SFEBES2022 Early Career and Plenary Orals Early Career Prize Lecture Clinical (1 abstracts)
Central adiposity raises serum calcium concentrations and increases risk of kidney stone disease
Catherine Lovegrove 1,2 , Jelena Besevic 3 , Akira Wiberg 4,2 , Ben Lacey 3 , Thomas Littlejohns 3 , Naomi Allen 3 , Michelle Goldsworthy 5 , Jihye Kim 6 , Fadil Hannan 7 , Gary Curhan 8 , Ben Turney 1,2 , Mark McCarthy 9 , Anubja Mahajan 9 , Rajesh Thakker 5 , Michael Holmes 10 , Dominic Furniss 4,2 & Sarah Howles 1,2,5
1Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom. 2Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 3Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. 4Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford, United Kingdom. 5Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. 6Chan School of Public Health, Boston, USA. 7Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, United Kingdom. 8Channing Division of Network Medicine and Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA. 9Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. 10Medical Research Council, Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
Background: Kidney stone disease (KSD) has been linked to obesity, metabolic syndrome and higher serum calcium concentration (SCa). The mechanisms underlying these associations are uncertain. Using conventional and genetic epidemiological techniques, we aimed to investigate the effects of adiposity on KSD.
Methods: Observational associations between adiposity and incident KSD in 479, 405 people from the UK Biobank were assessed. Genome-wide association studies (GWAS) of KSD in combined and sex-specific subsets of the UK Biobank were undertaken to facilitate Mendelian randomisation (MR). Univariable, multivariable and mediation MR analyses were undertaken to calculate odds ratios (OR) and beta coefficients (β) per genetically instrumented higher marker of adiposity, metabolic syndrome, biochemical phenotype, and inflammation.
Results: Central adiposity (waist-to-hip ratio (WHR) and waist circumference (WC)) were more strongly associated with KSD than general adiposity (body mass index (BMI)) on observational analyses. The association of BMI with KSD was almost completely attenuated adjusting for WC (HR=1.03, 95% CI=0.97-1.10 per 5kg/m2), whereas WC and WHR remained positively associated following adjustment for BMI (HR=1.26 95% CI=1.19-1.33 per 10cm higher WC, and HR=1.22, 95% CI=1.18-1.27 per 0.05 higher WHR). Three novel KSD-GWAS loci were identified (SLC2A12, TRPV5, and SLC28A1); no sex-specific loci were detected. Higher central adiposity was causally linked to KSD and higher adjusted SCa independent of BMI (1-standard deviation higher WHR: OR KSD=1.43, P=4.1×10-6; β SCa =0.11mmol/L, P=2.7×10-7) on MR analyses. Mediation analyses indicate that 12% of the effect of WHR on KSD is due its role in elevating SCa. Other components of metabolic syndrome, serum urate, and biomarkers of inflammation were unlikely to cause KSD.
Conclusions: We demonstrate that SCa is elevated by higher visceral adipose depots and this increases risk of KSD. There may be utility in using therapies that target central adipose deposition to modulate calcium homeostasis to prevent KSD.
Volume 86
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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