Skip to main content

Advertisement

Log in

Treatment-Induced Neuropathy of Diabetes

  • Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Treatment-induced neuropathy of diabetes (TIND) is an under-recognized iatrogenic painful sensory and autonomic neuropathy. This review highlights the clinical symptoms and signs, raises awareness of the cause, and provides education about prevention of TIND.

Recent Findings

TIND may be triggered by a rapid decline in the blood glucose levels following the use of insulin, oral hypoglycemic medications, or even diet only to control diabetes. This may be seen in up to 10% of patients with diabetic neuropathy and has the potential for significant long-term complications that could be avoided through careful disease management. Based on the available evidence, a decrease in the glycosylated hemoglobin A1C of more than 3 points in 3 months in individuals with chronic hyperglycemia increases the risk of developing TIND.

Summary

TIND is more common than previously suspected, and is tied to rates of glycemic control. Slower changes to glucose control are suggested, although there is no prospective data on disease prevention. Future research is necessary to guide treatment recommendations.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Caravati CM. Insulin neuritis: a case report. VaMedMonthly. 1933;59:745–6.

    Google Scholar 

  2. Kihara M, Zollman PJ, Smithson IL, Lagerlund TD, Low PA. Hypoxic effect of exogenous insulin on normal and diabetic peripheral nerve. AmJPhysiol. 1994;266(6 Pt 1):E980–E5.

    CAS  Google Scholar 

  3. Tesfaye S, Malik R, Harris N, Jakubowski JJ, Mody C, Rennie IG, et al. Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis). Diabetologia. 1996;39(3):329–35.

    Article  CAS  PubMed  Google Scholar 

  4. Dabby R, Sadeh M, Lampl Y, Gilad R, Watemberg N. Acute painful neuropathy induced by rapid correction of serum glucose levels in diabetic patients. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2009;63(10):707–9.

    Article  CAS  Google Scholar 

  5. Ellenberg M. Diabetic neuropathic cachexia. Diabetes. 1974;23:418–23.

    Article  CAS  PubMed  Google Scholar 

  6. Gade GN, Hofeldt FD, Treece GL. Diabetic neuropathic cachexia. Beneficial response to combination therapy with amitriptyline and fluphenazine. JAMA 1980;243(11):1160–1.

  7. Massey EW. Diabetic neuropathic cachexia and diabetic amyotrophy. Acta DiabetolLat. 1982;19(1):91–5.

    CAS  Google Scholar 

  8. Blau RH. Diabetic neuropathic cachexia. Report of a woman with this syndrome and review of the literature. ArchInternMed. 1983;143(10):2011–2.

    CAS  Google Scholar 

  9. Llewelyn JG, Thomas PK, Fonseca V, King RH, Dandona P, et al. Acta Neuropathol(Berl). 1986;72:157–63.

    Article  CAS  Google Scholar 

  10. Llewelyn JG, Thomas PK, Fonseca V, Dandona P. Acute painful diabetic neuropathy. Diabetes Care. 1988;11(9):748–9.

    Article  CAS  PubMed  Google Scholar 

  11. Knopp M, Srikantha M, Rajabally YA. Insulin neuritis and diabetic cachectic neuropathy: a review. Curr Diabetes Rev. 2013;9(3):267–74.

    Article  PubMed  Google Scholar 

  12. Gibbons CH, Freeman R. Treatment-induced diabetic neuropathy: a reversible painful autonomic neuropathy. Ann Neurol. 2010;67(4):534–41.

    Article  PubMed  PubMed Central  Google Scholar 

  13. •• Gibbons CH, Freeman R. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes. Brain. 2015;138(Pt 1):43–52. This is the first study describing the frequency of TIND in a referral population. This paper also links the rate of change in the HbA1C with the risk of complciations

    Article  PubMed  Google Scholar 

  14. CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. In: CDC, editor.: Department of Health and Human Services, Centers for Disease Control and Prevention; 2011.

  15. de Groot M, Golden SH, Wagner J. Psychological conditions in adults with diabetes. The American psychologist. 2016;71(7):552–62.

