Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study

Theresa Wimberley; Henriette T Horsdal; Isabell Brikell; Thomas M Laursen; Aske Astrup; Giuseppe Fanelli; Janita Bralten; Geert Poelmans; Veerle Van Gils; Willemijn J Jansen; Stephanie J B Vos; Valérie Bertaina-Anglade; Lucia Camacho-Barcia; Bernat Mora-Maltas; Fernando Fernandez-Aranda; Mònica B Bonet; Jordi Salas-Salvadó; Barbara Franke; Søren Dalsgaard

doi:10.1186/s12888-022-04163-z

Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study

Theresa Wimberley, Henriette T Horsdal, Isabell Brikell, Thomas M Laursen, Aske Astrup, Giuseppe Fanelli, Janita Bralten, Geert Poelmans, Veerle Van Gils, Willemijn J Jansen, Stephanie J B Vos, Valérie Bertaina-Anglade, Lucia Camacho-Barcia, Bernat Mora-Maltas, Fernando Fernandez-Aranda, Mònica B Bonet, Jordi Salas-Salvadó, Barbara Franke, Søren Dalsgaard

Child and Adolescent Mental Health Center, Mental Health Services

36 Citations (Scopus)

Abstract

BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders.

METHODS: In a population-based cohort-study of 1,883,198 Danish citizens, born 1955-1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors.

RESULTS: A total of 67,660 (3.6%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95% CI]: 2.64 [2.36-2.94]) and schizophrenia spectrum disorder (2.73 [2.63-2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57-1.91]) and epilepsy (1.67 [1.60-1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females.

CONCLUSIONS: T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.

Original language	English
Article number	573
Journal	BMC Psychiatry
Volume	22
Issue number	1
Pages (from-to)	573
ISSN	1471-244X
DOIs	https://doi.org/10.1186/s12888-022-04163-z
Publication status	Published - Dec 2022

Keywords

Epidemiology
Insulin signaling
Neurological disorders
Psychiatric disorders
Temporally ordered analysis
Type 2 diabetes mellitus

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10.1186/s12888-022-04163-z

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Wimberley, T., Horsdal, H. T., Brikell, I., Laursen, T. M., Astrup, A., Fanelli, G., Bralten, J., Poelmans, G., Gils, V. V., Jansen, W. J., Vos, S. J. B., Bertaina-Anglade, V., Camacho-Barcia, L., Mora-Maltas, B., Fernandez-Aranda, F., Bonet, M. B., Salas-Salvadó, J., Franke, B., & Dalsgaard, S. (2022). Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study. BMC Psychiatry, 22(1), 573. Article 573. https://doi.org/10.1186/s12888-022-04163-z

Wimberley, T, Horsdal, HT, Brikell, I, Laursen, TM, Astrup, A, Fanelli, G, Bralten, J, Poelmans, G, Gils, VV, Jansen, WJ, Vos, SJB, Bertaina-Anglade, V, Camacho-Barcia, L, Mora-Maltas, B, Fernandez-Aranda, F, Bonet, MB, Salas-Salvadó, J, Franke, B & Dalsgaard, S 2022, 'Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study', BMC Psychiatry, vol. 22, no. 1, 573, pp. 573. https://doi.org/10.1186/s12888-022-04163-z

@article{9ca09d177ffc42ae87cd51b0b8acc1bb,

title = "Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study",

abstract = "BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders.METHODS: In a population-based cohort-study of 1,883,198 Danish citizens, born 1955-1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95\% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors.RESULTS: A total of 67,660 (3.6\%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95\% CI]: 2.64 [2.36-2.94]) and schizophrenia spectrum disorder (2.73 [2.63-2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57-1.91]) and epilepsy (1.67 [1.60-1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females.CONCLUSIONS: T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.",

keywords = "Epidemiology, Insulin signaling, Neurological disorders, Psychiatric disorders, Temporally ordered analysis, Type 2 diabetes mellitus",

