Pancreatic islet autoantibodies and their association with glycemic status in cystic fibrosis patients: A comprehensive meta-analysis

Regina Molnár; Blanka Rebeka Bódy; Boróka Varga; Réka Tóth; Tamás Kói; Dorottya Gergő; Miklós Garami; Katalin Eszter Müller; Péter Hegyi; Klementina Ocskay; Andrea Párniczky

doi:10.1016/j.jcf.2025.04.011

Pancreatic islet autoantibodies and their association with glycemic status in cystic fibrosis patients: A comprehensive meta-analysis

J Cyst Fibros. 2025 May 19:S1569-1993(25)01466-3. doi: 10.1016/j.jcf.2025.04.011. Online ahead of print.

Authors

Affiliations

¹ Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
² Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
³ Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
⁴ Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Pharmacognosy, Semmelweis University, Budapest, Hungary.
⁵ Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Pediatric Center, Semmelweis University, Budapest, Hungary.
⁶ Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Family Care Methodology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
⁷ Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Institute for Pancreatic Diseases, Semmelweis University, Budapest, Hungary.
⁸ Heim Pál National Pediatric Institute, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary. Electronic address: andrea.parniczky@gmail.com.

PMID: 40393876
DOI: 10.1016/j.jcf.2025.04.011

Abstract

Background: The role of autoimmune beta-cell damage in cystic fibrosis-related glucose abnormalities remains unclear. This study evaluates the prevalence of pancreatic islet autoantibodies (AABs) by glycemic status and age, and assesses the risk of developing cystic fibrosis-related diabetes (CFRD) in people with cystic fibrosis (pwCF).

Methods: A random-effects meta-analysis examined AABs against glutamic acid decarboxylase (GADA), insulin (IAA), islet cell (ICA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in pwCF (CRD42023482663). Prevalence, odds ratios (OR), and 95 % confidence intervals (CI) were calculated with subgroup analyses by glycemic status and age.

Results: Analysis of 20 studies (2229 pwCF) found an overall islet AAB positivity rate of 4 % (CI: 2-9 %) and multiple positivity at 1 % (CI: 0-11 %). IAA had the highest prevalence at 6 % (CI: 3-14 %), and ICA the lowest at 1 % (CI: 0-9 %). Islet AAB prevalence trended higher in CFRD than non-CFRD patients and in children than adults. CFRD was significantly associated with islet AAB positivity, notably for GADA (OR 4.63, CI: 3.42-6.28), ICA (OR 3.57, CI: 1.05-12.18), and IA-2A (OR 2.36, CI: 1.29-4.34). Any and multiple AAB positivity were similarly correlated to CFRD (OR 2.82, CI: 1.22-6.51 and OR 2.71, CI: 1.49-4.93).

Conclusions: Pancreatic islet AABs are present in 1-6 % of pwCF and increase the risk of CFRD by 2.36 to 4.63 times. While there's a suggested link, limited study quality and inconsistent testing warrant cautious interpretation. Further robust studies are needed to confirm these findings and improve screening strategies.

Keywords: Beta-cell autoimmunity; Cystic fibrosis (CF); Cystic fibrosis-related diabetes (CFRD); Meta-Analysis; Pancreatic islet autoantibody; Prevalence.