To the Editor: Insulin resistance is a common precursor to type 2 diabetes mellitus. It is characterised by impaired insulin signalling in several tissues, with compensatory hyperinsulinaemia. Extreme insulin resistance, on the other hand, is very rare. Although the molecular basis for extreme insulin resistance remains unknown in many patients, lipodystrophies and loss-of-function mutations in the insulin receptor gene are well established causes of this phenotype. In patients with lipodystrophy, type 2 diabetes is usually associated with several metabolic disturbances, including low HDL-cholesterol, hypertriacylglycerolaemia and non-alcoholic fatty liver disease, among others [1]. Mutations in the insulin receptor gene produce a spectrum of diseases including Donohue’s syndrome, Rabson–Mendenhall syndrome and type A insulin resistance; patients with these conditions have several different characteristics [2]. Severe cases are diagnosed at birth or in infancy due to the presence of signs of severe hyperinsulinaemia such as acanthosis nigricans, abnormal dentition, hyperandrogenism and pseudo-acromegaly. Type 2 diabetes develops early in life and its treatment is usually extremely challenging. Insulin is often used in very high doses, but microvascular complications develop early and aggressively in these patients [2, 3]. The use of other therapies (leptin, IGF-1, metformin and pioglitazone) has already been described in scattered reports, but usually as monotherapy and with limited efficacy [4]. A 17-year-old boy was brought to our attention for treatment of type 2 diabetes. His BMI was in the ageand sex-specific normal range (weight 44.8 kg, height 161.0 cm) and he had no lipodystrophy. He was the older son of non-consanguinous parents and his development was unremarkable except for abnormal dentition and short stature. He had had a history of severe acanthosis nigricans since 6 months of age affecting cervical, axillary and inguinal areas, and macrogenitalism without macro-orchidism had been diagnosed in early life. On examination he had signs of pseudoacromegaly and hyperandrogenism. Initial fasting glucose and insulin were 6.8 mmol/l and 2,102 pmol/l, respectively, with postprandial glucose (at 2 h) of 23.5 mmol/l. Postprandial insulin was above the laboratory limit of detection. Fasting triacylglycerol and HDL-cholesterol were normal at 0.56 mmol/l and 1.0 mmol/l, while HbA1c was 11.9%. On clinical and biochemical grounds type 2 diabetes secondary to Rabson–Mendehall syndrome was diagnosed. Sequencing of the insulin receptor gene revealed two mutations: (1) Asn851Ser, a novel mutation changing an exquisitely conserved residue in one of the extracellular FnIII domains of the beta subunit of the receptor; and (2) the previously described Ala1135Val in the highly conserved catalytic loop of the tyrosine kinase domain of the receptor [5]. R. O. Moreira (*) :R. L. Zagury : L. Zagury Instituto Estadual de Diabetes e Endocrinologia, Rua Moncorvo Filho 90, Rio de Janeiro, RJ, Brazil e-mail: rom_br@yahoo.com