| Title: |
Effect Modification of Trimethylamine N-Oxide and Lipoprotein Insulin Resistance with Post-Transplantation Diabetes After Liver Transplant |
| Authors: |
Mateo Chvatal-Medina; Yakun Li; Adrian Post; Margery A. Connelly; Han Moshage; Stephan J. L. Bakker; Vincent E. de Meijer; Hans Blokzijl; Robin P. F. Dullaart; on behalf of TransplantLines Investigators on behalf of TransplantLines Investigators |
| Source: |
International Journal of Molecular Sciences ; Volume 27 ; Issue 4 ; Pages: 1959 |
| Publisher Information: |
Multidisciplinary Digital Publishing Institute |
| Publication Year: |
2026 |
| Collection: |
MDPI Open Access Publishing |
| Subject Terms: |
post-transplant diabetes mellitus; liver transplantation; trimethylamine N-oxide; lipoprotein insulin resistance score |
| Description: |
Post-transplant diabetes mellitus (PTDM) is a common complication after liver transplantation. Trimethylamine N-oxide (TMAO), a microbiota-derived metabolite, has been linked to insulin resistance, but epidemiological findings on type 2 diabetes remain inconsistent. The Lipoprotein Insulin Resistance (LP-IR) score is a nuclear magnetic resonance (NMR)-derived marker of insulin resistance, yet its role in PTDM and interaction with TMAO are unknown. Three hundred sixty-seven (367) liver transplant recipients (LTRs) from the TransplantLines cohort were studied. Baseline TMAO and LP-IR score were quantified by NMR spectroscopy. Incident PTDM was defined by international criteria. Associations were tested using logistic regression and Cox proportional regression analysis. Effect modification was tested with interaction terms. Thirty-one out of 246 LTRs at risk developed PTDM after a median follow-up of 7.1 years. Higher TMAO (OR 2.14, p = 0.015) and LP-IR score (OR 1.66, p = 0.015) were associated with increased PTDM risk after adjustment for eGFR and immunosuppressant use. A positive interaction was present (p = 0.029) with risk amplification when both biomarkers were elevated. TMAO’s association with PTDM was strongest at high LP-IR (90th percentile; OR 3.20, p = 0.005), and LP-IR’s association was strongest at high TMAO (90th percentile; OR 2.56, p = 0.002). Time-to-event analysis confirmed these findings. The independent and positive interaction of TMAO and LP-IR with PTDM in LTRs would suggest a pro-diabetic action of TMAO that depends on insulin resistance. |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Molecular Biology; https://dx.doi.org/10.3390/ijms27041959 |
| DOI: |
10.3390/ijms27041959 |
| Availability: |
https://doi.org/10.3390/ijms27041959 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.F3E94978 |
| Database: |
BASE |