Altered Glucagon Response to Oral Glucose in Individuals at Different Stages of Type 1 Diabetes Development.

Abstract

Autoimmune destruction of β cells and their functional decline precedes the clinical onset of type 1 diabetes. However, altered α-cell function and hyperglucagonemia may contribute to the development of hyperglycemia and ketoacidosis at onset. In this cross-sectional study, we analyzed glucagon concentrations during an oral glucose tolerance test (OGTT) in individuals at the early stages of type 1 diabetes to understand the role of α-cell function in the disease process. We recruited 47 participants, aged 4 to 25 years, from the Finnish Diabetes Prediction and Prevention (DIPP) study, and categorized them into the following groups: islet autoantibody (IAb) negative, single IAb positive, and stages 1 to 3 of type 1 diabetes. Glucagon levels were measured during a 6-point OGTT using a conventional radioimmunoassay, alongside insulin, C-peptide, glucose, and glucagon-like peptide-1 (GLP-1). Fasting plasma glucagon levels increased with disease progression. The longitudinal patterns of glucagon concentrations during the OGTT differed significantly between groups, with a paradoxical 15-minute glucagon increase observed only in individuals at early stage 3 of type 1 diabetes. These findings highlight the need for prospective studies to further elucidate the role of α cells in disease progression and support testing pharmacotherapies aimed at improving both α- and β-cell functions during disease development.