Skip to main content

Advertisement

Log in

Reducing glucose variability with continuous subcutaneous insulin infusion increases endothelial progenitor cells in type 1 diabetes: an observational study

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Circulating endothelial progenitor cells (EPCs) are involved in the repairing mechanisms of vascular damage. Glucose variability may contribute to the development of chronic vascular complications of diabetes. We evaluated whether reducing glucose variability with continuous subcutaneous insulin infusion (CSII) would increase circulating levels of EPCs in type 1 diabetes. The study population consisted of 106 type 1 diabetic patients: 41 subjects considered eligible for CSII completed a 6-month follow-up. Sixty-five patients on intensified insulin therapy with multiple daily injections served as control group. Seven EPCs phenotypes were assessed by flow cytometry, and glucose variability by mean amplitude of glycemic excursions (MAGE). Both CD34+KDR+ [difference between groups 32.0, 95 % CI (19.6–44.4) number/106 cells, P < 0.001] and CD34+KDR+CD133+ [12.5 (5.5–19.5), P < 0.001)] cell count increased at endpoint in the CSII group, associated with a reduction of MAGE [−1.1 (−2.1 to −0.1), P = 0.026]. No changes occurred in the control group. In multivariate analyses, changes in MAGE were independently associated with changes in both CD34+KDR+ (P = 0.019) and CD34+KDR+CD133+ (P = 0.022) cell count. Reducing glucose variability with CSII in type 1 diabetes increases circulating EPCs levels, suggesting a novel mechanism of vascular damage by oscillating glucose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. A. Avogaro, M. Albiero, L. Menegazzo, S. de Kreutzenberg, G.P. Fadini, Endothelial dysfunction in diabetes: the role of reparatory mechanisms. Diabetes Care 34(Suppl 2), S285–290 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  2. K.Y. Howangyin, J.S. Silvestre, Diabetes mellitus and ischemic diseases: molecular mechanisms of vascular repair dysfunction. Arterioscler. Thromb. Vasc. Biol. 34, 1126–1135 (2014)

    Article  CAS  PubMed  Google Scholar 

  3. S.A. Sorrentino, F.H. Bahlmann, C. Besler, M. Müller, S. Schulz, N. Kirchhoff, C. Doerries, T. Horváth, A. Limbourg, F. Limbourg, D. Fliser, H. Haller, H. Drexler, U. Landmesser, Oxidant stress impairs in vivo reendothelialization capacity of endothelial progenitor cells from patients with type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated receptor gamma agonist rosiglitazone. Circulation 116, 163–173 (2007)

    Article  CAS  PubMed  Google Scholar 

  4. S.L. Hernandez, J.H. Gong, L. Chen, I.H. Wu, J.K. Sun, H.A. Keenan, G.L. King, Characterization of circulating and endothelial progenitor cells in patients with extreme-duration type 1 diabetes. Diabetes Care 37, 2193–2201 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. T. Hörtenhuber, B. Rami-Mehar, M. Satler, K. Nagl, C. Höbaus, F. Höllerl, R. Koppensteiner, G. Schernthaner, E. Schober, G.H. Schernthaner, Endothelial progenitor cells are related to glycemic control in children with type 1 diabetes over time. Diabetes Care 36, 1647–1653 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  6. M. Gili, A. Orsello, S. Gallo, M.F. Brizzi, Diabetes-associated macrovascular complications: cell-based therapy a new tool? Endocrine 44, 557–575 (2013)

    Article  CAS  PubMed  Google Scholar 

  7. S. Frontoni, P. Di Bartolo, A. Avogaro, E. Bosi, G. Paolisso, A. Ceriello, Glucose variability: an emerging target for the treatment of diabetes mellitus. Diabetes Res. Clin. Pract. 102, 86–95 (2013)

    Article  CAS  PubMed  Google Scholar 

  8. F. Cavalot, Do data in the literature indicate that glycaemic variability is a clinical problem? Glycaemic variability and vascular complications of diabetes. Diabetes Obes. Metab. 15(Suppl 2), 3–8 (2013)

    Article  CAS  PubMed  Google Scholar 

  9. American Diabetes Association, Standards of medical care in diabetes—2015. Diabetes Care 38(Supp l1), S41–S48 (2015)

    Article  Google Scholar 

  10. M.I. Maiorino, G. Bellastella, M. Petrizzo, M.R. Improta, C. Brancario, F. Castaldo, L. Olita, D. Giugliano, K. Esposito, Treatment satisfaction and glycemic control in young Type 1 diabetic patients in transition from pediatric health care: CSII versus MDI. Endocrine 46, 256–262 (2014)

    Article  CAS  PubMed  Google Scholar 

  11. D. Bruttomesso, D. Crazzolara, A. Maran, S. Costa, M. Dal Pos, A. Girelli, G. Lepore, M. Aragona, E. Iori, U. Valentini, S. Del Prato, A. Tiengo, A. Buhr, R. Trevisan, A. Baritussio, In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine. Diabet. Med. 25, 326–332 (2008)

    Article  CAS  PubMed  Google Scholar 

  12. M.I. Maiorino, E. Della Volpe, L. Olita, G. Bellastella, D. Giugliano, K. Esposito, Glucose variability inversely associates with endothelial progenitor cells in type 1 diabetes. Endocrine 48, 342–345 (2015)

    Article  CAS  PubMed  Google Scholar 

  13. J.C. Pickup, P. Hammond, NICE guidance on continuous subcutaneous insulin infusion 2008: review of the technology appraisal guidance. Diabet. Med. 26, 1–4 (2009)

