Hannon, Tamara S.Kahn, Steven E.Utschneider, Kristina M.Buchanan, Thomas A.Nadeau, Kristen J.Zeitler, Philip S.Ehrmann, David A.Arslanian, Silva S.Caprio, SoniaEdelstein, Sharon L.Savage, Peter J.Mather, Kieren J.2017-08-022017-08-022017Hannon, T., Kahn, S., Utschneider, K., Bucahan, T., Nadeau, K., Zeitler, P., Ehrmann, D., Arslanian, S., Caprio, S., Edelstein, S., Savage, P., Mather, K. and for the RISE Consortium (2017), A Review of Methods for Measuring β-Cell Function: Design Considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes, Obesity, and Metabolism. Accepted Author Manuscript. doi:10.1111/dom.13005https://hdl.handle.net/1805/13697The Restoring Insulin Secretion (RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes (T2D). To design the RISE study, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. In the present paper, we review approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations. Methodologic considerations included: (1) the utility of each technique for evaluating key aspects of β-cell function (first- and second-phase insulin secretion, maximum insulin secretion, glucose sensitivity, incretin effects) and (2) tactics for incorporating a measurement of insulin sensitivity in order to adjust insulin secretion measures for insulin sensitivity appropriately. Of particular concern were the capacity to measure β-cell function accurately in those with poor function, as is seen in established T2D, and the capacity of each method for demonstrating treatment-induced changes in β-cell function. Feasibility considerations included: staff burden, including time and required methodological expertise; participant burden, including time and number of study visits; and ease of standardizing methods across a multicentre consortium. After this evaluation, we selected a 2-day measurement procedure, combining a 3-hour 75-g oral glucose tolerance test and a 2-stage hyperglycaemic clamp procedure, augmented with arginine.enPublisher PolicyRestoring Insulin Secretion (RISE) studytype 2 diabetesβ-cell failureArticle