title: Influence of insulin and glargine on outgrowth and number of circulating endothelial progenitor cells in type 2 diabetes patients: a partially double-blind, randomized, three-arm unicenter study.
abstract: BACKGROUND
  Endothelial progenitor cells (EPC) are bone marrow-derived cells which can undergo differentiation into endothelial cells and participate in endothelial repair and angiogenesis. Insulin facilitates this in vitro mediated by the IGF-1 receptor. Clinical trials showed that the number of circulating EPCs is influenced by glucose control and EPC are a predictor of cardiovascular death. To study direct effects of insulin treatment on EPCs in type 2 diabetes patients, add-on basal insulin treatment was compared to an escalation of oral medication aiming at similar glucose control between the groups.
  
  
  METHODS
  55 patients with type 2 diabetes (61.6±5.9 years) on oral diabetes medication were randomized in a 2:2:1 ratio in 3 groups. Patients were treated additionally with insulin glargine (n=20), NPH insulin (n=22) or escalated with oral medication (n=13). Number of circulating EPC, EPC-outgrowth, intima media thickness, skin microvascular function and HbA1c were documented at baseline and/or after 4 weeks and 4 months.
  
  
  RESULTS
  HbA1c at baseline was, 7.3+/-0.7% in the oral group, 7.3+/-0.9% and 7.5+/-0.7% in the glargine and NPH insulin respectively (p=0.713). HbA1c after 4 months decreased to 6.8+/-0.8%, 6.6+/-0.7% and 6.7+/-0.6%, in the oral, glargine and NPH insulin group respectively (p=0.61). FACS analysis showed no difference in number of circulating EPC between the groups after 4 weeks and 4 months. However, the outgrowth of EPCs as detected by colony forming assay was increased in the NPH insulin and glargine groups (29.2+/-6.4 and 29.4+/- 6.7 units respectively) compared to the group on oral medication (23.2+/-6.3, p=0.013) after 4 months of treatment. A significant decrease of IMT from 0.80mm (+/-0.14) at baseline to 0.76mm (+/-0.12) after 4 months could be observed in all patients only (p=0.03) with a trend towards a reduction of IMT after 4 months when all patients on insulin treatment were compared to the oral treatment group (p=0.06). Skin microvascular function revealed no differences between the groups (p=0.74).
  
  
  CONCLUSIONS
  The study shows that a 4-month treatment with add-on insulin significantly increases the outgrowth of EPC in patients with type 2 diabetes mellitus.
  
  
  BACKGROUND
  (Clinical Trials Identifier: NCT00523393).
authors.affiliation: Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, Heidelberg, 69120, Germany. dimitrios.oikonomou@med.uni-heidelberg.de.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Oikonomou
authors.forename: Stefan
authors.initials: S
authors.lastname: Kopf
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Bauer
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Djuric
authors.forename: Rita
authors.initials: R
authors.lastname: Cebola
authors.forename: Anja
authors.initials: A
authors.lastname: Sander
authors.forename: Stefan
authors.initials: S
authors.lastname: Englert
authors.forename: Spiros
authors.initials: S
authors.lastname: Vittas
authors.forename: Asa
authors.initials: A
authors.lastname: Hidmark
authors.forename: Michael
authors.initials: M
authors.lastname: Morcos
authors.forename: Grigorios
authors.initials: G
authors.lastname: Korosoglou
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Per M
authors.initials: PM
authors.lastname: Humpert
mesh_terms: D000328:Adult; D000368:Aged; D002452:Cell Count / Q000379:methods; D049108:Cell Enlargement / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine