Diabetologia

, Volume 35, Issue 6, pp 560–569

The reproducibility and sensitivity of sural nerve morphometry in the assessment of diabetic peripheral polyneuropathy

  • A. A. F. Sima
  • M. B. Brown
  • A. Prashar
  • S. Chakrabarti
  • C. Laudadio
  • D. A. Greene
Originals

Summary

The nerve fibre loss, atrophy and injury of diabetic peripheral polyneuropathy and their responses to metabolic intervention have been studied by morphometric analysis of sural nerve biopsies. The magnitudes and sources of intra- and inter-individual variation in these morphometric measures have not been investigated previously in a systematic manner. Morphometric parameters of nerve fibre damage were measured in four separate fascicles from bilateral sural nerve specimens obtained post-mortem from 13 diabetic and 13 non-diabetic subjects. Intra- and inter-individual coefficients of variation were computed and compared to the magnitude of the differences between normal and diabetic subjects. Several morphometric variables emerged as highly sensitive and reproducible measures of nerve fibre damage suitable for clinical studies of diabetic peripheral polyneuropathy. These observations provide a rational basis for the design of future clinical trials employing morphometric end-points.

Key words

Diabetes mellitus neuropathy morphometry sural nerve 

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References

  1. 1.
    Greene DA, Sima AAF, Albers JW, Pfeifer MA (1990) Pathophysiology of diabetic neuropathy. In: Rifkin H, Porte D (eds) Ellenberg and Rifkin's diabetes mellitus, 4th edn. Elsevier, Amsterdam, pp 710–755Google Scholar
  2. 2.
    Sima AAF, Greene DA (1991) Sural nerve fiber density and normality predict clinical sensory deficits and electrophysiology in chronic diabetic neuropathy. Diabetes 40: 554 A (Abstract)Google Scholar
  3. 3.
    Britland ST, Young RJ, Sharma AK, Clarke BF (1990) Association of painful and painless diabetic polyneuropathy with different patterns of nerve fiber degeneration and regeneration. Diabetes 39: 898–908PubMedGoogle Scholar
  4. 4.
    Dyck PJ, Karnes J, O'Brien PC (1987) Detection of thresholds of cutaneous sensation. In: Dyck PJ, Thomas PK, Asbury AK, Winegrad AI, Porte D, Jr (eds) Diabetic neuropathy. W.B. Saunders, Philadelphia, pp 107–121Google Scholar
  5. 5.
    Maser RE, Nielsen VK, Bass EB, et al. (1989) Measuring diabetic neuropathy: assessment and comparison of clinical examination and quantitative sensory testing. Diab Care 12: 270–275Google Scholar
  6. 6.
    Thiele K, Stålberg E (1975) Single fiber EMG findings in polyneuropathies of different etiology. J Neurol Neurosurg Neuropsychiatry 38: 881–887Google Scholar
  7. 7.
    Behse F, Buchthal F, Carlsen F (1977) Nerve biopsy and conduction studies in diabetic neuropathy. J Neurol Neurosurg Psychiatry 40: 1072–1082PubMedGoogle Scholar
  8. 8.
    Gregersen G (1968) Variations in motor conduction velocity produced by acute changes of the metabolic state in diabetic patients. Diabetologia 4: 273–277PubMedGoogle Scholar
  9. 9.
    Ward JD, Barnes CG, Fisher DJ, Jessop JD, Baker RW (1971) Improvement in nerve conduction following treatment in newly diagnosed diabetics. Lancet I: 428–430CrossRefGoogle Scholar
  10. 10.
    Troni W, Carta Q, Cantello R, Caselle MT, Rainero I (1984) Peripheral nerve function and metabolic control in diabetes mellitus. Ann Neurol 16: 178–183PubMedGoogle Scholar
  11. 11.
    Graf RJ, Halter JB, Pfeifer MD, et al. (1981) Glycemic control and nerve conduction abnormalities in noninsulin-dependent diabetic subjects. Ann Intern Med 94: 307–311PubMedGoogle Scholar
  12. 12.
    Holman RR, Dornan TL, Mayon-White VM, et al. (1983) Prevention of deterioration of renal and sensory-nerve function by more intensive management of insulin-dependent diabetic patients. A two-year randomized prospective study. Lancet I: 204–208CrossRefGoogle Scholar
  13. 13.
    Pietri A, Ehle A, Raskin P (1980) Changes in nerve conduction velocity after six weeks of glycoregulation with portable insulin infusion pumps. Diabetes 29: 668–671PubMedGoogle Scholar
  14. 14.
    Service FJ, Rizza RA, Daube JR, O'Brien PC, Dyck PJ (1985) Near normoglycaemia improved nerve conduction and vibration sensation in diabetic neuropathy. Diabetologia 28: 722–727PubMedGoogle Scholar
