Prediabetes is associated with structural brain abnormalities: the Maastricht study

Marnix J.M. van Agtmaal (Corresponding author), Alfons J.H.M. Houben, Vera de Wit, Ronald M.A. Henry, Nicolaas C. Schaper, Pieter C. Dagnelie, Carla J. van der Kallen, Annemarie Koster, Simone J. Sep, Abraham A. Kroon, Jacobus F.A. Jansen, Paul A. Hofman, Walter H. Backes, Miranda T. Schram, Coen D.A. Stehouwer

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)


OBJECTIVE Structural brain abnormalities are key risk factors for brain diseases, such as dementia, stroke, and depression, in type 2 diabetes. It is unknown whether structural brain abnormalities already occur in prediabetes. Therefore, we investigated whether both prediabetes and type 2 diabetes are associated with lacunar infarcts (LIs), white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and brain atrophy. RESEARCH DESIGN and METHODS We used data from 2,228 participants (1,373 with normal glucose metabolism [NGM], 347 with prediabetes, and 508 with type 2 diabetes (oversampled); mean age 59.2 6 8.2 years; 48.3% women) of the Maastricht Study, a population-based cohort study. Diabetes status was determined with an oral glucose tolerance test. Brain imaging was performed with 3 Tesla MRI. Results were analyzed with multivariable logistic and linear regression analyses. RESULTS Prediabetes and type 2 diabetes were associated with the presence of LIs (odds ratio 1.61 [95% CI 0.98-2.63] and 1.67 [1.04-2.68], respectively; P trend = 0.027), larger WMH (b 0.07 log10-transformed mL [log-mL] [95% CI 0.00-0.15] and 0.21 log-mL [0.14-0.28], respectively; P trend <0.001), and smaller white matter volumes (b 24.0 mL [27.3 to 20.6] and 27.2 mL [210.4 to 24.0], respectively; P trend <0.001) compared with NGM. Prediabetes was not associated with gray matter volumes or the presence of CMBs. CONCLUSIONS Prediabetes is associated with structural brain abnormalities, with further deterioration in type 2 diabetes. These results indicate that, in middle-aged populations, structural brain abnormalities already occur in prediabetes, which may suggest that the treatment of early dysglycemia may contribute to the prevention of brain diseases.

Original languageEnglish
Pages (from-to)2535-2543
Number of pages9
JournalDiabetes Care
Issue number12
Publication statusPublished - 1 Dec 2018


  • Adult
  • Aged
  • Atrophy/diagnosis
  • Brain/diagnostic imaging
  • Brain Diseases/diagnosis
  • Cohort Studies
  • Diabetes Mellitus, Type 2/complications
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Netherlands/epidemiology
  • Prediabetic State/complications
  • Risk Factors
  • Stroke/diagnosis

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