author = "Theresa Wimberley and Horsdal, \{Henriette T\} and Isabell Brikell and Laursen, \{Thomas M\} and Aske Astrup and Giuseppe Fanelli and Janita Bralten and Geert Poelmans and Gils, \{Veerle Van\} and Jansen, \{Willemijn J\} and Vos, \{Stephanie J B\} and Val{\'e}rie Bertaina-Anglade and Lucia Camacho-Barcia and Bernat Mora-Maltas and Fernando Fernandez-Aranda and Bonet, \{M{\`o}nica B\} and Jordi Salas-Salvad{\'o} and Barbara Franke and S{\o}ren Dalsgaard",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s12888-022-04163-z",

language = "English",

volume = "22",

pages = "573",

journal = "BMC Psychiatry",

issn = "1471-244X",

publisher = "BioMed Central Ltd",

number = "1",

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TY - JOUR

T1 - Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study

AU - Wimberley, Theresa

AU - Horsdal, Henriette T

AU - Brikell, Isabell

AU - Laursen, Thomas M

AU - Astrup, Aske

AU - Fanelli, Giuseppe

AU - Bralten, Janita

AU - Poelmans, Geert

AU - Gils, Veerle Van

AU - Jansen, Willemijn J

AU - Vos, Stephanie J B

AU - Bertaina-Anglade, Valérie

AU - Camacho-Barcia, Lucia

AU - Mora-Maltas, Bernat

AU - Fernandez-Aranda, Fernando

AU - Bonet, Mònica B

AU - Salas-Salvadó, Jordi

AU - Franke, Barbara

AU - Dalsgaard, Søren

PY - 2022/12

Y1 - 2022/12

N2 - BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders.METHODS: In a population-based cohort-study of 1,883,198 Danish citizens, born 1955-1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors.RESULTS: A total of 67,660 (3.6%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95% CI]: 2.64 [2.36-2.94]) and schizophrenia spectrum disorder (2.73 [2.63-2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57-1.91]) and epilepsy (1.67 [1.60-1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females.CONCLUSIONS: T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.

AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked with several neurodegenerative and psychiatric disorders, either as a comorbid condition or as a risk factor. We aimed to expand the evidence by examining associations with a broad range of brain disorders (psychiatric and neurological disorders, excluding late-onset neurodegenerative disorders), while also accounting for the temporal order of T2DM and these brain disorders.METHODS: In a population-based cohort-study of 1,883,198 Danish citizens, born 1955-1984 and followed until end of 2016, we estimated associations between T2DM and 16 brain disorders first diagnosed between childhood and mid-adulthood. We calculated odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) in temporally ordered analyses (brain disorder diagnosis after T2DM and vice versa), adjusted for sex, age, follow-up, birth year, and parental factors.RESULTS: A total of 67,660 (3.6%) of the study population were identified as T2DM cases after age 30 and by a mean age of 45 years (SD of 8 years). T2DM was associated with most psychiatric disorders. Strongest associations were seen with other (i.e. non-anorectic) eating disorders (OR [95% CI]: 2.64 [2.36-2.94]) and schizophrenia spectrum disorder (2.73 [2.63-2.84]). Among neurological disorders especially inflammatory brain diseases (1.73 [1.57-1.91]) and epilepsy (1.67 [1.60-1.75]) were associated with T2DM. Most associations remained in both directions in the temporally ordered analyses. For most psychiatric disorders, associations were strongest in females.CONCLUSIONS: T2DM was associated with several psychiatric and neurological disorders, and most associations were consistently found for both temporal order of disorders. This suggests a shared etiology of T2DM and those brain disorders. This study can form the starting point for studies directed at further elucidating potential causal links between disorders and shared biological mechanisms.

KW - Epidemiology

KW - Insulin signaling

KW - Neurological disorders

KW - Psychiatric disorders

KW - Temporally ordered analysis

KW - Type 2 diabetes mellitus

UR - https://www.scopus.com/pages/publications/85137083780

U2 - 10.1186/s12888-022-04163-z

DO - 10.1186/s12888-022-04163-z

M3 - Journal article

C2 - 36028833

SN - 1471-244X

VL - 22

SP - 573

JO - BMC Psychiatry

JF - BMC Psychiatry

IS - 1

M1 - 573

ER -

Temporally ordered associations between type 2 diabetes and brain disorders - a Danish register-based cohort study

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Keywords

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