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Acta Diabetologica

, Volume 49, Issue 1, pp 75–79 | Cite as

Long-lasting remission of type 1 diabetes following treatment with topiramate for generalized seizures

  • Alberto M. Davalli
  • Carla Perego
  • Franco B. Folli
  • Emanuele Bosi
Case Report

Abstract

We report a case of unusually long-lasting remission of type 1 diabetes (T1D). The patient, a Caucasian man, at the age of 43 years developed a ketotic diabetes, classified as type 1 based on clinical presentation and positivity for islet autoantibodies. Shortly after diabetes onset, oral topiramate was added to preexisting valproic acid for generalized seizures and maintained thereafter. Initial intensive insulin treatment was rapidly reduced to low doses (3 Units/day) maintained for a long time and then discontinued at month 55; fasting glucose and glycosylated hemoglobin were basically normalized at 58 months. An oral glucose tolerance test performed at month 53 showed an impaired fasting glucose (6.0 mmol/l) and a value slightly above the threshold for the diagnosis of diabetes at 2 h (11.2 mmol/l). We hypothesize that this unusually prolonged preservation of β-cell function might be ascribed to the concomitant therapy with topiramate, an antiepileptic agent with demonstrated efficacy as antidiabetic in type 2 diabetes (T2D). Topiramate should be further investigated as candidate agent for the preservation of β-cell function also in T1D.

Keywords

Type 1 diabetes (T1D) Remission phase Topiramate 

Notes

Acknowledgments

We thank L. Adorini for the critical review of the manuscript and advice.

