title: An unbalanced monocyte polarisation in peripheral blood and bone marrow of patients with type 2 diabetes has an impact on microangiopathy.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy. gianpaolo.fadini@unipd.it
authors.forename: G P
authors.initials: GP
authors.lastname: Fadini
authors.forename: S Vigili
authors.initials: SV
authors.lastname: de Kreutzenberg
authors.forename: E
authors.initials: E
authors.lastname: Boscaro
authors.forename: M
authors.initials: M
authors.lastname: Albiero
authors.forename: R
authors.initials: R
authors.lastname: Cappellari
authors.forename: N
authors.initials: N
authors.lastname: Kränkel
authors.forename: U
authors.initials: U
authors.lastname: Landmesser
authors.forename: A
authors.initials: A
authors.lastname: Toniolo
authors.forename: C
authors.initials: C
authors.lastname: Bolego
authors.forename: A
authors.initials: A
authors.lastname: Cignarella
authors.forename: F
authors.initials: F
authors.lastname: Seeger
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
authors.forename: A
authors.initials: A
authors.lastname: Zeiher
authors.forename: C
authors.initials: C
authors.lastname: Agostini
authors.forename: A
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D003925:Diabetic Angiopathies / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000276:immunology