{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:51:42Z","timestamp":1784224302461,"version":"3.55.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21899"],"award-info":[{"award-number":["21899"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Musculoskelet Disord"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Estimate the effect of type 2 diabetes on the development of frozen shoulder and investigate whether the effect is mediated by other metabolic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary care medical record-based cohort study containing 43,977 people newly diagnosed with type 2 diabetes and 43,977 without diabetes. Variables were identified using established Read codes. A weighting approach with Cox regression was used to decompose the total effect into the direct effect and indirect effect, mediated by metabolic health (which was defined as the number of metabolic factors developed during follow-up). Estimates were expressed as hazard ratios (HR). Confounders were identified using a DAG. Sensitivity to unmeasured confounding, extreme weights, and missing data were tested.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The total effect of type 2 diabetes on the development of frozen shoulder was HR\u2009=\u20094.38 (95% CI: 3.70\u20135.21), the natural indirect effect (mediated through metabolic health) was HR\u2009=\u20090.98 (95% CI: 0.93\u20131.03) and the natural direct effect was HR\u2009=\u20094.46 (95% CI: 3.68\u20135.41). Results were robust to unmeasured confounding, extreme weights, and missing data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study suggests that type 2 diabetes may be a cause of frozen shoulder but does not support the hypothesis that the effect is mediated by metabolic health. Clinicians should remain alert that shoulder pain in people with diabetes could be indicative of a frozen shoulder. This study should raise awareness that, despite often being overlooked, musculoskeletal conditions can be complications of diabetes and should be considered during clinical conversations with patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ISAC protocol registration number<\/jats:title>\n                    <jats:p>19_219R.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12891-025-08672-2","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T11:29:21Z","timestamp":1747222161000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Type 2 diabetes, metabolic health, and the development of frozen shoulder: a cohort study in UK electronic health records"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8039-7631","authenticated-orcid":false,"given":"Brett P.","family":"Dyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4688-3075","authenticated-orcid":false,"given":"Claire","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-4746","authenticated-orcid":false,"given":"Trishna","family":"Rathod-Mistry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-7771","authenticated-orcid":false,"given":"Mili\u00e7a","family":"Blagojevic-Bucknall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-6703","authenticated-orcid":false,"given":"Danielle A.","family":"van der Windt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"issue":"1","key":"8672_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1302\/0301-620X.94B1.27093","volume":"94","author":"CM Robinson","year":"2012","unstructured":"Robinson CM, Seah KTM, et al. Frozen shoulder. J Bone Joint Surg. 2012;94(1):1\u20139.","journal-title":"J Bone Joint Surg"},{"key":"8672_CR2","doi-asserted-by":"publisher","first-page":"e003452","DOI":"10.1136\/bmjopen-2013-003452","volume":"3","author":"S Jones","year":"2013","unstructured":"Jones S, Hanchard N, et al. A qualitative study of patients\u2019 perceptions and priorities when living with primary frozen shoulder. BMJ Open. 2013;3:e003452.","journal-title":"BMJ Open"},{"key":"8672_CR3","doi-asserted-by":"crossref","unstructured":"Dias R, Cutts S, et al. Frozen Shoulder BMJ. 2005;331(7530):1453\u20136.","DOI":"10.1136\/bmj.331.7530.1453"},{"issue":"4","key":"8672_CR4","first-page":"417","volume":"83","author":"A Ewald","year":"2011","unstructured":"Ewald A. Adhesive capsulitis: A review. Am Family Phys. 2011;83(4):417\u201322.","journal-title":"Am Family Phys"},{"issue":"7","key":"8672_CR5","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1302\/0301-620X.89B7.19097","volume":"89","author":"GCR Hand","year":"2007","unstructured":"Hand GCR, Athanasou NA, et al. The pathology of frozen shoulder. J Bone Joint Surg. 2007;89(7):928\u201332.","journal-title":"J Bone Joint Surg"},{"issue":"3","key":"8672_CR6","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1093\/mr\/road087","volume":"34","author":"K Tamai","year":"2024","unstructured":"Tamai K, Hamada J, et al. Frozen shoulder. An overview of pathology and biology with hopes to novel drug therapies. Mod Rheumatol. 