Intrapancreatic fat deposition and visceral fat volume are associated with the presence of diabetes after acute pancreatitis

Abstract

Ectopic fat and abdominal adiposity phenotypes have never been studied holistically in individuals after acute pancreatitis (AP). The aim of the study was to investigate phenotypical differences in ectopic fat and abdominal fat between individuals after AP (with and without diabetes) and to determine the role of pancreatitis-related factors. Eighty-four individuals were studied cross-sectionally after a median of 21.5 mo since last episode of AP and were categorized into “diabetes” and “no diabetes” groups. Twenty-eight healthy volunteers were also recruited. With the use of magnetic resonance imaging, intrapancreatic fat percentage, liver fat percentage, visceral fat volume (VFV), subcutaneous fat volume, and visceral-to-subcutaneous (V/S) fat volume ratio were quantified. Analysis of variance was used to investigate the differences in these phenotypes between the groups. All analyses were adjusted for age and sex. Linear regression analysis was used to investigate the association between pancreatitis-related factors and the studied phenotypes. Intrapancreatic fat percentage was significantly higher in the diabetes group (10.2 ± 1.2%) compared with the no diabetes (9.2 ± 1.7%) and healthy volunteers (7.9 ± 1.9%) groups ( P < 0.001). VFV was significantly higher in the diabetes (2,715.3 ±1,077.6 cm3) compared with no diabetes (1,983.2 ± 1,092.4 cm3) and healthy volunteer (1,126.2 ± 740.4 cm3) groups ( P < 0.001). V/S fat volume ratio was significantly higher in the diabetes (0.97 ± 0.27) compared with no diabetes (0.68 ± 0.42) and healthy volunteer (0.52 ± 0.34) groups ( P = 0.001). Biliary AP was associated with significantly higher intrapancreatic fat percentage (β = 0.67; 95% CI, 0.01, 1.33; P = 0.047). C-reactive protein levels during hospitalization for AP were associated with significantly higher VFV (β = 3.32; 95% CI, 1.68, 4.96; P < 0.001). In conclusion, individuals with diabetes after AP have higher intrapancreatic fat percentage, VFV, and V/S fat volume ratio. Levels of C-reactive protein during AP are significantly associated with VFV, whereas biliary AP is significantly associated with intrapancreatic fat percentage. NEW & NOTEWORTHY Individuals with diabetes after acute pancreatitis have significantly higher intrapancreatic fat percentage and visceral fat volume compared with individuals without diabetes after acute pancreatitis and healthy controls. C-reactive protein levels during hospitalization for acute pancreatitis and biliary etiology of acute pancreatitis are associated with significantly larger visceral fat and pancreatic fat depots, respectively.

Response to Comment on Cho et al. Antidiabetic Medications and Mortality Risk in Individuals With Pancreatic Cancer–Related Diabetes and Postpancreatitis Diabetes: A Nationwide Cohort Study. Diabetes Care 2019;42:1675–1683

“…The authors of the comment also speculated that the survival benefit of metformin might be limited to individuals with postacute pancreatitis diabetes mellitus (PPDM-A), and not those with postchronic pancreatitis diabetes mellitus (PPDM-C) because of possible excess adiposity of the former (resulting in higher effectiveness of metformin). Given that the 2019 MRI study of individuals after acute pancreatitis by our group showed the importance of visceral and ectopic fat (specifically, intrapancreatic fat deposition) in the pathogenesis of diabetes in this study population (5), we certainly agree that excess adiposity could act as an effect modifier of the association between the use of metformin and mortality in individuals following pancreatitis. Unfortunately, we did not have data related to adiposity in our nationwide epidemiological study.…”

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

“…However, in an earlier clinical study that investigated the associations between IPFD and nine indices of insulin secretion in individuals NODAP using a step-wise multivariable analysis, none of the indices of insulin secretion appeared in the final model [26], indicating that insulin sensitivity is a more relevant trait than insulin secretion when it comes to their associations with IPFD in individuals with NODAP. Fourth, although we excluded participants with chronic pancreatitis, recurrent attacks of AP might have affected the association between the indices of insulin sensitivity and IPFD [32]. Given that the number of participants with recurrent bouts was small, a meaningful statistical analysis was not possible.…”

“…IPFD (%) was measured using the "MR-opsy" method, a chemical shift MR imaging technique that provides unambiguous water-fat signal separation on in-phase and out-of-phase images [26,32,33]. Two slices with clear visualization of the entire pancreas were selected from a series of MR scans.…”

Use of Insulin and the Risk of Progression of Pancreatitis: A Population‐Based Cohort Study

“…Circulating levels of proinflammatory cytokines (in particular, interleukin‐6) are known to be elevated in individuals with diabetes after AP, the early course of which is characterized by increased insulin resistance and activated β‐cell compensatory mechanism . In their turn, proinflammatory cytokines are associated with circulating levels of pancreatic hormones (specifically, high levels of interleukin‐6 lead to hyperinsulinemia) and intrapancreatic fat deposition . In addition, hyperinsulinemia is known to lead to intrapancreatic fat deposition, which may perpetuate low‐grade inflammation and trigger pancreatic fibrogenesis .…”

“…22,23 In their turn, proinflammatory cytokines are associated with circulating levels of pancreatic hormones (specifically, high levels of interleukin-6 lead to hyperinsulinemia) 24 and intrapancreatic fat deposition. 25,26 In addition, hyperinsulinemia is known to lead to intrapancreatic fat deposition, 27 which may perpetuate low-grade inflammation and trigger pancreatic fibrogenesis. 28,29 Purposely designed translational studies are now warranted to gain deeper insights into the effect of insulin on progression of pancreatitis.…”