Congenital Endocrinopathies

New Insights into Endocrine Diseases and Diabetes
Workshop, Genova, January 2007

Editor(s): Lorini R. (Genova) 
Maghnie M. (Genova) 
D'Annunzio G. (Genova) 
Loche S. (Cagliari) 
Savage M.O. (London) 
Table of Contents
Vol. 11, No. , 2007
Section title: Paper
Lorini R, Maghnie M, D’Annunzio G, Loche S, Savage MO (eds): Congenital Endocrinopathies. New Insights into Endocrine Diseases and Diabetes. Endocr Dev. Basel, Karger, 2007, vol 11, pp 122-132

A Clinical Approach to Severe Insulin Resistance

Savage D.a · Semple R.a · Chatterjee V.a · Wales J.b · Ross R.c · O'Rahilly S.a
aDepartments of Clinical Biochemistry and Medicine, University of Cambridge, Cambridge, and b Department of Paediatric Endocrinology, Sheffield Children’s Hospital, and c Department of Diabetes and Endocrinology, Northern General Hospital, Sheffield, UK


Extreme forms of insulin resistance are a rare cause of type 2 diabetes. However, individuals with severe insulin resistance pose unique diagnostic and therapeutic challenges, and have often acted as ‘experiments of nature’ providing important novel information regarding endocrine physiology and mechanistic insights relevant to the study of more common disorders. Progress in understanding the molecular pathogenesis of such syndromes is also beginning to yield novel therapeutic options. Severe insulin resistance typically presents in 1 of 3 ways: (1) disordered glucose metabolism including both diabetes and/or paradoxical hypoglycaemia; (2) acanthosis nigricans, a velvety hyperpigmentation of axilliary and flexural skin often associated with skin tags; or (3) hyperandrogenism in girls (hirsutism, oligo-/amenorrhoea and polycystic ovaries). Lipodystrophy is a major cause of severe insulin resistance and needs to be looked for very carefully, particularly in the patients with significant dyslipidaemia and fatty liver. Specific treatments are now available for some forms of severe insulin resistance; for example, leptin replacement in patients with generalized lipodystrophy. In the absence of a specific diagnosis and therapy, metformin is a useful insulin sensitizer and should be used in conjunction with aggressive diet and exercise interventions.

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