Testing for associations between HbA1c levels, polygenic risk and brain health in UK Biobank (N = 39 283)

Ranglani, S., Ward, J. , Sattar, N. , Strawbridge, R. J. and Lyall, D. M. (2023) Testing for associations between HbA1c levels, polygenic risk and brain health in UK Biobank (N = 39 283). Diabetes, Obesity and Metabolism, 25(11), pp. 3136-3143. (doi: 10.1111/dom.15207) (PMID:37435691)

Abstract

Aim: To investigate whether continuous HbA1c levels and HbA1c-polygenic risk scores (HbA1c-PRS) are significantly associated with worse brain health independent of type 2 diabetes (T2D) diagnosis (vs. not), by examining brain structure and cognitive test score phenotypes. Methods: Using UK Biobank data (n = 39 283), we tested whether HbA1c levels and/or HbA1c-PRS were associated with cognitive test scores and brain imaging phenotypes. We adjusted for confounders of age, sex, Townsend deprivation score, level of education, genotyping chip, eight genetic principal components, smoking, alcohol intake frequency, cholesterol medication, body mass index, T2D and apolipoprotein (APOE) e4 dosage. Results: We found an association between higher HbA1c levels and poorer performance on symbol digit substitution scores (standardized beta [β] = −0.022, P = .001) in the fully adjusted model. We also found an association between higher HbA1c levels and worse brain MRI phenotypes of grey matter (GM; fully-adjusted β = −0.026, P < .001), whole brain volume (β = −0.072, P = .0113) and a general factor of frontal lobe GM (β = −0.022, P < .001) in partially and fully adjusted models. HbA1c-PRS were significantly associated with GM volume in the fully adjusted model (β = −0.010, P = .0113); however, when adjusted for HbA1c levels, the association was not significant. Conclusions: Our findings suggest that measured HbA1c is associated with poorer cognitive health, and that HbA1c-PRS do not add significant information to this.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ward, Dr Joey and Sattar, Professor Naveed and Lyall, Dr Donald and Strawbridge, Dr Rona and Ranglani, Mr Sanskar
• Authors: Ranglani, S., Ward, J., Sattar, N., Strawbridge, R. J., and Lyall, D. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 12 July 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Diabetes, Obesity and Metabolism 25(11): 3136-3143
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302131		Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness	Jill Pell	Medical Research Council (MRC)	MR/S003061/1	HW - Public Health