{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:00:03Z","timestamp":1791273603234,"version":"4.1.0"},"reference-count":190,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T00:00:00Z","timestamp":1415750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>\n                    Insulin resistance (\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    ) plays an important role in the pathogenesis of type 2 diabetes (\n                    <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                    ) and cardiovascular disease. Hence improving\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    is a major target of treatment in patients with\n                    <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                    . Obesity and lack of exercise are major causes of\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    . However, recent evidence implicates sleep disorders and disorders of the circadian rhythm in the pathogenesis of\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    . Weight loss and lifestyle changes are the cornerstone and most effective treatments of\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    , but adherence and patient's acceptability are poor. Bariatric surgery results in significant and sustainable long\u2010term weight loss associated with beneficial impact on\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    and glucose metabolism, making this an attractive treatment option for patients with\n                    <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                    . Currently available pharmacological options targeting\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    (such as metformin and thiazolidinediones) do not maintain glycaemic measures within targets long term and can be associated with significant side effects. Over the last two decades, many pharmacological agents targeting different aspects of the insulin signalling pathway were developed to improve\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    , but only a minority reached clinical trials. Such treatments need to be specific and reversible as many of the components of the insulin signalling pathway are involved in other cellular functions such as apoptosis. Recent evidence highlighted the role of circadian rhythm and sleep\u2010related disorders in the pathogenesis of\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    . In this article, we review the latest developments in the pharmacological and non\u2010pharmacological interventions targeting\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    including bariatric surgery. We will also review the role of circadian rhythm and sleep\u2010related disorders in the development and treatment of\n                    <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/dom.12400","type":"journal-article","created":{"date-parts":[[2014,10,11]],"date-time":"2014-10-11T18:51:13Z","timestamp":1413053473000},"page":"319-334","source":"Crossref","is-referenced-by-count":56,"title":["Novel therapeutics for type 2 diabetes: insulin resistance"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-1937","authenticated-orcid":false,"given":"Q.\u2010A.","family":"Altaf","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology Heart of England NHS Foundation Trust  Birmingham UK"},{"name":"Centre of Endocrinology, Diabetes and Metabolism University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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