HbA1c and brain health across the entire glycaemic spectrum

Garfield, Victoria; Farmaki, Aliki‐Eleni; Eastwood, Sophie V.; Mathur, Rohini; Rentsch, Christopher T; Bhaskaran, Krishnan; Smeeth, Liam; Chaturvedi, Nish

doi:10.1111/dom.14321

Cited by 35 publications

(52 citation statements)

References 36 publications

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“…These associations were present in our fully adjusted models for all neuroimaging outcomes, except for gFA (a measure of white matter integrity) and the amygdala (region associated with emotional processing and fear-related memories). These findings largely agree with previous studies of the association between diabetes and neuroimaging outcomes in the UKB [6, 7]. A key difference between our study and that of Cox et al though, is that we observed no relationship between diabetes and gFA, but they did.…”

Section: Discussionsupporting

confidence: 92%

“…This discrepancy could be due to differences in modelling approaches (including covariate adjustment), sample size (∼10,000 vs our sample of maximum ∼40,000) and definition of diabetes (self-reported vs use of a validated algorithm plus HbA1c measurements). Our study also investigated a much wider range of neuroimaging parameters compared to at least one of the earlier studies [7], which only included hippocampal and white matter hyperintensity volumes.…”

Section: Discussionmentioning

confidence: 99%

“…Type-2 diabetes is associated with excess risk of dementia [1,2], worse cognitive function [3,4] and changes in brain structure and function [1]. Large-scale population based studies, such as the UK Biobank (UKB), have recently expanded our understanding of the relationship between diabetes, cognitive function and brain health (as captured by magnetic resonance imaging (MRI) [5][6][7]). Important insights from these studies include that diabetes is associated with: slower reaction times [5,7], poorer brain health as indexed by structural and diffusion indices and increased risk of vascular, Alzheimer's and all-cause dementia [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Large-scale population based studies, such as the UK Biobank (UKB), have recently expanded our understanding of the relationship between diabetes, cognitive function and brain health (as captured by magnetic resonance imaging (MRI) [5][6][7]). Important insights from these studies include that diabetes is associated with: slower reaction times [5,7], poorer brain health as indexed by structural and diffusion indices and increased risk of vascular, Alzheimer's and all-cause dementia [6,7]. The relationship between hypertension and a range of adverse cognitive and brain health parameters is also well established [8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Understanding the interrelationships of type-2 diabetes and hypertension with brain and cognitive health: a UK Biobank study

Newby

Garfield

2021

Preprint

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Aims/hypothesisDiabetes and hypertension are associated with poorer cognitive and brain health. Less is known about comorbid diabetes and hypertension and: cognitive and brain health in mid-life. We hypothesised that individuals with both diabetes and hypertension have worse cognitive and brain health.MethodsWe used the UK Biobank cohort, a population-based study which recruited 500,000 individuals, aged 40-69 years. Type-2 diabetes was assigned using self-report, HbA1c and clinical data, while hypertension was defined based on self-report. Our outcomes included a breadth of brain structural magnetic resonance imaging (MRI) parameters and cognitive function tests in a maximum of 38918 individuals. We tested associations in a cross sectional design firstly between those with diabetes (n = 2043) versus those without (reference category, n = 36875) then we tested associations between comorbid diabetes/hypertension (reference category, n=1283) and our outcomes by comparing this group with those with only diabetes (n=760), hypertension (n=9649) and neither disease (n=27226). Our analytical approach comprised linear regression models, with adjustment for a range of demographic and health factors.ResultsThose with diabetes had worse overall brain health, as indexed by multiple neuroimaging parameters, with the exception of gFA (white matter integrity) and the amygdala. The largest difference was observed in the pallidum (β=0.179, 95%CI=0.137;0.220). Individuals with diabetes had poorer performance on certain cognitive tests, with the largest difference observed in the symbol digit substitution test (β=0.132, 95%CI=0.079;0.187). Compared to individuals with comorbid diabetes and hypertension, those with only hypertension had better brain health overall, with the largest difference observed in the pallidum (β=0.189, 95%CI=0.241;0.137), while those with only diabetes differed in total grey volume (β=0.150, 95%CI=0.122;0.179). Compared with individuals who had comorbid diabetes and hypertension, those with only diabetes performed distinctly better on the verbal and numeric reasoning task (β=0.129, 95%CI=0.077;0.261), whereas those with only hypertension performed better on the symbol digit substitution task (β=0.117, 95%CI=0.048;0.186)Conclusions/interpretationIndividuals with comorbid diabetes and hypertension have worse brain and cognitive health compared to those with only one of these diseases. These findings potentially suggest that prevention of both diabetes and hypertension may delay changes in brain structure, as well as cognitive decline and dementia diagnosis.Research in contextWhat is already known about this subject?Diabetes and hypertension are both independently associated with poorer brain health, cognition and increase in dementia risk50% of adults with diabetes also have hypertensionComorbid diabetes and hypertension are associated with excess dementia riskWhat is the key question?Do individuals with both diabetes and hypertension have worse cognitive and brain health?What are the new findings?Individuals with diabetes have poorer brain health and cognitive performance using a breadth of neuroimaging measures and cognitive testsThose with both diabetes and hypertension have worse brain health and cognitive performance (particularly processing speed) compared to those with only hypertensionHow might this impact on clinical practice in the foreseeable future?Prevention of both diabetes and hypertension may help delay changes in brain structure and cognitive decline as well as reduce future dementia risk.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Understanding the interrelationships of type-2 diabetes and hypertension with brain and cognitive health: a UK Biobank study

