Type 2 Diabetes as a Determinant of Parkinson's Disease Risk and Progression

Background Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta‐analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting. Objective The objective...

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Veröffentlicht in:Movement disorders Jg. 36; H. 6; S. 1420 - 1429
Hauptverfasser: Chohan, Harneek, Senkevich, Konstantin, Patel, Radhika K., Bestwick, Jonathan P., Jacobs, Benjamin M., Bandres Ciga, Sara, Gan‐Or, Ziv, Noyce, Alastair J.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Hoboken, USA John Wiley & Sons, Inc 01.06.2021
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ISSN:0885-3185, 1531-8257, 1531-8257
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Abstract Background Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta‐analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting. Objective The objective was to investigate T2DM as a determinant of PD through a meta‐analysis of observational and genetic summary data. Methods A systematic review and meta‐analysis of observational studies was undertaken by searching 6 databases. We selected the highest‐quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome‐wide association studies. Results In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07–1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39–0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 to −0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse‐variance weighted method [IVW] OR 1.08, 95% CI 1.02–1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01–1.20; P = 0.032) but not on cognitive progression. Conclusions Using meta‐analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
AbstractList BackgroundType 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta‐analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting.ObjectiveThe objective was to investigate T2DM as a determinant of PD through a meta‐analysis of observational and genetic summary data.MethodsA systematic review and meta‐analysis of observational studies was undertaken by searching 6 databases. We selected the highest‐quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome‐wide association studies.ResultsIn the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07–1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39–0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 to −0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse‐variance weighted method [IVW] OR 1.08, 95% CI 1.02–1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01–1.20; P = 0.032) but not on cognitive progression.ConclusionsUsing meta‐analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting.BACKGROUNDType 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting.The objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data.OBJECTIVEThe objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data.A systematic review and meta-analysis of observational studies was undertaken by searching 6 databases. We selected the highest-quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome-wide association studies.METHODSA systematic review and meta-analysis of observational studies was undertaken by searching 6 databases. We selected the highest-quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome-wide association studies.In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39-0.72) and cognitive decline (SMD -0.92, 95% CI -1.50 to -0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR 1.08, 95% CI 1.02-1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01-1.20; P = 0.032) but not on cognitive progression.RESULTSIn the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39-0.72) and cognitive decline (SMD -0.92, 95% CI -1.50 to -0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR 1.08, 95% CI 1.02-1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01-1.20; P = 0.032) but not on cognitive progression.Using meta-analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.CONCLUSIONSUsing meta-analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting. The objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data. A systematic review and meta-analysis of observational studies was undertaken by searching 6 databases. We selected the highest-quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome-wide association studies. In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39-0.72) and cognitive decline (SMD -0.92, 95% CI -1.50 to -0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR 1.08, 95% CI 1.02-1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01-1.20; P = 0.032) but not on cognitive progression. Using meta-analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Background Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta‐analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting. Objective The objective was to investigate T2DM as a determinant of PD through a meta‐analysis of observational and genetic summary data. Methods A systematic review and meta‐analysis of observational studies was undertaken by searching 6 databases. We selected the highest‐quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome‐wide association studies. Results In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07–1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39–0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 to −0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse‐variance weighted method [IVW] OR 1.08, 95% CI 1.02–1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01–1.20; P = 0.032) but not on cognitive progression. Conclusions Using meta‐analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Author Jacobs, Benjamin M.
Bandres Ciga, Sara
Bestwick, Jonathan P.
Noyce, Alastair J.
Chohan, Harneek
Senkevich, Konstantin
Gan‐Or, Ziv
Patel, Radhika K.
AuthorAffiliation 2 Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada
5 Department of Human Genetics, McGill University, Montréal, Quebec, Canada
1 Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
6 Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK
3 Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada
4 Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
AuthorAffiliation_xml – name: 2 Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada
– name: 1 Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
– name: 3 Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada
– name: 6 Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, London, UK
– name: 4 Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
– name: 5 Department of Human Genetics, McGill University, Montréal, Quebec, Canada
Author_xml – sequence: 1
  givenname: Harneek
  orcidid: 0000-0003-0561-758X
  surname: Chohan
  fullname: Chohan, Harneek
  organization: Queen Mary University of London
– sequence: 2
  givenname: Konstantin
  surname: Senkevich
  fullname: Senkevich, Konstantin
  organization: McGill University
– sequence: 3
  givenname: Radhika K.
  surname: Patel
  fullname: Patel, Radhika K.
  organization: Queen Mary University of London
– sequence: 4
  givenname: Jonathan P.
  surname: Bestwick
  fullname: Bestwick, Jonathan P.
  organization: Queen Mary University of London
– sequence: 5
  givenname: Benjamin M.
  surname: Jacobs
  fullname: Jacobs, Benjamin M.
  organization: Queen Mary University of London
– sequence: 6
  givenname: Sara
  surname: Bandres Ciga
  fullname: Bandres Ciga, Sara
  organization: National Institute on Aging, National Institutes of Health
– sequence: 7
  givenname: Ziv
  surname: Gan‐Or
  fullname: Gan‐Or, Ziv
  organization: McGill University
– sequence: 8
  givenname: Alastair J.
  orcidid: 0000-0003-3027-5497
  surname: Noyce
  fullname: Noyce, Alastair J.
  email: a.noyce@qmul.ac.uk
  organization: UCL Institute of Neurology
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33682937$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2021 The Authors. published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: 2021 The Authors. published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
– notice: 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
– notice: 2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Issue 6
Keywords Parkinson's disease
type 2 diabetes
Language English
License Attribution
2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Notes Z.G.‐O. received consultancy fees from Lysosomal Therapeutics Inc. (LTI), Idorsia, Prevail Therapeutics, Inceptions Sciences (now Ventus), Ono Therapeutics, Neuron23, Handl Therapeutics, Denali, and Deerfield. A.J.N. reports grants from the Barts Charity, Parkinson's UK, Aligning Science Across Parkinson's and Michael J. Fox Foundation, and the Virginia Keiley Benefaction. Personal fees/honoraria from Britannia, BIAL, AbbVie, Global Kinetics Corporation, Profile, Biogen, Roche, and UCB are outside of the submitted work.
Relevant conflicts of interest/financial disclosures
H.C. and K.S. contributed equally to this work.
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Snippet Background Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and...
Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have...
BackgroundType 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and...
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wiley
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StartPage 1420
SubjectTerms Aged
Aging
Causality
Cognitive ability
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Genetic analysis
Genome-Wide Association Study
Genomes
Humans
Meta-analysis
Movement disorders
Neurodegenerative diseases
Parkinson Disease - epidemiology
Parkinson Disease - genetics
Parkinson's disease
type 2 diabetes
Title Type 2 Diabetes as a Determinant of Parkinson's Disease Risk and Progression
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fmds.28551
https://www.ncbi.nlm.nih.gov/pubmed/33682937
https://www.proquest.com/docview/2542191336
https://www.proquest.com/docview/2498996760
https://pubmed.ncbi.nlm.nih.gov/PMC9017318
Volume 36
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