More structural brain abnormalities discovered in prediabetes compared to no diabetes

Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study

Literature - Van Agtmaal MJM, Houben AJHM, de Wit V et al. - Diab Care 2018; published online ahead of print

Introduction and methods

Type 2 diabetes (T2DM) has been associated with a higher risk of structural brain abnormalities and related brain disease, such as stroke, dementia and depression [1-9]. Structural brain abnormalities associated with T2DM include lacunar infarcts (LIs), white matter hyperintensities (WMHs), cerebral micro-bleeds (CMBs), and brain atrophy [10]. However, it is not clear whether prediabetes is also associated with the aforementioned risks. This analysis of the Maastricht Study [11] assessed whether prediabetes and T2DM are associated with structural brain abnormalities, including LIs, CMBs, WMHs, and impaired white matter volumes.

The Maastricht Study, an observational population-based cohort study, focusing on the etiology, pathophysiology, complications, and comorbidities of T2DM, included individuals aged 40-75 years, with or without T2DM. For the present analysis, data from 2,228 participants, who were recruited between November 2010 and September 2013, were selected. Diabetes status was defined using a standardized 2-h 75-g oral glucose tolerance test (OGTT), and according to the World Health Organization 2006 criteria [12] as follows:

  • normal glucose metabolism (NGM)
  • prediabetes: impaired fasting glucose (6.1–7.0 mmol/L) or impaired glucose tolerance (2-h post-dose OGTT glucose 7.8–11.1 mmol/L)
  • T2DM: fasting plasma glucose ≥7.1, 2-h post-dose OGTT glucose >11.1, or use of diabetes medication

Main results

Out of 2,228 participants 1,373 had NGM, 347 had prediabetes, and 508 had T2DM. After multivariable adjustment, and compared with NGM, prediabetes and T2DM were significantly associated with:

  • the presence of LIs (OR: 1.61; 95%CI: 0.98–2.63 for prediabetes; OR: 1.67; 95%CI: 1.04–2.68 for T2DM; P-trend = 0.027)
  • larger volumes of WMHs (β: 0.07 log-mL; 95%CI: 0.00–0.15 for prediabetes; β: 0.21 log-mL; 95%CI: 0.14–0.28 for T2DM; P-trend <0.001)
  • periventricular WMHs (β: 0.06 log-mL; 95%CI: -0.01 to 0.13 for prediabetes; β: 0.20 log-mL; 95%CI: 0.14–0.27 for T2DM; P-trend <0.001)
  • larger volumes of deep cortical WMHs (β: 0.07 log-mL; 95%CI: -0.01 to -0.15 for prediabetes; β: 0.16 log-mL; 95%CI: 0.08–0.24 for T2DM; P-trend <0.001)
  • smaller white matter volumes (β: -4.0 mL; 95%CI: -7.3 to -0.6 for prediabetes; β: -7.2 mL; 95%CI: -10.4 to -4.0 for T2DM; P-trend <0.001)
  • larger CSF volumes (β: 3.9 mL; 95%CI: 0.8–7.6 for prediabetes; β: 12.5 mL; 95%CI: 9.0–16.1 for T2DM; P-trend <0.001)


Structural brain abnormalities, including LIs, larger WMHs, and smaller white matter volumes, are more common in patients with prediabetes compared with NGM, and even more common in T2DM patients. These results suggest that the early treatment of prediabetes may contribute to the prevention of brain diseases.


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