Background/Aims: Lipoatrophy (LA) is a rare, possibly under-recognised side effect of insulin treatment of unclear aetiology. The aim of this study was to describe the characteristics of patients with type 1 diabetes (T1D) who have LA and to explore the relationship between LA and other autoimmune diseases based on the hypothesis that additional autoimmune phenomena are more prevalent in T1D patients with LA. Methods: This was a cross-sectional observational study of T1D patients with LA in comparison to T1D patients without LA who are registered with the Diabetes Patienten-Verlaufsdokumentationssystem database of 241,650 patients in Germany and Austria. Results: Hashimoto's thyroiditis and coeliac disease were more prevalent in patients with LA (p < 0.001 for both). LA was associated with an increased risk of Hashimoto's thyroiditis and coeliac disease in female patients [odds ratio (OR) 2.5, p = 0.003, and OR 3.1, p = 0.02, respectively]. This relationship persisted after adjustment for current age, duration of diabetes and calendar year of treatment (OR 2.7, p = 0.002, and OR 3.5, p = 0.01, respectively). Conclusion: These findings support the hypothesis that an immune complex-mediated inflammatory process may be important in the development of LA.

Keywords:
Type 1 diabetes, Lipoatrophy, Hashimoto’s thyroiditis , Coeliac disease, Diabetes Patienten-Verlaufsdokumentationssystem
1.
Paley RG: Lipodystrophy following insulin injections. Metabolism 1953;2:201-210.
2.
Peters MS, Winkelmann RK: Localized lipoatrophy (atrophic connective tissue disease panniculitis). Arch Dermatol 1980;116:1363-1368.
3.
Milan G, Murano I, Costa S, Pianta A, Tiengo C, Zulato E, Centobene C, Bruttomesso D, Cinti S, Vettor R: Lipoatrophy induced by subcutaneous insulin infusion: ultrastructural analysis and gene expression profiling. J Clin Endocrinol Metab 2010;95:3126-3132.
4.
Watson D, Vines R: Variations in the incidence of lipodystrophy using different insulins. Med J Aust 1973;1:248-250.
5.
Wright AD, Walsh CH, Fitzgerald MG, Malins JM: Very pure porcine insulin in clinical practice. Br Med J 1979;1:25-27.
6.
Reeves WG, Allen BR, Tattersall RB: Insulin-induced lipoatrophy: evidence for an immune pathogenesis. Br Med J 1980;280:1500-1503.
7.
Billings JK, Milgraum SS, Gupta AK, Headington JT, Rasmussen JE: Lipoatrophic panniculitis: a possible autoimmune inflammatory disease of fat. Report of three cases. Arch Dermatol 1987;123:1662-1666.
8.
Griffin ME, Feder A, Tamborlane WV: Lipoatrophy associated with lispro insulin in insulin pump therapy: an old complication, a new cause? Diabetes Care 2001;24:174.
9.
Ampudia-Blasco FJ, Hasbum B, Carmena R: A new case of lipoatrophy with lispro insulin in insulin pump therapy: is there any insulin preparation free of complications? Diabetes Care 2003;26:953-954.
10.
Dziura M, Wasikowa R: Lipoatrophy after use of long acting insulin glargine analogue in a 32-year-old patient with type 1 diabetes (in Polish). Pediatr Endocrinol Diabetes Metab 2008;14:61-63.
11.
Peteiro-Gonzalez D, Fernandez-Rodriguez B, Cabezas-Agricola JM, Araujo-Vilar D: Severe localized lipoatrophy related to therapy with insulin analogs in type 1a diabetes mellitus. Diabetes Res Clin Pract 2011;91:e61-e63.
12.
Boehm BO, Kuhnl P, Loliger C, Ketzler-Sasse U, Holzberger G, Seidl S, Bauerle R, Schifferdecker E, Usadel KH: HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors. Clin Investig 1993;71:221-225.
13.
Arbeitsgemeinschaft Pädiatrische Diabetologe im Auftrag der Deutschen Diabetes Gesellschaft benannten Expertengruppe: Diagnostik, Therapie und Verlaufskontrolle des Diabetes mellitus im Kindes- und Jugendalter. 2009, http://www.deutsche-diabetes-gesellschaft.de/fileadmin/Redakteur/Leitlinien/Evidenzbasierte_Leitlinien/EBL_Kindesalter_2010.pdf
14.
Clarke W, Jones T, Rewers A, Dunger D, Klingensmith GJ: Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr Diabetes 2009;10(suppl 12):134-145.
15.
Flechtner-Mors M, Thamm M, Wiegand S, Reinehr T, Schwab KO, Kiess W, Widhalm K, Holl RW: Comorbidities related to BMI category in children and adolescents: German/Austrian/Swiss Obesity Register APV compared to the German KiGGS Study. Horm Res Paediatr 2012;77:19-26.
16.
Whitley TH, Lawrence PA, Smith CL: Amelioration of insulin lipoatrophy by dexamethasone injection. JAMA 1976;235:839-840.
17.
Kumar O, Miller L, Mehtalia S: Use of dexamethasone in treatment of insulin lipoatrophy. Diabetes 1977;26:296-299.
18.
Jones GR, Statham B, Owens DR, Jones MK, Hayes TM: Lipoatrophy and monocomponent porcine insulin. Br Med J (Clin Res Ed) 1981;282:190.
19.
Atlan-Gepner C, Bongrand P, Farnarier C, Xerri L, Choux R, Gauthier JF, Brue T, Vague P, Grob JJ, Vialettes B: Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes. Diabetes Care 1996;19:1283-1285.
20.
Murao S, Hirata K, Ishida T, Takahara J: Lipoatrophy induced by recombinant human insulin injection. Intern Med 1998;37:1031-1033.
21.
Ramos AJ, Farias MA: Human insulin-induced lipoatrophy: a successful treatment with glucocorticoid. Diabetes Care 2006;29:926-927.
22.
Shimizu I, Furuya K, Osawa H, Fujii Y, Makino H: A case of insulin-induced localized lobular panniculitis with evidence for the phagocytosis of insulin by histiocytes. Endocr J 2007;54:477-480.
23.
Swelheim HT, Westerlaken C, van Pinxteren-Nagler E, Bocca G: Lipoatrophy in a girl with type 1 diabetes: beneficial effects of treatment with a glucocorticoid added to an insulin analog. Diabetes Care 2012;35:e22.
24.
Chandraprasert S, Bunnag SC: Insulin antibodies in diabetics after changeover from conventional NPH to highly purified insulin. Ann Acad Med Singapore 1985;14:289-293.
25.
Lopez X, Castells M, Ricker A, Velazquez EF, Mun E, Goldfine AB: Human insulin analog-induced lipoatrophy. Diabetes Care 2008;31:442-444.
26.
Babiker A, Datta V: Lipoatrophy with insulin analogues in type I diabetes. Arch Dis Child 2011;96:101-102.
27.
Jermendy G, Nadas J, Sapi Z: ‘Lipoblastoma-like' lipoatrophy induced by human insulin: morphological evidence for local dedifferentiation of adipocytes? Diabetologia 2000;43:955-956.
28.
Kivity S, Ehrenfeld M: Can we explain the higher prevalence of autoimmune disease in women? Expert Rev Clin Immunol 2010;6:691-694.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.