The impact of circadian rhythms on biomolecular set points: implications for disease diagnosis and monitoring

Abstract Laboratory data must be both analytically accurate and interpreted with clinically accuracy for safeguarding patient safety. However, variations – both analytical and biological – are inherent in all measurements obtained from patient samples. Biological variation observed in laboratory data can be broadly classified into two main categories: random and systematic variation. Among the systematic sources, in particular, circadian rhythms may have a significant influence on laboratory measurements. Understanding and recognizing the effects of circadian rhythms on both reference intervals and measurement results of analytes in both healthy individuals and patients is hence essential for enabling the accurate interpretation of laboratory data. In this review, we briefly discuss the major types of variation influencing laboratory data, with particular emphasis on systematic variation. We provide a detailed analysis of circadian rhythms and their impact on analyte concentrations and reference intervals, discuss the concept of set points and their variability in the context of diagnosis and monitoring of diseases, and examine mathematical models used to estimate physiological rhythms along with their respective advantages and limitations.