Wentworth, John M.Bediaga, Naiara G.Giles, Lynne C.Ehlers, MarioGitelman, Stephen E.Geyer, SusanEvans-Molina, CarmellaHarrison, Leonard C.2019-08-092019-08-092019-01Wentworth, J. M., Bediaga, N. G., Giles, L. C., Ehlers, M., Gitelman, S. E., Geyer, S., … Immune Tolerance Network Study Group (2019). Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. Diabetologia, 62(1), 33–40. doi:10.1007/s00125-018-4722-zhttps://hdl.handle.net/1805/20313AIMS/HYPOTHESIS: Beta cell function in type 1 diabetes is commonly assessed as the average plasma C-peptide concentration over 2 h following a mixed-meal test (CPAVE). Monitoring of disease progression and response to disease-modifying therapy would benefit from a simpler, more convenient and less costly measure. Therefore, we determined whether CPAVE could be reliably estimated from routine clinical variables. METHODS: Clinical and fasting biochemical data from eight randomised therapy trials involving participants with recently diagnosed type 1 diabetes were used to develop and validate linear models to estimate CPAVE and to test their accuracy in estimating loss of beta cell function and response to immune therapy. RESULTS: A model based on disease duration, BMI, insulin dose, HbA1c, fasting plasma C-peptide and fasting plasma glucose most accurately estimated loss of beta cell function (area under the receiver operating characteristic curve [AUROC] 0.89 [95% CI 0.87, 0.92]) and was superior to the commonly used insulin-dose-adjusted HbA1c (IDAA1c) measure (AUROC 0.72 [95% CI 0.68, 0.76]). Model-estimated CPAVE (CPEST) reliably identified treatment effects in randomised trials. CPEST, compared with CPAVE, required only a modest (up to 17%) increase in sample size for equivalent statistical power. CONCLUSIONS/INTERPRETATION: CPEST, approximated from six variables at a single time point, accurately identifies loss of beta cell function in type 1 diabetes and is comparable to CPAVE for identifying treatment effects. CPEST could serve as a convenient and economical measure of beta cell function in the clinic and as a primary outcome measure in trials of disease-modifying therapy in type 1 diabetes.en-USPublisher PolicyAdultBeta cell functionChildrenClinical trialLinear modelImmune therapyImmune Tolerance NetworkTrialNetType 1 diabetesArticle