Capturing residual beta cell function in type 1 diabetes
Since the 1970s, C-peptide has been used as a surrogate marker for monitoring the progression of type 1 and type 2 diabetes and to determine the effects of interventions designed to preserve or improve residual beta cell function. C-peptide measurement is a well-established surrogate of residual beta cell activity and of clinical significance as it is associated with HbA1c, risk for microvascular complications and the incidence of hyperglycaemia in longitudinal studies. Measurement of C-peptide after a mixed meal tolerance test is considered the gold standard of measuring beta cell function in type 1 diabetes, but the method is laborious and inconvenient. In this issue of Diabetologia, Wentworth et al ( https://doi.org/10.1007/s00125-018-4722-z) report an algorithm for estimating C-peptide (CPEST) based on six routine clinical measures. These do not include stimulated C-peptide measurement and outperform other prevailing algorithms for estimating residual beta cell function. Going forward it is very likely that this new algorithm will serve as a simple measure of beta cell function in routine practice and as a more acceptable primary outcome measure in future trials of disease-modifying therapies.
KeywordsBeta cell function C-peptide Glucagon stimulation test MMTT Modelling Type 1 diabetes
Glucagon stimulation test
Mixed meal tolerance test
The author was the sole contributor to this paper.
Funding for the author’s lab work on residual beta cell function is supported by the Novo Nordisk Foundation and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115797 (INNODIA), which receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA, JDRF and The Leona M. and Harry B. Helmsley Charitable Trust.
Duality of interest
The author declares that there is no duality of interest associated with this manuscript.
- 3.Handelsman Y, Bloomgarden ZT, Grunberger G et al (2015) American Association of Clinical Endocrinologists and American College of Endocrinology – clinical practice guidelines for developing a diabetes mellitus comprehensive care plan – 2015. Endocr Pract 21(Suppl 1):1–87. https://doi.org/10.4158/EP15672.GLSUPPL CrossRefGoogle Scholar
- 9.Bowman P, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2012) Validation of a single-sample urinary C-peptide creatinine ratio as a reproducible alternative to serum C-peptide in patients with type 2 diabetes. Diabet Med 29(1):90–93. https://doi.org/10.1111/j.1464-5491.2011.03428.x CrossRefGoogle Scholar
- 15.Ludvigsson J (1983) Methodological aspects on C-peptide measurements. Acta Medica Scand Suppl 671:53–59Google Scholar
- 23.The DCCT Research Group (1998) Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 128:517–523CrossRefGoogle Scholar
- 29.Andersen ML, Rasmussen MA, Pörksen S et al (2013) Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual β-cell function 1 year after diagnosis of type 1 diabetes. PLoS One 8(6):e64632. https://doi.org/10.1371/journal.pone.0064632 CrossRefGoogle Scholar
- 31.Nagl K, Hermann JM, Plamper M et al (2017) Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose-adjusted HbA1c in 3657 children and adolescents from Germany and Austria. Pediatr Diabetes 18(6):428–434. https://doi.org/10.1111/pedi.12413 CrossRefGoogle Scholar
- 34.Lundberg RL, Marino KR, Jasrotia A et al (2017) Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of <0.3 units/kg/day to the gold standard insulin-dose adjusted hemoglobin A1c of ≤9 for the detection of partial clinical remission. J Pediatr Endocrinol Metab 30(8):823–830. https://doi.org/10.1515/jpem-2017-0019 CrossRefGoogle Scholar
- 36.Wentworth JM, Bediaga NG, Giles LC et al (2018) Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables. Diabetologia. https://doi.org/10.1007/s00125-018-4722-z