Association of pancreas fat fraction with adverse kidney and cardiovascular outcomes

Background Pancreas fat accumulation has been associated with impaired glucose metabolism and stimulation of inflammation. The associations of pancreatic fat fraction (PFF) with adverse outcomes remain understudied. Methods We estimated baseline predicted PFF (pPFF) from abdominal magnetic resonance imaging (MRI) in 29 447 UK Biobank participants. Since the initial imaging visit occurred 9.3 [interquartile range (IQR) 8.2–10.2] years after baseline visit, we calculated annual change in PFF using linear regression in 337 participants who underwent repeat imaging 2.8 (IQR 2.2–4.8) years after the initial scan. We back-calculated pPFF by adding this change to each participant based on the time between baseline visit and initial MRI visit assuming linear change in PFF over time. Multivariable-adjusted proportional hazards models tested associations of pPFF with incident chronic kidney disease (CKD), cardiovascular disease (CVD) and death. Results Participants had a mean ± standard deviation age of 56 ± 8 years, mean eGFR of 98 ± 13 mL/min/1.73 m2, median (IQR) albuminuria of 5.7 (3.5–9.2) mg/g and median pPFF of 4.7 (1.6–10.3)%. During median follow-up of 13.8 years, there were 572 incident CKD, 1048 incident CVD and 468 death events. In final adjusted models, participants in the 4th, 3rd and 2nd quartiles had 1.58-, 1.42- and 1.76-fold higher risks of incident CKD compared with the 1st quartile, respectively. Participants in the 4th quartile had 1.27-fold higher risk of incident CVD compared with the lowest quartile. The associations of pPFF with incident CKD and CVD were each non-linear (each P < .001). pPFF was not associated with death. Conclusions Higher pPFF levels are associated with higher risk of incident CKD and CVD but not death. Future studies should investigate whether pancreas fat depots should serve as a target of current or emerging therapies.