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Insulin secretion and sensitivity in the prediction of type 1 diabetes in children with advanced β-cell autoimmunity

Heli T Siljander1, Robert Hermann, Anne Hekkala

  • 1Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PO Box 22, FI-00014 Helsinki, Finland.

European Journal of Endocrinology
|August 2, 2013
PubMed

Insights

Young age, higher BMI, and reduced first-phase insulin response (FPIR) predict type 1 diabetes (T1D) in children with autoimmunity. Insulin resistance played a minor role in disease progression.

Area of Science:

  • Pediatric Endocrinology
  • Immunology
  • Metabolic Disease Research

Background:

  • Type 1 diabetes (T1D) prediction in the general pediatric population requires further definition of early markers.
  • Reduced early insulin response is a known T1D predictor in relatives, but its role in the general population is less clear.
  • Insulin resistance's impact on T1D development in young children with autoimmunity is poorly understood.

Purpose of the Study:

  • To assess the predictive value of early insulin response and insulin resistance for T1D in children with advanced beta-cell autoimmunity.
  • To investigate the relationship between these metabolic markers and other T1D risk factors.
  • To stratify T1D risk based on metabolic status and body mass index (BMI) in susceptible children.

Main Methods:

  • Intravenous glucose tolerance tests (IVGTTs) were performed in 218 children with HLA-DQB1 susceptibility and persistent autoantibodies.
  • Collected data included baseline, metabolic, and growth parameters.
  • Hazard ratios for T1D predictors and progression rates were analyzed.

Main Results:

  • Children who developed T1D were younger at seroconversion, progressed faster, and had lower first-phase insulin response (FPIR) and HOMA-IR.
  • Higher levels of HOMA-IR/FPIR ratio, islet cell antibodies, insulin autoantibodies (IAA), and IA-2A were observed in progressors.
  • Predictive markers for T1D included BMI SDS, FPIR, age at IVGTT, IAA, and IA-2A.

Conclusions:

  • Younger age, elevated BMI SDS, reduced FPIR, and higher IAA/IA-2A levels are significant predictors of T1D in children with autoimmunity.
  • Metabolic status and BMI effectively stratified disease risk.
  • Insulin resistance was found to have a minor role in accelerating T1D progression.
Abstract

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