Type 1 diabetes is associated with higher plasma levels of biomarkers of neurodegeneration and neuroinflammation

Abstract

Introduction Type 1 diabetes (T1D) is associated with increased risk of dementias and other neurodegenerative diseases. Plasma biomarkers of neurodegeneration and neuroinflammation hold utility in risk prediction and diagnosis of neurodegenerative disease and other neuropathology, but there remains a paucity of data in the T1D population. This study quantified plasma levels of biomarkers of neurodegeneration and neuroinflammation [phosphorylated tau-181 (pTau-181), total tau (Tau), amyloid beta 42/amyloid beta 40 (Aβ42/40), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL)], and tested associations with T1D and related characteristics. Methods This cross-sectional analysis of a subset of participants from the Coronary Artery Calcification in Type 1 Diabetes study included adults with and without T1D. Biomarker levels were quantified using Quanterix Simoa, then log-transformed and analyzed using linear regression models adjusted for age, body mass index (BMI), race and ethnicity, smoking status, and estimated glomerular filtration rate (eGFR). A subsequent sensitivity analysis included diabetic retinopathy (DR). Results 136 adults with T1D (n=90, age 52 years, 58% female, average HbA1c 7.7%) and without T1D (n=46, age 53 years, 57% female, average HbA1c 5.4%) were included. In fully adjusted models, T1D was associated with higher pTau-181 [estimate (pg/mL) 1.221, (95% confidence interval 1.003, 1.486) p=0.046], GFAP [1.296 (1.129, 1.489), p<0.001], and NfL [1.355 (1.162, 1.579), p<0.001], relative to adults without T1D. In the sensitivity analysis, relative to adults without T1D, T1D with moderate/severe DR was associated with higher pTau-181 [1.330 (1.063, 1.663), p=0.013], GFAP [1.369 (1.653, 1.608), p<0.001], and NfL [1.495 (1.252, 1.786), p<0.001], and T1D with none/mild DR was associated with higher GFAP [1.228 (1.046, 1.442), p=0.013] and NfL [1.235 (1.037, 1.470), p=0.018]. As compared to T1D with none/mild DR, T1D with moderate/severe DR was associated with higher NfL [1.211 (1.011, 1.451), p=0.038]. Across both models, eGFR was inversely associated with pTau-181, NfL, and Tau (p<0.05 for all). Discussion T1D is associated with a greater burden of plasma biomarkers of neurodegeneration and neuroinflammation, and microvascular complications such as DR and impaired kidney function may contribute to this burden. Further study is needed to fully characterize the interplay between these biomarkers and neuropathology in T1D.