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

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.