Diabetes and other autoimmune endocrine diseases
Adaptive and innate peripheral immune populations exhibit regular circadian patterns in healthy human subjects. We sought to determine whether these rhythmic patterns are preserved in type 1 diabetes (T1D). We enrolled 10 T1D young adults (mean age 27y, 6 female) diagnosed for at least 12 mo. (mean time post-diagnosis 11y) and free of other diseases. Whole blood samples were collected every 4 hr. over 24 hr. and subjected to FACS analysis. Circadian rhythmicity patterns were determined using "COSINOR" analysis. Data were compared to a group of 10 non-T1D adult historical controls (HC) (mean age 32y, 4 female).
Daily variation within T1D subjects could be large (e.g., one subject had a 43.30% difference in the relative frequency of Granulocytic Leukocytes), but varied between cell populations from 0.34% in DC to 20.42% in unidentified lymphocytes, similar to HC. However, as a group, B-cells, DC, NKT, Treg, CD4 and CD8 naïve and effector memory populations in T1D patients all exhibited significant (p<0.05) circadian rhythmicity. Interestingly, compared to HC, B-cells peaked 3.0 hours later in the T1D subjects; CD4 Naïve peaked 2.6 hours earlier; CD4+CD8+ 2.1 hours later and IL-6 9.2 hours earlier. Importantly, cortisol levels did not differ between the two groups. Immune cell circadian patterns are altered in T1D. Further research is needed to investigate the etiology. Studies measuring immune cell populations in T1D must be designed with sample collection times that are appropriate given these underlying circadian patterns with collection times that optimize the likelihood of observing relevant treatment responses.