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Impact of glucose on risk of dementia: Mendelian randomisation studies in 115,875 individuals

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@article{6704b04f5911418082bd31013d61af65,
title = "Impact of glucose on risk of dementia: Mendelian randomisation studies in 115,875 individuals",
abstract = "AIMS/HYPOTHESIS: Mendelian randomisation studies have not shown a clear causal effect of high plasma glucose on the risk of Alzheimer's disease. We tested the hypothesis that high plasma glucose caused by genetic variation has a causal effect on the risk of unspecified dementia, Alzheimer's disease and vascular dementia in the general population.METHODS: A Mendelian randomisation design was used with data from 115,875 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study. Findings for Alzheimer's disease were validated in a two-sample Mendelian design with 455,258 individuals, including 71,880 individuals with Alzheimer's disease or a parent with Alzheimer's disease.RESULTS: In observational multifactorial-adjusted analyses, HRs were 1.15 (95{\%} CI 1.01, 1.32; p = 0.039) for unspecified dementia, 0.91 (95{\%} CI 0.79, 1.06; p = 0.22) for Alzheimer's disease and 1.16 (95{\%} CI 0.86, 1.55; p = 0.34) for vascular dementia in individuals with a glucose level higher than 7 vs 5-6 mmol/l. Corresponding HRs in individuals with vs without type 2 diabetes were 1.42 (95{\%} CI 1.24, 1.63; p < 0.001), 1.11 (95{\%} CI 0.95, 1.29; p = 0.18) and 1.73 (95{\%} CI 1.31, 2.27; p < 0.001). In genetic causal analyses, a 1 mmol/l higher plasma glucose level had RRs of 2.40 (95{\%} CI 1.18, 4.89; p = 0.016) for unspecified dementia, 1.41 (95{\%} CI 0.82, 2.43; p = 0.22) for Alzheimer's disease and 1.20 (95{\%} CI 0.82, 1.75; p = 0.36) for vascular dementia. Summary-level data from the Meta-Analyses of Glucose and Insulin-related Traits Consortium (MAGIC) combined with a consortium of the Alzheimer's Disease Sequencing Project (ADSP), the International Genomics of Alzheimer's Project (IGAP), the Alzheimer's Disease Working Group of the Psychiatric Genomics Consortium (PGC-ALZ) and the UK Biobank (UKB) gave an RR for Alzheimer's disease of 1.02 (95{\%} CI 0.92, 1.13; p = 0.42), and this consortium combined with Copenhagen studies gave an RR for Alzheimer's disease of 1.03 (95{\%} CI 0.93, 1.13; p = 0.36).CONCLUSIONS/INTERPRETATION: Observational and genetically high plasma glucose are causally related to the risk of unspecified dementia, but not to Alzheimer's disease or vascular dementia.",
author = "Marianne Benn and Nordestgaard, {B{\o}rge G} and Anne Tybj{\ae}rg-Hansen and Ruth Frikke-Schmidt",
year = "2020",
month = "6",
doi = "10.1007/s00125-020-05124-5",
language = "English",
volume = "63",
pages = "1151--1161",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Impact of glucose on risk of dementia

