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C-Peptide and Diabetic Neuropathy in Patients with Type 1 Diabetes

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Diabetes & C-Peptide

Part of the book series: Contemporary Diabetes ((CDI))

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Abstract

Neuropathy is one of the most common long-term complications accompanying diabetes mellitus. It affects patients with both type 1 and type 2 diabetes, but it progresses more rapidly and its manifestations are more severe in type 1 diabetes [1, 2]. Diabetic neuropathy is defined by the presence of detectable sensory, motor, and autonomic nerve abnormalities on clinical examination, with or without the presence of symptoms [3, 4]. As many as 50% of the patients may be asymptomatic; diagnosis may only be made on examination or, in some cases, when the patient presents with a painless foot ulcer [5]. Other patients may not report symptoms, but admit on inquiry that their feet feel numb. A careful neurological examination of the lower limb usually reveals sensory loss as reflected by abnormal vibration, pressure, pain, or temperature perception, mediated by small and large fibers, as well as absence of ankle reflexes. Signs of autonomic neuropathy may include manifestations of, for example, impaired cardiovascular and gastrointestinal functions.

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References

  1. Dyck PJ, Davies D, Wilson F, et al. Risk factors for severity of diabetic polyneuropathy: intensive longitudinal assessment of the Rochester Diabetic Neuropathy Study cohort. Diabetes Care. 1999;2(9):1479–86.

    Article  Google Scholar 

  2. Sugimoto K, Murakawa Y, Sima AAF. Diabetic neuropathy – a continuing enigma. Diabetes Metab Res Rev. 2000;16(6):408–33.

    Article  PubMed  CAS  Google Scholar 

  3. Asbury AK, Porte Jr D, Genuth SM, et al. Report and recommendations of the San Antonio conference on diabetic neuropathy. Ann Neurol. 1988;24(1):99–104.

    Article  Google Scholar 

  4. Ziegler D. Treatment of diabetic polyneuropathy. Ann N Y Acad Sci. 2006;1084:250–66.

    Article  PubMed  CAS  Google Scholar 

  5. Boulton A, Vinik A, Arezzo J, et al. Diabetic neuropathies. Diabetes Care. 2005;24(4):956–60.

    Article  Google Scholar 

  6. Said G, Slama G, Selva J. Progressive centripetal degeneration of axons in small fibre diabetic polyneuropathy. Brain. 1983;106(4):791–807.

    Article  PubMed  Google Scholar 

  7. Thomas PK. Diabetic neuropathy: mechanisms and future treatment options. J Neurol Neurosurg Psychiatry. 1999;67(3):277–9.

    Article  PubMed  CAS  Google Scholar 

  8. Shaw J, Zimmet P, Gries F, Ziegler D. Epidemiology of diabetic neuropathy. In: Gries F, Cameron NE, Low P, Ziegler D, editors. Textbook of diabetic neuropathy. New York: Thieme; 2003. p. 64–82.

    Google Scholar 

  9. Coppini D, Bowtell P, Weng C, et al. Showing neuropathy is related to increased mortality in diabetic patients – a survival analysis using an accelerated failure time model. J Clin Epidemiol. 2000;53(5):519–23.

    Article  PubMed  CAS  Google Scholar 

  10. Forsblom CM, Sane T, Groop PH, et al. Risk factors for mortality in type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4. Diabetologia. 1998;41(11):1253–62.

    Article  PubMed  CAS  Google Scholar 

  11. Brownlee M. The pathobiology of diabetic complications. Diabetes. 2005;54(6):1615–25.

    Article  PubMed  CAS  Google Scholar 

  12. Greene DA, Sima AAF, Stevens M, et al. Complications: neuropathy, pathogenic considerations. Diabetes Care. 1992;15(12):1902–25.

    Article  PubMed  CAS  Google Scholar 

  13. Low P, Nickander K, Scionti L. Role of hypoxia, oxidative stress, and excitatory neurotoxins in diabetic neuropathy. In: Dyck P, Thomas P, editors. Diabetic neuropathy. Philadelphia: W.B. Saunders; 1999. p. 317–29.

