{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:18:12Z","timestamp":1760059092600,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This study investigated the prevalence of cystic fibrosis-related diabetes (CFRD) in the Croatian cystic fibrosis (CF) population, the age at diagnosis, insulin requirements, and the relationship between age at diagnosis and other clinical parameters. Medical records from 152 patients with genetically and laboratory-confirmed CF were reviewed through to 2025. The American Diabetes Association criteria were used to diagnose CFRD. Anthropometric and clinical data were collected from the latest medical records. A total of 17 out of 152 patients had CFRD, with a prevalence of 4.8% in the paediatric population (4\/84) and 19.1% in adults (13\/68). The median age of CFRD diagnosis was 14 years (range 9\u201322 years, SD = 3.95). Thirteen patients used insulin: one used bolus only, seven used basal-bolus multiple daily injections, and five used insulin pumps. The average total daily insulin (TDI) per kilogram (kg) body weight was 0.447 U\/kg (SD = 0.429). The age at CFRD diagnosis was positively correlated with the body mass index (BMI) (p = 0.029). Patients requiring insulin by age 15 had higher TDI and were more likely to have CF liver disease (p = 0.027, p = 0.037, respectively). The prevalence of CFRD and age at diagnosis aligned with previous studies. Patients diagnosed at a younger age and requiring insulin earlier had lower BMIs, likely due to a faster decline in beta cell function and earlier onset of insulinopenia.<\/jats:p>","DOI":"10.3390\/life15050815","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:54:28Z","timestamp":1747724068000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence and Characteristics of Patients with Cystic Fibrosis-Related Diabetes in Croatia"],"prefix":"10.3390","volume":"15","author":[{"given":"Lora Stanka","family":"Kirigin Bilo\u0161","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases \u201cMladen Sekso\u201d, University Hospital Centre \u201cSestre Milosrdnice\u201d, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-8407","authenticated-orcid":false,"given":"Maja","family":"Bareti\u0107","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Cystic Fibrosis Centre for Paediatrics and Adults, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-3325","authenticated-orcid":false,"given":"Andrea","family":"Vuki\u0107 Dugac","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Cystic Fibrosis Centre for Paediatrics and Adults, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Clinic for Respiratory Diseases \u201cJordanovac\u201d, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kre\u0161imir","family":"Schoenwald","sequence":"additional","affiliation":[{"name":"General Hospital Dubrovnik, 20000 Dubrovnik, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-1092","authenticated-orcid":false,"given":"Ivan","family":"Bambir","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Centre for Paediatrics and Adults, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Paediatrics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3742-6358","authenticated-orcid":false,"given":"Du\u0161ka","family":"Tje\u0161i\u0107 Drinkovi\u0107","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Centre for Paediatrics and Adults, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Paediatrics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nevena","family":"Krni\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Cystic Fibrosis Centre for Paediatrics and Adults, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Paediatrics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-9870","authenticated-orcid":false,"given":"Velimir","family":"Altabas","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases \u201cMladen Sekso\u201d, University Hospital Centre \u201cSestre Milosrdnice\u201d, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/S0140-6736(09)60327-5","article-title":"Cystic Fibrosis","volume":"373","author":"Freedman","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1530\/JOE-18-0468","article-title":"Survival in a Bad Neighborhood: Pancreatic Islets in Cystic Fibrosis","volume":"241","author":"Norris","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/apa.15155","article-title":"Cystic Fibrosis in the Year 2020: A Disease with a New Face","volume":"109","year":"2020","journal-title":"Acta Paediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.2337\/db22-0949","article-title":"Cystic