Autoantibodies to Insulin and Dysglycemia in People With and Without Diabetes: An Underdiagnosed Association.

Abstract

The potential effects of inhibitory immunoglobulins to insulin were first described in insulin-treated patients many decades ago (1). This antibody response is thought to occur in at least 40% of patients on insulin therapy (2). Subsequent case reports documented glycemic excursions in the form of markedly increased insulin requirements and unpredictable hypoglycemic episodes, both of which were attributable to insulin autoantibodies (3). Autoantibodies to insulin also can occur occasionally in patients who have not been previously exposed to insulin. Autoimmune hypoglycemia resulting from high titers of insulin autoantibodies have been reported, mostly from Japan, as a rare cause of hyperinsulinemic hypoglycemia (4). There has only been one confirmed case of autoimmune hypoglycemia reported from India (5). The estimation of insulin autoantibodies is an integral part of the diagnosis in such cases. Apart from insulin, other inciting agents implicated include sulfahydryl group–containing drugs and alpha-lipoic acid (ALA). Autoimmune hypoglycemia also has been reported to be associated with autoimmune disorders and plasma cell dyscrasias (6). Spontaneous resolution has been reported in a few cases of autoimmune hypoglycemia, and a dramatic response to steroids was seen in some other cases that manifested both hypoglycemia and hyperglycemia. In this article, we describe our experience with patients who presented with glycemic excursions resulting from insulin autoantibodies from a single university referral teaching center in South India. ### Case Presentation At the Department of Endocrinology of Amrita Institute of Medical Sciences in Kochi, Kerala, India, a large tertiary care center, between 2008 and 2014, we diagnosed eight cases in which insulin autoantibodies could be implicated as the etiological factor responsible for spontaneous hyperinsulinemic hypoglycemia. One patient presented exclusively with postprandial hypoglycemia–related symptoms, whereas the others presented with a combination of fasting and postprandial symptoms. During the same time period, there were only seven cases of histopathologically proven insulinomas …