title: Methylglyoxal, A Metabolite Increased in Diabetes is Associated with Insulin Resistance, Vascular Dysfunction and Neuropathies.
abstract: BACKGROUND
  Diabetes mellitus (DM) is a pandemic metabolic disease characterized by a chronically elevated blood glucose concentration (hyperglycemia) due to insulin dysfunction. Approximately 50% of diabetics show diabetes complications by the time they are diagnosed. Vascular dysfunction, nephropathy and neuropathic pain are common diabetes complications. Chronic hyperglycemia contributes to reactive oxygen species (ROS) generation such as methylglyoxal (MGO).
  
  
  METHODS
  Peer reviewed research papers were studied through bibliographic databases searching focused on review questions and inclusion/exclusion criteria. The reviewed papers were appraised according to the searching focus. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to the included studies using a conceptual framework to yield this comprehensive systematic review.
  
  
  RESULTS
  Sixty-six papers were included in this review. Eleven papers related methylglyoxal generation to carbohydrates metabolism, ten papers related lipid metabolism to methylglyoxal and 5 papers showed the proteolytic pathways that contribute to methylglyoxal generation. Methylglyoxal metabolism was derived from 7 papers. Descriptive figure 1 was drawn to explain methylglyoxal sources and how diabetes increases methylglyoxal generation. Furthermore, twenty-six papers related methylglyoxal to diabetes complications from which 9 papers showed methylglyoxal ability to induce insulin dysfunction, an effect which was described in schematic figure 2. Additionally, fifteen papers revealed methylglyoxal contribution to vascular dysfunction and 3 papers showed methylglyoxal to cause neuropathic pain. Methylglyoxal-induced vascular dysfunction was drawn in a comprehensive figure 3. This review correlated methylglyoxal with diabetes and diabetes complications which were summarised in table 1.
  
  
  CONCLUSIONS
  The findings of this review suggesting methylglyoxal as an essential therapeutic target for managing diabetes in the future.
authors.affiliation: Department of Pharmacology, School of Life and Medical Sciences, College lane, University of Hertfordshire, Hatfield, Hertfordshire, AL109AB, UK. y.shamsaldeen2@herts.ac.uk.
authors.forename: Yousif A
authors.initials: YA
authors.lastname: Shamsaldeen
authors.forename: Louise S
authors.initials: LS
authors.lastname: Mackenzie
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lione
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Benham
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000097:blood / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D009437:Neuralgia / Q000097:blood / Q000378:metabolism; D011765:Pyruvaldehyde / Q000097:blood / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011765:Pyruvaldehyde