Quantifying beta cell function in the preclinical stages of type 1 diabetes – published online 15/09/2023

Alfonso Galderisi, Alice L. J. Carr, Mariangela Martino, Peter Taylor, Peter Senior, Colin Dayan

The recent approval by the US Food and Drug Administration of the use of teplizumab in preclinical (stage 2) type 1 diabetes represents a paradigm shift in our therapeutic approach to this disease. Rather than focusing on improvements in insulin replacement, the development of low-risk agents to preserve beta cell function in the preclinical phases of the disease may avert the need for insulin, providing years of burden-free life with near-perfect glucose control. However, to develop new drugs in this space, it is of pivotal importance to be able to accurately measure changes in beta cell function before significant rises in glucose occur, using methods that can be applied in large clinical trial populations. In this issue, Galderisi et al (https://doi.org/10.1007/s00125-023-06011-5) describe the metabolic changes occurring during the preclinical stages of type 1 diabetes and discuss the pros and cons of the available methodologies to quantify beta cell function in these early disease phases. They state that metabolic modelling of the data derived from standard tests, such as the OGTT or mixed meal tolerance test, may provide more accurate estimates of insulin secretion and insulin sensitivity in early-stage type 1 diabetes than C-peptide measurement alone. The authors conclude that such models should be validated in large longitudinal cohorts to confirm their value as effective measures of beta cell function in the early stage of the disease. The figures from this review are available as a downloadable slideset

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