Article

Diabetologia

, Volume 56, Issue 8, pp 1856-1866

First online:

An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy

  • G. P. FadiniAffiliated withDivision of Metabolic Diseases, Department of Medicine, University of PadovaVenetian Institute of Molecular Medicine (VIMM) Email author 
  • , S. Vigili de KreutzenbergAffiliated withDivision of Metabolic Diseases, Department of Medicine, University of Padova
  • , E. BoscaroAffiliated withDivision of Metabolic Diseases, Department of Medicine, University of Padova
  • , M. AlbieroAffiliated withVenetian Institute of Molecular Medicine (VIMM)
  • , R. CappellariAffiliated withVenetian Institute of Molecular Medicine (VIMM)
  • , N. KränkelAffiliated withInstitute of Physiology, Cardiovascular Research, University of ZurichDepartment of Cardiology, University Hospital Zurich
  • , U. LandmesserAffiliated withInstitute of Physiology, Cardiovascular Research, University of ZurichDepartment of Cardiology, University Hospital Zurich
  • , A. TonioloAffiliated withDepartment of Pharmaceutical Sciences, University of Padova
  • , C. BolegoAffiliated withDepartment of Pharmaceutical Sciences, University of Padova
    • , A. CignarellaAffiliated withDepartment of Pharmaceutical Sciences, University of Padova
    • , F. SeegerAffiliated withCentre of Molecular Medicine, Institute for Cardiovascular RegenerationDepartment of Medicine III, Frankfurt University
    • , S. DimmelerAffiliated withCentre of Molecular Medicine, Institute for Cardiovascular Regeneration
    • , A. ZeiherAffiliated withCentre of Molecular Medicine, Institute for Cardiovascular RegenerationDepartment of Medicine III, Frankfurt University
    • , C. AgostiniAffiliated withDivision of Metabolic Diseases, Department of Medicine, University of PadovaVenetian Institute of Molecular Medicine (VIMM)
    • , A. AvogaroAffiliated withDivision of Metabolic Diseases, Department of Medicine, University of PadovaVenetian Institute of Molecular Medicine (VIMM)

Abstract

Aim/hypothesis

Monocytes/macrophages play important roles in adipose and vascular tissues and can be polarised as inflammatory M1 or anti-inflammatory M2. We sought to analyse monocyte polarisation status in type 2 diabetes, which is characterised by chronic inflammation.

Methods

We enrolled 60 individuals without diabetes and 53 patients with type 2 diabetes. We quantified standard monocyte subsets defined by cluster of differentiation (CD)14 and CD16. In addition, based on the phenotype of polarised macrophages in vitro, we characterised and quantified more definite M1 (CD68+CCR2+) and M2 (CX3CR1+CD206+/CD163+) monocytes. We also analysed bone marrow (BM) samples and the effects of granulocyte-colony stimulating factor (G-CSF) stimulation in diabetic and control individuals.

Results

We found no alterations in standard monocyte subsets (classical, intermediate and non-classical) when comparing groups. For validation of M1 and M2 phenotypes, we observed that M2 were enriched in non-classical monocytes and had lower TNF-α content, higher LDL scavenging and lower transendothelial migratory capacity than M1. Diabetic patients displayed an imbalanced M1/M2 ratio compared with the control group, attributable to a reduction in M2. The M1/M2 ratio was directly correlated with waist circumference and HbA1c and, among diabetic patients, M2 reduction and M1/M2 increase were associated with microangiopathy. A decrease in M2 was also found in the BM from diabetic patients, with a relative M2 excess compared with the bloodstream. BM stimulation with G-CSF mobilised M2 macrophages in diabetic but not in healthy individuals.

Conclusions/interpretation

We show that type 2 diabetes markedly reduces anti-inflammatory M2 monocytes through a dysregulation in bone-marrow function. This defect may have a negative impact on microangiopathy.

Keywords

Complications Immune cells Inflammation Obesity