title: Proteomic analysis in type 2 diabetes patients before and after a very low calorie diet reveals potential disease state and intervention specific biomarkers.
abstract: Very low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼ 450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin), obesity-associated (complement C3), and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers.
  
  
  BACKGROUND
  Controlled-Trials.com ISRCTN76920690.
authors.affiliation: Departments of General Internal Medicine and Endocrinology & Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sleddering
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Markvoort
authors.affiliation: Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Harish K
authors.initials: HK
authors.lastname: Dharuri
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Skhandhan
authors.initials: S
authors.lastname: Jeyakar
authors.affiliation: Departments of General Internal Medicine and Endocrinology & Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Snel
authors.affiliation: BG Medicine Inc., Waltham, Massachusetts, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Juhasz
authors.affiliation: BG Medicine Inc., Waltham, Massachusetts, United States of America.
authors.forename: Moira
authors.initials: M
authors.lastname: Lynch
authors.affiliation: BG Medicine Inc., Waltham, Massachusetts, United States of America.
authors.forename: Wade
authors.initials: W
authors.lastname: Hines
authors.affiliation: BG Medicine Inc., Waltham, Massachusetts, United States of America.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Departments of General Internal Medicine and Endocrinology & Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Jazet
authors.affiliation: BG Medicine Inc., Waltham, Massachusetts, United States of America.
authors.forename: Aram
authors.initials: A
authors.lastname: Adourian
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Peter A J
authors.initials: PA
authors.lastname: Hilbers
authors.affiliation: Departments of General Internal Medicine and Endocrinology & Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Departments of General Internal Medicine and Endocrinology & Metabolism, Leiden University Medical Center, Leiden, The Netherlands; Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: Van Dijk
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human