    Google Scholar 

  14. Cameron NE, Eaton EM, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia. 2001;44(11):1973–88.

    Article  PubMed  CAS  Google Scholar 

  15. Brismar T, Sima AAF, Greene DA. Reversible and irreversible nodal dysfunction in diabetic neuropathy. Ann Neurol. 1987;21(5):504–7.

    Article  PubMed  CAS  Google Scholar 

  16. Cherian VP, Kamijo M, Angelides KJ, Sima AAF. Nodal Na+-channel displacement is associated with nerve-conduction slowing in the chronic diabetic BB/W rat: prevention by aldose reductase inhibition. J Diabet Complications. 1996;10(4):192–200.

    Article  Google Scholar 

  17. Sima AAF, Nathaniel V, Bril V, et al. 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. 1988;81(2):349–64.

    Article  PubMed  CAS  Google Scholar 

  18. Murakawa Y, Zhang W, Pierson CR, et al. Impaired glucose tolerance and insulinopenia in the GK-rat causes peripheral neuropathy. Diabetes Metab Res Rev. 2002;18(6):473–83.

    Article  PubMed  CAS  Google Scholar 

  19. Sima AAF. New insights into the metabolic and molecular basis for diabetic neuropathy. Cell Mol Life Sci. 2003;60(11):2445–64.

    Article  PubMed  CAS  Google Scholar 

  20. DCCT Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995;122:561–8.

    Google Scholar 

  21. DCCT Research Group. Effect of intensive diabetes treatment on nerve conduction in the diabetes control and complications trial. Ann Neurol. 1995;38(6):869–80.

    Article  Google Scholar 

  22. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993;329(5):304–9.

    Article  PubMed  CAS  Google Scholar 

  23. Rigler R, Pramanik A, Jonasson P, et al. Specific binding of proinsulin C-peptide to human cell membranes. Proc Natl Acad Sci U S A. 1999;96(23):13318–23.

    Article  PubMed  CAS  Google Scholar 

  24. Wahren E, Ekberg k, Jörnvall H. C-peptide is a bioactive peptide. Diabetologia. 2007;50(3):503–9.

    Article  PubMed  CAS  Google Scholar 

  25. Pierson CR, Zhang W, Sima AAF. Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration. J Neuropathol Exp Neurol. 2003;62(7):765–79.

    PubMed  CAS  Google Scholar 

  26. Hansen A, Johansson BL, Wahren J, von Bibra H. C-peptide exerts beneficial effects on myocardial blood flow and function in patients with type 1 diabetes. Diabetes. 2002;51(10):3077–82.

    Article  PubMed  CAS  Google Scholar 

  27. Johansson BL, Linde B, Wahren J. Effects of C-peptide on blood flow, capillary diffusion capacity and glucose utilization in the exercising forearm of type 1 (insulin-dependent) diabetic patients. Diabetologia. 1992;35(12):1151–8.

    Article  PubMed  CAS  Google Scholar 

  28. Johansson BL, Sjöberg S, Wahren J. The influence of human C-peptide on renal function and glucose utilization in type 1 (insulin-dependent) diabetic patients. Diabetologia. 1992;35(2):121–8.

    Article  PubMed  CAS  Google Scholar 

  29. Johansson BL, von Bibra A, Hansen A, Wahren J. Effects of C-peptide on regional myocardial function in patients with type 1 diabetes. Diabetes. 2001;50:A256.

    Google Scholar 

  30. Johansson BL, Borg K, Fernqvist-Forbes E, et al. Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus. Diabet Med. 2000;17(3):181–9.

    Article  PubMed  CAS  Google Scholar 

  31. Sjöberg S, Gunnarsson R, Gjötterberg M, et al. Residual insulin production, glycemic control and prevalence of microvascular lesions and polyneuropathy in long-term type 1 (insulin-dependent) ­diabetes mellitus. Diabetologia. 1987;30(4):208–13.

    Article  PubMed  Google Scholar 

  32. Sjöberg S, Götterberg M, Berglund L, et al. Residual C-peptide excretion is associated with a better long-term glycemic control and slower progress of retinopathy in type I (insulin-dependent) diabetes mellitus. J Diabet Complications. 1991;5(1):18–22.

    Article  PubMed  Google Scholar 

  33. Zerbini G, Mangili R, Luzi L. Higher post-absorptive C-peptide levels in type 1 diabetic patients without renal complications. Diabet Med. 1999;16(12):1048–9.

