Skip to main content
Top
Published in: Endocrine 2/2016

01-05-2016 | Original Article

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

Authors: Maria Ida Maiorino, Ofelia Casciano, Elisabetta Della Volpe, Giuseppe Bellastella, Dario Giugliano, Katherine Esposito

Published in: Endocrine | Issue 2/2016

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
2.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
3.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
4.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
5.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
6.
go back to reference M. Gili, A. Orsello, S. Gallo, M.F. Brizzi, Diabetes-associated macrovascular complications: cell-based therapy a new tool? Endocrine 44, 557–575 (2013)CrossRefPubMed M. Gili, A. Orsello, S. Gallo, M.F. Brizzi, Diabetes-associated macrovascular complications: cell-based therapy a new tool? Endocrine 44, 557–575 (2013)CrossRefPubMed
7.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
8.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
9.
go back to reference American Diabetes Association, Standards of medical care in diabetes—2015. Diabetes Care 38(Supp l1), S41–S48 (2015)CrossRef American Diabetes Association, Standards of medical care in diabetes—2015. Diabetes Care 38(Supp l1), S41–S48 (2015)CrossRef
10.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
11.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
12.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
13.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
14.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
15.
go back to reference N. Mauras, L. Fox, K. Englert, R.W. Beck, Continuous glucose monitoring in type 1 diabetes. Endocrine 43, 41–50 (2013)CrossRefPubMed N. Mauras, L. Fox, K. Englert, R.W. Beck, Continuous glucose monitoring in type 1 diabetes. Endocrine 43, 41–50 (2013)CrossRefPubMed
16.
go back to reference G.P. Fadini, A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia 57, 4–15 (2014)CrossRefPubMed G.P. Fadini, A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications. Diabetologia 57, 4–15 (2014)CrossRefPubMed
17.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
18.
go back to reference 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)CrossRef 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)CrossRef
19.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
20.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
21.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
22.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
23.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
24.
go back to reference 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)CrossRefPubMedPubMedCentral 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)CrossRefPubMedPubMedCentral
25.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
26.
go back to reference 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 PubMedPubMedCentral 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 PubMedPubMedCentral
27.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
28.
go back to reference T. Battelino, J.Š. Omladič, M. Phillip, Closed loop insulin delivery in diabetes. Best Pract. Res. Clin. Endocrinol. Metab. 29, 315–325 (2015)CrossRefPubMed T. Battelino, J.Š. Omladič, M. Phillip, Closed loop insulin delivery in diabetes. Best Pract. Res. Clin. Endocrinol. Metab. 29, 315–325 (2015)CrossRefPubMed
29.
30.
go back to reference 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)CrossRefPubMed 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)CrossRefPubMed
Metadata
Title
Reducing glucose variability with continuous subcutaneous insulin infusion increases endothelial progenitor cells in type 1 diabetes: an observational study
Authors
Maria Ida Maiorino
Ofelia Casciano
Elisabetta Della Volpe
Giuseppe Bellastella
Dario Giugliano
Katherine Esposito
Publication date
01-05-2016
Publisher
Springer US
Published in
Endocrine / Issue 2/2016
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-015-0686-7

Other articles of this Issue 2/2016

Endocrine 2/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.