To investigate the relationship between left ventricular hypertrophy (LVH), plasma neurofilament light chain protein (NfL) levels and brain atrophy in people with type 2 diabetes mellitus (T2DM).

LVH is common in T2DM, and both are independently associated with increased dementia risk. The relationships between LVH, NfL and brain atrophy have not been investigated in T2DM.

Participants with T2DM aged ≥50 years (n=137) from the Diabetes and Dementia study (ACTRN126160005464590) in Melbourne, Australia completed detailed assessments including 3T brain MRI, transthoracic echocardiograms, and 24-hour ambulatory blood pressure. FreeSurfer estimated brain volume measures; plasma NfL assayed on Simoa® Quanterix HD-X Analyzer™. Differences in the mean cortical thickness and cortex were examined using multivariate general linear models. Multiple linear regression models examined the relationship between NfL and LVH. Comparisons were made between those with and without LVH.

Participant details: age=65±7(mean±SD) years, BMI=30±6kg/m², 44% women, HbA1c=60±14mmol/mol, diabetes duration=median15[IQR7, 22] years, 21% APOE ε4 carriers; 25% educated<12 years; 28% LVH.

LVH was significantly associated with older age, female sex, obesity (BMI33±6 vs 29±5kg/m²), hypertension history (95%vs.67%), less education (37% vs 20%), greater cortical thinning and lower cortex. Plasma NfL was correlated positively with age, HbA1c, and LV mass and negatively with cortical thickness. Median plasma NfL levels were significantly higher in LVH participants (21(14, 28) vs. 15(11, 22) pg/mL). Differences with LVH remained significant after adjustment for age, BMI, gender, education, and total intracranial volume for cortical thickness and TBV, but not after adjustment for hypertension.  LVH was an independent predictor of NfL levels (coefficient 0.19, p=0.04).

Accelerated structural brain aging is seen in people with T2DM. LVH and hypertension appear conflated as risk factors for brain atrophy. Plasma NfL levels are associated with LVH and cerebral atrophy.  LVH and plasma NfL are potential early biomarkers of neurodegeneration in T2DM.