Pioglitazone increases the numbers and improves the functional capacity of endothelial progenitor cells in patients with diabetes mellitus.
BACKGROUND
Endothelial progenitor cells (EPCs) are present in peripheral blood and can promote postnatal angiogenesis. The number and function of circulating EPCs are altered in diabetics. This study sought to investigate whether the number and functional properties of EPCs from patients with type II diabetes could be improved by pioglitazone.


METHODS
For this randomized controlled study, we recruited 36 type II diabetic patients on metformin monotherapy with a glycohemoglobin A1c of <7%. Patients were separated into pioglitazone (n = 24) and control (n = 12) groups. The number and functional activity of EPCs, and the brachial artery flow-mediated dilation were determined before and after pioglitazone treatment (8 weeks) as an add-on therapy to metformin. In addition, direct effects of pioglitazone on EPCs were also investigated.


RESULTS
After pioglitazone treatment, the numbers of circulating EPCs significantly increased (from 0.44% +/- 0.14% to 0.89% +/- 0.29%, P = .01). The migratory response and the adhesive capacity to fibronectin and collagen were improved by 158%, 34%, and 83%, respectively (all P < .05). Treatment with pioglitazone significantly lowered triglyceride, very low density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hsCRP) levels, and increased high-density lipoprotein levels and insulin sensitivity (all P < .05). The increase in the number of circulating EPCs and the improvement in the migratory response after pioglitazone treatment were independently correlated to the decrease in hsCRP levels (P < or = .01). The increase in the adhesive capacity was independently correlated to the decreases in very low density lipoprotein cholesterol (P = .01) and hsCRP levels (P = .03). In addition, pioglitazone was also demonstrated to have direct effects on increasing EPC proliferation and colony formation, and attenuating EPC apoptosis (all P < .05, versus the controls). There were no significant changes in flow-mediated dilation in either group.


CONCLUSIONS
Pioglitazone significantly increased the number and improved the functional properties of EPCs in type II diabetic patients through direct effects and/or anti-inflammation and lipid modification effects.
Wang
Chao-Hung
CH
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan. bearty@adm.cgmh.org.tw
Ting
Ming-Kuo
MK
Verma
Subodh
S
Kuo
Li-Tang
LT
Yang
Ning-I
NI
Hsieh
I-Chang
IC
Wang
Shin-Yi
SY
Hung
Agnes
A
Cherng
Wen-Jin
WJ
D000368:Aged; D001916:Brachial Artery / Q000503:physiopathology; D002448:Cell Adhesion; D002452:Cell Count; D002465:Cell Movement; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012039:Regional Blood Flow; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone