Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with characterisation of HLA alleles and insulin autoantibodies

Servico de Endocrinologia e Centro de Investigacao de Patobiologia Molecular, Lisbon, Portugal.

OBJECTIVE: Insulin autoimmune syndrome (IAS) has been reported mainly in Japan and so far only 27 IAS cases have been described from outside Asia. We describe two unrelated Portuguese patients with IAS and characterise their insulin autoantibodies and HLA alleles. PATIENTS: Patient 1, a 24-year-old white female suffered an episode of unconsciousness in the late postprandial state and blood glucose was found to be 33 mg/dl with serum insulin levels of >3980 microIU/ml (normal range 0-30 microIU/ml). She was receiving monthly injections of penicillin G for the prophylaxis of recurrent tonsillitis. Patient 2, was a 19-year-old white female, with episodes of sweating, hand tremor, weakness and hunger occurring in the postprandial state and blood glucose levels during the attacks of 28-56 mg/dl. Very high insulin levels (602-708 microIU/ml) were present. METHODS AND RESULTS: Anti-insulin antibodies, determined by a semi-quantitative method, were strongly positive in both patients (91.7% in patient 1 and 88.6% in patient 2; normal range < or =7%). Sephadex G-100 chromatography of the sera showed most of insulin immunoreactivity present in the void volume which was retained by an affinity column with anti-human-immunoglobulin G antibodies (87% and 95% from patients 1 and 2 respectively). Scatchard plot analysis and molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in patient 1, and a monoclonal antibody and DRB1*0403 in patient 2. CONCLUSIONS: These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with penicillin, and DRB1*0403 and a monoclonal antibody in a patient with "idiopathic" IAS.

This article has been cited by other articles:

				D. J. Halsall, M. Mangi, M. Soos, M. N. Fahie-Wilson, G. Wark, R. Mainwaring-Burton, and S. O'Rahilly Hypoglycemia due to an Insulin Binding Antibody in a Patient with an IgA-{kappa} Myeloma J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2013 - 2016. [Abstract] [Full Text] [PDF]

				C. H. Kim, J. H. Park, T. S. Park, and H. S. Baek Autoimmune Hypoglycemia in a Type 2 Diabetic Patient With Anti-Insulin and Insulin Receptor Antibodies Diabetes Care, January 1, 2004; 27(1): 288 - 289. [Full Text] [PDF]

				N. H. Esfandiari Case Study: A 90-Year-Old Man With Confusion and Night Sweats Clin. Diabetes, April 1, 2003; 21(2): 95 - 96. [Full Text] [PDF]

				W. Jeske, W. Zgliczynski, and P. Zdunowski Laboratory and Clinical Experience in 55 Patients with Macroprolactinemia Identified by a Simple Polyethylene Glycol Precipitation Method J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1909 - 1910. [Full Text] [PDF]