Factors associated with protection from MASLD in type 2 diabetes: A prospective study integrating longitudinal MRI/MRE and stable isotope tracing

IF 8.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

JHEP Reports Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI:10.1016/j.jhepr.2026.101733

Federica Tavaglione , Veeral Ajmera , Luis Antonio Díaz , Kelvin Li , Egbert Madamba , Ricki Bettencourt , Lisa Richards , Marc Hellerstein , Rohit Loomba

{"title":"Factors associated with protection from MASLD in type 2 diabetes: A prospective study integrating longitudinal MRI/MRE and stable isotope tracing","authors":"Federica Tavaglione , Veeral Ajmera , Luis Antonio Díaz , Kelvin Li , Egbert Madamba , Ricki Bettencourt , Lisa Richards , Marc Hellerstein , Rohit Loomba","doi":"10.1016/j.jhepr.2026.101733","DOIUrl":null,"url":null,"abstract":"<div><h3>Background & Aims</h3><div>Type 2 diabetes is one of the strongest risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we aimed to identify factors associated with protection from MASLD in a prospective cohort of individuals with type 2 diabetes.</div></div><div><h3>Methods</h3><div>This prospective study included 148 individuals with type 2 diabetes who underwent advanced liver phenotyping using MRI and MRE techniques at baseline and 2-year follow-up. Protection from MASLD was defined as the absence of hepatic steatosis (MRI-proton density fat fraction <5%) and significant fibrosis (MRE <3 kPa) at both time points. Factors associated with protection from MASLD were assessed using Firth’s penalized logistic regression. Regularized logistic regression models were fitted as complementary analyses.</div></div><div><h3>Results</h3><div>The mean (SD) age and BMI were 65 (8) years and 30.4 (4.3) kg/m<sup>2</sup>, respectively. After a median follow-up of 2 (1.5–2.4) years, 27 (18%) individuals demonstrated an absence of MASLD. Across all modeling approaches, lower BMI (odds ratio [OR] 0.81, 95% CI 0.64–0.98; <em>p =</em> 0.029), lower HOMA-IR (OR 0.59, 95% CI 0.39–0.83; <em>p =</em> 8.6e-4), and lower circulating triglycerides (OR 0.986, 95% CI 0.973–0.997; <em>p =</em> 0.011) emerged as the strongest predictors of protection from MASLD. An exploratory analysis of 11 individuals with type 2 diabetes from an independent cohort, with hepatic <em>de novo</em> lipogenesis quantified by stable isotope tracing, revealed lower hepatic <em>de novo</em> lipogenesis in those free from MASLD.</div></div><div><h3>Conclusions</h3><div>Managing modifiable risk factors, such as body weight and lipid profile, may be critical for preventing MASLD development in individuals with type 2 diabetes.</div></div><div><h3>Impact and implications</h3><div>Understanding factors conferring protection from metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with type 2 diabetes represents a novel research avenue which has not been systematically explored. In this prospective cohort of 148 individuals with type 2 diabetes undergoing advanced liver phenotyping at baseline and 2-year follow-up, we identified lower BMI, lower HOMA-IR, and lower circulating triglycerides as the strongest predictors of remaining free of MASLD. Additionally, by performing an exploratory analysis in an independent cohort of 11 individuals with type 2 diabetes with tracer data, we found that lower hepatic <em>de novo</em> lipogenesis may underlie this protective phenotype. These findings suggest that managing modifiable risk factors, such as body weight and lipid profile, may be critical for preventing MASLD development and progression in individuals with type 2 diabetes.</div></div>","PeriodicalId":14764,"journal":{"name":"JHEP Reports","volume":"8 3","pages":"Article 101733"},"PeriodicalIF":8.7000,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JHEP Reports","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589555926000030","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background & Aims

Type 2 diabetes is one of the strongest risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we aimed to identify factors associated with protection from MASLD in a prospective cohort of individuals with type 2 diabetes.

Methods

This prospective study included 148 individuals with type 2 diabetes who underwent advanced liver phenotyping using MRI and MRE techniques at baseline and 2-year follow-up. Protection from MASLD was defined as the absence of hepatic steatosis (MRI-proton density fat fraction <5%) and significant fibrosis (MRE <3 kPa) at both time points. Factors associated with protection from MASLD were assessed using Firth’s penalized logistic regression. Regularized logistic regression models were fitted as complementary analyses.

