levels, reflecting active autoimmune processes, might serve as biomarkers for T1DM.
  
  
  METHODS
  The study groups consisted of 26 subjects with acute-onset T1DM, 20 with slowly progressive T1DM, and 20 with type 2 diabetes mellitus as disease controls. All subjects were Japanese. CXCL1 in sera were quantified by solid phase enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Serum CXCL1 levels were significantly higher in subjects with acute-onset [median 113.2 ng/mL (41.75-457.2)] or slowly progressive [median 100.8 ng/mL (32.87-225.0)] T1DM than in those with type 2 diabetes mellitus [median 71.58 ng/mL (32.45-152.6), p=0.01 and 0.03, respectively, Mann-Whitney U-test]. Decreases in fasting C-peptide levels per year correlated significantly with CXCL1 levels (n=11, r2=0.524, p=0.012) in a subpopulation of slowly progressive T1DM subjects displaying preserved beta-cell function.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study to show elevated serum CXCL1 in T1DM subjects, regardless of diabetes subtype, as compared to control type 2 diabetes mellitus subjects. We propose serum CXCL1 elevation to be a good T1DM marker, possibly indicating a predisposition to autoimmune disease development.
authors: Division of Diabetes and Metabolism, Department of Internal Medicine, Iwate Medical University, Morioka, Japan. kazumat@iwate-med.ac.jp
authors: Kazuma
authors: K
authors: Takahashi
authors: Mio
authors: M
authors: Ohara
authors: Takayoshi
authors: T
authors: Sasai
authors: Hiroyuki
authors: H
authors: Homma
authors: Kan
authors: K
authors: Nagasawa
authors: Toru
authors: T
authors: Takahashi
authors: Mitsuhiro
authors: M
authors: Yamashina
authors: Mototsugu
authors: M
authors: Ishii
authors: Fumikado
authors: F
authors: Fujiwara
authors: Takashi
authors: T
authors: Kajiwara
authors: Haruhito
authors: H
authors: Taneichi
authors: Noriko
authors: N
authors: Takebe
authors: Jo
authors: J
authors: Satoh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood; D054360:Chemokine CXCL1 / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D002096:C-Peptide; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1