Fatty Pancreas and Risk of Type 2 Diabetes, Chronic Kidney Disease and Cardiovascular Events: Evidence From a...

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).

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.

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).

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.