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

the Type 1 Diabetes TrialNet Study Group, the Immune Tolerance Network Study Group

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
JournalDiabetologia
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Type 1 Diabetes Mellitus
Fasting
C-Peptide
ROC Curve
Insulin
Therapeutics
Sample Size
Meals
Disease Progression
Linear Models
Outcome Assessment (Health Care)
Glucose

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

the Type 1 Diabetes TrialNet Study Group, & the Immune Tolerance Network Study Group (Accepted/In press). Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. Diabetologia. https://doi.org/10.1007/s00125-018-4722-z

Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. / the Type 1 Diabetes TrialNet Study Group; the Immune Tolerance Network Study Group.

In: Diabetologia, 01.01.2018.

Research output: Contribution to journalArticle

the Type 1 Diabetes TrialNet Study Group, the Immune Tolerance Network Study Group. Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. Diabetologia. 2018 Jan 1. https://doi.org/10.1007/s00125-018-4722-z
the Type 1 Diabetes TrialNet Study Group ; the Immune Tolerance Network Study Group. / Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. In: Diabetologia. 2018.
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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.",
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AU - the Immune Tolerance Network Study Group

AU - Wentworth, John M.

AU - Bediaga, Naiara G.

AU - Giles, Lynne C.

AU - Ehlers, Mario

AU - Gitelman, Stephen E.

AU - Geyer, Susan

AU - Evans-Molina, Carmella

AU - Harrison, Leonard C.

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N2 - 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.

AB - 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.

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KW - Beta cell function

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KW - Immune therapy

KW - Immune Tolerance Network

KW - Linear model

KW - TrialNet

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