Deteriorating beta‐cell function in type 2 diabetes: a long‐term model

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Abstract
Background: Type 2 diabetes is characterized by insulin resistance and the progressive loss of islet beta‐cell function. Although the former is already established at diagnosis and changes little thereafter, beta‐cell function continues to decline, leading to secondary failure of anti‐hyperglycaemic therapies. Aim: To develop a quantitative model of the process of beta‐cell function decay over time, using trial data. Design: Re‐analysis of published data. Methods: The results of the Belfast Diet Study were re‐analysed. Assuming patients are diagnosed at different stages in the disease process, time displacement of data was used to obtain a bi‐partite spline model describing loss of insulin secretion over a 6‐year period. Results: The model was developed combining two phases, in which a long slow gradual loss of beta‐cell function leads to a crisis in metabolic regulation, precipitating a much more rapid decay phase. This paradigm was consistent with a previous non‐linear model of beta‐cell mass regulation. Discussion: This model may have important implications for targeting appropriate therapy to patients in each phase: delaying or avoiding full clinical type 2 diabetes in the first phase; and preventing the development of diabetic complications in the second phase.