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Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients

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Summary

To investigate the presence of autoantibodies against sympathetic nervous tissue and their correlation with cardiac sympathetic dysinnervation in insulin-dependent diabetes mellitus (IDDM), 20 newly diagnosed (age 26±6 years) and 48 long-term IDDM patients (age 40±13 years, duration of diabetes 22±12 years) without myocardial perfusion abnormalities (normal 99mTC-methoxyisobutylisonitrile uptake) were assessed for myocardial 123I-metaiodobenzylguanidine (123I-MIBG) uptake and complement-fixing sympathetic ganglia (CF-SG) autoantibodies. Both groups of patients were also studied for islet cell antibodies (ICA) and ECG-based cardiac autonomic neuropathy. Eighty control subjects (age 18–49 years) were investigated for CF-SG autoantibodies. Eight newly diagnosed (40%) and 12 long-term (25%) IDDM patients exhibited CF-SG autoantibodies, compared to 4 control subjects (5%; p<0.01, p<0.05). In long-term diabetic patients, the reduction of global but not of regional myocardial 123I-MIBG uptake correlated with CF-SG autoantibodies (r=0.34, p=0.02). Newly diagnosed diabetic patients did not show an association between CF-SG autoantibodies and global or regional myocardial 123I-MIBG uptake. ECG-based cardiac autonomic neuropathy (≥ two of five cardiac reflex tests abnormal) was present in 22 and absent in 26 long-term IDDM patients, of whom 9 (41%) and 3 (12%), respectively were positive for CF-SG autoantibodies (p=0.02). Only 1 newly diagnosed IDDM patient demonstrated ECG-based cardiac autonomic neuropathy and was also positive for CF-SG autoantibodies. Although they are somewhat suggestive, results concerning autoantibodies against sympathetic nervous tissue and cardiac sympathetic dysinnervation do not strongly support the view that autoimmune mechanisms play a major role in the pathogenesis of cardiac sympathetic neuropathy in IDDM.

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Abbreviations

MIBG:

Metaiodobenzylguanidine

SPECT:

single-photon emission computed tomography

CF-SG:

complement-fixing sympathetic ganglia

MIBI:

methoxyisobutylisonitrile

ICA:

islet cell antibodies

MU:

myocardial uptake

References

  1. Gilbey SG, Guy RJ, Jones H, Vergani D, Watkins PJ (1986) Diabetes and autonomic neuropathy: an immunological association? Diabet Med 3: 241–245

    PubMed  CAS  Google Scholar 

  2. Guy RJC, Richards F, Edmonds ME, Watkins PJ (1984) Diabetic autonomic neuropathy and iritis: an association suggesting an immunological cause. BMJ 289: 343–345

    Article  PubMed  CAS  Google Scholar 

  3. Duchen LW, Anjorin A, Watkins PJ, Mackay JD (1980) Pathology of autonomic neuropathy in diabetes mellitus. Ann Intern Med 92: 301–303

    PubMed  CAS  Google Scholar 

  4. Rabinowe SL, Brown FM, Watts M, Smith AM (1990) Complement-fixing antibodies to sympathetic and para-sympathetic tissues in IDDM. Diabetes Care 13: 1084–1088

    Article  PubMed  CAS  Google Scholar 

  5. Zanone MM, Peakman M, Purewal T, Watkins PJ, Vergani D (1993) Autoantibodies to nervous tissue structures are associated with autonomic neuropathy in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 36: 564–569

    Article  PubMed  CAS  Google Scholar 

  6. Sundkvist G, Lind P, Bergström B, Lilja B, Rabinowe SL (1991) Autonomic nerve antibodies and autonomic nerve function in type 1 and type 2 diabetic patients. J Intern Med 229: 505–510

    PubMed  CAS  Google Scholar 

  7. Brown FM, Kamalesh M, Adri MNS, Rabinowe SL (1988) Anti-adrenal medullary antibodies in IDDM subjects and subjects at high risk of developing IDDM. Diabetes Care 11: 30–33

    Article  PubMed  CAS  Google Scholar 

  8. Rabinowe SL, Brown FM, Watts M, Kadrofske MM, Vinik AI (1989) Anti-sympathetic ganglia antibodies and postural blood pressure in IDDM subjects of varying duration and patients at high risk of developing IDDM. Diabetes Care 12: 1–6

    Article  PubMed  CAS  Google Scholar 

  9. Sundkvist G, Velloso LA, KÄmpe O et al. (1994) Glutamic acid decarboxylase antibodies, autonomic nerve antibodies and autonomic neuropathy in diabetic patients. Diabetologia 37: 293–299

    Article  PubMed  CAS  Google Scholar 

  10. Ewing DJ, Clarke BF (1982) Diagnosis and management of diabetic autonomic neuropathy. BMJ 285: 916–918

    Article  PubMed  CAS  Google Scholar 

  11. MÄntysaari M, Kuikka J, Mustonen J et al. (1992) Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using (123I) metaiodobenzylguanidine. Diabetes 41: 1069–1075