Fibrosis-Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes","volume":"72","author":"Putman","year":"2023","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.2337\/dc25-S002","article-title":"2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025","volume":"48","author":"ElSayed","year":"2025","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jcf.2019.08.016","article-title":"Cystic Fibrosis Related Diabetes: Pathophysiology, Screening and Diagnosis","volume":"18","author":"Granados","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.2337\/diabetes.48.5.1082","article-title":"Hepatic Insulin Resistance and Defects in Substrate Utilization in Cystic Fibrosis","volume":"48","author":"Hardin","year":"1999","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gojsina, B., Minic, P., Todorovic, S., Soldatovic, I., and Sovtic, A. (2021). Continuous Glucose Monitoring as a Valuable Tool in the Early Detection of Diabetes Related to Cystic Fibrosis. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.659728"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E851","DOI":"10.1210\/jc.2010-2460","article-title":"Gastric Emptying, Incretin Hormone Secretion, and Postprandial acemia in Cystic Fibrosis--Effects of Pancreatic Enzyme Supplementation","volume":"96","author":"Kuo","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1179551419851770","DOI":"10.1177\/1179551419851770","article-title":"Cystic Fibrosis-Related Diabetes: Pathophysiology and Therapeutic Challenges","volume":"12","author":"Kelsey","year":"2019","journal-title":"Clin. Med. Insights Endocrinol. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.cmet.2017.06.010","article-title":"Insulin Regulation of Proteostasis and Clinical Implications","volume":"26","author":"James","year":"2017","journal-title":"Cell Metab. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jcf.2006.03.009","article-title":"Airway Glucose Concentrations and Effect on Growth of Respiratory Pathogens in Cystic Fibrosis","volume":"6","author":"Brennan","year":"2007","journal-title":"J. Cyst. Fibros."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kayani, K., Mohammed, R., and Mohiaddin, H. (2018). Cystic Fibrosis-Related Diabetes. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00020"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.2337\/dc10-1768","article-title":"Clinical Care Guidelines for Cystic Fibrosis\u2013Related Diabetes","volume":"33","author":"Moran","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mozzillo, E., Franceschi, R., Piona, C., Passanisi, S., Casertano, A., Pjetraj, D., Maltoni, G., Calcaterra, V., Cauvin, V., and Cherubini, V. (2021). Diabetes and Prediabetes in Children With Cystic Fibrosis: A Systematic Review of the Literature and Recommendations of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED). Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.673539"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Anton-P\u0103duraru, D.T., Murgu, A.M., Donos, M.A., Trofin, F., Azoic\u0103i, A.N., Popovici, P., Stana, A.B., Gheorghiescu, I., and Trandafir, L.M. (2023). An Update in Cystic Fibrosis-Related Diabetes in Children and Adolescents. Children, 10.","DOI":"10.3390\/children10121879"},{"key":"ref_17","unstructured":"Doan, L.V., and Madison, L.D. (2024, January 29). Cystic Fibrosis\u2013Related Diabetes; StatPearls [Internet]. 2023 Aug 14, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK545192\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jcf.2019.10.009","article-title":"Cystic Fibrosis Related Diabetes in Europe: Prevalence, Risk Factors and Outcome; Olesen et al","volume":"19","author":"Olesen","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.2337\/dc09-0586","article-title":"Cystic Fibrosis\u2013Related Diabetes: Current Trends in Prevalence, Incidence, and Mortality","volume":"32","author":"Moran","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jcf.2019.05.015","article-title":"Disease Progression in Patients with Cystic Fibrosis Treated with Ivacaftor: Data from National US and UK Registries","volume":"19","author":"Volkova","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1136\/bmj.311.7006.655","article-title":"Glucose Tolerance in Patients with Cystic Fibrosis: Five Year Prospective Study","volume":"311","author":"Lanng","year":"1995","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.jcf.2019.07.010","article-title":"The Association of Pediatric Cystic Fibrosis-Related Diabetes Screening on Clinical Outcomes by Center: A CF Patient Registry Study","volume":"19","author":"Watson","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_23","unstructured":"Patient Registry (2023, July 31). Cystic Fibrosis Foundation 2021 Cystic Fibrosis Foundation Patient Registry Highlights. Available online: https:\/\/www.cff.org\/medical-professionals\/patient-registry."