Plasma biomarkers of neurodegeneration and their associations with type 1 diabetes characteristics and glycemia.

AIMS: Type 1 diabetes (T1D) is associated with an increased risk of Alzheimer's disease and related dementias (AD/ADRD), although mechanisms remain unclear. This study examined the relationships between blood-based biomarkers of ADRD, diabetes-related factors, and glycemia in adults with T1D.

METHODS

This study analyzed 114 adults from the Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes (GluCog) Study with available plasma samples. Regression models assessed relationships between biomarkers (Aβ42/Aβ40 ratio, GFAP, NfL, pTau181, pTau217), diabetes characteristics, and continuous glucose monitoring metrics (up to 20 days), adjusting for demographics and kidney disease. False discovery rate (FDR) correction was applied.

RESULTS

Lower Aβ42/Aβ40 ratios were associated with older age of T1D diagnosis and higher NfL concentrations with higher mean glucose, lower glucose time in range, more time spent with glucose above 180 and 250 mg/dL, higher HbA1c, neuropathy, and diabetic ketoacidosis. These remained significant after additional adjustment for kidney disease, although residual confounding by renal function cannot be excluded.

CONCLUSIONS

Higher NfL was linked with multiple measures of hyperglycemia and other diabetes-related complications, consistent with neuronal injury rather than suggesting an ADRD-specific process. Longitudinal studies are needed to clarify the mechanisms between NfL and glycemia in T1D.