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• This study was undertaken to investigate possible factors [ill]ontributing to altered glucose homeostasis in a patient with a [ill]story of total pancreatectomy and intermittent sepsis. Blood [ill]as drawn when the patient had received no exogenous [ill]sulin for the previous 24 hours, had a serum insulin level of [ill]3 μU/mL, and gave an inappropriately low glucose response [ill]large amounts of infused glucose. The IgG fraction prepared [ill]om this serum stimulated glucose oxidation in vitro and [ill]hibited binding of insulin labeled with I 125 to isolated rat [ill]dipocytes, thus fulfilling some of the criteria for autoan[ill]bodies to the insulin receptor. The results are compatible with [ill]e hypothesis that insulin-receptor autoantibodies may have [ill]eveloped as a result of perturbation of this patient's immune [ill]tatus promoted by intermittent septic episodes and that, [ill]eterminally, as these antibodies converted in vivo to their in [ill]tro—type behavior, they may have been partially responsible [ill]or the severe disturbances of glucose homeostasis.(Arch Intern Med 1984;144:2019-2022)