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

Objective: Insulin autoimmune syndrome (IAS) has been reported mainly in Ja pan 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 unco nsciousness in the late postprandial state and blood glucose was found to b e 33 mg/dl with serum insulin levels of > 3980 mu IU/ml (normal range 0-30 mu IU/ml). She was receiving monthly injections of penicillin G for the pro phylaxis of recurrent tonsillitis. Patient 2, was a 19-year-old white femal e, with episodes of sweating, hand tremor, weakness and hunger occurring in the postprandial state and blood glucose levels during the attacks of 28-5 6 mg/dl. Very high insulin levels (602-708 mu IU/ml) were present. Methods and Results: Anti-insulin antibodies, determined by a semi-quantita tive method, were strongly positive in both patients (91.7% in patient 1 an d 88.6% in patient 2; normal range less than or equal to7%). 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-huma n-immunoglobulin G antibodies (87% and 95% from patients I and 2 respective ly). Scatchard plot analysis and molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in patient 1, and a monoclonal antibod y and DRB1*0403 in patient 2. Conclusions: These two Portuguese patients with IAS had different HLA-DR4 s ubtypes 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.