Postprandial Hypoglycemia Associated With <i>Insulin Receptor</i> Gene Variant G1146R

Hypoglycemia in people without diabetes can be caused by a variety of factors and may become life-threatening if compensatory mechanisms are overwhelmed. We present a case of postprandial hypoglycemia associated with a heterozygous <i>insulin receptor</i> (<i>INSR</i>) gene variant, G1146R, in an 82-year-old Caucasian man with glucose intolerance and an extensive family history of similar symptoms. His hypoglycemia worsened with advancing age and eventually required a continuous blood glucose sensor with alarms to avoid severe hypoglycemia. This <i>INSR</i> variant is predicted to disrupt the autophosphorylation function of the receptor and was previously reported in an individual with severe insulin resistance presenting in childhood, but who did not experience hypoglycemia. This case highlights the clinical variability of <i>INSR</i> gene variants and may lead to reclassification of G1146R <i>INSR</i>, currently a variant of uncertain significance, as a likely pathogenic variant.