Acta Diabetologica

, Volume 50, Issue 3, pp 373–382

Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial

Authors

    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Enrico Marone
    • Vascular Surgery Division, Cardio-Thoraco-Vascular Department and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Manuela Mantero
    • Cardiovascular DepartmentMultimedica IRCCS
  • Emanuela Setola
    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Elena Galluccio
    • Cardio-Diabetes and Core Lab Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Pietro Lucotti
    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Ermal Shehaj
    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Valentina Villa
    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Francesca Perticone
    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Massimo Venturini
    • Department of Radiology and Center for Experimental ImagingSan Raffaele Scientific Institute
  • Alessio Palini
    • Flow Cytometry Resource LaboratorySan Raffaele Scientific Institute
  • Flavio Airoldi
    • Cardiovascular DepartmentMultimedica IRCCS
  • Ezio Faglia
    • Cardiovascular DepartmentMultimedica IRCCS
  • Alessandro Del Maschio
    • Department of Radiology and Center for Experimental ImagingSan Raffaele Scientific Institute
  • Antonio Colombo
    • Interventional Cardiology Division, Cardio-Thoraco-Vascular Department and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Roberto Chiesa
    • Vascular Surgery Division, Cardio-Thoraco-Vascular Department and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Emanuele Bosi
    • Cardio-Metabolism and Clinical Trials Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
    • Cardio-Diabetes and Core Lab Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
  • Lucilla D. Monti
    • Cardio-Diabetes and Core Lab Unit, Department of Internal Medicine and Metabolic and Cardiovascular Science DivisionSan Raffaele Scientific Institute
Original Article

DOI: 10.1007/s00592-012-0426-x

Cite this article as:
Piatti, P.M., Marone, E., Mantero, M. et al. Acta Diabetol (2013) 50: 373. doi:10.1007/s00592-012-0426-x

Abstract

Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34+ and CD34+KDR+ progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21–1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41–19.5, p < 0.02). Baseline CD34+KDR+ were higher in rs753482AA (166.2 ± 154.0 × 106 events) than in rs753482AC+CC (63.1 ± 26.9 × 106 events, p < 0.01). At the end of the study, the highest circulating CD34+KDR+ were found in IIT rs753482AA (246.9 ± 194.0 × 106 events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 106 events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.

Keywords

Intensified insulin therapyType 2 diabetesCritical limb ischemiaeNOS polymorphismEndothelial progenitor cellsRestenosisAmputation

Supplementary material

592_2012_426_MOESM1_ESM.doc (70 kb)
Supplementary material 1 (DOC 69 kb)

Copyright information

© Springer-Verlag 2012