  15. 15.
    Steno Study Group (1982) Effect of 6 months strict metabolic control on eye and kidney function in insulin-dependent diabetes with background retinopathy. Lancet I: 121–124Google Scholar
  16. 16.
    Judzewitsch RG, Jaspan JB, Polonsky KS, et al. (1983) Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med 308: 119–125PubMedGoogle Scholar
  17. 17.
    Daube JR (1987) Electrophysiologic testing in diabetic neuropathy. In: Dyck PJ, Thomas PK, Asbury AK, Winegrad AI, Porte D, Jr (eds) Diabetic neuropathy. W.B. Saunders, Philadelphia, pp 162–176Google Scholar
  18. 18.
    Greene DA (1987) Metabolic control. In: Dyck PJ, Thomas PK, Asbury AK, Winegrad AI, Porte D, Jr (eds) Diabetic neuropathy. W.B. Saunders, Philadelphia, pp 177–187Google Scholar
  19. 19.
    Dyck PJ, Karnes JL, Daube J, O'Brien P, Service FJ (1985) Clinical and neuropathologic criteria for the diagnosis and staging of diabetic polyneuropathy. Brain 108: 861–880PubMedGoogle Scholar
  20. 20.
    Dyck PJ, Lais A, Karnes JL, O'Brien P, Rizza R (1986) Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol 19: 425–439PubMedGoogle Scholar
  21. 21.
    Sima AAF, Nathaniel V, Bril V, McEwen TAJ, Greene DA (1988) Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy. J Clin Invest 81: 349–364PubMedGoogle Scholar
  22. 22.
    Sima AAF, Lattimer SA, Yagihashi S, Greene DA (1986) ‘Axoglial dysjunction’ a novel structural lesion that accounts for poorly-reversible slowing of nerve conduction in the spontaneously diabetic BB-rat. J Clin Invest 77: 474–484PubMedGoogle Scholar
  23. 23.
    Sima AAF, Brismar T (1985) Reversible diabetic nerve dysfunction. Structural correlates to electrophysiological abnormalities. Ann Neurol 18: 21–29PubMedGoogle Scholar
  24. 24.
    Brismar T, Sima AAF, Greene DA (1987) Reversible and irreversible nodal dysfunction in diabetic neuropathy. Ann Neurol 21: 504–507PubMedGoogle Scholar
  25. 25.
    Sima AAF, Greene DA, Sorbinil and Tolrestat Neuropathy Study Groups (1991) Sural nerve fiber density and normality predict clinical sensory deficits and electrophysiology in chronic diabetic neuropathy. IDF-Satellite Symposium on Diabetic Neuropathy, New York, NY (Abstract)Google Scholar
  26. 26.
    Sima AAF, Bril V, Nathaniel V, et al. (1988) Regeneration and repair of myelinated fibers in sural nerve biopsies from patients with diabetic neuropathy treated with sorbinil, an investigational aldose reductase inhibitor. N Engl J Med 319: 548–555PubMedGoogle Scholar
  27. 27.
    Pfeifer MA, Porte D, Bril V, et al. and the Sorbinil Neuropathy Study Group (1989) Clinical response to sorbinil treatment in diabetic neuropathy. Diabetes 38: 14 (Abstract)Google Scholar
  28. 28.
    Boulton AJM, Levis S, Comstock JA (1990) A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy. Diabetologia 33: 431–437PubMedGoogle Scholar
  29. 29.
    American Diabetes Association (1988) Report and recommendations of the San Antonio conference on diabetic neuropathy. Diabetes 37: 1000–1004Google Scholar
  30. 30.
    Dyck PJ, Busek W, Spring EM, et al. (1987) Vibratory and cooling detection thresholds compared with other tests in diagnosing and staging diabetic neuropathy. Diab Care 10: 432–440Google Scholar
  31. 31.
    Dyck P, O'Brien PC (1989) Meaningful degrees of prevention or improvement of nerve conduction in controlled clinical trials of diabetic neuropathy. Diab Care 12: 649–652Google Scholar
  32. 32.
    Dyck PJ, Karnes J, O'Brien PC (1987) Diagnosis, staging, and classification of diabetic neuropathy and associations with other complications. In: Dyck PJ, Thomas PK, Asbury AK, Winegrad AI, Porte D, Jr (eds) Diabetic neuropathy. W.B. Saunders, Philadelphia, pp 36–44Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • A. A. F. Sima
    • 1
    • 2
  • M. B. Brown
    • 1
    • 2
  • A. Prashar
    • 3
  • S. Chakrabarti
    • 3
  • C. Laudadio
    • 4
  • D. A. Greene
    • 1
    • 2
  1. 1.Departments of Pathology, Biostatistics and Internal MedicineUniversity of MichiganAnn ArborUSA
  2. 2.The Michigan Diabetes Research and Training CenterUniversity of MichiganAnn ArborUSA
  3. 3.Department of PathologyUniversity of ManitobaWinnipegCanada
  4. 4.School of Life and Health SciencesUniversity of DelawareNewarkUSA

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