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20210307","DOI":"10.36416\/1806-3756\/e20210307","article-title":"Can Continuous Glucose Monitoring Predict Cystic Fibrosis-Related Diabetes and Worse Clinical Outcome?","volume":"48","author":"Zorron","year":"2022","journal-title":"J. Bras. Pneumol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hicks, R., Ode, K.L., Vigers, T., and Chan, C.L. (2023). A Provider Survey of Cystic Fibrosis Related Diabetes Screening and Management Practices at North American CF Centers. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1183288"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e512","DOI":"10.1542\/peds.2012-4029","article-title":"Improving Screening for Cystic Fibrosis-Related Diabetes at a Pediatric Cystic Fibrosis Program","volume":"132","author":"Kern","year":"2013","journal-title":"Pediatrics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/pedi.13453","article-title":"ISPAD Clinical Practice Consensus Guidelines 2022: Management of Cystic Fibrosis-related Diabetes in Children and Adolescents","volume":"23","author":"Ode","year":"2022","journal-title":"Pediatr. Diabetes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.jcf.2019.08.011","article-title":"Cystic Fibrosis Related Diabetes: Nutrition and Growth Considerations","volume":"18","author":"Kaminski","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Edlund, A., Esguerra, J.L.S., Wendt, A., Flodstr\u00f6m-Tullberg, M., and Eliasson, L. (2014). CFTR and Anoctamin 1 (ANO1) Contribute to CAMP Amplified Exocytosis and Insulin Secretion in Human and Murine Pancreatic Beta-Cells. BMC Med., 12.","DOI":"10.1186\/1741-7015-12-87"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4420","DOI":"10.1038\/ncomms5420","article-title":"Glucose-Induced Electrical Activities and Insulin Secretion in Pancreatic Islet \u03b2-Cells Are Modulated by CFTR","volume":"5","author":"Guo","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107845","DOI":"10.1016\/j.jdiacomp.2020.107845","article-title":"Effect of CFTR Modulator Therapy on Cystic Fibrosis-Related Diabetes","volume":"35","author":"Gaines","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107664","DOI":"10.1016\/j.rmed.2024.107664","article-title":"Long-Term Therapy with CFTR Modulators Consistently Improves Glucose Metabolism in Adolescents and Adults with Cystic Fibrosis","volume":"228","author":"Cohen","year":"2024","journal-title":"Respir. Med."},{"key":"ref_33","first-page":"100283","article-title":"Cystic Fibrosis Related Liver Disease and Endocrine Considerations","volume":"27","author":"Sherwood","year":"2021","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shi, J., Fan, J., Su, Q., and Yang, Z. (2019). Cytokines and Abnormal Glucose and Lipid Metabolism. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00703"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1365-2249.1994.tb06609.x","article-title":"Circulating Proinflammatory Cytokines (IL-1 Beta, TNF-Alpha, and IL-6) and IL-1 Receptor Antagonist (IL-1Ra) in Fulminant Hepatic Failure and Acute Hepatitis","volume":"98","author":"Sekiyama","year":"1994","journal-title":"Clin. Exp. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.2337\/db20-1788-P","article-title":"1788-P: Islet Function in Youth with Cystic Fibrosis with and without Liver Disease","volume":"69","author":"Rayas","year":"2020","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jcf.2014.07.014","article-title":"Retinal Screening of Patients with Cystic Fibrosis-Related Diabetes in Wales\u2014A Real Eye Opener","volume":"14","author":"Roberts","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.2337\/dc06-1576","article-title":"Microvascular Complications in Cystic Fibrosis-Related Diabetes","volume":"30","author":"Schwarzenberg","year":"2007","journal-title":"Diabetes Care"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/5\/815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:35:38Z","timestamp":1760031338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/5\/815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["life15050815"],"URL":"https:\/\/doi.org\/10.3390\/life15050815","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,5,20]]}}}