Skip to main content

Advertisement

Log in

Atherosclerotic coronary plaque in subjects with diabetic neuropathy: the prognostic cardiovascular role of Charcot neuroarthropathy—a case–control study

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case–control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3–43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.

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
Fig. 4

Similar content being viewed by others

References

  1. Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ et al (2007) Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 28:88–136

    Article  PubMed  Google Scholar 

  2. Alexander CM, Landsman PB, Teutsch SM (2000) Diabetes mellitus, impaired fasting glucose, atherosclerotic risk factors, and prevalence of coronary heart disease. Am J Cardiol 86:897–902

    Article  CAS  PubMed  Google Scholar 

  3. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators (1996) Comparison of coronary artery bypass surgery with angioplasty in patients with multivessel disease (correction 1997;336:147. N Engl J Med 335:217–225

    Article  Google Scholar 

  4. American Diabetes Association (1998) Consensus development conference on the diagnosis of coronary heart disease in people with diabetes. Diabetes Care 21:1551–1559

    Article  Google Scholar 

  5. Miller TD, Redberg RF, Wackers FJT (2006) Screening asymptomatic diabetic patients for coronary artery disease: why not? J Am Coll Cardiol 48:761–764

    Article  PubMed  Google Scholar 

  6. Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE, DIAD Investigators (2009) Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA 301:1547–1555

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Rathmann W, Ziegler D, Jahnke M, Haastert B, Gries FA (1993) Mortality in diabetic patients with cardiovascular autonomic neuropathy. Diabet Med 10:820–824

    Article  CAS  PubMed  Google Scholar 

  8. Liao D, Carnethon M, Evans GW, Cascio WE, Heiss G (2002) Lower heart rate variability is associated with the development of coronary heart diseases in individuals with diabetes: the Atherosclerosis Risk in Communities Study. Diabetes 51:3524–3531

    Article  CAS  PubMed  Google Scholar 

  9. Jeffcoate W, Lima J, Nobrega L (2000) The Charcot foot. Diabet Med 17:253–258

    Article  CAS  PubMed  Google Scholar 

  10. Mortality associated with acute Charcot foot and neuropathic foot ulceration and diabetes alone diabetes care (2009) 32:816–821

  11. Taylor AJ, Cerqueira M, Hodgson JM, Mark D, Min J, O’Gara P, Rubin GD (2010) ACCF/SCCT/ACR/AHA/ASE/ASN/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. Circulation 122:e525–e555

    Article  PubMed  Google Scholar 

  12. Young MJ, Breddy JL, Veves A, Boulton AJM (1994) The prediction of diabetic neuropathy foot using vibration perception threshold: a prospective study. Diabetes Care 17:557–560

    Article  CAS  PubMed  Google Scholar 

  13. Young MJ, Boulton AJM, Macleod AF, Williamd DRR, Sonksen PK (1993) A multicentre study of the prevalence of diabetic peripheral neuropathy in the UK hospital clinic population. Diabetologia 36:150–154

    Article  CAS  PubMed  Google Scholar 

  14. Ewing DJ, Clarke BF (1982) Diagnosis and management of diabetic autonomic neuropathy. Br Med J 285:916–918

    Article  CAS  Google Scholar 

  15. Cavanagh PR, Young MJ, Adams JE, Vickers KL, Boulton AJM (1994) Radiographic abnormalities in the feet of patients with diabetic neuropathy. Diabetes Care 17:201–209

    Article  CAS  PubMed  Google Scholar 

  16. Tomas MB, Patel M, Marvin SE, Palestro CJ (2000) The diabetic foot. Br J Radiol 73:443–450

    Article  CAS  PubMed  Google Scholar 

  17. European Society of Hypertension-European Society of Cardiology Guidelines Committee (2003) European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 21(6):1011–1053

    Google Scholar 

  18. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 285(19):2486–2497

    Google Scholar 

  19. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report (1998) National Institutes of Health. Obes Res 6(Suppl 2):51S–209S

    Google Scholar 

  20. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B et al (2001) Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286:421–426

    Article  CAS  PubMed  Google Scholar 

  21. Taylor AJ, Bindeman J, Feuerstein I, Cao F, Brazaitis M, O’Malley PG (2005) Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors: mean three-year outcomes in the Prospective Army Coronary Calcium (PACC) project. J Am Coll Cardiol 46(5):807–814

    Article  CAS  PubMed  Google Scholar 

  22. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832

    Article  CAS  PubMed  Google Scholar 

  23. Meijboom WB, Van Mieghem CAG, van Pelt N et al (2008) Comprehensive assessment of coronary artery stenoses: computed tomography coronary angiography versus conventional coronary angiography and correlation with fractional flow reserve in patients with stable angina. J Am Coll Cardiol 52:636–643

