SFEBES2021 Poster Presentations Metabolism, Obesity and Diabetes (78 abstracts)
Central adiposity and diabetes are causally associated with kidney stone disease
Catherine Lovegrove 1,2 , Akira Wiberg 3,4 , Thomas Littlejohns 5 , Naomi Allen 5 , Benjamin Turney 2,6 , Anubha Mahajan 7 , Mark McCarthy 7 , Rajesh Thakker 1 , Dominic Furniss 3,4 & Sarah Howles 1,2,6
1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; 2University of Oxford Nuffield Department of Surgical Sciences, Oxford, United Kingdom; 3Department of Plastic Surgery, Oxford University Hospitals NHS Trust, Oxford, United Kingdom; 4University of Oxford Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford, United Kingdom; 5University of Oxford Nuffield Department of Public Health, Oxford, United Kingdom; 6Department of Urology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom; 7Wellcome Centre for Human Genetics, University of Oxford Nuffield Department of Medicine, Oxford, United Kingdom
Introduction: The pathogenesis of kidney stone disease (KSD) is poorly understood and has been linked to features of metabolic syndrome (MetS). Using conventional and genetic epidemiological analyses we studied associations of MetS phenotypes with risk of KSD.
Methods: Multivariate Cox-proportional hazard models were used to assess association of BMI and waist-hip ratio (WHR) with KSD in 492,380 UK Biobank participants. Causal relationships between WHR, BMI, hypertension, hyperlipidaemia, hypercholesterolaemia, fasting insulin, fasting glucose and type 2 diabetes (T2DM) and KSD were interrogated using Mendelian Randomisation (MR).
Results: Data from the UKBiobank demonstrated that high WHR (men ≥0.9, women ≥0.85) confers >40% increased risk of KSD in patients with BMI ≥25<30 kg/m2 compared to individuals of normal WHR in this BMI range. MR, using SNPs from published genome-wide association studies, demonstrated that one standard deviation (SD) increase in BMI conferred 28% increased risk of KSD and 1SD increase in WHR was associated with 43% increased risk of KSD. Multivariable MR incorporating WHR and BMI found that WHR retains 44% increased risk of KSD whereas the effect of BMI was attenuated. T2DM and high HDL conferred increased risk of KSD (8% and 18% increased risk per 1SD increase respectively). Multivariable MR incorporating T2DM and WHR showed that both parameters remained causal for KSD (OR 1.34 (95% CI 1.15-1.56) P < 0.001 and OR 1.08 (95% CI 1.03-1.15) P = 0 .004 respectively). Risk from high HDL showed horizontal pleiotropy. No other MetS phenotypes demonstrated causality with KSD.
Conclusion: Central adiposity and T2DM are causally associated with KSD; elevated HDL demonstrates a pleiotropic relationship with KSD suggesting that genetic variants associated with HDL increase risk of KSD by mechanisms other than a direct effect of altered HDL concentrations. These findings motivate weight management and glycaemic control in KSD prevention. Further studies are required to define mechanisms by which associations arise.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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