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

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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 languageEnglish
Pages (from-to)2535-2543
Number of pages9
JournalDiabetes Care
Volume41
Issue number12
DOIs
Publication statusPublished - 1 Dec 2018

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Prediabetic State
Type 2 Diabetes Mellitus
Brain
Lacunar Stroke
Brain Diseases
Glucose
Glucose Tolerance Test
Neuroimaging
Population
Atrophy
Dementia
Linear Models
Cohort Studies
Logistic Models
Stroke
Odds Ratio
Regression Analysis
Depression

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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., ... 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
van Agtmaal, Marnix J.M. ; Houben, Alfons J.H.M. ; de Wit, Vera ; Henry, Ronald M.A. ; Schaper, Nicolaas C. ; Dagnelie, Pieter C. ; van der Kallen, Carla J. ; Koster, Annemarie ; Sep, Simone J. ; Kroon, Abraham A. ; Jansen, Jacobus F.A. ; Hofman, Paul A. ; Backes, Walter H. ; Schram, Miranda T. ; Stehouwer, Coen D.A. / Prediabetes is associated with structural brain abnormalities : the Maastricht study. In: Diabetes Care. 2018 ; Vol. 41, No. 12. pp. 2535-2543.
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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.",
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.}",
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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

Prediabetes is associated with structural brain abnormalities : the Maastricht study. / van Agtmaal, Marnix J.M. (Corresponding author); Houben, Alfons J.H.M.; de Wit, Vera; Henry, Ronald M.A.; Schaper, Nicolaas C.; Dagnelie, Pieter C.; van der Kallen, Carla J.; Koster, Annemarie; Sep, Simone J.; Kroon, Abraham A.; Jansen, Jacobus F.A.; Hofman, Paul A.; Backes, Walter H.; Schram, Miranda T.; Stehouwer, Coen D.A.

In: Diabetes Care, Vol. 41, No. 12, 01.12.2018, p. 2535-2543.

Research output: Contribution to journalArticleAcademicpeer-review

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.

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van Agtmaal MJM, Houben AJHM, de Wit V, Henry RMA, Schaper NC, Dagnelie PC et al. Prediabetes is associated with structural brain abnormalities: the Maastricht study. Diabetes Care. 2018 Dec 1;41(12):2535-2543. https://doi.org/10.2337/dc18-1132