American Diabetes Association
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The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

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posted on 2023-06-27, 18:34 authored by Oliver I Brown, Michael Drozd, Hugo McGowan, Marilena Giannoudi, Marcella Conning-Rowland, John Gierula, Sam Straw, Stephen B Wheatcroft, Katherine Bridge, Lee D Roberts, Eylem Levelt, Ramzi Ajjan, Kathryn J Griffin, Marc A Bailey, Mark T Kearney, Richard M Cubbon



Obesity and diabetes frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events and mortality in UK Biobank stratified by body mass index (BMI) and diabetes.

Research design and Methods

451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischemic stroke and cardiovascular death, with normal weight non-diabetes as comparator. 


5% of participants had diabetes (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-diabetes). In the non-diabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (p<0.005), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke and cardiovascular mortality rose across increasing BMI categories without diabetes (p<0.005); this was comparable in the diabetes groups (p-interaction>0.05). Normal weight diabetes had comparable adjusted cardiovascular mortality to obese non-diabetes (IRR 1.22 [95% confidence interval: 0.96-1.56]; p=0.1).


Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. 


This research was funded by the British Heart Foundation (RG/F/22/110076). At no time did any authors, nor their institutions, receive other payment or services from a third party for any aspect of the submitted work. This research has been conducted using the UK Biobank resource - application number 59585. This work uses data provided by patients and collected by the NHS as part of their care and support; Copyright © (2022), NHS Digital; Re-used with the permission of UK Biobank. All rights reserved. This research used data assets made available by National Safe Haven as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (research which commenced between 1st October 2020 – 31st March 2021 grant ref MC_PC_20029; 1st April 2021 -30th September 2022 grant ref MC_PC_20058). MD was supported by a British Heart Foundation Clinical Research Training Fellowship. SS is supported by a British Heart Foundation Clinical Research Training Fellowship. EL is funded by Wellcome Trust Clinical Career Development Fellowship (221690/Z/20/Z) and receives support from National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. LDR was supported by the Diabetes UK RD Lawrence Fellowship (16/0005382). KJG is a National Institute for Health and Care Research Academic Clinical Lecturer. MAB is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/12/33270). MTK is a British Heart Foundation professor. RMC was supported by a British Heart Foundation Intermediate Clinical Research Fellowship.