title: Increased serum levels of the specific advanced glycation end product methylglyoxal-derived hydroimidazolone are associated with retinopathy in patients with type 2 diabetes mellitus.
abstract: Advanced glycation end products (AGEs) are thought to play a major pathogenic role in diabetic retinopathy. The most important AGE is unknown, but as increased serum methylglyoxal-derived hydroimidazolone has been demonstrated in patients with type 2 diabetes mellitus, the aim of the present study was to elucidate possible associations between serum levels of hydroimidazolone and retinopathy in patients with type 2 diabetes mellitus. We recruited 227 patients with type 2 diabetes mellitus and retinopathy ranging from none to proliferative. Level of retinopathy was determined from 7 standard field stereo photographs per eye according to the Early Treatment Diabetic Retinopathy Study. The patients were 66 +/- 11 years old, with a known diabetes duration of 14 +/- 9 years. Serum levels of hydroimidazolone were determined with a competitive immunoassay. Serum levels of hydroimidazolone were increased in nonproliferative (median, 4.50 U/mL; interquartile range, 3.69-5.77 U/mL) and proliferative retinopathy (median, 4.88 U/mL; interquartile range, 3.70-6.52 U/mL) compared with patients without retinopathy (median, 4.02 U/mL; interquartile range, 3.47-4.88 U/mL) (P = .008 and .002, respectively). There was no association between hydroimidazolone and hemoglobin A1c (r = 0.04, P = .57). In addition, patients with proliferative retinopathy and a relatively short known duration of diabetes, that is, less than the median of 14 years, had increased serum levels of hydroimidazolone (median, 6.91 U/mL; interquartile range, 4.70-8.91 U/mL) compared with those with nonproliferative retinopathy (median, 4.34; interquartile range, 3.86-5.53U/mL, P = .015). Serum levels of hydroimidazolone are increased in type 2 diabetic patients with retinopathy. This association is independent of hitherto known associated factors, such as hemoglobin A1c.
authors.affiliation: Diabetes Research Centre, Aker and Ullevål University Hospitals, N-0514 Oslo, Norway. dag.fosmark@medisin.uio.no
authors.forename: Dag Sigurd
authors.initials: DS
authors.lastname: Fosmark
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: Bente K
authors.initials: BK
authors.lastname: Kilhovd
authors.forename: Tore J
authors.initials: TJ
authors.lastname: Berg
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Hanssen
authors.forename: Carl-David
authors.initials: CD
authors.lastname: Agardh
authors.forename: Elisabet
authors.initials: E
authors.lastname: Agardh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology / Q000652:urine; D003930:Diabetic Retinopathy / Q000097:blood* / Q000473:pathology / Q000652:urine; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D014792:Visual Acuity / Q000502:physiology
chemical_list: D003404:Creatinine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007093:Imidazoles; C117197:imidazolone