    Article  CAS  PubMed  Google Scholar 

  14. M.I. Maiorino, G. Bellastella, M. Petrizzo, E. Della Volpe, R. Orlando, D. Giugliano, K. Esposito, Circulating endothelial progenitor cells in type 1 diabetic patients with erectile dysfunction. Endocrine 49, 415–421 (2015)

    Article  CAS  PubMed  Google Scholar 

  15. N. Mauras, L. Fox, K. Englert, R.W. Beck, Continuous glucose monitoring in type 1 diabetes. Endocrine 43, 41–50 (2013)

    Article  CAS  PubMed  Google Scholar 

  16. G.P. Fadini, A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia 57, 4–15 (2014)

    Article  CAS  PubMed  Google Scholar 

  17. N. Werner, S. Kosiol, T. Schiegl, P. Ahlers, K. Walenta, A. Link, M. Böhm, G. Nickenig, Circulating endothelial progenitor cells and cardiovascular outcomes. N. Engl. J. Med. 353, 999–1007 (2005)

    Article  CAS  PubMed  Google Scholar 

  18. S. Sen, S.P. McDonald, P.T. Coates, C.S. Bonder, Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease. Clin. Sci. (Lond.) 120, 263–283 (2011)

    Article  CAS  Google Scholar 

  19. C. Dessapt, J. Karalliedde, M. Hernandez-Fuentes, P. Prieto Martin, G. Maltese, N. Dattani, R. Atkar, G. Viberti, L. Gnudi, Circulating vascular progenitor cells in patients with type 1 diabetes and microalbuminuria. Diabetes Care. 33, 875–877 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  20. L. Sibal, A. Aldibbiat, S.C. Agarwal, G. Mitchell, C. Oates, S. Razvi, J.U. Weaver, J.A. Shaw, P.D. Home, Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia 52, 1464–1473 (2009)

    Article  CAS  PubMed  Google Scholar 

  21. L. Monnier, E. Mas, C. Ginet, F. Michel, L. Villon, J.P. Cristol, C. Colette, Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295, 1681–1687 (2006)

    Article  CAS  PubMed  Google Scholar 

  22. I.M. Wentholt, W. Kulik, R.P. Michels, J.B. Hoekstra, J.H. DeVries, Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes. Diabetologia 51, 183–190 (2008)

    Article  CAS  PubMed  Google Scholar 

  23. E.S. Kilpatrick, A.S. Rigby, S.L. Atkin, The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 29, 1486–1490 (2006)

    Article  CAS  PubMed  Google Scholar 

  24. E.S. Kilpatrick, A.S. Rigby, S.L. Atkin, Effect of glucose variability on the long-term risk of microvascular complications in type 1 diabetes. Diabetes Care 32, 1901–1903 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  25. G. Derosa, I. Franzetti, F. Querci, D. Romano, A. D’Angelo, P. Maffioli, Glucose-lowering effect and glycaemic variability of insulin glargine, insulin detemir and insulin lispro protamine in people with type 1 diabetes. Diabetes Obes. Metab. 17, 554–559 (2015)

    Article  CAS  PubMed  Google Scholar 

  26. T. Nakamura, K. Sakaguchi, A. So, S. Nakajima, M. Takabe, H. Komada, Y. Okuno, Y. Hirota, T. Nakamura, K. Iida, M. Kajikawa, M. Nagata, W. Ogawa, S. Seino, Effects of insulin degludec and insulin glargine on day-to-day fasting plasma glucose variability in individuals with type 1 diabetes: a multicentre, randomised, crossover study. Diabetologia (2015). doi:10.1007/s00125-015-3648-y

    PubMed  PubMed Central  Google Scholar 

  27. M.I. Maiorino, M. Petrizzo, A. Capuano, D. Giugliano, K. Esposito, The development of new basal insulins: is there any clinical advantage with their use in type 2 diabetes? Expert Opin. Biol. Ther. 14, 799–808 (2014)

    Article  CAS  PubMed  Google Scholar 

  28. T. Battelino, J.Š. Omladič, M. Phillip, Closed loop insulin delivery in diabetes. Best Pract. Res. Clin. Endocrinol. Metab. 29, 315–325 (2015)

    Article  CAS  PubMed  Google Scholar 

  29. E. Standl, O. Schnell, A. Ceriello, Postprandial hyperglycemia and glycemic variability: should we care? Diabetes Care 34(Suppl 2), S120–127 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  30. L. Heinemann, G.A. Fleming, J.R. Petrie, R.W. Holl, R.M. Bergenstal, A.L. Peters, Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs. A joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. Diabetes Care 38, 716–772 (2015)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Ida Maiorino.

Ethics declarations

Conflict of interest

The authors have nothing to declare.

Additional information

The METRO Study Group members are listed in Appendix.

Appendix

Appendix

The Management and Technology for Transition (METRO) Study Group

Medical expertise

Filomena Castaldo, MD, Diabetes Center at Second University of Naples, Naples, Italy.

Maria Rosaria Improta, MD, PhD, Diabetes Center at Second University of Naples, Naples, Italy.

Michela Petrizzo, MD; IOS and Coleman – Medicina Futura Medical Center, Centro Direzionale, Naples, Italy.

Nursing assistance

Concetta Verazzo, Diabetes Center at Second University of Naples, Naples, Italy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maiorino, M.I., Casciano, O., Volpe, E.D. et al. Reducing glucose variability with continuous subcutaneous insulin infusion increases endothelial progenitor cells in type 1 diabetes: an observational study. Endocrine 52, 244–252 (2016). https://doi.org/10.1007/s12020-015-0686-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0686-7

Keywords

Navigation