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Exp Clin Endocrinol Diabetes 2008; 116(5): 293-297
DOI: 10.1055/s-2007-1004565
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Insulin Binding to Antibodies is a Risk Factor for Inexplicable Severe Hypoglycaemia in Children with Type-1 Diabetes Mellitus[*]

O. Seewi 1 , C. Jaeger 2 , R. G. Bretzel 2 , E. Schönau 1
  • 1Childrens Hospital of the University of Cologne, Germany
  • 2Third Medical Department and Policlinic, University Clinic of Giessen and Marburg GmbH, Giessen, Germany
Further Information

Publication History

received 06.10.2007 first decision 25.10.2007

accepted 12.12.2007

Publication Date:
19 May 2008 (online)

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Abstract

Background: Type-1 diabetic individuals differ with regard to both, the formation of circulating insulin antibodies, and the incidence of severe hypoglycaemia.

Aim of the study: To assess the association of insulin binding to antibodies with the incidence of severe hypoglycaemia.

Patients and methods: In a cross sectional study, 73 children with type-1 diabetes mellitus (median age 14 years, duration of diabetes 6 years) were investigated, 22 of whom had experienced severe hypoglycaemia during the past 18 months, and 51 had never experienced severe hypoglycaemia. Of the patients with severe hypoglycaemia 16 had experienced severe unexplained hypoglycaemias, and 6 had experienced severe hypoglycaemias which were explicable (by missed meals, unplanned physical exercise etc.). Insulin binding was measured in a blinded central laboratory by radioimmunoassay, and expressed as ratio bound/unbound insulin; a binding >15% was considered relevant insulin binding.

Results: A total of 38 patients displayed relevant insulin binding (17 of whom had experienced severe hypoglycaemia), and 35 patients did not (5 of whom had experienced severe hypoglycaemia; p=0.0055, Fisher's exact test). Patients with relevant insulin binding were younger (12.2 vs 14.5 years, p=0.006) than patients without relevant insulin binding. From the 16 patients with inexplicable severe hypoglycaemia, 15 displayed relevant insulin binding, compared to 2 of the 6 patients with explicable severe hypoglycaemia (p=0.009). The association of any severe hypoglycaemia, and of inexplicable severe hypoglycaemia, with relevant insulin binding was significant (odds ratio 4.8 (95%CI 1.5-15.2), and 22.1(95%CI 2.7-179.6), p<0.006). Patients with/without relevant insulin binding, or with/without severe hypoglycaemia, did not differ significantly regarding sex, duration of diabetes, number of insulin injections per day, HbA1c and C-peptide levels (ANOVA).

Conclusion: Insulin binding to antibodies >15% appears to be a strong risk factor for inexplicable severe hypoglycaemias in type-1 diabetic children.

Key words

autoimmunity - antibodies - diabetes

1 The study was presented in parts at the 43 rd EASD Annual Meeting 2007 in Amsterdam/The Netherlands, and at the 13th Annual Meeting of the ISPAD 2007 in Berlin /Germany.

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1 The study was presented in parts at the 43 rd EASD Annual Meeting 2007 in Amsterdam/The Netherlands, and at the 13th Annual Meeting of the ISPAD 2007 in Berlin /Germany.

Correspondence

Dr.med. O. Seewi

Diabetesambulanz

Klinik und Poliklinik für Allgemeine Kinderheilkunde

Klinikum der Universität zu Köln

Kerpener Str. 62

50924 Köln

Phone: +49/0221/478 43 59

Fax: +49/0221/478 34 79

Email: ora.seewi@uk-koeln.de

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