Conflict of interest

All the Authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

References

  1. 1.
    Aly H, Gottlieb P (2009) The honeymoon phase: intersection of metabolism and immunology. Curr Opin Endocrinol Diabetes Obes 16(4):286–292PubMedCrossRefGoogle Scholar
  2. 2.
    Bonfanti R, Bazzigaluppi E, Calori G, Riva MC, Viscardi M, Bognetti E, Meschi F, Bosi E, Chiumello G, Bonifacio E (1998) Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus. Diabet Med 15(10):844–850PubMedCrossRefGoogle Scholar
  3. 3.
    Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, Lachin JM, Polonsky KS, Pozzilli P, Skyler JS, Steffes MW (2004) C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop. Diabetes 53:250–264PubMedCrossRefGoogle Scholar
  4. 4.
    DCCT Research Group (1998) Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 128:517–523Google Scholar
  5. 5.
    US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) (2008) Diabetes mellitus: developing drugs and therapeutic biologics for treatment and prevention, draft guidance. http://www.fda.gov/cder/guidance/7630dft.pdf
  6. 6.
    Calcaterra V, Bottazzi A, Tzialla C, D’Arrigo S, Larizza D (2011) Iatrogenic diabetes mellitus during ACTH therapy in an infant with West syndrome. Acta Diabetol. doi: 10.1007/s00592-011-0253-5
  7. 7.
    Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M (2004) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes 28(11):1399–1410CrossRefGoogle Scholar
  8. 8.
    Toplak H, Hamann A, Moore R, Masson E, Gorska M, Vercruysse F, Sun X, Fitchet M (2007) Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Int J Obes 31(1):138–146CrossRefGoogle Scholar
  9. 9.
    Stenlöf K, Rössner S, Vercruysse F, Kumar A, Fitchet M, Sjöström L (2007) Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes. Diabetes Obes Metab 9(3):360–368PubMedCrossRefGoogle Scholar
  10. 10.
    Rosenstock J, Hollander P, Gadde KM, Sun X, Strauss R, Leung A (2007) A randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of topiramate controlled release in the treatment of obese type 2 diabetic patients. Diabetes Care 30(6):1480–1486PubMedCrossRefGoogle Scholar
  11. 11.
    Törn C, Mueller PW, Schlosser M, Bonifacio E, Bingley PJ (2008) Diabetes antibody standardization program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2. Diabetologia 51(5):846–852PubMedCrossRefGoogle Scholar
  12. 12.
    Rolandsson O, Palmer JP (2010) Latent autoimmune diabetes in adults (LADA) is dead: long live autoimmune diabetes! Diabetologia 53(7):1250–1253Google Scholar
  13. 13.
    Jin P, Huang G, Lin J, Luo S, Zhou Z (2011) Epitope analysis of GAD65 autoantibodies in adult-onset type 1 diabetes and latent autoimmune diabetes in adults with thyroid autoimmunity. Acta Diabetol. doi: 10.1007/s00592-010-0250-0
  14. 14.
    Solimena M, Folli F, Denis-Donini S, Comi GC, Pozza G, De Camilli P, Vicari AM (1988) Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. N Engl J Med 318(16):1012–1020PubMedCrossRefGoogle Scholar
  15. 15.
    Olson JA, Olson DM, Sandborg C, Alexander S, Buckingham B (2002) Type 1 diabetes mellitus and epilepsia partialis continua in a 6-year-old boy with elevated anti-GAD65 antibodies. Pediatrics 109(3):E50Google Scholar
  16. 16.
    McCorry D, Nicolson A, Smith D, Marson A, Feltbower RG, Chadwick DW (2006) An association between type 1 diabetes and idiopathic generalized epilepsy. Ann Neurol 59(1):204–206PubMedCrossRefGoogle Scholar
  17. 17.
    Buzzetti R, Di Pietro S, Giaccari A, Petrone A, Locatelli M, Suraci C, Capizzi M, Arpi ML, Bazzigaluppi E, Dotta F, Bosi E (2007) High titre of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Diabetes Care 30:932–938PubMedCrossRefGoogle Scholar
  18. 18.
    Bottazzo GF, Bosi E, Cull CA, Bonifacio E, Locatelli M, Zimmet P, Mackay IR, Holman RR (2005) IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71). Diabetologia 48:703–708PubMedCrossRefGoogle Scholar
  19. 19.
    Liang Y, Chen X, Osborne M, DeCarlo SO, Jetton TL, Demarest K (2005) Topiramate ameliorates hyperglycaemia and improves glucose-stimulated insulin release in ZDF rats and db/db mice. Diabetes Obes Metab 7(4):360–369PubMedCrossRefGoogle Scholar
  20. 20.
    Frigerio F, Chaffard G, Berwaer M, Maechler P (2006) The antiepileptic drug topiramate preserves metabolism-secretion coupling in insulin secreting cells chronically exposed to the fatty acid oleate. Biochem Pharmacol 72(8):965–973PubMedCrossRefGoogle Scholar
  21. 21.
    Eyal S, Yagen B, Sobol E, Altschuler Y, Shmuel M, Bialer M (2004) The activity of antiepileptic drugs as histone deacetylase inhibitors. Epilepsia 45(7):737–744PubMedCrossRefGoogle Scholar
  22. 22.
    Gray SG, De Meyts P (2005) Role of histone and transcription factor acetylation in diabetes pathogenesis. Diabetes Metab Res Rev 21(5):416–433PubMedCrossRefGoogle Scholar
  23. 23.
    Larsen L, Tonnesen M, Ronn SG, Størling J, Jørgensen S, Mascagni P, Dinarello CA, Billestrup N, Mandrup-Poulsen T (2007) Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells. Diabetologia 50(4):779–789PubMedCrossRefGoogle Scholar
  24. 24.
    Haumaitre C, Lenoir O, Scharfmann R (2008) Histone deacetylase inhibitors modify pancreatic cell fate determination and amplify endocrine progenitors. Mol Cell Biol 28(20):6373–6383PubMedCrossRefGoogle Scholar
  25. 25.
    Tao R, de Zoeten EF, Ozkaynak E, Chen C, Wang L, Porrett PM, Li B, Turka LA, Olson EN, Greene MI, Wells AD, Hancock WW (2007) Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med 13(11):1299–1307PubMedCrossRefGoogle Scholar
  26. 26.
    Li B, Samanta A, Song X, Iacono KT, Bembas K, Tao R, Basu S, Riley JL, Hancock WW, Shen Y, Saouaf SJ, Greene MI (2007) FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression. Proc Natl Acad Sci USA 104(11):4571–4576PubMedCrossRefGoogle Scholar
  27. 27.
    Luo X, Herold KC, Miller SD (2010) Immunotherapy of type 1 diabetes: where are we and where should we be going? Immunity 32(4):488–499PubMedCrossRefGoogle Scholar
  28. 28.
    Matthews JB, Staeva TP, Bernstein PL, Peakman M, von Herrath M (2010) ITN-JDRF Type 1 diabetes combination therapy assessment group. Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Diabetes Combination Therapy Assessment Group. Clin Exp Immunol 160(2):176–184PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Alberto M. Davalli
    • 1
  • Carla Perego
    • 2
  • Franco B. Folli
    • 3
  • Emanuele Bosi
    • 1
  1. 1.Department of Internal Medicine, Diabetes and Endocrinology UnitSan Raffaele Scientific Institute, and Vita-Salute San Raffaele UniversityMilanItaly
  2. 2.Department of Molecular ScienceUniversità degli Studi di MilanoMilanItaly
  3. 3.Department of Medicine Diabetes DivisionUniversity of Texas Health Science CenterSan AntonioUSA

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