{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:02:11Z","timestamp":1790755331616,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Diabetes is a frequent complication of Cushing\u2019s disease, but metabolic differences between normal glucose tolerance, prediabetes, and diabetes remain incompletely characterised. We aimed to characterise glucose metabolism across these groups, assess abnormalities in patients with normal glucose tolerance, and identify clinical, hormonal, and body-composition factors associated with glycaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Cross-sectional analysis of a prospective cohort with matched healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>The study included 50 patients with Cushing\u2019s disease and 52 age- and sex-matched healthy controls who underwent detailed metabolic phenotyping, including multi-timepoint oral glucose tolerance testing with assessment of insulin sensitivity and \u03b2-cell compensatory function, and body composition analysis by dual-energy X-ray absorptiometry. Forward stepwise linear regression was performed separately in each group to identify variables independently associated with HbA1c.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Glucose metabolism disturbances affected 68% of patients with Cushing\u2019s disease, including prediabetes in 42% and diabetes in 26%, with most diabetes cases previously undiagnosed. Even patients with normal glucose tolerance showed lower insulin sensitivity and enhanced \u03b2-cell secretory activity compared with healthy controls. Prediabetes was characterised mainly by lower insulin sensitivity with preserved \u03b2-cell compensation, whereas diabetes was associated with a reduced insulin-to-glucose AUC ratio without significantly lower insulin sensitivity than in prediabetes. In Cushing\u2019s disease, age, morning cortisol, waist-to-hip ratio, and proinsulin were independently associated with HbA1c, explaining 59.5% of its variance; in controls, only age and BMI were associated with HbA1c. BMI was not significantly correlated with HbA1c in Cushing\u2019s disease, whereas trunk fat percentage was positively associated with HbA1c.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In Cushing\u2019s disease, reduced insulin sensitivity with preserved \u03b2-cell compensation is detectable even in patients with normal glucose tolerance, whereas overt diabetes is characterised by impaired \u03b2-cell compensation without significantly lower insulin sensitivity than in prediabetes. Age, morning cortisol, waist-to-hip ratio, and proinsulin are independently associated with HbA1c. Central fat distribution may be more closely related to glycaemia than BMI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1941836","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:48:26Z","timestamp":1790754506000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes in Cushing\u2019s disease: age, hypercortisolism, central adiposity, and \u03b2-cell stress as determinants of glycaemia"],"prefix":"10.3389","volume":"17","author":[{"given":"Przemys\u0142aw","family":"Witek","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology and Diabetes, Medical University of Warsaw","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Witek","sequence":"additional","affiliation":[{"name":"Department of Diabetology, Institute of Mother and Child","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Szamotulska","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Institute of Mother and Child","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Military Institute of Medicine, National Research Institute","place":["Warsaw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3171\/2016.1.jns152119","article-title":"Cushing's disease: pathobiology, diagnosis, and management","volume":"126","author":"Lonser","year":"2017","journal-title":"J Neurosurg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-022-01754-1","article-title":"Global Cushing's disease epidemiology: a systematic review and meta-analysis of observational studies","volume":"45","author":"Giuffrida","year":"2022","journal-title":"J Endocrinol Invest"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12975","article-title":"Current management of Cushing's disease","volume":"286","author":"Tritos","year":"2019","journal-title":"J Intern Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2021.101521","article-title":"Epidemiology and mortality of Cushing's syndrome","volume":"35","author":"Hakami","year":"2021","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-015-0645-6","article-title":"Comorbidities in cushing's disease","volume":"18","author":"Sharma","year":"2015","journal-title":"Pituitary"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(16)00086-3","article-title":"Complications of Cushing's syndrome: state of the art","volume":"4","author":"Pivonello","year":"2016","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B7","article-title":"Complications of Cushing's disease - prospective evaluation and clinical characteristics. Do they affect the efficacy of surgical treatment","volume":"63","author":"Witek","year":"2012","journal-title":"Endokrynol Pol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(21)00235-7","article-title":"Consensus on diagnosis and management of Cushing's disease: a guideline update","volume":"9","author":"Fleseriu","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/db25-0120","article-title":"Cushing syndrome, hypercortisolism, and glucose homeostasis: A review","volume":"74","author":"DeFronzo","year":"2025","journal-title":"Diabetes"},{"key":"B10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1210\/er.2016-1105","article-title":"Glucose metabolism abnormalities in cushing syndrome: from molecular basis to clinical management","volume":"38","author":"Scaroni","year":"2017","journal-title":"Endocr Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00284","article-title":"Diabetes mellitus secondary to cushing's disease","volume":"9","author":"Barbot","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1248985","article-title":"Practical therapeutic approach in the management of diabetes mellitus secondary to Cushing's syndrome, acromegaly and neuroendocrine tumours","volume":"14","author":"Guarnotta","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/s0026-0495(98)90184-6","article-title":"Dexamethasone inhibits insulin-stimulated recruitment of GLUT4 to the cell surface in rat skeletal muscle","volume":"47","author":"Weinstein","year":"1998","journal-title":"Metabolism"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111334109","article-title":"Genome-wide analysis of glucocorticoid receptor-binding sites in myotubes identifies gene networks modulating insulin signaling","volume":"109","author":"Kuo","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.12.012","article-title":"Glucocorticoid induces human beta cell dysfunction by involving riborepressor GAS5 LincRNA","volume":"32","author":"Esguerra","year":"2020","journal-title":"Mol Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1923","article-title":"Glucocorticoid-induced suppression of beta-cell proliferation is mediated by Mig6","volume":"154","author":"Colvin","year":"2013","journal-title":"Endocrinology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.tem.2011.09.001","article-title":"Diabetes in Cushing syndrome: basic and clinical