Results

The mean (SD) age and BMI were 65 (8) years and 30.4 (4.3) kg/m², respectively. After a median follow-up of 2 (1.5–2.4) years, 27 (18%) individuals demonstrated an absence of MASLD. Across all modeling approaches, lower BMI (odds ratio [OR] 0.81, 95% CI 0.64–0.98; p = 0.029), lower HOMA-IR (OR 0.59, 95% CI 0.39–0.83; p = 8.6e-4), and lower circulating triglycerides (OR 0.986, 95% CI 0.973–0.997; p = 0.011) emerged as the strongest predictors of protection from MASLD. An exploratory analysis of 11 individuals with type 2 diabetes from an independent cohort, with hepatic de novo lipogenesis quantified by stable isotope tracing, revealed lower hepatic de novo lipogenesis in those free from MASLD.

Conclusions

Managing modifiable risk factors, such as body weight and lipid profile, may be critical for preventing MASLD development in individuals with type 2 diabetes.

Impact and implications

Understanding factors conferring protection from metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with type 2 diabetes represents a novel research avenue which has not been systematically explored. In this prospective cohort of 148 individuals with type 2 diabetes undergoing advanced liver phenotyping at baseline and 2-year follow-up, we identified lower BMI, lower HOMA-IR, and lower circulating triglycerides as the strongest predictors of remaining free of MASLD. Additionally, by performing an exploratory analysis in an independent cohort of 11 individuals with type 2 diabetes with tracer data, we found that lower hepatic de novo lipogenesis may underlie this protective phenotype. These findings suggest that managing modifiable risk factors, such as body weight and lipid profile, may be critical for preventing MASLD development and progression in individuals with type 2 diabetes.

Abstract Image

查看原文本刊更多论文

2型糖尿病患者MASLD保护相关因素：一项整合纵向MRI/MRE和稳定同位素示踪的前瞻性研究

背景与目的：2型糖尿病是代谢功能障碍相关脂肪变性肝病（MASLD）发生和发展的最强危险因素之一。在这项研究中，我们的目的是在一组前瞻性2型糖尿病患者中确定与MASLD保护相关的因素。方法：这项前瞻性研究包括148名2型糖尿病患者，他们在基线和2年随访期间使用MRI和MRE技术进行了晚期肝脏表型分析。对MASLD的保护被定义为没有肝脂肪变性（mri质子密度脂肪分数）。结果：平均（SD）年龄为65(8)岁，BMI为30.4 (4.3)kg/m2。中位随访2年（1.5-2.4年）后，27例（18%）患者无MASLD。在所有建模方法中，较低的BMI（比值比[OR] 0.81, 95% CI 0.64-0.98; p = 0.029）、较低的HOMA-IR（比值比[OR] 0.59, 95% CI 0.39-0.83; p = 8.6e-4）和较低的循环甘油三酯（比值比[OR] 0.986, 95% CI 0.973-0.997; p = 0.011）成为MASLD保护的最强预测因子。一项对来自独立队列的11名2型糖尿病患者的探索性分析，通过稳定同位素示踪量化了肝脏新生脂肪生成，发现无MASLD患者的肝脏新生脂肪生成较低。结论：控制可改变的危险因素，如体重和血脂，可能是预防2型糖尿病患者发生MASLD的关键。影响和意义：了解2型糖尿病患者代谢功能障碍相关脂肪变性肝病（MASLD）的保护因素是一个尚未系统探索的新研究途径。在这项前瞻性队列研究中，148名2型糖尿病患者在基线和2年随访时进行了晚期肝脏表型分析，我们发现较低的BMI、较低的HOMA-IR和较低的循环甘油三酯是保持无MASLD的最强预测因子。此外，通过对11名2型糖尿病患者的独立队列进行探索性分析，我们发现肝脏新生脂肪生成较低可能是这种保护性表型的基础。这些发现表明，控制可改变的风险因素，如体重和血脂，可能是预防2型糖尿病患者MASLD发生和进展的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

12.40

自引率

2.40%

发文量

161

审稿时长

36 days

期刊介绍： JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.