Prediabetes is associated with structural brain abnormalities: the Maastricht study

Marnix J.M. van Agtmaal; 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

doi:10.2337/dc18-1132

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

Signal Processing Systems

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 language	English
Pages (from-to)	2535-2543
Number of pages	9
Journal	Diabetes Care
Volume	41
Issue number	12
DOIs	https://doi.org/10.2337/dc18-1132
Publication status	Published - 1 Dec 2018

Funding

Acknowledgments. The researchers are in debted to the participants for their willingness to participate in the study. Funding. This study was supported in part by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs and Climate Policy (grant 31O.041), Stichting De Weijerhorst (Maas-tricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), the Cardiovascular Center (Maastricht, the Netherlands), the School for Cardiovascular Diseases (CARIM), the Care and Public Health Research Institute, the School for Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), and Health Foundation Lim-burg (Maastricht, the Netherlands). Duality of Interest. This study was also supported by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands), and Sanofi Netherlands B.V. (Gouda, the Netherlands). No other potential conflicts of interest relevant to this article were reported. Author Contributions. M.J.M.v.A., A.J.H.M.H., V.d.W., R.M.A.H., N.C.S., P.C.D., C.J.v.d.K., A.K., S.J.S., A.A.K., J.F.A.J., P.A.H., W.H.B., M.T.S., and C.D.A.S. were involved in the design or conduct of the study, the preparation of the manuscript, and the decision to submit it for publication and all verify the accuracy and completeness of the data and analyses. M.J.M.v.A., A.J.H.M.H., M.T.S., and C.D.A.S. analyzed data and drafted the manuscript. A.J.H.M.H., R.M.A.H., N.C.S., P.C.D., C.J.v.d.K., A.K., S.J.S., A.A.K., J.F.A.J., P.A.H., W.H.B., M.T.S., and C.D.A.S. commented on the drafts and contributed to writing. V.d.W. analyzed data. M.J.M.v.A., A.J.H.M.H., V.d.W., R.M.A.H., N.C.S., P.C.D., C.J.v.d.K., A.K., S.J.S., A.A.K., J.F.A.J., P.A.H., W.H.B., M.T.S., and C.D.A.S. approved the final version. M.J.M.v.A. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/dc18-1132

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van Agtmaal, M. J. M., Houben, A. J. H. M., de Wit, V., Henry, R. M. A., Schaper, N. C., Dagnelie, P. C., van der Kallen, C. J., Koster, A., Sep, S. J., Kroon, A. A., Jansen, J. F. A., Hofman, P. A., Backes, W. H., Schram, M. T., & Stehouwer, C. D. A. (2018). Prediabetes is associated with structural brain abnormalities: the Maastricht study. Diabetes Care, 41(12), 2535-2543. https://doi.org/10.2337/dc18-1132

@article{274d1c09ecf9434c88fc606b11a43bd6,

title = "Prediabetes is associated with structural brain abnormalities: the Maastricht study",

abstract = " 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. ",

keywords = "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",

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

year = "2018",

month = dec,

day = "1",

doi = "10.2337/dc18-1132",

language = "English",

volume = "41",

pages = "2535--2543",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "12",

}

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 2018, 'Prediabetes is associated with structural brain abnormalities: the Maastricht study', Diabetes Care, vol. 41, no. 12, pp. 2535-2543. https://doi.org/10.2337/dc18-1132

TY - JOUR

T1 - Prediabetes is associated with structural brain abnormalities

T2 - the Maastricht study

AU - van Agtmaal, Marnix J.M.

AU - Houben, Alfons J.H.M.

AU - de Wit, Vera

AU - Henry, Ronald M.A.

AU - Schaper, Nicolaas C.

AU - Dagnelie, Pieter C.

AU - van der Kallen, Carla J.

AU - Koster, Annemarie

AU - Sep, Simone J.

AU - Kroon, Abraham A.

AU - Jansen, Jacobus F.A.

AU - Hofman, Paul A.

AU - Backes, Walter H.

AU - Schram, Miranda T.

AU - Stehouwer, Coen D.A.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Atrophy/diagnosis

KW - Brain/diagnostic imaging

KW - Brain Diseases/diagnosis

KW - Cohort Studies

KW - Diabetes Mellitus, Type 2/complications

KW - Female

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Netherlands/epidemiology

KW - Prediabetic State/complications

KW - Risk Factors

KW - Stroke/diagnosis

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U2 - 10.2337/dc18-1132

DO - 10.2337/dc18-1132

M3 - Article

C2 - 30327356

AN - SCOPUS:85056803159

SN - 0149-5992

VL - 41

SP - 2535

EP - 2543

JO - Diabetes Care

JF - Diabetes Care

IS - 12

ER -

Prediabetes is associated with structural brain abnormalities: the Maastricht study

Abstract

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Keywords

UN SDGs

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