Early Alpha Cell Dysfunction During the Development of Type 1 Diabetes

PURPOSE The presence of islet autoantibodies (AAB) is currently the best biomarker for the future development of type 1 diabetes (T1D), with T1D developing in just 15% of single AAB+ individuals, but a much higher rate in individuals who progress to positivity for two or more AAB. Thus, the single AAB positive state may represent a key window for intervention to prevent progression to T1D. Here we functionally and metabolically phenotype human islets from deceased non-diabetic, single AAB+ and T1D donors to identify early defects in AAB+ donor islets that could serve as biomarkers for disease development and potential nodes for therapeutic intervention.