Postprandial Hypoglycemia Associated With Insulin Receptor Gene Variant G1146R

Abstract

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 insulin receptor (INSR) 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 INSR 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 INSR gene variants and may lead to reclassification of G1146R INSR, currently a variant of uncertain significance, as a likely pathogenic variant.

Keywords: gene variant; hyperinsulinemia hypoglycemia; insulin receptor.

Figure 1.

Daily continuous glucose monitoring. Blood glucose (mg/dL) measured by a subcutaneous continuous glucose monitor is indicated over the course of 10 days, with the range of 65 to 180 mg/dL (SI: 3.6-10.0 mmol/L) shown in gray. On day 7, the timing of reported typical hypoglycemia symptoms (S) and the preceding meal (M) of apple turnover pastry are indicated with arrows.