Skip to main content

Advertisement

SpringerLink
Log in

Transition from insulin to sulfonylurea in a child with diabetes due to a mutation in KCNJ11 encoding Kir6.2—initial and long-term response to sulfonylurea therapy

  • Short Report
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Background

Mutations in the KCNJ11 gene encoding the adenosine triphosphate (ATP)-sensitive potassium channel (KATP) subunit Kir6.2 are the most frequent cause of diabetes in infancy. Sulfonylurea (SU) treatment restores insulin secretion in patients with KCNJ11 mutations.

Materials and methods

We report a 9-year-old boy who presented at the age of three months with diabetic ketoacidosis. Results Sequencing of the KCNJ11 gene revealed an R201H mutation. Therefore, he was transferred from insulin to oral SU therapy. He required a high-threshold dose before insulin could be discontinued. After transition, a subsequent dose reduction was necessary to avoid hypoglycemia. Improved sustained metabolic control without complications was achieved on a low SU maintenance dose twice daily over 36 months.

Conclusion

SU therapy is safe for patients with diabetes due to KCNJ11 mutations. The mechanism of a threshold dose and the twice-daily requirement needs further attention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

SU:

Sulfonylurea

ATP:

Adenosine triphosphate

SUR:

Sulfonylurea receptor subunit

HbA1c :

Hemoglobin A1c

References

  1. Chan Y-M, Laffel LMB (2007) Transition from insulin to glyburide in a 4-month-old girl with neonatal diabetes mellitus caused by a mutation in KCNJ11. Pediatric Diabetes 8:235–238. DOI 10.1111/j.1399-5448.2007.00231.x

    Article  PubMed  Google Scholar 

  2. Codner E, Flanagan SE, Ugarte F, García H, Vidal T, Ellard S, Hattersley AT (2007) Sulfonylurea treatment in young children with neonatal diabetes: dealing with hyperglycemia, hypoglycemia, and sick days. Diabetes Care 30:e28–e29. DOI 10.2337/dc06-2134

    Article  PubMed  Google Scholar 

  3. Flanagan SE, Edghill EL, Gloyn AL, Ellard S, Hattersley AT (2006) Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the 6 six months of life, with the phenotype determined by genotype. Diabetologia 49:1190–1197. DOI 10.1007/s00125-006-0246-z

    Article  PubMed  CAS  Google Scholar 

  4. Flanagan SE, Patch AM, Mackay DJ, Edghill EL, Gloyn AL, Robinson D, Shield JP, Temple K, Ellard S, Hattersley AT (2007) Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes 56:1930–1937. DOI 10.2337/db07-0043

    Article  PubMed  CAS  Google Scholar 

  5. Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njølstad PR, Ashcroft FM, Hattersley AT (2004) Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 350:1838–1849. DOI 10.1056/NEJMoa032922

    Article  PubMed  CAS  Google Scholar 

  6. Gribble FM, Reimann F (2003) Sulphonylurea action revisited: the post-cloning era. Diabetologia 46:875–891. DOI 10.1007/s00125-003-1143-3

    Article  PubMed  CAS  Google Scholar 

  7. Hattersley AT, Ashcroft FM (2005) Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes 54:2503–2513. DOI 10.2337/diabetes.54.9.2503

    Article  PubMed  CAS  Google Scholar 

  8. Pearson ER, Flechtner I, Njølstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Søvik O, Polak M, Hattersley AT; Neonatal Diabetes International Collaborative Group (2006) Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 355:467–477. DOI 10.1056/NEJMoa061759

    Article  PubMed  CAS  Google Scholar 

  9. Proks P, Antcliff JF, Lippiat J, Gloyn AL, Hattersley AT, Ashcroft FM (2004) Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features. Proc Nat Acad Sci USA 101:17539–17544. DOI 10.1073/pnas.0404756101

    Article  PubMed  CAS  Google Scholar 

  10. Sagen JV, Ræder H, Hathout E, Shehadeh N, Gudmundsson K, Bævre H, Abuelo D, Phornphutkul C, Molnes J, Bell GI, Gloyn AL, Hattersley AT, Molven A, Søvik O, Njølstad PR (2004) Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes 53:2713–2718. DOI 10.2337/diabetes.53.10.2713

    Article  PubMed  CAS  Google Scholar 

  11. Tonini G, Bizzarri C, Bonfanti R, Vanelli M, Cerutti F, Faleschini E, Meschi F, Prisco F, Ciacco E, Cappa M, Torelli C, Cauvin V, Tumini S, Iafusco D, Barbetti F; Early-Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology (2006) Sulfonylurea treatment outweighs insulin therapy in short-term metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (Kir6.2) gene. Diabetologia 49:2210–2213. DOI 10.1007/s00125-006-0329-x

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, University of Lübeck, Lübeck, Germany

    Verena M. Wagner, Britta Kremke & Olaf Hiort

  2. Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK

    Sarah E. Flanagan

  3. Division of Medicine and Therapeutics, University of Dundee, Dundee, Scotland, UK

    Ewan R. Pearson

  4. Klinik für Kinder- und Jugendmedizin, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Verena M. Wagner

Authors
  1. Verena M. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Britta Kremke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olaf Hiort
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sarah E. Flanagan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ewan R. Pearson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Verena M. Wagner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wagner, V.M., Kremke, B., Hiort, O. et al. Transition from insulin to sulfonylurea in a child with diabetes due to a mutation in KCNJ11 encoding Kir6.2—initial and long-term response to sulfonylurea therapy. Eur J Pediatr 168, 359–361 (2009). https://doi.org/10.1007/s00431-008-0757-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-008-0757-3

Keywords

Search

Navigation