    Article  PubMed  Google Scholar 

  12. Claus D, Feistel H, Brunhölzl C, Platsch G, Neundörfer B, Wolf F (1994) Investigation of parasympathetic and sympathetic cardiac innervation in diabetic neuropathy: heart rate variation versus meta-iodo-benzylguanidine measured by single photon emission computed tomography. Clinical autonomic Research 4: 117–123

    Article  PubMed  CAS  Google Scholar 

  13. Langer A, Freeman MR, Josse RG, Armstrong PW (1995) Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia. J Am Coll Cardiol 25: 610–618

    Article  PubMed  CAS  Google Scholar 

  14. Kreiner G, Wolzt M, Fasching P et al. (1995) Myocardial m-(123I)Iodobenzylguanidine scintigraphy for the asssessment of adrenergic cardiac innervation in patients with IDDM. Diabetes 44: 543–549

    Article  PubMed  CAS  Google Scholar 

  15. Schnell O, Kirsch C-M, Stemplinger J, Haslbeck M, Standl E (1995) Scintigraphic evidence for cardiac sympathetic dysinnervation in long-term IDDM patients with and without ECG-based autonomic neuropathy. Diabetologia 38: 1345–1352

    Article  PubMed  CAS  Google Scholar 

  16. Khafagi FA, Shapiro B, Fig LM, Malette S, Sisson JC (1989) Labetol reduces iodine-131 MIBG uptake by pheochromocytoma and normal tissues. J Nucl Med 30: 481–489

    PubMed  CAS  Google Scholar 

  17. Bonifacio E, Bingley PJ, Shattock M et al. (1990) Quantification of islet cell antibodies and prediction of insulin-dependent diabetes. Lancet 335: 147–149

    Article  PubMed  CAS  Google Scholar 

  18. Ziegler D, Laux G, Dannehl K et al.(1992) Assessment of cardiovascular function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med 9: 166–175

    Article  PubMed  CAS  Google Scholar 

  19. Sisson JC, Shapiro B, Meyers L et al. (1987) Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 28: 1625–1636

    PubMed  CAS  Google Scholar 

  20. Tobes MC, Jaques S, Wieland DM, Sisson JC (1985) Effect of uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine. J Nucl Med 26: 897–907

    PubMed  CAS  Google Scholar 

  21. Iversen LL (1971) Role of transmitter uptake mechanisms in synaptic neurotransmission. Br J Pharmacol 41: 571–591

    PubMed  CAS  Google Scholar 

  22. Wellman HN, Zipes DP (1990) Cardiac sympathetic imaging with radioionated metaiodobenzylguanidine (MIBG). In: Zipes DP, Rowlands DJ (eds) Progress in cardiology 3/1. Lea and Febiger, Philadelphia London, pp 161–174

    Google Scholar 

  23. Minardo JD, Tuli MM, Mock BH et al. (1988) Scintigraphic and electrophysiologic evidence of canine myocardial sympathetic denervation and reinervation produced by myocardial infarction or phenol application. Circulation 78: 1008–1019

    PubMed  CAS  Google Scholar 

  24. Kirsch C-M, Moser E, Buell U (1985) Quantitative Auswertung von 201Tc-Myocardszintigrammen in SPECT Technik. Nuc Compact 16: 230–234

    Google Scholar 

  25. Duchen LW, Anjorin A, Watkins PJ, Mackay JD (1980) Pathology of autonomic neuropathy in diabetes mellitus. Ann Intern Med 92: 301–303

    PubMed  CAS  Google Scholar 

  26. Drell DW, Notkins AL (1987) Multiple immunological abnormalities in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 132–143

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Diabetes Research Institute, Kölner Platz 1, D-80804, Munich, Germany

    O. Schnell, D. Muhr, A. G. Ziegler, M. Haslbeck & E. Standl

  2. Third Medical Department, Schwabing City Hospital, Munich, Germany

    O. Schnell, A. G. Ziegler, M. Haslbeck & E. Standl

  3. Department of Nuclear Medicine, University of Munich, Germany

    S. Dresel & K. Tatsch

Authors
  1. O. Schnell
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  2. D. Muhr
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  3. S. Dresel
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  4. K. Tatsch
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  5. A. G. Ziegler
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  6. M. Haslbeck
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  7. E. Standl
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Schnell, O., Muhr, D., Dresel, S. et al. Autoantibodies against sympathetic ganglia and evidence of cardiac sympathetic dysinnervation in newly diagnosed and long-term IDDM patients. Diabetologia 39, 970–975 (1996). https://doi.org/10.1007/BF00403917

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  • DOI: https://doi.org/10.1007/BF00403917

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