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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Fasting / blood*
  • Female
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Male
  • Metabolic Diseases / blood
  • Metabolic Diseases / metabolism
  • Triglycerides / blood


  • Triglycerides