Stephen Burgess1,2, Rainer Malik3, Bowen Liu2, Amy M Mason2, Marios K Georgakis3, Martin Dichgans3,4,5, Dipender Gill6,7,8,9. 1. Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK. 2. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 3. Institute for Stroke and Dementia Research, University Hospital of Ludwig-Maximilians-University, Munich, Germany. 4. Munich Cluster for Systems Neurology, Munich, Germany. 5. German Centre for Neurodegenerative Diseases, Munich, Germany. 6. Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London, London, UK. dgill@sgul.ac.uk. 7. Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London, UK. dgill@sgul.ac.uk. 8. Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford, UK. dgill@sgul.ac.uk. 9. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. dgill@sgul.ac.uk.
Abstract
AIMS/HYPOTHESIS: Our aim was to investigate the relationship between average blood glucose levels and incident CHD in individuals without diabetes mellitus. METHODS: To investigate average blood glucose levels, we studied HbA1c as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA1c. Linear and non-linear Mendelian randomisation analyses were performed to investigate associations with incident CHD risk in 324,830 European ancestry individuals from the UK Biobank without diabetes mellitus. RESULTS: Every one mmol/mol increase in genetically proxied HbA1c was associated with an 11% higher CHD risk (HR 1.11, 95% CI 1.05, 1.18). The dose-response curve increased at all levels of HbA1c, and there was no evidence favouring a non-linear relationship over a linear one. CONCLUSIONS/INTERPRETATIONS: In individuals without diabetes mellitus, lowering average blood glucose levels may reduce CHD risk in a dose-dependent way.
AIMS/HYPOTHESIS: Our aim was to investigate the relationship between average blood glucose levels and incident CHD in individuals without diabetes mellitus. METHODS: To investigate average blood glucose levels, we studied HbA1c as predicted by 40 variants previously shown to be associated with both type 2 diabetes and HbA1c. Linear and non-linear Mendelian randomisation analyses were performed to investigate associations with incident CHD risk in 324,830 European ancestry individuals from the UK Biobank without diabetes mellitus. RESULTS: Every one mmol/mol increase in genetically proxied HbA1c was associated with an 11% higher CHD risk (HR 1.11, 95% CI 1.05, 1.18). The dose-response curve increased at all levels of HbA1c, and there was no evidence favouring a non-linear relationship over a linear one. CONCLUSIONS/INTERPRETATIONS: In individuals without diabetes mellitus, lowering average blood glucose levels may reduce CHD risk in a dose-dependent way.
Entities:
Keywords:
Average blood glucose levels; CHD; Mendelian randomisation
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