Key result
Higher glycemic variability was significantly associated with increased regional brain atrophy, with temporal lobe volume decreasing by an average of 1.2% for each 1 mmol/L increase in mean amplitude of glycemic excursion over 7 years.
Why the study?
Although type 2 diabetes mellitus is linked to lower gray matter volumes, little is known about how glycemic control and glycemic variability affect brain atrophy over time.
Does glycemic variability increase long-term brain atrophy in individuals with type 2 diabetes?
Cohort (n=27)
No
Does glycemic variability increase long-term brain atrophy in individuals with type 2 diabetes?
Higher glycemic variability in type 2 diabetes is associated with accelerated longitudinal gray matter atrophy in brain regions involved in habit-learning, decision-making, and memory.
Answers are grounded in this paper and cite their sources.
Should not yet change practice; hypothesis-generating for glycemic variability as a neurodegeneration risk factor.
Objective Type 2 diabetes mellitus (T2DM) is associated with lower gray matter (GM) volumes. However, little is known about the impact of glycemic control on brain atrophy, especially in highly susceptible regions. Therefore, we aim to identify the effect of glycemic variability (GV) on long-term changes in brain volume among individuals with T2DM. Methods A longitudinal clinical, biochemical, and imaging assessment was conducted at a baseline visit on 170 individuals (85 with T2DM), from which 29 (15 with T2DM) were evaluated at a 7-year follow-up visit. Brain regional volumes were evaluated with 3 T MRI, using the FreeSurfer 7 longitudinal pipeline. GV metrics such as SD, M-value, MAG (mean absolute glucose change), MAGE (mean amplitude of glycemic excursion), and CoV (coefficient of variation) were calculated in both visits. Results Statistically significant negative correlations between GV metrics and symmetrized percent change (SPC) of GM volumes were found in specific cortical and subcortical regions of individuals with T2DM. MAGE was correlated with regionally specific atrophy on the temporal lobe (r = −0.63, p = 0.021), insula (ρ = −0.62, p = 0.022), thalamus (r = −0.64; p = 0.024), hippocampus (r = −0.59; p = 0.034), and putamen (ρ = −0.65, p = 0.017). Concerning the hippocampal subregions, the presubiculum was significantly correlated with MAGE (r = −0.73; p = 0.005). Baseline GV was consistently associated with temporal lobe SPC. Linear regression analysis showed that, for each increase of 1 mmol/L in MAGE value, the SPC of the temporal lobe decreases on average by 1.2% (higher atrophy rate). Conclusion The relationship between longitudinal GM atrophy and GV has a regionally specific pattern, suggesting localized brain susceptibility to intra-daily glucose fluctuations. Negative correlations between GV metrics and SPC volume of regions involved in habit-learning, decision-making, and memory highlight GV as a mediator of the neural impact of T2DM on the reward prediction-error circuits.
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d’Almeida et al. (2025) conducted a cohort in Type 2 diabetes mellitus (n=27). Glycemic variability vs. Lower glycemic variability was evaluated on Symmetrized percent change (SPC) of temporal lobe gray matter volume (r = -0.63, p=0.021). Higher glycemic variability was significantly associated with increased regional brain atrophy, with temporal lobe volume decreasing by an average of 1.2% for each 1 mmol/L increase in mean amplitude of glycemic excursion over 7 years.
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