Elsevier

Biotechnology Advances

Volume 39, March–April 2020, 107359
Biotechnology Advances

Research review paper
Harmonization of immunoassays for biomarkers in diabetes mellitus

https://doi.org/10.1016/j.biotechadv.2019.02.015Get rights and content
Under a Creative Commons license
open access

Highlights

  • Harmonization of immunoassays for biomarkers is important for world-wide comparability of laboratory values

  • Diabetes biomarkers contribute essentially to the diagnosis, classification, prediction and treatment of individuals

  • HbA1c and C-peptide assays have been harmonized; efforts for harmonization of insulin immunoassays are still ongoing

  • Comparability of immunoassays for beta-cell related autoantibodies determination have markedly improved

Abstract

Harmonization of biomarkers is important for the comparability of laboratory results as it allows the definition of universal reference values and clinical decision limits. In diabetology, immunoassays are widely used to determine HbA1c, C-peptide, insulin, and autoantibodies to beta cell proteins, which are essential biomarkers for the diagnosis and classification of diabetes mellitus. Furthermore, as large clinical studies have identified HbA1c as a predictor for the development of diabetic complications, HbA1c has evolved as the general treatment target. For decades, the use of non-harmonized assays caused confusion. After the standardization of HbA1c, the worldwide comparability improved and increased the confidence in this laboratory biomarker. Insulin and C-peptide are not only valuable biomarkers to assess beta-cell function, but may also be used to evaluate insulin resistance, a metabolic feature of type 2 diabetes often occurring before its manifestation. Long-lasting efforts led to substantial improvements in the harmonization process of C-peptide assays, but harmonization of insulin assays is still ongoing. Therefore, C-peptide is now sometimes used as a surrogate biomarker for insulin. Furthermore, autoantibodies against beta cell components are important biomarkers for the accurate differentiation of type 1, type 2, and other special types of diabetes. Owing to the heterogeneity of these autoantibodies against beta cell proteins, harmonization is very difficult to achieve. International efforts are in progress to harmonize the current assays, as the presence of autoantibodies against beta cell proteins predicts the development of type 1 diabetes in early life. In conclusion, clinical studies linking diagnosis, classification, prediction, and treatment to laboratory values of the respective biomarkers need to be harmonized to avoid misdiagnosis and incorrect clinical decisions, thus improving patient care and safety.

Keywords

Autoantibodies
Biomarker
Classification
C-peptide
Diabetes mellitus
Glycated hemoglobin
Harmonization
Immunoassay
Insulin
Prediction
Standardization

Abbreviations

ADA
American Diabetes Association
CAP
College Of American Pathologists
CE
Capillary Electrophoresis
DASP
Diabetes Antibody Standardization Program
DCCT
Diabetes Control And Complications Trial
DCM
Designated Method Comparison
EASD
European Association For The Study Of Diabetes
ECBS
Expert Committee On Biological Standardization
ECL
Electrochemiluminescence
ELISA
Enzme-Linked Immunosorbant Assay
GAD
Glutamate Decarboxylase
GADA
Autoantibodies To GAD
GHb
Total Glycated Hemoglobin
HbA1c
Glycated Hemoglobin
HOMA
Homeostasis Model Assessment
HPLC
High Pressure Liquid Chromatography
IA-2A
Autoantibodies To IA-2
IAA
insulin autoantibodies
IASP
Islet Autoantibody Standardization Program
ICA
Islet Cell Antibodies
IDF
International Diabetes Federation
IDS
Immunology Of Diabetes Society
IFCC
International Federation Of Clinical Chemistry
IRR
International Reference Reagent
JCTLM
Joint Committee For Traceability In Laboratory Medicine
LADA
Late Onset Autoimmune Diabetes In The Adult
LC-MS
Liquid Chromatography–Tandem Mass Spectrometry
LIPS
Luciferase Immunoprecipitation System
MODY
Maturity Onset Diabetes Of The Young
MS
Mass Spectroscopy
NGSP
National Glycohemoglobin Standardization Program”
NIBSC
National Institute For Biological Standards And Control
NIDDK
National Institute Of Diabetes And Digestive And Kidney Diseases
NMIJ
National Metrology Institute Of Japan
PRM
Primary Reference Material
RBA
Radio-binding Assay
RIA
Radioimmunoassay
RMP
Reference Measurement Procedure
UKPDS
United Kingdom Prospective Diabetes Study
WHO
World Health Organization
ZnT8
Zink Transporter-8
ZnT8A
Autoantibodies To ZnT8

Cited by (0)