2024;34(3):439\u201343.","journal-title":"Mod Rheumatol"},{"issue":"4","key":"8672_CR7","first-page":"517","volume":"5","author":"D Cucchi","year":"2017","unstructured":"Cucchi D, Marmotti A, et al. Risk factors for shoulder stiffness: current concepts. Joints. 2017;5(4):517\u2013223.","journal-title":"Joints"},{"issue":"5","key":"8672_CR8","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1111\/jdi.12491","volume":"7","author":"CL Hsu","year":"2016","unstructured":"Hsu CL. Sheu. Diabetes and shoulder disorders. J Diabetes Investig. 2016;7(5):649\u201351. https:\/\/doi.org\/10.1111\/jdi.12491.","journal-title":"J Diabetes Investig"},{"issue":"1","key":"8672_CR9","doi-asserted-by":"publisher","first-page":"26","DOI":"10.32098\/mltj.01.2016.04","volume":"6","author":"NH Zreik","year":"2016","unstructured":"Zreik NH, Malik RA, et al. Adhesive capsulitis of the shoulder and diabetes: a meta-analysis of prevalence. Muscle Ligament Tendons. 2016;6(1):26\u201334.","journal-title":"Muscle Ligament Tendons"},{"issue":"1","key":"8672_CR10","doi-asserted-by":"publisher","first-page":"e062377","DOI":"10.1136\/bmjopen-2022-062377","volume":"13","author":"BP Dyer","year":"2013","unstructured":"Dyer BP, Rathod-Mistry T, et al. Diabetes as a risk factor for the onset of frozen shoulder: a systematic review and meta-analysis. BMJ Open. 2013;13(1):e062377.","journal-title":"BMJ Open"},{"issue":"6","key":"8672_CR11","doi-asserted-by":"publisher","first-page":"869","DOI":"10.4093\/dmj.2022.0275","volume":"47","author":"J-H Kim","year":"2023","unstructured":"Kim J-H, Kim B-S, et al. The risk of shoulder adhesive capsulitis in individuals with prediabetes and type 2 diabetes mellitus: A longitudinal nationwide Population-Based study. Diabetes Metab J. 2023;47(6):869\u201378.","journal-title":"Diabetes Metab J"},{"key":"8672_CR12","doi-asserted-by":"publisher","first-page":"15261","DOI":"10.1038\/s41598-024-66360-y","volume":"14","author":"G Sun","year":"2024","unstructured":"Sun G, Li Q, et al. Risk factors and predictive models for frozen shoulder. Sci Rep. 2024;14:15261.","journal-title":"Sci Rep"},{"key":"8672_CR13","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1186\/s12891-024-07614-8","volume":"25","author":"X Abudula","year":"2024","unstructured":"Abudula X, Maimaiti P, et al. Factors associated with frozen shoulder in adults: a retrospective study. BMC Musculoskelet Disord. 2024;25:493.","journal-title":"BMC Musculoskelet Disord"},{"issue":"49","key":"8672_CR14","doi-asserted-by":"publisher","first-page":"e36470","DOI":"10.1097\/MD.0000000000036470","volume":"102","author":"W Yang","year":"2023","unstructured":"Yang W, Yang Y, et al. Socioeconomic status, obesity, individual behaviors, diabetes, and risk for frozen shoulder: a Mendelian randomization study. Medicine. 2023;102(49):e36470.","journal-title":"Medicine"},{"issue":"6","key":"8672_CR15","doi-asserted-by":"publisher","first-page":"e1009577","DOI":"10.1371\/journal.pgen.1009577","volume":"17","author":"HD Green","year":"2021","unstructured":"Green HD, et al. A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor. PLoS Genet. 2021;17(6):e1009577.","journal-title":"PLoS Genet"},{"issue":"6","key":"8672_CR16","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/j.jse.2015.10.015","volume":"25","author":"KR Hwang","year":"2016","unstructured":"Hwang KR, Murrell GA, et al. Advanced glycation end products in idiopathic frozen shoulders. J Shoulder Elbow Surg. 2016;25(6):981\u20138.","journal-title":"J Shoulder Elbow Surg"},{"key":"8672_CR17","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.mehy.2016.01.002","volume":"88","author":"M Pietrzak","year":"2016","unstructured":"Pietrzak M. Adhesive capsulitis: an age-related symptom of metabolic syndrome and chronic low-grade inflammation? Med Hypotheses. 2016;88:12\u20137.","journal-title":"Med Hypotheses"},{"key":"8672_CR18","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.jse.2013.11.004","volume":"23","author":"DC Austin","year":"2014","unstructured":"Austin DC, Gans I, et al. The association of metabolic syndrome markers with adhesive capsulitis. J Shoulder Elbow Surg. 2014;23:1043\u201351.","journal-title":"J Shoulder Elbow Surg"},{"issue":"21","key":"8672_CR19","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.2106\/JBJS.M.00936","volume":"96","author":"CM Sung","year":"2014","unstructured":"Sung CM, Sung TS, et al. Are serum lipids involved in primary frozen shoulder? A case-control study. J Bone Joint Surg. 2014;96(21):1828\u201333.","journal-title":"J Bone Joint Surg"},{"issue":"13","key":"8672_CR20","doi-asserted-by":"publisher","first-page":"697","DOI":"10.18410\/jebmh\/2017\/135","volume":"4","author":"SP Nayak","year":"2017","unstructured":"Nayak SP. Panda. Is hyperlipidaemia a cause of primary frozen shoulder? A case-controlled study. J Evid Based Med Healthc. 