title: Differentiation of type 2 diabetes mellitus with different complications by proteomic analysis of plasma low abundance proteins.
abstract: BACKGROUND
  Few biomarkers of type 2 diabetes mellitus (T2DM) are replicable in the differentiation of T2DM with different complications. We aimed to identify proteomic biomarkers among T2DM patients with nephropathy or retinopathy.
  
  
  METHODS
  Plasma low abundance proteins were enriched by depletion of 14 high abundance proteins using an affinity removal system, and subjected to nanoflow liquid chromatography electrospray ionization (nano LC-ESI) mass spectrometry after a gel electrophoresis with in-gel digestion. The plasma differential proteomes between normal adults and diabetic patients were validated by another cohort of 149 T2DM patients.
  
  
  RESULTS
  A total of 826 proteins in plasma were consistently identified from 8 plasma samples of normal adults, and 817 proteins were consistently identified in 8 plasma samples of T2DM patients. Using the MetaCore analysis, low abundance proteins in plasma between normal adults and T2DM patients were significantly different in 5 functional pathways. Moreover, plasma prolactin-induced protein (PIP), thrombospondin-2 (THBS2), L1 cell adhesion molecule (L1CAM) and neutrophil gelatinase-associated lipocalin (NGAL) levels were higher in T2DM patients. Further, PIP, THBS2 and NGAL were significantly higher in T2DM patients with nephropathy (albuminuria) but not in those with retinopathy, while L1CAM levels were higher in T2DM patients with retinopathy.
  
  
  CONCLUSIONS
  This study identified that higher PIP, THBS2 and/or NGAL levels were significantly associated with nephropathy of T2DM, and higher L1CAM but normal PIP, THBS2 or NGAL was significantly associated with retinopathy of T2DM.
authors.affiliation: Institute of Long-term Care, MacKay Medical College, Sanzhi District New Taipei City, 252 Taiwan.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Yeh
authors.affiliation: Department of Medical Research, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, 833 Taiwan.
authors.forename: Wan-Ching
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Proteomic Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833 Taiwan.
authors.forename: Hau
authors.initials: H
authors.lastname: Chuang
authors.affiliation: Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833 Taiwan.
authors.forename: Hui-Cheng
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Division of Endocrinology & Metabolism, Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University, Kaohsiung, 833 Taiwan.
authors.forename: Rue-Tsuan
authors.initials: RT
authors.lastname: Liu
authors.affiliation: Department of Research & Development, MacKay Memorial Hospital, Taipei 104, New Taipei City, 252 Taiwan ; Department of Medicine, MacKay Medical College, New Taipei City, 252 Taiwan.
authors.forename: Kuender D
authors.initials: KD
authors.lastname: Yang
keywords: Albuminuria; Low abundance proteins; Nephropathy; Plasma proteome; Retinopathy; Type 2 diabetes