Diabetes (DM) can occur as a complication of acute, acute recurrent, or chronic pancreatitis, affecting more than 30% of adults with chronic pancreatitis. Data on the pathophysiology and management are limited, especially in pediatric population. Proposed mechanisms include insulin deficiency, insulin resistance, decreased pancreatic polypeptide, and possible beta-cell autoimmunity (in a small subset). Risk factors for developing diabetes in those with pancreatitis may include hypertriglyceridemia, obesity, necrotizing pancreatitis, exocrine pancreatic insufficiency, and pancreatic calcifications, among others. Further studies are required to understand pathophysiology of pancreatogenic DM, in order to define optimal treatment approaches.

Gastrointestinal (GI) symptoms and weight loss develop during and after acute pancreatitis (AP), but remain understudied. In this prospective, multicenter study, we aim to assess GI symptom burden and weight loss and their correlation with exocrine function up to 12 months post-AP.

GI symptom burden, anthropometrics, and exocrine pancreatic function were systematically measured in adults (≥18 years) with AP at predefined intervals: hospitalization (enrollment), 3 months, and 12 months post-AP. Symptoms were evaluated using a 15-item tracker, including abdominal symptoms, stool characteristics, and activities of daily living, higher scores indicating greater symptom burden (range 0-45). Exocrine function was assessed with fecal elastase-1 (FE-1) levels.

GI symptoms were collected in 97 participants with 12-month follow-up. The median (interquartile range) GI-symptom score was 7 (3-12) with 55 participants (57%) experiencing at least one symptom frequently (often or almost always). In multivariable linear regression, younger age, lower Charlson Comorbidity Index, smoking, recurrent AP, and alcoholic or idiopathic etiologies were associated with significantly higher GI-symptom burden at 12 months. A significant negative correlation was found between GI symptoms and FE-1 levels during hospitalization ( ρ = -0.288; P = 0.015) and at 12 months ( ρ = -0.219; P = 0.046). Eighteen participants (18.6%) lost ≥10% body weight between hospitalization and 12 months, and had significantly lower median FE-1 levels at 12 months compared with the group without weight loss (166 vs 332 µg/g, P = 0.016).

This is the first study to prospectively assess GI-symptom burden and exocrine function post-AP. Lower exocrine pancreatic function at 12 months was associated with increased symptom burden and weight loss. These findings support further investigations to define and improve patient-reported outcomes post-AP. This study is registered with ClinicalTrials.gov , NCT03063398.

Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children.

This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15.

A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74.

In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.

Exocrine Pancreatic insufficiency (EPI) occurs following acute pancreatitis (AP) at variably reported rates and with unclear recovery timeline. The aim of this study was to establish the prevalence and predictors of EPI at 12 months after AP in a prospective cohort.

In this prospective, multicentre, longitudinal cohort study, adult participants (≥18 years) admitted to the hospital with an AP attack (defined by Revised Atlanta Classification) were enrolled in a United States multi-centre longitudinal cohort (Sites: The Ohio State University, University of Pittsburgh, and Johns Hopkins University). Patients were excluded if they had pancreatic cancer, chronic pancreatitis, or malabsorptive disease (including previously diagnosed EPI). Participant data was obtained by interview and by review of the electronic medical record. EPI was assessed by stool fecal elastase (FE-1) levels collected at baseline, 3 months, and 12 months (primary endpoint). EPI was defined by FE-1 <200 μg/g; severe FE-1 level ≤100 μg/g; mild FE-1 101-200 μg/g. Multivariable logistic regression was used to identify predictors of EPI at 12 months. This study is registered with ClinicalTrials.gov, NCT03063398.

EPI was observed in 29 (34.1%) of the 85 participants [44 (51.8%) male, mean age 54.7 ± 14.1 years] who provided stool samples at 12 months. For the study overall, participants were recruited between June 22, 2017 and October 18, 2021. A total of 5794 individuals were screened, 311 of whom were eligible for the study. 112 participants provided stool samples at baseline, 79 completed stool samples at 3 months, and 85 completed samples at 12 months. 64 participants included samples at all 3 timepoints. In univariable analysis, factors significantly associated with EPI at 12 months included recurrent (versus index) AP, pre-existing diabetes, alcohol, and idiopathic etiologies, and increasing severity of AP. In multivariable analysis, the odds of having EPI at 12 months increased 4-fold with idiopathic AP etiology (Odds Ratio 4.095, 95% Confidence Interval [CI] 1.418, 11.826), and 3-fold with moderately severe or severe AP (Odds Ratio 3.166, 95% CI 1.156, 8.670), and baseline diabetes mellitus (Odds Ratio 3.217, 95% CI 1.113, 9.298). Even individuals with an index mild attack of AP (n = 39) developed severe EPI at 12 months (prevalence 12.8%).

EPI as diagnosed by FE-1 is present in over one third of prospectively assessed patients at 12 months post-AP. Since EPI develops in patients with mild AP, investigations are needed to understand the mechanisms of injury and identify methods for tailored screening.

This study was supported by an Investigator Initiated Research Grant from AbbVie, Inc.

Diabetes mellitus (DM) is relatively common following acute pancreatitis (AP), even after mild acute pancreatitis (MAP), the most frequent AP presentation, in which there is no overt beta cell injury. Post-AP related diabetes is widely misdiagnosed, resulting in potentially inappropriate treatment and worse outcomes than type 2 diabetes (T2D). Thus, it is important to understand risk across the spectrum of AP severity.

Biological mechanisms are unclear and may include local and systemic inflammation leading to beta cell dysfunction and insulin resistance, altered gut barrier and/or gut peptides and possibly islet autoimmunity, though no studies have specifically focused on MAP. While studies examining clinical risk factors on MAP exclusively are lacking, there are studies which include MAP. These studies vary in scientific rigor, approaches to rule out preexisting diabetes, variable AP severity, diagnostic testing methods, and duration of follow-up. Overall, disease related factors, including AP severity, as well as established T2D risk factors are reported to contribute to the risk for DM following AP.

Though numerous studies have explored risk factors for DM after AP, few studies specifically focused on MAP, highlighting a key knowledge gap that is relevant to the majority of patients with AP.

Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps.

Pancreatic surgery units undertake several complex operations, albeit with considerable morbidity and mortality, as is the case for the management of complicated acute pancreatitis or chronic pancreatitis. The centralisation of pancreatic surgery services, with the development of designated large-volume centres, has contributed to significantly improved outcomes. In this editorial, we discuss the complex associations between diabetes mellitus (DM) and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis, highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services. Type 3c pancreatogenic DM, refers to DM developing in the setting of exocrine pancreatic disease, and its identification and management can be challenging, while the glycaemic control of such patients may affect their course of treatment and outcome. Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period. The incidence of new onset diabetes after pancreatic resection is widely variable in the literature, and depends on the type and extent of pancreatic resection, as is the case with pancreatic parenchymal loss in the context of severe pancreatitis. Early involvement of a specialist diabetes team is essential to ensure a holistic management. In the current era, large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery, with inclusion of provisions for optimisation of the perioperative glycaemic control, to improve outcomes. While various guidelines are available to aid perioperative management of DM, auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement. The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined, a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis. Therefore, pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams. With the ongoing accumulation of evidence, it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.