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Open Access 01-12-2018 | Commentary

How to interpret the role of SDF-1α on diabetic complications during therapy with DPP-4 inhibitors

Authors: Gian Paolo Fadini, Angelo Avogaro

Published in: Cardiovascular Diabetology | Issue 1/2018

Excerpt

In a review article on this Journal, Milton Packer discusses the “potential confounding effect of stem-cell chemokines (SDF-1α)” on diabetic vascular complications during therapy with DPP-4 inhibitors [1]. This misconception is also part of the underlying hypothesis in another author’s recent article [2]. The purpose of this commentary is to show that such misinterpretation is not supported by data and derives from a partial and selective consideration of the literature. …

Packer M. Have dipeptidyl peptidase-4 inhibitors ameliorated the vascular complications of type 2 diabetes in large-scale trials? The potential confounding effect of stem-cell chemokines. Cardiovasc Diabetol. 2018;17(1):9.CrossRefPubMedPubMedCentral

Packer M. Is the popularity of dipeptidyl-peptidase-4 inhibitors justified? Insights from mechanistic studies and clinical trials. Am J Med. 2018. https://doi.org/10.1016/j.amjmed.2017.11.055.

Fadini GP, Bonora BM, Cappellari R, Menegazzo L, Vedovato M, Iori E, Marescotti MC, Albiero M, Avogaro A. Acute effects of linagliptin on progenitor cells, monocyte phenotypes, and soluble mediators in type 2 diabetes. J Clin Endocrinol Metab. 2016;101(2):748–56.CrossRefPubMed

Ghasemzadeh N, Hritani AW, De Staercke C, Eapen DJ, Veledar E, Al Kassem H, Khayata M, Zafari AM, Sperling L, Hooper C, Vaccarino V, Mavromatis K, Quyyumi AA. Plasma stromal cell-derived factor 1alpha/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease. Atherosclerosis. 2015;238(1):113–8.CrossRefPubMed

Subramanian S, Liu C, Aviv A, Ho JE, Courchesne P, Muntendam P, Larson MG, Cheng S, Wang TJ, Mehta NN, Levy D. Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk. Arterioscler Thromb Vasc Biol. 2014;34(9):2100–5.CrossRefPubMedPubMedCentral

Dei Cas A, Spigoni V, Cito M, Aldigeri R, Ridolfi V, Marchesi E, Marina M, Derlindati E, Aloe R, Bonadonna RC, Zavaroni I. Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes. Cardiovasc Diabetol. 2017;16(1):27.CrossRefPubMedPubMedCentral

Aiuti A, Webb IJ, Bleul C, Springer T, Gutierrez-Ramos JC. The chemokine SDF-1 is a chemoattractant for human CD34⁺ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34⁺ progenitors to peripheral blood. J Exp Med. 1997;185(1):111–20.CrossRefPubMedPubMedCentral

Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K, Calandra G, DiPersio JF. Rapid mobilization of CD34⁺ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin’s lymphoma. J Clin Oncol. 2004;22(6):1095–102.CrossRefPubMed

Kim BJ, Lee JK, Schuchman EH, Jin HK, Bae JS. Synergistic vasculogenic effects of AMD3100 and stromal-cell-derived factor-1alpha in vasa nervorum of the sciatic nerve of mice with diabetic peripheral neuropathy. Cell Tissue Res. 2013;354(2):395–407.CrossRefPubMed

10.

Fadini GP, Boscaro E, Albiero M, Menegazzo L, Frison V, de Kreutzenberg S, Agostini C, Tiengo A, Avogaro A. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care. 2010;33(7):1607–9.CrossRefPubMedPubMedCentral

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Poncina N, Albiero M, Menegazzo L, Cappellari R, Avogaro A, Fadini GP. The dipeptidyl peptidase-4 inhibitor saxagliptin improves function of circulating pro-angiogenic cells from type 2 diabetic patients. Cardiovasc Diabetol. 2014;13:92.CrossRefPubMedPubMedCentral

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Fadini GP, Rigato M, Cappellari R, Bonora BM, Avogaro A. Long-term prediction of cardiovascular outcomes by circulating CD34⁺ and CD34⁺CD133⁺ stem cells in patients with type 2 diabetes. Diabetes Care. 2017;40(1):125–31.CrossRefPubMed

13.

