Article Text

White matter hyperintensity volume in pre-diabetes, diabetes and normoglycemia
  1. Sergio Grosu1,
  2. Roberto Lorbeer1,
  3. Felix Hartmann1,
  4. Susanne Rospleszcz2,3,
  5. Fabian Bamberg4,
  6. Christopher L Schlett4,
  7. Franziska Galie1,
  8. Sonja Selder1,
  9. Sigrid Auweter1,
  10. Margit Heier2,5,
  11. Wolfgang Rathmann6,7,
  12. Katharina Mueller-Peltzer4,
  13. Karl-Heinz Ladwig2,8,
  14. Annette Peters2,3,
  15. Birgit B Ertl-Wagner1,9,
  16. Sophia Stoecklein1
  1. 1Department of Radiology, University Hospital, LMU Munich, Munich, Germany
  2. 2Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany
  3. 3Department of Epidemiology, Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany
  4. 4Department of Diagnostic and Interventional Radiology, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  5. 5KORA Study Centre, University Hospital of Augsburg, Augsburg, Germany
  6. 6Institute for Biometrics and Epidemiology, German Diabetes Center, Duesseldorf, Germany
  7. 7German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
  8. 8Department of Psychosomatic Medicine and Psychotherapy, Hospital Rechts der Isar, Technical University Munich, Munich, Germany
  9. 9Department of Radiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Sergio Grosu; sergio.grosu{at}; Dr Sophia Stoecklein; sophia.stoecklein{at}


Introduction As white matter hyperintensities (WMHs) of the brain are associated with an increased risk of stroke, cognitive decline, and depression, elucidating the associated risk factors is important. In addition to age and hypertension, pre-diabetes and diabetes may play important roles in the development of WMHs. Previous studies have, however, shown conflicting results. We aimed to investigate the effect of diabetes status and quantitative markers of glucose metabolism on WMH volume in a population-based cohort without prior cardiovascular disease.

Research design and methods 400 participants underwent 3 T MRI. WMHs were manually segmented on 3D fluid-attenuated inversion recovery images. An oral glucose tolerance test (OGTT) was administered to all participants not previously diagnosed with diabetes to assess 2-hour serum glucose concentrations. Fasting glucose concentrations and glycated hemoglobin (HbA1c) levels were measured. Zero-inflated negative binomial regression analyses of WMH volume and measures of glycemic status were performed while controlling for cardiovascular risk factors and multiple testing.

Results The final study population comprised 388 participants (57% male; age 56.3±9.2 years; n=98 with pre-diabetes, n=51 with diabetes). Higher WMH volume was associated with pre-diabetes (p=0.001) and diabetes (p=0.026) compared with normoglycemic control participants after adjustment for cardiovascular risk factors. 2-hour serum glucose (p<0.001), but not fasting glucose (p=0.389) or HbA1c (p=0.050), showed a significant positive association with WMH volume after adjustment for cardiovascular risk factors.

Conclusion Our results indicate that high 2-hour serum glucose concentration in OGTT, but not fasting glucose levels, may be an independent risk factor for the development of WMHs, with the potential to inform intensified prevention strategies in individuals at risk of WMH-associated morbidity.

  • pre-diabetic state
  • MRI
  • brain diseases
  • metabolic
  • diabetes complications

Data availability statement

Data are available upon reasonable request. The informed consent given by KORA study participants does not cover data posting in public databases. However, data are available upon request from KORA/KORA-gen ( by means of a project agreement. Requests should be sent to and are subject to approval by the KORA Board.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available upon reasonable request. The informed consent given by KORA study participants does not cover data posting in public databases. However, data are available upon request from KORA/KORA-gen ( by means of a project agreement. Requests should be sent to and are subject to approval by the KORA Board.

View Full Text

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Contributors SG, RL and SSt wrote the main manuscript text and prepared the figures and tables. SG, FH and SSt performed the analyses of the imaging data. RL and SR performed the statistical analyses. SG, RL, SR and SSt analyzed and interpreted the findings. SG, RL, SR, FB, CLS, SSe, SA, MH, WR, KM-P, K-HL, AP, BBE-W and SSt were involved in the design and supervision of the research. All authors contributed to the interpretation of the results and reviewed the manuscript.

  • Funding The KORA study was initiated and financed by the Helmholtz Zentrum München - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences, Ludwig-Maximilians-Universität, as part of LMUinnovativ. The KORA MRI substudy received funding by the German Research Foundation (Deutsche Forschungsgemeinschaft). The KORA MRI substudy was supported by an unrestricted research grant from Siemens Healthcare.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.