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

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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 +/- 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 (beta 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

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

Keywords

SMALL VESSEL DISEASE
WHITE-MATTER HYPERINTENSITIES
TYPE-2 DIABETES-MELLITUS
LATE-LIFE DEPRESSION
ALZHEIMERS-DISEASE
MICROVASCULAR DYSFUNCTION
COGNITIVE DYSFUNCTION
GLUCOSE-METABOLISM
TISSUE SEGMENTATION
VASCULAR 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., 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{07e757b013d147cbb5f69a3ebdaa339d,

title = "Prediabetes Is Associated With Structural Brain Abnormalities: The Maastricht Study",

abstract = "OBJECTIVEStructural 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 METHODSWe 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 +/- 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.RESULTSPrediabetes 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 (beta 0.07 log10-transformed mL [log-mL] [95\% CI 0.00-0.15] and 0.21 log-mL [0.14-0.28], respectively; P-trendCONCLUSIONSPrediabetes 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 = "SMALL VESSEL DISEASE, WHITE-MATTER HYPERINTENSITIES, TYPE-2 DIABETES-MELLITUS, LATE-LIFE DEPRESSION, ALZHEIMERS-DISEASE, MICROVASCULAR DYSFUNCTION, COGNITIVE DYSFUNCTION, GLUCOSE-METABOLISM, TISSUE SEGMENTATION, VASCULAR DEPRESSION",

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",

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 - OBJECTIVEStructural 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 METHODSWe 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 +/- 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.RESULTSPrediabetes 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 (beta 0.07 log10-transformed mL [log-mL] [95% CI 0.00-0.15] and 0.21 log-mL [0.14-0.28], respectively; P-trendCONCLUSIONSPrediabetes 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 - OBJECTIVEStructural 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 METHODSWe 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 +/- 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.RESULTSPrediabetes 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 (beta 0.07 log10-transformed mL [log-mL] [95% CI 0.00-0.15] and 0.21 log-mL [0.14-0.28], respectively; P-trendCONCLUSIONSPrediabetes 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 - SMALL VESSEL DISEASE

KW - WHITE-MATTER HYPERINTENSITIES

KW - TYPE-2 DIABETES-MELLITUS

KW - LATE-LIFE DEPRESSION

KW - ALZHEIMERS-DISEASE

KW - MICROVASCULAR DYSFUNCTION

KW - COGNITIVE DYSFUNCTION

KW - GLUCOSE-METABOLISM

KW - TISSUE SEGMENTATION

KW - VASCULAR DEPRESSION

U2 - 10.2337/dc18-1132

DO - 10.2337/dc18-1132

M3 - Article

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

Keywords

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