Rigato M, Bittante C, Albiero M, Avogaro A, Fadini GP. Circulating progenitor cell count predicts microvascular outcomes in type 2 diabetic patients. J Clin Endocrinol Metab. 2015;100(7):2666–72.CrossRefPubMed

14.

Takashima S, Fujita H, Fujishima H, Shimizu T, Sato T, Morii T, Tsukiyama K, Narita T, Takahashi T, Drucker DJ, Seino Y, Yamada Y. Stromal cell-derived factor-1 is upregulated by dipeptidyl peptidase-4 inhibition and has protective roles in progressive diabetic nephropathy. Kidney Int. 2016;90(4):783–96.CrossRefPubMed

15.

Siddiqi FS, Chen LH, Advani SL, Thai K, Batchu SN, Alghamdi TA, White KE, Sood MM, Gibson IW, Connelly KA, Marsden PA, Advani A. CXCR4 promotes renal tubular cell survival in male diabetic rats: implications for ligand inactivation in the human kidney. Endocrinology. 2015;156(3):1121–32.CrossRefPubMed

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Fujita H, Taniai H, Murayama H, Ohshiro H, Hayashi H, Sato S, Kikuchi N, Komatsu T, Komatsu K, Narita T, Yamada Y. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1alpha in type 2 diabetic patients with incipient nephropathy. Endocr J. 2014;61(2):159–66.CrossRefPubMed

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Chang YP, Sun B, Han Z, Han F, Hu SL, Li XY, Xue M, Yang Y, Chen L, Li CJ, Chen LM. Saxagliptin attenuates albuminuria by inhibiting podocyte epithelial- to-mesenchymal transition via SDF-1alpha in diabetic nephropathy. Front Pharmacol. 2017;8:780.CrossRefPubMedPubMedCentral

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Scheen AJ, Delanaye P. Renal outcomes with dipeptidyl peptidase-4 inhibitors. Diabetes Metab. 2017;. https://doi.org/10.1016/j.diabet.2017.07.011.

19.

Cooper ME, Perkovic V, McGill JB, Groop PH, Wanner C, Rosenstock J, Hehnke U, Woerle HJ, von Eynatten M. Kidney disease end points in a pooled analysis of individual patient-level data from a large clinical trials program of the dipeptidyl peptidase 4 inhibitor linagliptin in type 2 diabetes. Am J Kidney Dis. 2015;66(3):441–9.CrossRefPubMed

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Avogaro A, Fadini GP. The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications. Diabetes Care. 2014;37(10):2884–94.CrossRefPubMed

21.

Fadini GP, Saragoni S, Russo P, Degli Esposti L, Vigili de Kreutzenberg S, Melazzini M, Avogaro A. Intraclass differences in the risk of hospitalization for heart failure among patients with type 2 diabetes initiating a dipeptidyl peptidase-4 inhibitor or a sulphonylurea: results from the OsMed health-DB registry. Diabetes Obes Metab. 2017;19(10):1416–24.CrossRefPubMed

22.

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23.

Fadini GP, Avogaro A. SGTL2 inhibitors and amputations in the US FDA adverse event reporting system. Lancet Diabetes Endocrinol. 2017;5(9):680–1.CrossRefPubMed

24.

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.CrossRefPubMed

Title: How to interpret the role of SDF-1α on diabetic complications during therapy with DPP-4 inhibitors
Authors: Gian Paolo Fadini
Angelo Avogaro
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Cardiovascular Diabetology / Issue 1/2018
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-018-0668-1

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