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

Cardiovascular Diabetology

Original Investigation

Grigorios Korosoglou¹  Rita Cebola¹  Asa Hidmark²  Peter P Nawroth²  Dimitrios Oikonomou²  Spiros Vittas²  Stefan Kopf²  Rüdiger von Bauer²  Per M Humpert³  Michael Morcos³  Anja Sander⁴  Stefan Englert⁴  Zdenka Djuric⁵ 

[1] Department of Cardiology, University of Heidelberg, Heidelberg, Germany;Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany;Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany;Stoffwechselzentrum Rhein Pfalz, Germany, Mannheim;Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany;Roche Diagnostics Deutschland GmbH Mannheim, Mannheim, Germany;

关键词: Insulin glargine;    Type 2 diabetes;    Endothelial progenitor cells;   

DOI  :  10.1186/s12933-014-0137-4

 received in 2014-06-06, accepted in 2014-09-30,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundEndothelial 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.Methods55 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.ResultsHbA1c 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).ConclusionThe study shows that a 4-month treatment with add-on insulin significantly increases the outgrowth of EPC in patients with type 2 diabetes mellitus.Trial registration(Clinical Trials Identifier: NCT00523393).

【 授权许可】

CC BY   
© Oikonomou et al.; licensee BioMed Central Ltd. 2014