The maintenance of normal glucose levels depends primarily on close coupling between the circulating glucose level and the rate of binding between insulin and insulin receptors regulating glucose uptake. Any process that disrupts this coupling may produce hypoglycemia. Most commonly, this results when exogenous insulin, sulfonylurea medications, or an insulinoma inappropriately raise the circulating insulin level.

Insulin and the insulin receptor are proteins and thus have the potential to interact with endogenous antibodies. The rare phenomenon of autoimmune hypoglycemia occurs when antibodies directed against either insulin or the insulin receptor bind the hormone or receptor and disrupt the normal relationship between glucose and the insulin–insulin receptor interaction.