Hyperinsulinemic hypoglycemia due to pathogenic INSR variants: metabolic signature, phenotypic overlap, and semidominant inheritance
By
Ramon Marcelino do Nascimento
Andrey dos Santos
Dioze Guadagnini
Lucas Santos de Santana
Augusto Cezar Junior Santomauro
Caroline Gouveia Buff Passone
Milena Gurgel Teles Bezerra
Larissa Garcia Gomes
Maria Lucia Corrêa-Giannella
Marcia Nery
Mario José Abdalla Saad
Delmar Muniz Junior Lourenço
Maria Adelaide Albergaria Pereira
May 7, 2026
Clinical Scorecard: Pathogenic Variants in the Insulin Receptor Gene Linked to Hyperinsulinemic Hypoglycemia: Metabolic Profiles, Phenotypic Similarities, and Semidominant Inheritance Patterns
At a Glance
Category Detail
Condition Key Mechanisms Autosomal dominant and semidominant inheritance of heterozygous pathogenic variants leading to insulin resistance and hypoglycemia Target Population Care Setting
Key Highlights
78% of individuals with PGV-INSR present with postprandial hypoglycemia All carriers exhibit insulin resistance; 60% of women have PCOS Marked intrafamilial variability and phenotypic overlap among HHF5, TAIRS, and RMS Distinct metabolic profile includes elevated insulin levels, normal triglycerides, and variable degrees of IR Recognition of this pattern may enhance genetic counseling and clinical management Guideline-Based Recommendations
Diagnosis
Management
Monitoring & Follow-up
Regularly assess insulin levels and metabolic profiles in affected individuals Monitor for development of diabetes and other complications Implement lifestyle modifications to manage insulin resistance Risks
Patient & Prescribing Data
Management strategies should focus on monitoring and addressing hypoglycemic episodes, insulin resistance, and include dietary modifications.
Clinical Best Practices
Utilize a multidisciplinary approach for management involving endocrinologists and genetic counselors Educate patients and families about the condition and its implications, including genetic counseling and family testing Encourage lifestyle modifications to manage insulin resistance Related Resources & Content