    Article  PubMed  Google Scholar 

  24. Austen WG, Edwards JE, Frye RL et al (1975) A reporting system on patients evaluated for coronary artery disease. Report of the ad hoc committee for grading of coronary artery disease, council on cardiovascular surgery, American Heart Association. Circulation 51:5–40

    Article  CAS  PubMed  Google Scholar 

  25. Nathan DM, Meigs J, Singer DE (1997) The epidemiology of cardiovascular disease in type 2 diabetes mellitus: how sweet it is … or is it. Lancet 350(Suppl 1):SI4–SI9

    Article  PubMed  Google Scholar 

  26. Kamalesh M, Feigenbaum H, Sawada S (2007) Assessing prognosis in patients with diabetes mellitus: the Achilles’ heel of cardiac stress imaging tests? Am J Cardiol 99(7):1016–1019

    Article  PubMed  Google Scholar 

  27. Beck MO, Silveiro SP, Friedman R, Clausell N, Gross JL (1999) Asymptomatic coronary artery disease is associated with cardiac autonomic neuropathy and diabetic nephropathy in type 2 diabetic patients. Diabetes Care 22(10):1745–1747

    Article  CAS  PubMed  Google Scholar 

  28. Jeffcoate WJ, Game F, Cavanagh PR (2005) The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet 366:2058–2061

    Article  CAS  PubMed  Google Scholar 

  29. Libby P, Sukhova G, Lee RT, Galis ZS (1995) Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol 25:S9–S12

    Article  CAS  PubMed  Google Scholar 

  30. Tamaru M, Tomura K, Sakamoto S, Tezuka K, Tamatani T et al (1998) Interleukin-1 beta induces tissue- and cell-specific expression of adhesion molecules in vivo. Arterioscler Thromb Vasc Biol 18:1292–1303

    Article  CAS  PubMed  Google Scholar 

  31. Ikeda U, Ikeda M, Oohara T, Kano S, Yaginuma T (1990) Mitogenic action of interleukin-1 alpha on vascular smooth muscle cells mediated by PDGF. Atherosclerosis 84(2–3):183–188

    Article  CAS  PubMed  Google Scholar 

  32. Napoli CF, de Nigris Palinski W (2001) Multiple role of reactive oxygen species in the arterial wall. J Cell Biochem 82(4):674–682

    Article  CAS  PubMed  Google Scholar 

  33. Touyz RM, Schiffrin EL (2004) Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol 122(4):339–352

    Article  CAS  PubMed  Google Scholar 

  34. Cave AC, Brewer AC, Narayanapanicker A et al (2006) NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal 8(5–6):691–728

    Article  CAS  PubMed  Google Scholar 

  35. Li JM, Shah AM (2004) Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol 287(5):R1014–R1030

    CAS  PubMed  Google Scholar 

  36. Kaiser N, Sasson S, Feener EP, Boukobza-Vardi N, Higashi S, Moller DE, Davidheiser S, Przybylski RJ, King GL (1993) Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes 42:80–89

    Article  CAS  PubMed  Google Scholar 

  37. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625

    Article  CAS  PubMed  Google Scholar 

  39. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790

    Article  CAS  PubMed  Google Scholar 

  40. Nascimento NR, Lessa LM, Kerntopf MR, Sousa CM, Alves RS, Queiroz MG, Price J, Heimark DB, Larner J, Du X, Brownlee M, Gow A, Davis C, Fonteles MC (2006) Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide. Proc Natl Acad Sci USA 103:218–223

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Van Baal J, Hubbard R, Game F, Jeffcoate W (2010) Mortality associated with acute Charcot Foot and neuropathic foot ulceration. Diabetes Care 33(5):1086–1089

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

D. Pitocco, R. Marano, E. Di Stasio, G. Scavone, G. Savino, F. Zaccardi, A. Rizzi, F. Martini, T. Musella, V. Silvestri, F. Costantini, M. Galli, S. Caputo, L. Bonomo and G. Ghirlanda declare they have no conflict of interest.

Human and Animal Rights

All the procedures have been followed in accordance with the guidelines of our institutional ethics committee and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

All persons gave their informed consent prior to their inclusion in the study. No identifying details are shown in the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Pitocco.

Additional information

Communicated by Massimo Federici.

D. Pitocco, R. Marano, and E. Di Stasio have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 40 kb)

Supplementary material 2 (DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pitocco, D., Marano, R., Di Stasio, E. et al. Atherosclerotic coronary plaque in subjects with diabetic neuropathy: the prognostic cardiovascular role of Charcot neuroarthropathy—a case–control study. Acta Diabetol 51, 587–593 (2014). https://doi.org/10.1007/s00592-014-0559-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-014-0559-1

Keywords

Navigation