aspects","volume":"22","author":"Mazziotti","year":"2011","journal-title":"Trends Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2022.109994","article-title":"beta-cell function and insulin sensitivity contributions on incident diabetes in patients with endogenous Cushing's syndrome","volume":"190","author":"Gong","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1530\/eje-13-0754","article-title":"Is diabetes in Cushing's syndrome only a consequence of hypercortisolism","volume":"170","author":"Giordano","year":"2014","journal-title":"Eur J Endocrinol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaf693","article-title":"Cardiometabolic outcomes after surgical remission of endogenous hypercortisolism: a prospective cohort study","volume":"111","author":"Chacko","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-01839-7","article-title":"Factors predicting long-term comorbidities in patients with Cushing's syndrome in remission","volume":"64","author":"Schernthaner-Reiter","year":"2019","journal-title":"Endocrine"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-S002","article-title":"2. Classification and diagnosis of diabetes: standards of care in diabetes-2023","volume":"46","author":"ElSayed","year":"2023","journal-title":"Diabetes Care"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2011.09.002","article-title":"Postprandial metabolic responses to mixed versus liquid meal tests in healthy men and men with type 2 diabetes","volume":"94","author":"Brodovicz","year":"2011","journal-title":"Diabetes Res Clin Pract"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.11613\/bm.2013.033","article-title":"Diabetes and beta cell function: from mechanisms to evaluation and clinical implications","volume":"23","author":"Cernea","year":"2013","journal-title":"Biochem Med (Zagreb)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-025-02572-x","article-title":"Cardiometabolic complications after Cushing's disease remission","volume":"48","author":"Tizianel","year":"2025","journal-title":"J Endocrinol Invest"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab169","article-title":"The effect of curative treatment on hyperglycemia in patients with cushing syndrome","volume":"6","author":"Herndon","year":"2022","journal-title":"J Endocr Soc"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2715-x","article-title":"The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors: the EPIC-InterAct study","volume":"56","author":"InterAct","year":"2013","journal-title":"Diabetologia"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.010","article-title":"Diabetes mellitus and the beta cell: the last ten years","volume":"148","author":"Ashcroft","year":"2012","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"55","DOI":"10.5144\/0256-4947.2024.55","article-title":"Sex-related differences in Cushing's disease: a systematic review and meta-analysis","volume":"44","author":"Alqeeq","year":"2024","journal-title":"Ann Saudi Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2337\/dcs13-2011","article-title":"Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes","author":"DeFronzo","year":"2013","journal-title":"Diabetes Care"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1172\/jci129188","article-title":"beta Cell dysfunction during progression of metabolic syndrome to type 2 diabetes","volume":"129","author":"Hudish","year":"2019","journal-title":"J Clin Invest"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s508365","article-title":"Association between body mass index and glycemic control in type 2 diabetes mellitus: A cross-sectional study","volume":"18","author":"Deng","year":"2025","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.036","article-title":"Glucocorticoid-induced skeletal muscle atrophy","volume":"45","author":"Schakman","year":"2013","journal-title":"Int J Biochem Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.626427","article-title":"The interaction of insulin and pituitary hormone syndromes","volume":"12","author":"Schernthaner-Reiter","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.117215","article-title":"Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment","volume":"17","author":"Gupta","year":"2013","journal-title":"Indian J Endocrinol Metab"},{"key":"B36","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s12020-016-0883-z","article-title":"Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing's syndrome","volume":"53","author":"Roerink","year":"2016","journal-title":"Endocrine"},{"key":"B37","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1530\/eje-11-0722","article-title":"Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome","volume":"166","author":"Trementino","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.coph.2004.09.001","article-title":"11beta-hydroxysteroid dehydrogenases: changing glucocorticoid action","volume":"4","author":"Seckl","year":"2004","journal-title":"Curr Opin Pharmacol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066285","article-title":"A transgenic model of visceral obesity and the metabolic syndrome","volume":"294","author":"Masuzaki","year":"2001","journal-title":"Science"},{"key":"B40","doi-asserted-by":"publisher","first-page":"41968","DOI":"10.1038\/s41598-025-25941-1","article-title":"11\u03b2-HSD1 inhibitor alleviates lipid metabolism disorder by activating the AMPK signaling pathway","volume":"15","author":"Han","year":"2025","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v16.i3.100580","article-title":"Continuum of glucose and bone metabolism impairment across autonomous cortisol secretion: A cross-sectional study","volume":"16","author":"Han","year":"2025","journal-title":"World J Diabetes"},{"key":"B42","doi-asserted-by":"publisher","first-page":"9933219","DOI":"10.1155\/jdr\/9933219","article-title":"Comparison of hbA1c and OGTT results in obese and morbidly obese patients: A single-center evaluation from an obesity clinic","volume":"2025","author":"Acmaz","year":"2025","journal-title":"J Diabetes Res"},{"key":"B43","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3390\/ijerph21050517","article-title":"The association between body mass index and glycohemoglobin (HbA1c) in the US population's diabetes status","volume":"21","author":"Lin","year":"2024","journal-title":"Int J Environ Res Public Health"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.3390\/diagnostics13091576","article-title":"The significance of dual-energy X-ray absorptiometry (DXA) examination in cushing's syndrome-A systematic review","volume":"13","author":"Radecka","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2025.1554717","article-title":"Exploring proinsulin proteostasis: insights into beta cell health and diabetes","volume":"12","author":"Zavarzadeh","year":"2025","journal-title":"Front Mol Biosci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"623","DOI":"10.3390\/ijms22020623","article-title":"Molecular mechanisms of glucocorticoid-induced insulin resistance","volume":"22","author":"Beaupere","year":"2021","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1941836\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:48:27Z","timestamp":1790754507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1941836\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":46,"alternative-id":["10.3389\/fendo.2026.1941836"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1941836","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1941836"}}