title: Increased levels of N(ε)- Carboxy methyl lysine (N(ε)-CML) are associated with topographic alterations in retinal pigment epithelium: A preliminary study.
abstract: To evaluate the association of serum levels of N(ε)- Carboxy methyl lysine (N(ε)-CML), an advanced glycation end product with topographic alterations in retinal pigment epithelium (RPE) in diabetic retinopathy on spectral domain optical coherence tomography (SD-OCT).
  
  
  
  Consecutive cases of type 2 diabetes mellitus with no retinopathy (n=20); non-proliferative diabetic retinopathy (n=20); proliferative diabetic retinopathy (n=20) and healthy controls (n=20) between the ages of 40 and 65years were included. RPE alterations were graded on segmentation map of SD-OCT: grade 0, No RPE alterations; grade 1, RPE alterations in up to two quadrants and grade 2, RPE alterations in more than two quadrants. Serum level of N(ε)-CML and glycated hemoglobin (HbA1c) was analyzed using the standard protocol. Statistical analysis was done.
  
  
  
  Significant increase in N(ε)-CML was observed with increased severity of diabetic retinopathy (F=34.1; p<0.0001). Fisher exact test revealed significant increase in grades of RPE alterations with increased severity of diabetic retinopathy (p<0.001). Univariate ordinal regression analysis was done to calculate the risk of progression in grades of RPE alteration with individual changes in variables like duration of diabetes (odds ratio=1.37; p=0.001), HbA1c (odds ratio=1.37; p=0.002) and Nε-CML (odds ratio=1.37; p<0.0001). Multivariate ordinal regression analysis for predicting progression in grades of RPE alteration revealed Nε-CML to be an independent predictor of increase in grades of RPE alteration (adjusted odds ratio=1.07; p<0.01) when duration of diabetes and HbA1c were held constant.
  
  
  
  Increase in serum levels of N(ε)- Carboxy methyl lysine is significantly associated with topographic alterations in RPE. Grades of RPE alteration increase significantly with increased severity of diabetic retinopathy.
authors.affiliation: Department of Ophthalmology, King George's Medical University, Lucknow, India.
authors.forename: Nibha
authors.initials: N
authors.lastname: Mishra
authors.affiliation: Department of Ophthalmology, King George's Medical University, Lucknow, India. Electronic address: sandeepsaxena2020@yahoo.com.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Department of Ophthalmology, King George's Medical University, Lucknow, India.
authors.forename: Surabhi
authors.initials: S
authors.lastname: Ruia
authors.affiliation: Department of Community Medicine, King George's Medical University, Lucknow, India.
authors.forename: Senthamizh
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Ophthalmology, King George's Medical University, Lucknow, India.
authors.forename: Vinita
authors.initials: V
authors.lastname: Singh
authors.affiliation: Developmental Toxicology Division, Indian Institute of Toxicology Research, Lucknow, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Khanna
authors.affiliation: 2(nd) Department of Surgery, Faculty of Medicine, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Staffa
authors.affiliation: 2(nd) Department of Internal Medicine, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia. Electronic address: ludovitgaspar@gmail.com.
authors.forename: Ludovit
authors.initials: L
authors.lastname: Gaspar
authors.affiliation: Laboratory of Structural Biology, Central Laboratories, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic; Department of Medical Physics and Biophysics, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic. Electronic address: kruzliakpeter@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D055213:Retinal Pigment Epithelium / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D015854:Up-Regulation; D018630:Vitreoretinopathy, Proliferative / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D008239:Lysine; C517652:hemoglobin A1c protein, human; C048496:N(6)-carboxymethyllysine
keywords: Advanced glycation end product; Diabetic retinopathy; N(ε)- Carboxy methyl lysine; Retinal pigment epithelium; Spectral domain optical coherence tomography