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Diabetes Obes Metab. 2018 Jan;20(1):14-24. doi: 10.1111/dom.13005. Epub 2017 Jun 22.

Review of methods for measuring β-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium.

Author information

Departments of Pediatrics (T. S. H.) and Medicine (K. J. M.), Indiana University School of Medicine, Indianapolis, Indiana.
VA Puget Sound Health Care System and Department of Medicine, University of Washington, Seattle, Washington.
University of Southern California Keck School of Medicine/Kaiser Permanente Southern California, Department of Medicine, Los Angeles, California.
University of Colorado Denver/Children's Hospital Colorado, Department of Pediatrics, Denver, Colorado.
University of Chicago, Chicago, Illinois.
Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Department of Pediatrics, Pittsburgh, Pennsylvania.
Department of Pediatrics, Yale University, New Haven, Connecticut.
George Washington University Biostatistics Center (RISE Coordinating Center), Rockville, Maryland.
National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland.


The 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.

TRIAL REGISTRATION: NCT01779362 NCT01779375 NCT01763346.


glucose metabolism; insulin resistance; insulin secretion; type 2 diabetes; β cell

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