    Article  PubMed  PubMed Central  Google Scholar 

  16. • Colton PA, Olmsted MP, Daneman D, Farquhar JC, Wong H, Muskat S, et al. Eating disorders in girls and women with type 1 diabetes: a longitudinal study of prevalence, onset, remission, and recurrence. Diabetes Care. 2015;38(7):1212–7. An important publication on the frequency and relapse rates of eating disorders in diabetes

    Article  PubMed  Google Scholar 

  17. • Gibbons CH. Treatment induced neuropathy of diabetes—long term implications in type 1 diabetes. J Diabetes Complicat. 2017;31(4):715–20. The first long-term follow-up study of individuals with type 1 diabetes and TIND

    Article  PubMed  Google Scholar 

  18. Gibbons CH, Freeman R, Tecilazich F, Dinh T, Lyons TE, Gnardellis C, et al. The evolving natural history of neurophysiologic function in patients with well-controlled diabetes. Journal of the peripheral nervous system : JPNS. 2013;18(2):153–61.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Takii M, Uchigata Y, Tokunaga S, Amemiya N, Kinukawa N, Nozaki T, et al. The duration of severe insulin omission is the factor most closely associated with the microvascular complications of type 1 diabetic females with clinical eating disorders. IntJEatDisord. 2008;41(3):259–64.

    Google Scholar 

  20. Bryden KS, Neil A, Mayou RA, Peveler RC, Fairburn CG, Dunger DB. Eating habits, body weight, and insulin misuse. A longitudinal study of teenagers and young adults with type 1 diabetes. Diabetes Care. 1999;22(12):1956–60.

    Article  CAS  PubMed  Google Scholar 

  21. Peveler RC, Fairburn CG. Anorexia nervosa in association with diabetes mellitus—a cognitive-behavioural approach to treatment. Behav Res Ther. 1989;27(1):95–9.

    Article  CAS  PubMed  Google Scholar 

  22. Chantelau E, Meyer-Schwickerath R. Reversion of ‘early worsening’ of diabetic retinopathy by deliberate restoration of poor metabolic control. Ophthalmologica. 2003;217(5):373–7.

    Article  CAS  PubMed  Google Scholar 

  23. Group DR. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. NEnglJ Med. 1993;329(14):977–86.

    Article  Google Scholar 

  24. Pop-Busui R, Herman WH, Feldman EL, Low PA, Martin CL, Cleary PA, et al. DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history. CurrDiabRep. 2010;10(4):276–82.

    Google Scholar 

  25. Group DR. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998;116(7):874–86.

    Article  Google Scholar 

  26. Davis MD, Beck RW, Home PD, Sandow J, Ferris FL. Early retinopathy progression in four randomized trials comparing insulin glargine and NPH insulin. ExpClinEndocrinolDiabetes. 2007;115(4):240–3.

    CAS  Google Scholar 

  27. Albers JW, Herman WH, Pop-Busui R, Feldman EL, Martin CL, Cleary PA, et al. Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Diabetes Care. 2010;33(5):1090–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pop-Busui R, Low PA, Waberski BH, Martin CL, Albers JW, Feldman EL, et al. Effects of prior intensive insulin therapy on cardiac autonomic nervous system function in type 1 diabetes mellitus: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC). Circulation. 2009;119(22):2886–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gibbons CH, Bonyhay I, Benson A, Wang N, Freeman R. Structural and functional small fiber abnormalities in the neuropathic postural tachycardia syndrome. PLoS One. 2013;8(12):e84716.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher H. Gibbons.

Ethics declarations

Conflict of Interest

Christopher H. Gibbons has received research funding from Celgene and Grifols, and has served on advisory boards for Lundbeck and Pfizer, and served on data safety monitoring boards of Janssen and Astellas.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Microvascular Complications—Neuropathy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gibbons, C.H. Treatment-Induced Neuropathy of Diabetes. Curr Diab Rep 17, 127 (2017). https://doi.org/10.1007/s11892-017-0960-6

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11892-017-0960-6

Keywords

Navigation