MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy - real world evidence

Endokrynol Pol. 2018;69(3):264-268. doi: 10.5603/EP.a2018.0028.

Abstract

Introduction:To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms.

Methods: 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in combination with metformin (n=102) were enrolled in the study. The amount of macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were determined.

Results: Metabolic parameters including fasting blood glucose, postprandial 2 hours blood glucose, hemoglobin A1c, MIF and CD74 in serum were comparable between the two groups. Moreover, metformin add-on therapy showed significantly better efficacy in reducing UMCR, UCCR, UPCR and UACR in comparison with those in sulfonylurea monotherapy group, respectively. UPCR had positive correlation with UACR, UMCR and UCCR (r=0.73, r=0.69, r=0.62, P < 0.01), respectively.

Conclusions: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response. < p > < /p >.

Keywords: CD74; macrophage migration inhibitory factor; metformin; podocyte; type 2 diabetes.

MeSH terms

  • Adult
  • Antigens, Differentiation, B-Lymphocyte / blood*
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / urine
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / analysis
  • Histocompatibility Antigens Class II / blood*
  • Humans
  • Intramolecular Oxidoreductases / blood*
  • Intramolecular Oxidoreductases / urine
  • Macrophage Migration-Inhibitory Factors / blood*
  • Macrophage Migration-Inhibitory Factors / urine
  • Male
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Middle Aged
  • Podocytes
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use
  • Sialoglycoproteins / urine*
  • Sulfonylurea Compounds
  • Treatment Outcome

Substances

  • Antigens, Differentiation, B-Lymphocyte
  • Blood Glucose
  • Glycated Hemoglobin A
  • Histocompatibility Antigens Class II
  • Macrophage Migration-Inhibitory Factors
  • Protective Agents
  • Sialoglycoproteins
  • Sulfonylurea Compounds
  • invariant chain
  • podocalyxin
  • Metformin
  • Intramolecular Oxidoreductases
  • MIF protein, human