2017;4(13):697\u2013701.","journal-title":"J Evid Based Med Healthc"},{"issue":"3","key":"8672_CR21","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1093\/ije\/dyv098","volume":"44","author":"E Herrett","year":"2015","unstructured":"Herrett E, Gallagher AM, et al. Data resource profile: clinical practice research datalink (CPRD). Int J Epidemiol. 2015;44(3):827\u201336.","journal-title":"Int J Epidemiol"},{"key":"8672_CR22","unstructured":"Clinical Practice Research Datalink. 2021, Available from: https:\/\/www.cprd.com [accessed 17th February 2022]."},{"key":"8672_CR23","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10654-018-0442-4","volume":"34","author":"S Padmanabhan","year":"2019","unstructured":"Padmanabhan S, Carty L, et al. Approach to record linkage of primary care data from clinical practice research datalink to other health-related patient data: overview and implications. Eur J Epidemiol. 2019;34:91\u20139.","journal-title":"Eur J Epidemiol"},{"key":"8672_CR24","doi-asserted-by":"crossref","unstructured":"Kontopantelis E, Reeves D, et al. Recorded quality of primary care for patients with diabetes in England before and after the introduction of a financial incentive scheme: a longitudinal observational study. BMJ quality & safety; 2013;53\u201364.","DOI":"10.1136\/bmjqs-2012-001033"},{"key":"8672_CR25","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1111\/j.1464-5491.2007.02276.x","volume":"24","author":"K Khunti","year":"2007","unstructured":"Khunti K, Gadsby R, et al. Quality of diabetes care in the UK: comparison of published quality-of-care reports with results of the quality and outcomes framework for diabetes. Diabet Med. 2007;24:1436\u201341.","journal-title":"Diabet Med"},{"key":"8672_CR26","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1097\/00001648-199901000-00008","volume":"10","author":"S Greenland","year":"1999","unstructured":"Greenland S, Pearl J, et al. Causal diagrams for epidemiologic research. Epidemiology. 1999;10:37\u201348.","journal-title":"Epidemiology"},{"key":"8672_CR27","doi-asserted-by":"crossref","unstructured":"Tennant PWG, Murray EJ et al. Use of directed acyclic graphs (DAGs) to identify confounders in applied health research: review and recommendations. Int J Epidemiol, 2020;50(2):620\u201332.","DOI":"10.1093\/ije\/dyaa213"},{"issue":"3","key":"8672_CR28","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1093\/aje\/kwr525","volume":"176","author":"T Lange","year":"2012","unstructured":"Lange T, Vansteelandt S, et al. A simple unified approach for estimating natural direct and indirect effects. Am J Epidemiol. 2012;176(3):190\u20135.","journal-title":"Am J Epidemiol"},{"key":"8672_CR29","unstructured":"Hong G. Ratio of mediator probability weighting for estimating natural direct and indirect effects. JSM Proceedings, Biometrics Section, 2010;2401\u20132415."},{"issue":"3","key":"8672_CR30","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3102\/1076998615583902","volume":"40","author":"G Hong","year":"2015","unstructured":"Hong G, Deutsch J, et al. Ratio-of-mediator-probability weighting for causal mediation analysis in the presence of treatment-by-mediator interaction. J Educational Behav Stat. 2015;40(3):307\u201340.","journal-title":"J Educational Behav Stat"},{"key":"8672_CR31","unstructured":"T. J. Vander Weele. Explanation in causal inference. Oxford University Press, 2015."},{"key":"8672_CR32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1146\/annurev-publhealth-032315-021402","volume":"37","author":"TJ VanderWeele","year":"2016","unstructured":"Vander Weele TJ. Mediation analysis: A practitioner\u2019s guide. Annu Rev Public Health. 2016;37:17\u201332.","journal-title":"Annu Rev Public Health"},{"issue":"4","key":"8672_CR33","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","volume":"167","author":"TJ VanderWeele","year":"2017","unstructured":"VanderWeele TJ, Peng D. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167(4):268\u201374.","journal-title":"Ann Intern Med"},{"key":"8672_CR34","doi-asserted-by":"publisher","first-page":"e031537","DOI":"10.1136\/bmjopen-2019-031537","volume":"9","author":"K Mansfield","year":"2019","unstructured":"Mansfield K, Crellin E, et al. Completeness and validity of alcohol recording in general practice within the UK: a cross-sectional study. BMJ Open. 2019;9:e031537.","journal-title":"BMJ Open"},{"key":"8672_CR35","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1093\/rheumatology\/kei139","volume":"45","author":"L Linsell","year":"2006","unstructured":"Linsell L, Dawson J, et al. Prevalence and incidence of adults consulting for shoulder conditions in UK primary care; patterns of diagnosis and referral. Rheumatology. 