Journal article
Metabolite perturbations in type 1 diabetes associated with metabolic dysfunction-associated steatotic liver disease
Frontiers in endocrinology, Vol.16, 1500242
06/02/2025
DOI: 10.3389/fendo.2025.1500242
PMCID: PMC12188458
PMID: 40568565
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Although MASLD has been widely studied in persons with Type 2 diabetes (T2D), far less in known about the pathogenesis and severity of MASLD in Type 1 diabetes (T1D).
Objectives: Determine metabolic perturbations associated with MASLD in persons with T1D.
Study Design: We conducted a cross-sectional study of 30 participants with T1D. Based on the results of a FibroScan, participants were stratified as cases (MASLD) or controls. Metabolomic analyses were performed on plasma obtained from all participants after an overnight (after midnight) fast.
Results: 17 of 30 participants were classified as cases (MASLD) and 13 as controls. Cases had higher BMI (p=<0.001) and were taking higher daily insulin doses than controls (p=0.003). Metabolomic analyses revealed that those with MASLD had elevated levels of gluconeogenic substrates pyruvate (p=0.001) and lactate (p=0.043), gluconeogenic amino acids alanine (p<0.001) and glutamate (p=0.004), phenylalanine (p=0.003), and anthranilic acid (p=0.015). Lipidomics revealed, elevated ceramides (P=0.02), diacylglycerols (p=0.0009) and triacylglycerols (P=0.0004) in MASLD group. In those with MASLD, the acylcarnitines, isovalerylcarnitine (CAR.5.0) (P=0.002) and L-Palmitoylcarnitine (CAR.16.0) (P=0.048), were elevated. Pathway analyses using MetaboAnalyst 5.0 Software revealed that, pathways including phenylalanine and tyrosine metabolism, tryptophan metabolism, glucose-alanine cycle, glutamate metabolism, and glutathione metabolism were significantly enriched in those with MASLD.
Conclusion: Participants with T1D and MASLD manifest features of insulin resistance and metabolite perturbations suggesting enhanced gluconeogenesis, dysfunctional fat synthesis, and perturbed TCA cycle activity.
Details
- Title: Subtitle
- Metabolite perturbations in type 1 diabetes associated with metabolic dysfunction-associated steatotic liver disease
- Creators
- Adeyinka Taiwo - University of Iowa, Endocrinology and MetabolismRonald A Merrill - University of Iowa, Molecular Physiology and BiophysicsLinder Wendt - University of IowaDaniel Pape - University of Iowa Hospitals and ClinicsHimani Thakkar - University of Iowa, Internal MedicineJ Alan Maschek - University of UtahJames Cox - University of UtahScott A. Summers - University of UtahBhagirath Chaurasia - University of Iowa, Endocrinology and MetabolismNikitha PothireddyBianca B CarlsonAntonio Sanchez - University of Iowa, Gastroenterology and HepatologyPatrick Ten Eyck - University of Iowa, BiostatisticsDiana I Jalal - University of Iowa, NephrologyAyotunde O Dokun - University of Iowa, Endocrinology and MetabolismEric B Taylor - University of Iowa, Fraternal Order of Eagles Diabetes Research CenterWilliam I Sivitz - University of Iowa, Endocrinology and Metabolism
- Resource Type
- Journal article
- Publication Details
- Frontiers in endocrinology, Vol.16, 1500242
- DOI
- 10.3389/fendo.2025.1500242
- PMID
- 40568565
- PMCID
- PMC12188458
- NLM abbreviation
- Front Endocrinol (Lausanne)
- ISSN
- 1664-2392
- Publisher
- FRONTIERS MEDIA SA; LAUSANNE
- Grant note
- Division of Endocrinology and Metabolism, at the University of Iowa Hospitals and Clinics: ET - NIHR01DK104998, DJ - NIH1RO1HL134738, WIS - NIH1R01DK123043 PT - Clinical and Translational Science: UM1TR004403 DP - American Heart Association predoctoral training grant: AHA 23PRE1020471 Iowa MSTP training grant: NIH T32 GM139776
The author(s) declare that financial support was received for the research and/or publication of this article.: The study was conducted using an Internal grant from the Division of Endocrinology and Metabolism, at the University of Iowa Hospitals and Clinics. This study was also supported by the following grants: ET - NIHR01DK104998, DJ - NIH1RO1HL134738, WIS - NIH1R01DK123043, LW and PT - Clinical and Translational Science Award UM1TR004403, DP - American Heart Association predoctoral training grant (AHA 23PRE1020471), and the Iowa MSTP training grant (NIH T32 GM139776).
- Language
- English
- Date published
- 06/02/2025
- Academic Unit
- Molecular Physiology and Biophysics; Gastroenterology and Hepatology; Biostatistics; Fraternal Order of Eagles Diabetes Research Center; Nephrology; Endocrinology and Metabolism; Internal Medicine; Design Biostat and Ethics
- Record Identifier
- 9984822148702771
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