Adults with type 1 diabetes mellitus (T1DM) face an elevated risk of cognitive decline, but the relationship between glycemia and biomarkers of neuronal injury remains unclear. An observational analysis published in Diabetes Research and Clinical Practice evaluated blood-based biomarkers of Alzheimer’s disease and related dementias (AD/ADRD) in relation to glycemic metrics and diabetes-related factors.

The study included 114 adults with T1DM from the Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes (GluCog) study who had available plasma samples. Regression models assessed associations between biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau (pTau181 and pTau217), and amyloid beta (Aβ42/Aβ40 ratio), with diabetes characteristics and continuous glucose monitoring metrics over up to 20 days. Analyses were adjusted for demographics and kidney disease, with false discovery rate correction applied.

Higher NfL concentrations were observed with higher mean glucose, increased glycated hemoglobin (HbA1c), reduced time in range, and greater time spent above 180 mg/dL and 250 mg/dL. NfL levels also corresponded with diabetes-related complications, including neuropathy and diabetic ketoacidosis. Lower Aβ42/Aβ40 ratios were noted with older age at T1DM diagnosis. These findings remained consistent after adjustment for kidney disease, although residual confounding related to renal function could not be excluded.

These findings indicate that higher NfL reflects glycemic burden and diabetes-related complications in T1DM. The results support a pattern consistent with neuronal injury rather than an Alzheimer’s disease-specific process. Longitudinal studies are required to clarify the relationship between glycemia and neuronal injury markers.