Daily Endocrinology Research Analysis
Three impactful endocrinology-adjacent studies advance metabolic liver disease care and mechanistic understanding. A UK Biobank cohort links MASLD to higher mortality and multimorbidity; a multinational cohort associates SGLT-2 inhibitors with reduced liver-related events in T2D with MASLD; and a mechanistic mouse study shows nori-derived porphyran prevents obesity, diabetes, steatohepatitis, and HCC via a microbiota–bile acid–ceramide axis.
Summary
Three impactful endocrinology-adjacent studies advance metabolic liver disease care and mechanistic understanding. A UK Biobank cohort links MASLD to higher mortality and multimorbidity; a multinational cohort associates SGLT-2 inhibitors with reduced liver-related events in T2D with MASLD; and a mechanistic mouse study shows nori-derived porphyran prevents obesity, diabetes, steatohepatitis, and HCC via a microbiota–bile acid–ceramide axis.
Research Themes
- Risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD)
- Antidiabetic agents and hepatoprotection in T2D with MASLD
- Microbiota–bile acid–ceramide signaling in metabolic disease prevention
Selected Articles
1. The relationships between MASLD, extrahepatic multimorbidity and all-cause mortality in UK Biobank cohort.
In 438,840 UK Biobank participants, MASLD (defined by FLI ≥60 plus cardiometabolic risk factors) was present in 29.9% and associated with greater extrahepatic multimorbidity and 16% higher all-cause mortality over 13 years. Mortality risk was stronger in women and those with fewer long-term conditions, and each additional condition further amplified mortality risk.
Impact: This very large, well-adjusted cohort quantifies the independent mortality burden of MASLD and highlights specific multimorbidity patterns, informing risk stratification and integrated care.
Clinical Implications: Clinicians should proactively screen for and manage extrahepatic long-term conditions in MASLD, particularly in women, and consider integrated cardio-renal-metabolic pathways to reduce mortality.
Key Findings
- MASLD prevalence was 29.9% and associated with higher extrahepatic multimorbidity (21.3% vs 14.4%).
- MASLD increased all-cause mortality by 16% over a median 13 years (HR 1.16, 95% CI 1.13–1.19).
- Mortality associations were stronger in females and those with fewer LTCs; each additional LTC increased mortality by 30% in MASLD.
- Sixteen of 47 extrahepatic long-term conditions were linked to increased mortality among MASLD patients.
Methodological Strengths
- Very large sample size with long-term (median 13 years) follow-up
- Adjusted Cox models with detailed multimorbidity profiling across 47 extrahepatic conditions
Limitations
- MASLD defined using FLI and risk factors, not imaging or histology
- Potential selection bias of UK Biobank and residual confounding inherent to observational design
Future Directions: Validate risk stratification using imaging- or biopsy-defined MASLD and test integrated management pathways in interventional studies, with sex-specific analyses.
2. Porphyran from discolored nori prevents metabolic syndrome through microbiota-bile acid-ceramide pathway.
In mouse models, porphyran from discolored nori prevented obesity, diabetes, MASH, and HCC, mechanistically linked to reduced secondary bile acids, suppressed intestinal FXR signaling, and decreased circulating ceramides. This positions porphyran as a promising nutraceutical candidate that also aligns with sustainability goals.
Impact: This work uncovers a microbiota–bile acid–FXR–ceramide axis by which a food-derived polysaccharide exerts broad metabolic and oncologic protection, suggesting a novel, sustainable prevention strategy.
Clinical Implications: While preclinical, the findings justify early-phase human trials of porphyran for metabolic disease prevention and support dietary strategies that modulate intestinal FXR and ceramides.
Key Findings
- Porphyran administration prevented obesity, diabetes, MASH, and HCC in mice.
- Protection correlated with decreased secondary bile acids and suppressed intestinal FXR signaling.
- Marked reductions in circulating ceramides accompanied metabolic and oncologic benefits.
- Discolored nori, typically discarded, is a rich, sustainable source of porphyran.
Methodological Strengths
- In vivo demonstration of multi-disease prevention with mechanistic linkage to FXR and ceramides
- Systems-level assessment of gut microbiota, bile acids, and lipid mediators
Limitations
- Findings are limited to mouse models; human translation unknown
- Dose, formulation, and long-term safety in humans are not established
Future Directions: Conduct dose-ranging, biomarker-driven human trials assessing FXR activity and ceramides; define microbial contributors and scalable food-grade formulations.
3. Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD.
In 7,867 T2D patients with MASLD across 16 centers, SGLT-2 inhibitor use was associated with markedly lower risks of liver-related events (sdHR 0.23) and slower progression of liver stiffness (HR 0.54) over a median of 5.1 years, after propensity matching and confounder adjustment.
Impact: This study links a widely used antidiabetic class to improved hepatic outcomes in T2D with MASLD, providing real-world evidence to inform drug selection while awaiting randomized trials.
Clinical Implications: For T2D patients with MASLD or elevated liver stiffness risk, clinicians may preferentially consider SGLT-2 inhibitors to potentially lower liver-related events, alongside comprehensive metabolic care.
Key Findings
- SGLT-2 inhibitor use was associated with lower liver-related events (sdHR 0.23, 95% CI 0.08–0.69).
- SGLT-2 inhibitor use was associated with slower liver stiffness progression (HR 0.54, 95% CI 0.35–0.86).
- Use of GLP-1RAs and SGLT-2 inhibitors increased over time, with higher adoption in Asian centers.
Methodological Strengths
- Multicenter cohort with propensity score matching and competing risk analyses
- Assessment of both clinical events and liver stiffness progression over >5 years
Limitations
- Observational design with potential residual confounding and channeling bias
- Medication adherence, dosing, and imaging modality heterogeneity were not fully controlled
Future Directions: Randomized trials comparing SGLT-2 inhibitors to other classes in MASLD with T2D, with standardized elastography and histologic endpoints, are warranted.