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Updated: Nov 5, 2025

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes
Craig A Beam1, Eleni Beli2,3,4, Clive H Wasserfall5,6
1Department of Biomedical Sciences, Homer Stryker MD School of Medicine, Western Michigan University, Kalamazoo, MI, USA. craig.beam@med.wmich.edu.
Aims/Hypothesis:
The circadian clock influences both diabetes and immunity. Our goal in this study was to characterise more thoroughly the circadian patterns of immune cell populations and cytokines that are particularly relevant to the immune pathology of type 1 diabetes and thus fill in a current gap in our understanding of this disease.
Methods:
Ten individuals with established type 1 diabetes (mean disease duration 11 years, age 18-40 years, six female) participated in a circadian sampling protocol, each providing six blood samples over a 24 h period.
Results:
Daily ranges of population frequencies were sometimes large and possibly clinically significant. Several immune populations, such as dendritic cells, CD4 and CD8 T cells and their effector memory subpopulations, CD4 regulatory T cells, B cells and cytokine IL-6, exhibited statistically significant circadian rhythmicity. In a comparison with historical healthy control individuals, but using shipped samples, we observed that participants with type 1 diabetes had statistically significant phase shifts occurring in the time of peak occurrence of B cells (+4.8 h), CD4 and CD8 T cells (~ +5 h) and their naive and effector memory subsets (~ +3.3 to +4.5 h), and regulatory T cells (+4.1 h). An independent streptozotocin murine experiment confirmed the phase shifting of CD8 T cells and suggests that circadian dysrhythmia in type 1 diabetes might be an effect and not a cause of the disease.
Conclusions/Interpretation:
Future efforts investigating this newly described aspect of type 1 diabetes in human participants are warranted. Peripheral immune populations should be measured near the same time of day in order to reduce circadian-related variation.
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