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Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study.

van Agtmaal MJM, Houben AJHM, de Wit V, Henry RMA, Schaper NC, Dagnelie PC, van der Kallen CJ, Koster A, Sep SJ, Kroon AA, Jansen JFA, Hofman PA, Backes WH, Schram MT, Stehouwer CDA. 


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.


We used data from 2,228 participants (1,373 with normal glucose metabolism [NGM], 347 prediabetes, and 508 type 2 diabetes (oversampled); mean age 59.2 ± 8.2 years; and 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.


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 (β 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 (β -4.0 mL [-7.3 to -0.6] and -7.2 mL [-10.4 to -4.0], respectively; P trend<0.001) compared with NGM. Prediabetes was not associated with gray matter volumes or the presence of CMBs.


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.

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