Fatty Pancreas and Risk of Type 2 Diabetes, Chronic Kidney Disease and Cardiovascular Events: Evidence From a Population‐Based Cohort
Nicola Pugliese, Oveis Jamialahmadi, Arturo Cesaro, Valentina Flagiello, Rosellina M. Mancina, Alessio Aghemo, Stefano RomeoABSTRACT
Background
Fatty pancreas is a metabolically active ectopic fat depot, but its cardiometabolic implications have been assessed using heterogeneous thresholds. We investigated the association of fatty pancreas, quantified using MRI‐derived proton density fat fraction (PDFF) and categorised according to 2026 international consensus thresholds, with prevalent and incident type 2 diabetes (T2D), chronic kidney disease (CKD) and major adverse cardiovascular events (MACE).
Methods
We analysed 19,255 European‐ancestry participants from the UK Biobank imaging sub‐study. Pancreatic PDFF was categorised as normal (< 6%), mild (6 to < 16%) and moderate‐to‐severe fatty pancreas (≥ 16%). Outcomes were ascertained through national health records. Associations were estimated using multivariable logistic regression and Cox models, adjusted for age, sex, BMI‐defined obesity, elevated MRI‐derived visceral adipose tissue and outcome‐specific covariates.
Results
Moderate‐to‐severe fatty pancreas was associated with prevalent and incident T2D (OR 3.25, 95% CI 2.49–4.27; p < 0.001; HR 2.72, 1.66–4.46; p < 0.001), incident CKD (HR 1.82, 1.29–2.57; p < 0.001), and prevalent and incident MACE (OR 1.26, 1.04–1.56; p = 0.022; HR 1.30, 1.02–1.66; p = 0.034). Mild fatty pancreas was associated with incident T2D (HR 2.19, 1.40–3.42; p < 0.001) and incident MACE (HR 1.29, 1.06–1.59; p = 0.013). Each 5% increase in pancreatic PDFF was associated with higher odds and hazard of T2D (OR 1.16, 1.12–1.21; HR 1.17, 1.09–1.25; both p < 0.001).
Conclusions
Fatty pancreas was independently associated with prevalent and incident T2D, incident CKD and, more modestly, with MACE. These findings position fatty pancreas within the cardiovascular‐kidney‐metabolic continuum and support the clinical relevance of consensus‐based PDFF thresholds for cardiometabolic risk assessment in European‐ancestry populations.