T2 - Mendelian randomisation studies in 115,875 individuals

AU - Benn, Marianne

AU - Nordestgaard, Børge G

AU - Tybjærg-Hansen, Anne

AU - Frikke-Schmidt, Ruth

PY - 2020/6

Y1 - 2020/6

N2 - AIMS/HYPOTHESIS: Mendelian randomisation studies have not shown a clear causal effect of high plasma glucose on the risk of Alzheimer's disease. We tested the hypothesis that high plasma glucose caused by genetic variation has a causal effect on the risk of unspecified dementia, Alzheimer's disease and vascular dementia in the general population.METHODS: A Mendelian randomisation design was used with data from 115,875 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study. Findings for Alzheimer's disease were validated in a two-sample Mendelian design with 455,258 individuals, including 71,880 individuals with Alzheimer's disease or a parent with Alzheimer's disease.RESULTS: In observational multifactorial-adjusted analyses, HRs were 1.15 (95% CI 1.01, 1.32; p = 0.039) for unspecified dementia, 0.91 (95% CI 0.79, 1.06; p = 0.22) for Alzheimer's disease and 1.16 (95% CI 0.86, 1.55; p = 0.34) for vascular dementia in individuals with a glucose level higher than 7 vs 5-6 mmol/l. Corresponding HRs in individuals with vs without type 2 diabetes were 1.42 (95% CI 1.24, 1.63; p < 0.001), 1.11 (95% CI 0.95, 1.29; p = 0.18) and 1.73 (95% CI 1.31, 2.27; p < 0.001). In genetic causal analyses, a 1 mmol/l higher plasma glucose level had RRs of 2.40 (95% CI 1.18, 4.89; p = 0.016) for unspecified dementia, 1.41 (95% CI 0.82, 2.43; p = 0.22) for Alzheimer's disease and 1.20 (95% CI 0.82, 1.75; p = 0.36) for vascular dementia. Summary-level data from the Meta-Analyses of Glucose and Insulin-related Traits Consortium (MAGIC) combined with a consortium of the Alzheimer's Disease Sequencing Project (ADSP), the International Genomics of Alzheimer's Project (IGAP), the Alzheimer's Disease Working Group of the Psychiatric Genomics Consortium (PGC-ALZ) and the UK Biobank (UKB) gave an RR for Alzheimer's disease of 1.02 (95% CI 0.92, 1.13; p = 0.42), and this consortium combined with Copenhagen studies gave an RR for Alzheimer's disease of 1.03 (95% CI 0.93, 1.13; p = 0.36).CONCLUSIONS/INTERPRETATION: Observational and genetically high plasma glucose are causally related to the risk of unspecified dementia, but not to Alzheimer's disease or vascular dementia.

AB - AIMS/HYPOTHESIS: Mendelian randomisation studies have not shown a clear causal effect of high plasma glucose on the risk of Alzheimer's disease. We tested the hypothesis that high plasma glucose caused by genetic variation has a causal effect on the risk of unspecified dementia, Alzheimer's disease and vascular dementia in the general population.METHODS: A Mendelian randomisation design was used with data from 115,875 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study. Findings for Alzheimer's disease were validated in a two-sample Mendelian design with 455,258 individuals, including 71,880 individuals with Alzheimer's disease or a parent with Alzheimer's disease.RESULTS: In observational multifactorial-adjusted analyses, HRs were 1.15 (95% CI 1.01, 1.32; p = 0.039) for unspecified dementia, 0.91 (95% CI 0.79, 1.06; p = 0.22) for Alzheimer's disease and 1.16 (95% CI 0.86, 1.55; p = 0.34) for vascular dementia in individuals with a glucose level higher than 7 vs 5-6 mmol/l. Corresponding HRs in individuals with vs without type 2 diabetes were 1.42 (95% CI 1.24, 1.63; p < 0.001), 1.11 (95% CI 0.95, 1.29; p = 0.18) and 1.73 (95% CI 1.31, 2.27; p < 0.001). In genetic causal analyses, a 1 mmol/l higher plasma glucose level had RRs of 2.40 (95% CI 1.18, 4.89; p = 0.016) for unspecified dementia, 1.41 (95% CI 0.82, 2.43; p = 0.22) for Alzheimer's disease and 1.20 (95% CI 0.82, 1.75; p = 0.36) for vascular dementia. Summary-level data from the Meta-Analyses of Glucose and Insulin-related Traits Consortium (MAGIC) combined with a consortium of the Alzheimer's Disease Sequencing Project (ADSP), the International Genomics of Alzheimer's Project (IGAP), the Alzheimer's Disease Working Group of the Psychiatric Genomics Consortium (PGC-ALZ) and the UK Biobank (UKB) gave an RR for Alzheimer's disease of 1.02 (95% CI 0.92, 1.13; p = 0.42), and this consortium combined with Copenhagen studies gave an RR for Alzheimer's disease of 1.03 (95% CI 0.93, 1.13; p = 0.36).CONCLUSIONS/INTERPRETATION: Observational and genetically high plasma glucose are causally related to the risk of unspecified dementia, but not to Alzheimer's disease or vascular dementia.

U2 - 10.1007/s00125-020-05124-5

DO - 10.1007/s00125-020-05124-5

M3 - Journal article

VL - 63

SP - 1151

EP - 1161

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 6

ER -

ID: 60073946