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Diabetologia. 2019 Jan;62(1):33-40. doi: 10.1007/s00125-018-4722-z. Epub 2018 Aug 30.

Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.

Author information

1
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia. wentworth@wehi.edu.au.
2
Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia. wentworth@wehi.edu.au.
3
Department of Diabetes and Endocrinology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia. wentworth@wehi.edu.au.
4
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.
5
Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
6
School of Public Health, The University of Adelaide, Adelaide, SA, Australia.
7
Clinical Trials Group, Immune Tolerance Network, San Francisco, CA, USA.
8
Eli Lilly and Company, San Diego, CA, USA.
9
University of California at San Francisco, San Francisco, CA, USA.
10
University of South Florida, Tampa, FL, USA.
11
Indiana University School of Medicine, Indianapolis, IN, USA.

Abstract

AIMS/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.

KEYWORDS:

Adult; Beta cell function; Children; Clinical trial; Immune Tolerance Network; Immune therapy; Linear model; TrialNet; Type 1 diabetes

PMID:
30167735
DOI:
10.1007/s00125-018-4722-z

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