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

Ji Hee Yu, Regina E.Y. Kim, So Young Park, Da Young Lee, Hyun Joo Cho, Nam Hoon Kim, Hye Jin Yoo, Ji A. Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Chol Shin, Nan Hee Kim

Research output: Contribution to journalArticlepeer-review


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. Time-weighted 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 = −1.96 ml, 95% CI: −3.73, −0.18) and executive function decline (adjusted Z score difference = −0.14, 95% CI: −0.23, −0.05) 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.

Original languageEnglish
Pages (from-to)1091-1100
Number of pages10
JournalDiabetes, Obesity and Metabolism
Issue number4
Publication statusPublished - 2023 Apr

Bibliographical note

Funding Information:
This workwas supported by funds from the Korean Centers for Disease Control and Prevention (2011‐E71004‐00, 2012‐E71005‐00, 2013‐E71005‐00, 2014‐E71003‐00, 2015‐P71001‐00, 2016‐E71003‐00, 2017‐E71001‐00, 2018‐E71001‐00), the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (2019M3E5D3073102, 2019R1H1A2039682, 2020R1F1A1074265), a Korea University grant (K1824431 and K1810951), an Ansan‐Si hidden champion fostering and supporting project funded by Ansan city, and computational resources provided by the University of Iowa, Iowa City, Iowa.

Publisher Copyright:
© 2022 John Wiley & Sons Ltd.


  • brain atrophy
  • cognitive decline
  • hyperglycaemia
  • insulin resistance
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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