Document Type
Journal Article
Publication Date
5-3-2018
Journal
Cardiovascular diabetology [electronic resource]
Volume
17
Issue
1
DOI
10.1186/s12933-018-0709-9
Abstract
AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients.
METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for < 10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (p < 0.05).
RESULTS: Although there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (p < 0.05) and a downregulation in CD34- cells for IL-6 (p < 0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (p < 0.05).
CONCLUSION: Saxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Dore, F., Domingues, C., Ahmadi, N., Kundu, N., Kropotova, Y., Houston, S., Rouphael, C., Mammadova, A., Witkin, L., Khiyami, A., Amdur, R., & Sen, S. (2018). The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.. Cardiovascular diabetology [electronic resource], 17 (1). http://dx.doi.org/10.1186/s12933-018-0709-9
Peer Reviewed
1
Open Access
1
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Surgery Commons
Comments
Reproduced with permission of BioMed Central Ltd. Cardiovascular Diabetology