P-280: Transition from severe insulin resistance to autoimmune insulin deficiency in a child with polyglandular autoimmunity: a metabolic–autoimmune endotype
C Tatiana, C M MihaiAbstract
Introduction
The coexistence of insulin resistance and pancreatic autoimmunity in children represents an emerging metabolic–immune endotype that challenges the traditional distinction between type 1 and type 2 diabetes. Some pediatric patients exhibit a hybrid phenotype combining autoimmune β-cell destruction with marked insulin resistance. Familial clustering of autoimmune and metabolic disorders may contribute to this complex presentation.
Objectives
To describe the longitudinal metabolic and immunologic evolution of a pediatric patient progressing from severe insulin resistance to overt autoimmune diabetes in the context of familial polyautoimmunity.
Methods
We conducted a longitudinal clinical analysis of a boy diagnosed with autoimmune thyroiditis at age 11 and treated with levothyroxine. Serial evaluations included fasting glucose, HbA1c, insulin, C-peptide, HOMA-IR, pancreatic autoantibodies (anti-GAD, anti-insulin, IA-2), thyroid antibodies, lipid profile, renal parameters, and vitamin D levels. A four-generation pedigree was constructed to assess familial clustering of autoimmune and metabolic diseases.
Results
At 12 years and 9 months, the patient had obesity, impaired fasting glucose, marked hyperinsulinemia, and insulin resistance (HbA1c 5.7%). Over 18 months, glucose increased to 237 mg/dL and HbA1c to 9.3%. C-peptide declined from 11 to 0.75 ng/mL, indicating β-cell failure. Anti-GAD and anti-insulin antibodies were strongly positive, with persistent thyroid autoimmunity and vitamin D deficiency. Insulin therapy achieved suboptimal control. Family history revealed clustering of diabetes and autoimmune diseases.
Conclusions
This case shows progression from insulin resistance to autoimmune β-cell failure. Elevated anti-GAD and anti-insulin antibodies suggest an intermediate autoimmune phase before insulin dependence, highlighting the need for early family screening and integrated monitoring.