Hyperinsulinemic hypoglycemia due to pathogenic INSR variants: metabolic signature, phenotypic overlap, and semidominant inheritance - Scorecard - MDSpire

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

  • 0 min

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Clinical Scorecard: Pathogenic Variants in the Insulin Receptor Gene Linked to Hyperinsulinemic Hypoglycemia: Metabolic Profiles, Phenotypic Similarities, and Semidominant Inheritance Patterns

At a Glance

CategoryDetail
Condition
Key MechanismsAutosomal 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

        Original Source(s)

        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

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