Hyperglycemia is a causal risk factor for upper limb pathologies
dc.contributor.author | Green, HD | |
dc.contributor.author | Burden, E | |
dc.contributor.author | Chen, J | |
dc.contributor.author | Evans, J | |
dc.contributor.author | Patel, K | |
dc.contributor.author | Wood, AR | |
dc.contributor.author | Beaumont, RN | |
dc.contributor.author | Tyrrell, J | |
dc.contributor.author | Frayling, TM | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Oram, RA | |
dc.contributor.author | Bowden, J | |
dc.contributor.author | Barroso, I | |
dc.contributor.author | Smith, C | |
dc.contributor.author | Weedon, MN | |
dc.date.accessioned | 2024-01-04T12:19:15Z | |
dc.date.issued | 2024-01-10 | |
dc.date.updated | 2024-01-04T09:56:59Z | |
dc.description.abstract | Background: Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test the causal link between glycemia, obesity, and musculoskeletal conditions. Methods: In the UK Biobank’s unrelated European cohort (N=379,708) we performed Mendelian Randomisation (MR) analyses to test for a causal effect of long-term high glycaemia and adiposity on four musculoskeletal pathologies: frozen shoulder, Dupuytren’s disease, carpal tunnel syndrome and trigger finger. We also performed single-gene MR using rare variants in the GCK gene. Results: Using MR, we found evidence that long-term high glycaemia has a causal role in the aetiology of upper limb conditions. A 10 mmol/mol increase in genetically predicted haemoglobin A1C (HbA1c) was associated with frozen shoulder: odds ratio (OR)=1.50 (95% confidence interval (CI) 1.20-1.88), Dupuytren’s disease: OR=1.17 (95% CI 1.01-1.35), trigger finger: OR=1.30 (95% CI 1.09-1.55) and carpal tunnel syndrome: OR=1.20 (95% CI 1.09-1.33). Carriers of GCK mutations have increased odds of frozen shoulder: OR=7.16 (95% CI 2.93-17.51) and carpal tunnel syndrome: OR=2.86 (95% CI 1.50-5.44) but not Dupuytren’s disease or trigger finger. We found evidence that an increase in genetically predicted body mass index (BMI) of 5 kg/m^2 was associated with carpal tunnel syndrome: OR=1.13 (95% CI 1.10-1.16) and associated negatively with Dupuytren’s disease: OR=0.94 (95% CI 0.90-0.98), but no evidence of association with frozen shoulder or trigger finger. Trigger finger (OR 1.96 (95% CI 1.42-2.69) P=3.6e-05) and carpal tunnel syndrome (OR 1.63 (95% CI 1.36-1.95) P=8.5e-08) are associated with genetically predicted unfavourable adiposity increase of 1 standard deviation of body fat. Conclusions: Our study consistently demonstrates a causal role of long-term high glycaemia in the aetiology of upper limb musculoskeletal conditions. Clinicians treating diabetes patients should be aware of these complications in clinic, specifically those managing the care of GCK mutation carriers. Upper limb musculoskeletal conditions should be considered diabetes complications. | en_GB |
dc.description.sponsorship | Exeter Centre of Excellence for Diabetes Research (EXCEED) | en_GB |
dc.description.sponsorship | National Institute for Health and Care Research (NIHR) | en_GB |
dc.identifier.citation | Published online 10 January 2024 | en_GB |
dc.identifier.doi | https://doi.org/10.1093/ije/dyad187 | |
dc.identifier.uri | http://hdl.handle.net/10871/134894 | |
dc.identifier | ORCID: 0000-0002-5105-184X (Green, Harry) | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press / International Epidemiological Association. | en_GB |
dc.relation.url | https://www.ukbiobank.ac.uk | en_GB |
dc.relation.url | https://www.finngen.fi/en/access_results/ | en_GB |
dc.rights | © The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited | |
dc.subject | Diabetes | en_GB |
dc.subject | Hyperglycaemia | en_GB |
dc.subject | Musculoskeletal | en_GB |
dc.subject | Mendelian Randomisation | en_GB |
dc.subject | Frozen Shoulder | en_GB |
dc.subject | Dupuytren’s | en_GB |
dc.subject | Trigger Finger | en_GB |
dc.subject | Carpal Tunnel Syndrome | en_GB |
dc.subject | Causality | en_GB |
dc.title | Hyperglycemia is a causal risk factor for upper limb pathologies | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-01-04T12:19:15Z | |
dc.description | This is the final version. Available on open access from Oxford University Press via the DOI in this record | en_GB |
dc.description | Data Availability: All individual level data used in this paper was obtained from the UK Biobank resource, and can be obtained from the UK Biobank at https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. Information on recruitment, locations and data collection methods can be found in 11. Access to summary statistics from the FinnGen resource can be obtained at https://www.finngen.fi/en/access_results/. | en_GB |
dc.identifier.eissn | 1464-3685 | |
dc.identifier.journal | International Journal of Epidemiology | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-12-17 | |
dcterms.dateSubmitted | 2023-01-06 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-12-17 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-01-04T09:57:01Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2024-01-16T12:12:44Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which
permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited