Philip A. Hart

Background/Objectives: Plant-based diets are widely recommended for lowering the risk of type 2 diabetes, with the caveat that their health benefits depend on the quality of the foods consumed. This analysis examined associations between five dietary patterns and pre-existing diabetes among patients with acute pancreatitis (AP), a population in which the relationship between diet and diabetes has not been well characterized. Methods: Participants were drawn from the Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) study, an ongoing multicenter study of adults aged 18 to 75 years with AP in the U.S. This cross-sectional analysis evaluated five dietary patterns using food frequency questionnaires (FFQ): the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), the reverse Empirical Dietary Inflammatory Pattern (rEDIP), the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). We used multivariable logistic regression models to estimate odds ratios (ORs) for pre-existing diabetes (i.e., prior to the AP episode). Results: A total of 647 participants (mean age 49.1 ± 14.5 years) were included. In multivariable-adjusted analyses, participants in the highest versus lowest tertile of PDI had 55% lower odds of pre-existing diabetes (adjusted OR: 0.45; 95% CI: 0.25–0.80; p-trend = 0.005). No statistically significant associations were detected for rEDIP, rEDIH, hPDI, or uPDI. Conclusions: Higher overall PDI scores were associated with lower odds of prevalent diabetes. Among patients with AP, further studies are needed to evaluate dietary contributions to future diabetes development following AP and identify potential dietary strategies for diabetes prevention.

Objective: Patient-reported outcome (PRO) measures are essential for evaluating symptom burden and quality of life (QoL) in acute and chronic pancreatitis (AP/CP), yet many instruments used in this patient population lack robust psychometric evidence. The Patient-Reported Outcomes Measurement Information System (PROMIS) offers standardized measures designed for comparability across populations, but their suitability for AP/CP has not been comprehensively evaluated. The objective of this study was t o assess the psychometric properties of PROMIS-29, PROMIS-Global Health, and PROMIS Pain Quality scales in individuals with AP/CP and provide an overview of psychometric standards that facilitate selection of PROs for use in clinical research and patient care. Methods: Data were drawn from 1,927 participants enrolled in PROCEED, a multi-site longitudinal study across the pancreatitis spectrum, including healthy controls, chronic abdominal pain, acute/recurrent acute pancreatitis and definite CP. Factor models and regressions were used to psychometrically evaluate univariate construct validity, known-groups validity, convergent validity, reliability, structural validity and population invariance. Results: PROMIS measures exceeded all psychometric benchmarks tested. Scores were approximately normally distributed and comprehensively covered the range of each symptom domain. Correlations with other commonly used QoL measures supported convergent validity. PROMIS scores discriminated effectively among diagnostic subgroups and exhibited excellent structural validity and internal consistency reliability. Population invariance assessments indicated that scores are comparable across age, sex, race, and diagnostic subgroups. Conclusions: This study provides strong preliminary evidence that PROMIS measures meet rigorous psychometric standards that supports their use in patient research and care in AP/CP. Their adoption may enhance measurement consistency and support core outcome sets in clinical research and trials of AP/CP.

Introduction: Acute pancreatitis (AP) is a common inflammatory disorder that is associated with increased risk for diabetes mellitus (DM). It remains unclear whether recurrent acute pancreatitis (RAP) is associated with further increased risk of incident DM. This study aims to investigate the association between RAP and incident DM using real-world data. Methods: We conducted a retrospective cohort study using the Merative ^TM MarketScan® claims database (2016–2023), identifying patients with AP and no prior history of DM at baseline. The primary exposure of interest, RAP, was defined as one or more episodes of AP occurring ≥90 days after the index AP diagnosis, whereas one episode of AP referred to a single episode of AP (SAP) with no subsequent recurrence within 90 days following the index event. A multivariable stratified Cox proportional hazards regression models were used to determine the association between RAP and incident DM, identified using ICD-10 codes. Results: In total, 16,184 individuals with AP (mean [SD] age: 45.8 [12.3]) contributed 40,712 person-years of follow-up, during which 1,477 incident cases of DM were documented. Individuals with RAP had an increased risk of incident DM compared with those with a SAP(adjusted HR, 1.92; 95% CI, 1.61-2.29). The risk increased significantly with the frequency of RAP. In comparing the modifying effect of patient demographics and comorbidities, a stronger association between RAP and incident DM was observed in females (adjusted HR, 2.44; 95% CI, 1.87-3.19) than in males (adjusted HR, 1.64; 95% CI, 1.30-2.07; P _interaction =0.03). Also, stronger associations were observed among younger patients (18–46 y) (adjusted HR=2.56; 95% CI, 1.97-3.31) and among non-tobacco abuse (adjusted HR=2.19; 95% CI, 1.81-2.65), with significant interactions for all comparisons ( P _interaction <0.05 Conclusions: In this real-world study, RAP was associated with an increased risk of incident DM. Our findings highlight an opportunity for glycemic monitoring and proactive management of patients with RAP to mitigate their risk of developing DM.

Objective: We previously validated a short endoscopic test with pancreas fluid enzyme activity in pediatrics and young adults. We assessed the role of pancreatic fluid enzyme activity as a candidate to address the lack of a diagnostic biomarker for chronic pancreatitis (CP). Methods: In this pilot study, we assessed pancreatic fluid samples collected endoscopically 30-minute post-secretin injection from adult controls (n=10) and CP subjects (n=20). Protein-normalized enzymatic activity for amylase, lipase, trypsin, chymotrypsin, and elastase was compared between CP and control groups using logistic regression, and diagnostic performance was evaluated by ROC analysis. Results: Acinar cell enzyme levels were decreased in pancreatic fluid from CP subjects compared with controls, with significant differences observed for lipase and trypsin activity (AUC≥0.82; p’s=0.01). Eighty-six percent of controls had normal enzymatic activity across all five analytes, compared with only 43% of CP subjects, who more frequently exhibited multi-enzyme abnormalities. A graded pattern of reduction was observed from controls to equivocal (Eq) CP to definitive (Def) CP, indicating that enzyme activity generally shifts with advancing CP disease, although Eq and Def CP did not differ significantly from one another. Conclusions: This pilot study explored the potential of pancreatic fluid enzymatic activity as a functional assessment of exocrine activity in CP, with potential correlation to disease severity. Pancreatic fluid represents a promising, proximal biomarker source; however, larger prospective studies are needed to validate pancreas fluid biomarkers and define their relationship to disease stage, EPD, and other CP-related clinical outcomes.

Dietary patterns have been associated with altered risk of diabetes mellitus (DM) in the general population. These patterns can estimate habitual intake of food groups associated with decreased or increased (e.g., greater intake of red meats) risk of DM. This analysis aimed to examine the underexplored associations of four dietary patterns in patients presenting with an acute pancreatitis (AP) diagnosis based on the presence of pre-existing DM. Study participants were selected from the Diabetes RElated to Acute Pancreatitis and its Mechanisms (DREAM) study, an ongoing, multicenter study of adults (18–75 years) with AP in the US. This is a cross-sectional analysis of baseline data collected using the VioScreen computer-administered Food Frequency Questionnaire. We examined four dietary patterns: the Alternate Mediterranean Diet (AMED), the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND), the Healthy Eating Index-2020 (HEI-2020), and the Alternate Healthy Eating Index-2010 (AHEI-2010). Multivariable logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The study population included 647 individuals with AP (mean (SD) baseline age, 49.1 (14.5) years). Participants in the highest tertile of dietary index scores were more likely to be older, female, non-Hispanic White, and to have higher educational attainment. In multivariable analyses, greater adherence to the AMED and the MIND dietary patterns was associated with lower odds of pre-existing DM. Multivariable ORs for the odds of pre-existing DM comparing the highest to lowest tertile of diet scores were 0.44 (95% CI: 0.23, 0.84; P-trend = 0.01) for AMED, 0.46 (95% CI: 0.26, 0.82; P-trend = 0.01) for MIND, indicating lower odds for participants with a healthier dietary pattern. In this analysis, greater adherence to selected healthy dietary patterns was associated with lower odds of pre-existing DM at the time of AP presentation. The online version contains supplementary material available at 10.1186/s12937-026-01294-x.

INTRODUCTION: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis, and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis. METHODS: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0–10 (n = 110) and 10–20 (n = 111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n = 75) and urine (n = 71) from the same subjects. Subjects were enrolled in the PROCEED study and classified symptomatic controls, acute/recurrent acute pancreatitis (AP/RAP), or CP. RESULTS: A significant main effect was detected in 10–20 minutes pancreas fluid ( P = 0.027) and plasma ( P = 0.046); post hoc testing showed PGE2 was lower in the AP/RAP group compared with symptomatic controls. There was also trend toward lower PGE2 in urine ( P = 0.062). To elucidate the active downstream pathways, calcitonin gene-related peptide, substance P, and matrix metalloproteinases (MMPs) 1, 2, 3, 7, 9, and 13 were measured in pancreas fluid. A significant difference between the 3 groups was detected for both MMP7 and MMP9. MMP7 was elevated in individuals with CP vs AP/RAP ( P = 0.012) for samples collected early but both time points for MMP9 ( P = 0.027, P = 0.002). DISCUSSION: While PGE2 is detectable in pancreas fluid, these data suggest that it may not be sensitive enough to distinguish between AP/RAP and CP. However, MMPs may distinguish between stages of pancreatitis and require further testing as potential diagnostic biomarkers.

INTRODUCTION: Chronic pancreatitis (CP) remains difficult to manage with few treatment options. Prior studies have implicated prostaglandin E₂ (PGE₂) in mediating chronic inflammation in the pancreas. Therefore, we aimed to evaluate whether indomethacin, a cyclooxygenase-2 enzyme inhibitor, would reduce PGE₂ levels in CP. METHODS: In this pilot multicenter randomized controlled trial, participants with CP received oral indomethacin (50 mg) or placebo twice daily for 28 days. Measurement of PGE₂ levels in pancreatic fluid collected endoscopically after secretin administration at baseline and posttreatment (day 28) was performed. Quality of life and pain were also assessed at baseline and posttreatment. RESULTS: A total of 27 participants were randomized (indomethacin = 13, placebo = 14). Although PGE₂ levels decreased after treatment in pancreas fluid, plasma, and saliva in the indomethacin group, there was no significant difference in mean change in pancreas fluid PGE₂ levels between the indomethacin and placebo groups (−457.7 pg/mL vs −840.4 pg/mL, P = 0.25). There was also no significant change in pain severity composite score (−1.3 indomethacin vs −0.5 placebo, P = 0.33), but the improvement in pain interference score (−2.9 indomethacin vs −0.4, P = 0.058) trended toward significance. There was no difference in adverse events between the 2 groups. DISCUSSION: In this phase 1/2 study, oral indomethacin was safe and well tolerated by patients with CP. Although there was no significant difference in change in PGE₂ levels, further studies are needed to determine the effect of indomethacin on the inflammatory pathway of CP and patient-centered outcomes.