    Article  PubMed  CAS  Google Scholar 

  34. Cotter MA, Ekberg K, Wahren J, Cameron NE. Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition. Diabetes. 2003;52(7):1812–7.

    Article  PubMed  CAS  Google Scholar 

  35. Sima AAF, Zhang W, Sugimoto K, et al. C-peptide prevents and improves chronic type I diabetic polyneuropathy in the BB/Wor rat. Diabetologia. 2001;44(7):889–97.

    Article  PubMed  CAS  Google Scholar 

  36. Stevens M, Li F, Zhang W, Sima AAF. C-peptide corrects endoneurial blood flow but not effect oxidative stress in type 1 BB/Wor rats. Am J Physiol Endocrinol Metab. 2004;287:E497–505.

    Article  PubMed  CAS  Google Scholar 

  37. Ekberg K, Brismar T, Johansson BL, et al. Amelioration of sensory nerve dysfunction by C-peptide in patients with type 1 diabetes. Diabetes. 2003;52(2):536–41.

    Article  PubMed  CAS  Google Scholar 

  38. Ekberg K, Brismar T, Johansson BL, et al. C-peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy. Diabetes Care. 2007;30(1):71–6.

    Article  PubMed  CAS  Google Scholar 

  39. Johansson BL, Borg K, Fernqvist-Forbes E, et al. C-peptide improves autonomic nerve function in IDDM patients. Diabetologia. 1996;39(6):687–95.

    Article  PubMed  CAS  Google Scholar 

  40. Ido Y, Vindigni A, Chang K, et al. Prevention of vascular and neural dysfunction in diabetic rats by C-peptide. Science. 1997;277(5325):563–6.

    Article  PubMed  CAS  Google Scholar 

  41. Stevens M, Dananberg J, Feldman E, et al. The linked roles of nitric oxide, aldose reductase and, (Na+, K+)-ATPase in the slowing of nerve conduction in the streptozotocin diabetic rat. J Clin Invest. 1994;94(2):853–9.

    Article  PubMed  CAS  Google Scholar 

  42. Hotta N. New approaches for treatment in diabetes: aldose reductase inhibitors. Biomed Pharmacother. 1995;49(5):232–43.

    Article  PubMed  CAS  Google Scholar 

  43. Sima AAF, Bril V, Nathaniel V, et al. Regeneration and repair of myelinated fibers in sural-nerve biopsy specimens from patients with diabetic neuropathy treated with sorbinil. N Engl J Med. 1988;319(9):548–55.

    Article  PubMed  CAS  Google Scholar 

  44. Bril V, Buchanan R, AS-3201 Study Group. Aldose reductase inhibition by AS-3201 in sural nerve from patients with diabetic sensorimotor polyneuropathy. Diabetes Care. 2004;27(10):2369–75.

    Article  PubMed  CAS  Google Scholar 

  45. Bril V, Buchanan R, Ranirestat Study Group. Long-term effects of Ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy. Diabetes Care. 2006;29:68–72.

    Article  PubMed  CAS  Google Scholar 

  46. Foppiano M, Lombardo G. Worldwide pharmacovigilance systems and tolrestat withdrawal. Lancet. 1997;349(9049):399–400.

    Article  PubMed  CAS  Google Scholar 

  47. Vinik A, Bril V, Kempler P, et al. Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C β-inhibitor ruboxistaurin mesylate during a 1-year, randomized, placebo-controlled, ­double-blind clinical trial. Clin Ther. 2005;27(8):1164–80.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Fogdevreten 2, 171 77, Stockholm, Sweden

    Karin Ekberg & John Wahren

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  1. Karin Ekberg
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  2. John Wahren
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Correspondence to John Wahren .

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Editors and Affiliations

  1. Departments of Pathology and Neurology, Wayne State University, Detroit, 48201, Michigan, USA

    Anders A.F. Sima

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Ekberg, K., Wahren, J. (2012). C-Peptide and Diabetic Neuropathy in Patients with Type 1 Diabetes. In: Sima, A. (eds) Diabetes & C-Peptide. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-61779-391-2_12

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  • DOI: https://doi.org/10.1007/978-1-61779-391-2_12

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-390-5

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