title: Diabetes results in structural alteration of chondroitin sulfate in the urine.
abstract: OBJECTIVE
  The assessment of the clinical significance of chondroitin sulfate in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between chondroitin sulfate (CS) structure and disease.
  
  
  METHODS
  Healthy control (n=15), type 2 diabetic patients with normalbuminuria (n=12), and patients with microalbuminuria (n=13) were enrolled in the study. Total sulfated glycosaminoglycans (GAGs) concentration in the first morning urine was evaluated by 1,9-dimethylmethylene blue method and the composition was determined by agarose gel electrophoresis. Urinary chondroitin sulfate was quantified by a combination of treatment with specific lyase digestions and separation of products by SAX-HPLC.
  
  
  RESULTS
  GAGs concentration significantly increased in diabetic patients with microalbuminuria compared to diabetic patients with normalbuminuria. Qualitative analysis of urinary GAGs revealed the presence of chondroitin sulfate, heparan sulfate, and low-sulphated chondroitin sulphate-protein complex (LSC-PG). There was a decrease in CS and an increase in LSC-PG in the urine of patients with diabetes compared to healthy controls. Moreover, in diabetic patients, chondroitin sulfate contains more 6-sulfated disaccharide and less 4-sulfated disaccharide. There was a statistically significant difference in ratio of 6-sulfated disaccharide to 4-sulfated disaccharide among the three groups.
  
  
  CONCLUSIONS
  GAGs were significantly increased in diabetic patients with microalbuminuria. The levels of urinary GAGs, ratio of LSC-PG/CS, as well as ratio of 6-sulfated to 4-sulfated disaccharides could be useful markers for diagnosis of patients with diabetic nephropathy.
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lu
authors.forename: Neal M
authors.initials: NM
authors.lastname: Davies
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Guo
authors.forename: Haojun
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Hong
authors.forename: Guixiang
authors.initials: G
authors.lastname: Fu
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D002809:Chondroitin Sulfates / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine; D004587:Electrophoresis, Agar Gel / Q000379:methods; D005260:Female; D006497:Heparan Sulfate / Q000652:urine; D006801:Humans; D008297:Male; D008751:Methylene Blue / Q000031:analogs & derivatives / Q000737:chemistry; D008875:Middle Aged
chemical_list: D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D008751:Methylene Blue; C016401:1,9-dimethylmethylene blue