CIRCULATING microRNAs shifted during OGTT, distinguishing cystic fibrosis-related diabetes from earlier intolerance in CF cohorts.
Cystic Fibrosis-Related Diabetes Signals in Blood
Cystic fibrosis-related diabetes (CFRD) remains the most common comorbidity in cystic fibrosis (CF), and it can be difficult to detect early because glucose abnormalities may be subtle. In a Danish cohort study of 93 adults with CF, researchers investigated whether circulating microRNAs differ by glucose tolerance status and whether they change rapidly after a glucose challenge.
Participants were grouped into four categories: normal glucose tolerance, indeterminate glucose tolerance, impaired glucose tolerance, and CFRD. Serum samples were collected during an oral glucose tolerance test (OGTT) at baseline and multiple timepoints after glucose ingestion, enabling the team to track dynamic shifts rather than relying on a single measurement.
Oral Glucose Tolerance Test Reveals Rapid microRNA Shifts
Using sequencing in a selected subset and follow-up validation in the full cohort, the investigators identified microRNAs that differed at baseline and others that changed in response to glucose ingestion. Four microRNAs showed differential expression at baseline, and an additional set displayed different response patterns during the OGTT depending on glucose tolerance state.
The study highlighted miR-34a-5p and miR-122-5p as elevated at baseline in indeterminate glucose tolerance and CFRD, with associations to elevated liver damage markers. A third candidate, miR-223-3p, showed distinct OGTT response patterns by glucose tolerance category, supporting the idea that the circulating microRNA response to glucose challenge may help discriminate metabolic states in CF.
Candidate Biomarkers with Functional Signals
To explore potential mechanistic relevance, the researchers assessed effects in insulin-secreting cells. Overexpression of miR-122-5p or miR-223-3p increased glucose-stimulated insulin secretion, while overexpression of miR-34a-5p decreased cell viability. The authors propose that circulating microRNAs could support diagnosis and monitoring in cystic fibrosis-related diabetes and may reflect broader crosstalk between metabolic organs and the endocrine pancreas.
Reference: Westholm E et al. Dynamic changes in circulating microRNAs during oral glucose tolerance testing support their potential as diagnostic and monitoring biomarkers in cystic fibrosis-related diabetes. Diabetologia. 2026; doi:10.1007/s00125-025-06645-7.
