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Background <p>Growing evidence supports a role for high intrapancreatic fat deposition&#xa0;(IPFD) in the pathogenesis of type 2 diabetes mellitus (T2DM); however, the magnitude&#xa0;of this association and the extent to which it is influenced by body mass index (BMI),&#xa0;liver fat content (LFC), and age remain uncertain.</p> Objective <p>To quantitatively evaluate IPFD measured by magnetic resonance imaging&#xa0;(MRI) in individuals with T2DM and to investigate study-level factors contributing to&#xa0;between-study variability.</p> Methods <p>We systematically searched PubMed and Embase for observational studies&#xa0;comparing MRI-measured IPFD in individuals with T2DM versus non-diabetic controls,&#xa0;excluding studies in which IPFD quantification was performed using AI-based models.&#xa0;Pooled standardized mean differences (SMDs) were estimated using a restricted&#xa0;maximum likelihood approach with Hartung-Knapp adjustment. Heterogeneity was&#xa0;explored through subgroup, meta-regression, and sensitivity analyses.</p> Results <p>Thirty studies (<i>n</i>=3,980) were included. Individuals with T2DM had&#xa0;significantly higher IPFD than non-diabetic controls (SMD 1.13, 95% CI 0.74 to 1.51), with no significant differences when stratified by pancreatic region, MRI technique,&#xa0;geographic region, sample size, and risk of bias. In multivariable models, BMI remained&#xa0;the only consistent moderating covariate, and the excess IPFD in T2DM persisted after&#xa0;adjusting for BMI, LFC, and age (intercept=0.797, p=0.010, false discovery rate-adjusted&#xa0;p=0.018). Advanced heterogeneity exploration identified no structural outliers, and the pooled effect size remained consistent across multiple sensitivity&#xa0;analyses.</p> Conclusion <p>T2DM is associated with substantially higher MRI-quantified IPFD, independent of study-level differences in BMI, LFC, and age. Although causality cannot be inferred, these findings support the hypothesis that IPFD may be involved in the underlying mechanism of T2DM. They also suggest that high IPFD could represent a metabolic hallmark, with potential implications for risk stratification and therapeutic targeting. </p> Graphical Abstract <p></p>

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Burden of Intrapancreatic Fat Deposition in Type 2 Diabetes and the Role of Obesity: A Systematic Review and Meta-Analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月21日

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  • Hyun Hee Sul,
  • Saeed Ahmad,
  • Pojsakorn Danpanichkul,
  • Alessandro Mantovani,
  • Matheus Souza,
  • Maxim S. Petrov

摘要

Background

Growing evidence supports a role for high intrapancreatic fat deposition (IPFD) in the pathogenesis of type 2 diabetes mellitus (T2DM); however, the magnitude of this association and the extent to which it is influenced by body mass index (BMI), liver fat content (LFC), and age remain uncertain.

Objective

To quantitatively evaluate IPFD measured by magnetic resonance imaging (MRI) in individuals with T2DM and to investigate study-level factors contributing to between-study variability.

Methods

We systematically searched PubMed and Embase for observational studies comparing MRI-measured IPFD in individuals with T2DM versus non-diabetic controls, excluding studies in which IPFD quantification was performed using AI-based models. Pooled standardized mean differences (SMDs) were estimated using a restricted maximum likelihood approach with Hartung-Knapp adjustment. Heterogeneity was explored through subgroup, meta-regression, and sensitivity analyses.

Results

Thirty studies (n=3,980) were included. Individuals with T2DM had significantly higher IPFD than non-diabetic controls (SMD 1.13, 95% CI 0.74 to 1.51), with no significant differences when stratified by pancreatic region, MRI technique, geographic region, sample size, and risk of bias. In multivariable models, BMI remained the only consistent moderating covariate, and the excess IPFD in T2DM persisted after adjusting for BMI, LFC, and age (intercept=0.797, p=0.010, false discovery rate-adjusted p=0.018). Advanced heterogeneity exploration identified no structural outliers, and the pooled effect size remained consistent across multiple sensitivity analyses.

Conclusion

T2DM is associated with substantially higher MRI-quantified IPFD, independent of study-level differences in BMI, LFC, and age. Although causality cannot be inferred, these findings support the hypothesis that IPFD may be involved in the underlying mechanism of T2DM. They also suggest that high IPFD could represent a metabolic hallmark, with potential implications for risk stratification and therapeutic targeting.

Graphical Abstract