Association of long‐term hyperglycaemia and insulin resistance with brain atrophy and cognitive decline: A longitudinal cohort study

Abstract

Aim: To investigate the longitudinal changes in brain volume and cognitive function associated with diabetes at midlife, and to examine whether long-term hyperglycaemia, insulin resistance or secretory function is associated with brain atrophy and cognitive decline. Materials and Methods:We used data from 2377 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. Timeweighted mean glycaemic values were calculated using all measurements over an average duration of 10.6 years from cohort initiation to baseline visits.Results: Type 2 diabetes was associated with greater white matter volume reduction (adjusted volume difference = À1.96 ml, 95% CI: À3.73, À0.18) and executive function decline (adjusted Z score difference = À0.14, 95% CI: À0.23, À0.05) during the follow-up period of 4.2 years. Decline of verbal and visual memory or verbal fluency was not associated with diabetes. Greater executive function decline was associated with higher time-weighted mean HbA1c level over the preceding 10.6 years (P < .001), but not with insulin resistance markers in the diabetes group. Participants with diabetes, whose time-weighted average HbA1c level was maintained above 6.5% over the previous decade, showed greater decline in executive function and global cognition than the normal glucose group.Conclusions: Long-term hyperglycaemia was a major independent factor associated with rapid cognitive decline in middle-aged adults with diabetes. Maintaining ideal glucose levels in diabetes at midlife might prevent later rapid cognitive decline.

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment

“…Dysfunctional insulin signaling and elevated blood glucose levels lead to heightened expression and activation of NF-κB, a pivotal participant in the inflammatory cascade and a regulator of apoptosis ( Sima et al, 2009 ; Moulton et al, 2015 ). Moreover, advanced glycation end products, also leads to inflammation, as a consequence of chronic activation of microglia, leading to neuronal and glial apoptosis ( Moulton et al, 2015 ; Sun et al, 2020 ; Yu et al, 2023 ). We favour the view that neurodegenerative processes underlying T2DM’s pathophysiology might also leads to the presence of brain atrophy, where toxic glucose levels have a harmful impact on various biochemical processes associated with tau integrity, promoting tau cleavage and phosphorylation ( Kubis-Kubiak et al, 2019 ; Huang et al, 2020 ).…”

Triglyceride and Glucose Index and Sex Differences in Relation to Cognitive Impairment in Hypertensive Patients without Diabetes

“…Furthermore, previous studies have shown that IR is the main mechanism of brain abnormalities in magnetic resonance imaging (MRI) of patients with or without diabetes. [25,26] Neverthless, Ji Hee Yu, et al [27] examined whether long-term hyperglycemia, insulin resistance, or secretory function is associated with brain atrophy and cognitive decline in subjects from the Ansan cohort of the Korean Genome Epidemiology Study (KoGES) , finding time-weighted HOMA-IR level during a 10-year period did not show an association with brain atrophy, unlike baseline insulin resistance markers. Similarly, a longitudinal study reported that there was no correlation between insulin secretion assessed by insulinogenic index (IGI) obtained through oral glucose tolerance test (OGTT) and cognitive function of participants without diabetes.…”

The Impact of Free and Added Sugars on Cognitive Function: A Systematic Review and Meta-Analysis

“…Thanks to glucose homeostatic mechanisms, the brain is resilient to minor changes in blood glucose levels, but moderate or severe hypo- or hyperglycaemia can impair neuronal functioning and lead to cell death [ 20 , 21 , 22 ]. Recurrent episodes of hypo- or hyperglycaemic states are associated with increased risk of cognitive impairment and dementia [ 23 , 24 ].…”