Newby

Garfield

2021

Preprint

Self Cite

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“…In addition, mediation effects were observed on glycated hemoglobin A (HbA1c) and glucose, which were biomarkers of diabetes. High HbA1c level (hyperglycaemia) is associated with worse brain health and cognitive functions 52 , such as memory loss, poorer processing speed, attention, concentration, and executive functions 53,54 . As the primary source of energy for the brain, glucose metabolism plays an important role in the physiological and pathological functioning of the brain 55 .…”

Section: Resultsmentioning

confidence: 99%

Heart-brain connections: phenotypic and genetic insights from 40,000 cardiac and brain magnetic resonance images

Zhao

Fan

et al. 2021

Preprint

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Cardiovascular health interacts with cognitive and psychological health in complex ways. Yet, little is known about the phenotypic and genetic links of heart-brain systems. Using cardiac and brain magnetic resonance imaging (CMR and brain MRI) data from over 40,000 UK Biobank subjects, we developed detailed analyses of the structural and functional connections between the heart and the brain. CMR measures of the cardiovascular system were strongly correlated with brain basic morphometry, structural connectivity, and functional connectivity after controlling for body size and body mass index. The effects of cardiovascular risk factors on the brain were partially mediated by cardiac structures and functions. Using 82 CMR traits, genome-wide association study identified 80 CMR-associated genomic loci (P < 6.09 × 10-10), which were colocalized with a wide spectrum of heart and brain diseases. Genetic correlations were observed between CMR traits and brain-related complex traits and disorders, including schizophrenia, bipolar disorder, anorexia nervosa, stroke, cognitive function, and neuroticism. Our results reveal a strong heart-brain connection and the shared genetic influences at play, advancing a multi-organ perspective on human health and clinical outcomes.

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Long‐term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered‐matched landmark analysis over 25 years

Yu,

Wang,

Osuagwu

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONWe aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years.METHODSTapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5‐ and 10‐year IR of dementia was estimated by weighted Cox models.RESULTSThe onset of T2D was significantly associated with the 10‐year IR of dementia, especially in the socioeconomically deprived, those of non‐NZ European ethnicity, those currently smoking, and patients with higher metabolic measures.DISCUSSIONOur findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds.Highlights Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

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HbA1c and brain health across the entire glycaemic spectrum

Cited by 35 publications

References 36 publications

Understanding the interrelationships of type-2 diabetes and hypertension with brain and cognitive health: a UK Biobank study

Understanding the interrelationships of type-2 diabetes and hypertension with brain and cognitive health: a UK Biobank study

Heart-brain connections: phenotypic and genetic insights from 40,000 cardiac and brain magnetic resonance images

Long‐term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered‐matched landmark analysis over 25 years

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