Albuminuria in Patients With Type 1 Diabetes Linked to Neurodegeneration

According to a recent study in Frontiers in Neuroscience, patients with type 1 diabetes (T1D) exhibited “a reduced response of the lactate concentration as an indication of impaired glycolytic activity, which correlated with brain atrophy.”

Investigators examined whether patients with T1D exhibiting indicators of microvascular damage (evaluated by the presence of albuminuria) exhibited an escalated pace of brain atrophy and if this finding could be linked to potential cerebrovascular or glycolytic dysfunction.

The case-control study matched 33 patients with T1D (mean age, 50.8 years) with 19 nondiabetic controls (mean age, 45 years). Of the patients with T1D, 11 (33%) had albuminuria.

The study employed anatomical magnetic resonance imaging (MRI) to measure parameters such as total brain volume, brain parenchymal fraction, gray matter volume, and white matter volume. Cerebral vascular and glycolytic functions were assessed through the measurement of global cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), and cerebral lactate concentration. This evaluation was performed in response to the inhalation of hypoxic air (containing only 12%-14% fractional oxygen), utilizing phase-contrast MRI and magnetic resonance spectroscopy techniques.

Patients with T1D and albuminuria showed significant reductions in total brain volume, brain parenchymal fraction, and gray matter volume when compared with healthy controls and T1D patients without albuminuria.

The inhalation of hypoxic air increased CBF and lactate in all groups, indicating a collective response to the physiological stressor. However, patients with albuminuria exhibited a notably lower lactate response than healthy controls. While the CBF response in patients with albuminuria was also lower than that in healthy controls, it did not reach statistical significance. CMRO₂ remained unaffected by the hypoxic challenge across all groups.

Furthermore, the study established a crucial correlation between a low lactate response and brain atrophy. Specifically, reduced total brain volume and gray matter volume were significantly associated with a diminished lactate response, highlighting the importance of glycolytic activity in maintaining brain health.

“A reduced cerebral glycolytic activity could be a driver of neurodegeneration and be related to the increased risk of dementia development,” investigators wrote. “Counteracting the reduction in cerebral glycolytic activity could be a possible point of intervention for preventing detrimental neurodegeneration in patients with T1D.”