Introduction: Accurate pancreatic islet autoantibody (Aab) measurement is vital for risk-screening, early-stage treatment, and prevention study eligibility assessment in persons with and at risk of type 1 diabetes (T1D). Although Aab measurement has been standardized by addressing lab assay differences, intra-individual variation in these assays by time of day has not yet been carefully assessed.

Objective: To assess the extent of Aab diurnal variation in persons with established T1D.

Methods: Ten persons (mean age 27y) within 1-19y post T1D diagnosis had 6 blood samples taken at 4-h intervals starting at 09:00. Aab titers were measured by radiobinding assays and diurnal patterns investigated using a “Cosinor” method.

Results: We observed daily within-subject differences in Insulin Aab (IAA) titers (max-min) with a median daily difference of 18 units and variation as great as 80 units in one individual. Aab titer differences affected assay sensitivity; one person was IA-2 Aab positive on samples taken at 09:00, 13:00 and 21:00, yet negative at the other 3 times. IAA levels followed a 24-h single phase cosine curve (p=0.0028) with peak IAA titer estimated at 04:08 hrs (95% confidence interval: 01:34 to 06:34). Zinc Transporter 8 Aabs also varied according to this pattern (ZnT8RA p=0.0057 and ZnT8WA p<0.0001) with morning peaks: ZnT8RA peak at 07:06 (04:07, 09:55), ZnT8WA at 08:55 (05:41, 12:10). Variance components analyses implied that sample time of day was a greater source of variation than intra-assay variation alone for IAA, GADA and ZnT8WA.

Conclusion: Circulating islet Aab titers vary significantly over 24 hrs, and Aab detection can be time-of-day dependent. Since our pilot data suggest several Aab peak in the morning, morning may be the best time of day for Aab detection. Our findings only reflect variations occurring in established T1D and therefore should be investigated in other T1D populations. Diurnal variation as a source of Aab variation must be considered in future efforts to improve Aab measurements.

Disclosure

L.A. DiMeglio: Research Support; Dompé, Lilly Diabetes, MannKind Corporation, Medtronic, Provention Bio, Inc., Sanofi, Zealand Pharma A/S, Amgen Inc. Advisory Panel; Vertex Pharmaceuticals Incorporated, Abata Therapeutics. C. Beam: None. J.A. Pearson: None.

Funding

JDRF INO-2017-458-A-N Indiana NIH UL1TR001108

© 2024 by the American Diabetes Association
2024
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