2006;45:215\u201321.","journal-title":"Rheumatology"},{"issue":"2","key":"8672_CR36","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1093\/rheumatology\/keq333","volume":"50","author":"O Dorrestijn","year":"2011","unstructured":"Dorrestijn O, Greving K. Patients with shoulder complaints in general practice: consumption of medical care. Rheumatology. 2011;50(2):389\u201395.","journal-title":"Rheumatology"},{"key":"8672_CR37","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s10654-018-0447-z","volume":"34","author":"J Choi","year":"2019","unstructured":"Choi J, Dekkers OM, et al. A comparison of different methods to handle missing data in the context of propensity score analysis. Eur J Epidemiol. 2019;34:23\u201336.","journal-title":"Eur J Epidemiol"},{"key":"8672_CR38","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s00296-013-2847-4","volume":"34","author":"S-F Lo","year":"2014","unstructured":"Lo S-F, Chu S-W, et al. Diabetes mellitus and accompanying hyperlipidemia are independent risk factors for adhesive capsulitis: a nationwide population-based cohort study. Rheumatol Int. 2014;34:67\u201374.","journal-title":"Rheumatol Int"},{"issue":"7","key":"8672_CR39","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1002\/acr.21938","volume":"65","author":"Y-P Huang","year":"2013","unstructured":"Huang Y-P, Fann C-Y, et al. Association of diabetes mellitus with the risk of developing adhesive capsulitis of the shoulder: A longitudinal population-based follow-up study. Arthritis Care Res. 2013;65(7):1197\u2013202.","journal-title":"Arthritis Care Res"},{"issue":"10","key":"8672_CR40","doi-asserted-by":"publisher","first-page":"919","DOI":"10.2106\/JBJS.J.01930","volume":"94","author":"H Yian","year":"2012","unstructured":"Yian H, Contreras R, et al. Effects of glycemic control on prevalence of diabetic frozen shoulder. J Bone Joint Surg. 2012;94(10):919\u201323.","journal-title":"J Bone Joint Surg"},{"issue":"10","key":"8672_CR41","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1016\/j.jse.2017.03.015","volume":"26","author":"JH Chan","year":"2017","unstructured":"Chan JH, Ho BS, et al. The relationship between the incidence of adhesive capsulitis and haemoglobin A1c. J Shoulder Elb Surg. 2017;26(10):1834\u20137.","journal-title":"J Shoulder Elb Surg"}],"container-title":["BMC Musculoskeletal Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12891-025-08672-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12891-025-08672-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12891-025-08672-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T11:29:25Z","timestamp":1747222165000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmusculoskeletdisord.biomedcentral.com\/articles\/10.1186\/s12891-025-08672-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8672"],"URL":"https:\/\/doi.org\/10.1186\/s12891-025-08672-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4954094\/v1","asserted-by":"object"}]},"ISSN":["1471-2474"],"issn-type":[{"value":"1471-2474","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]},"assertion":[{"value":"21 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors confirm that this study adhered to the Declaration of Helsinki. The CPRD has been granted generic ethics approval for observational studies that make use of only anonymised data and linked anonymised NHS health-care data (Multiple Research Ethics Committee ref. 05\/MRE04\/87). All CPRD studies require scientific approval from the MHRA Independent Scientific Advisory Committee (ISAC). The ISAC was established by the Secretary of State for Health in February 2006 to review the scientific merit of proposals for research using data from the CPRD as well as the Yellow Card Scheme database. This study\u2019s protocol was approved and is registered as #19_219R. All the participants provided their informed consent and each individual GP practice participating in CPRD\u2019s collection of their primary care data can choose to revoke their consent for data collection at any point. CPRD respects all patient opt-outs. Patients who have registered an opt-out will not be extracted for CPRD research or for data linkage. Researchers using the data must adhere to robust terms and conditions governing how the anonymized data is used.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"471"}}