Transdermal Blood Sampling for C-Peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes

Diabetes Care. 2024 Feb 1;47(2):239-245. doi: 10.2337/dc23-1379.

Abstract

Objective: C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative.

Research design and methods: Ninety-one individuals (71 with type 1 diabetes, 20 control; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1-17.1], diabetes duration 4.0 years [1.5-7.7]; control individuals: 42.2 years [38.0-52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire.

Results: Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40-50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] - TCB ln[C-peptide] = 0.008, 95% CI [-0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided).

Conclusions: Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies
  • Biomarkers
  • Blood Specimen Collection
  • C-Peptide
  • Child
  • Diabetes Mellitus, Type 1*
  • Glutamate Decarboxylase
  • Humans

Substances

  • C-Peptide
  • Autoantibodies
  • Biomarkers
  • Glutamate Decarboxylase