Acute pancreatitis (AP) is an inflammatory reaction of the pancreas. When the disease is severe, it is often accompanied by destruction of the pancreatic islets, resulting in dysfunction of the endocrine system of the pancreas. Stress hyperglycemia is a transient increase in glucose during a critical illness, and its possible mechanism is related to abnormal glucose metabolism and insulin resistance due to the increased release of counterregulatory hormones and cytokines, such as glucagon, cortisol, and catecholamines. Numerous studies have shown that stress hyperglycemia is strongly associated with morbidity, mortality, and increased risk of post-acute pancreatitis diabetes in AP patients. Therefore, stress hyperglycemia may be a significant independent risk factor for poor clinical outcomes and prognosis in patients with AP. This article reviews the clinical features, risk factors, and mechanisms of action of stress hyperglycemia in AP and its influence on adverse clinical outcomes and the prognosis of inpatients with AP. For AP patients with stress hyperglycemia, it is necessary to comprehensively consider their blood glucose levels, daily habits, and complications to develop an appropriate treatment plan for hyperglycemia. Limited evidence indicates that in the case of acute hyperglycemia in critically ill patients, especially during the first 3 days of hospitalization, insulin therapy should not be undertaken if the blood glucose level does not exceed 10 mmol/L. However, some important questions related to clinical practice remain to be answered. More clinical trials and studies are needed in the future to provide a sufficient basis for clinical practice.

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.

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.

Diverse animal models have been used to study postpancreatitis diabetes mellitus (PPDM) development; however, no study has yet conducted a comparative analysis of the specific differences in glucose homeostasis and islet injury between these models. Therefore, we investigated the differences in pancreatic islet injury and glucose homeostasis among diverse strains in a cerulein-induced acute pancreatitis (AP) model to determine the appropriate animal model for PPDM. BALB/cJ, C57BL/6J, C57BL/6 N, and FVB/NJ mice were administered cerulein to induce AP. Serum amylase levels, pancreatic acinar injury, blood glucose homeostasis, islet function, and islet injury were measured and analyzed. All strains exhibited elevated amylase secretion post pancreatitis, and BALB/cJ, C57BL/6J, and C57BL/6 N mice exhibited sex-related differences. All strains exhibited pancreatic acinar injury post pancreatitis but mostly recovered within 15 days. Overall, glucose homeostasis remained balanced post pancreatitis in all strains compared to that in the control groups, except in FVB/NJ male and female mice, which exhibited an imbalance in glucose homeostasis on day 7 post pancreatitis. All the strains, except BALB/cJ mice, exhibited a decline in Homeostasis model assessment-β(HOMA-β) values post pancreatitis, with significant decrease in C57BL/6J females and FVB/NJ males. Islet size decreased post pancreatitis in all strains, except BALB/cJ mice. Pancreatic islet insulin secretion levels significantly decreased in male FVB/NJ mice post pancreatitis onset and did not recover within 15 days. Therefore, FVB/NJ male mice are a useful model for studying PPDM.

Within 5 years of having acute pancreatitis (AP), approximately 20% of patients develop diabetes mellitus (DM), which later increases to approximately 40%. Some studies suggest that the prevalence of prediabetes (PD) and/or DM can grow as high as 59% over time. However, information on risk factors is limited. We aimed to identify risk factors for developing PD or DM following AP.

We systematically searched three databases up to 4 September 2023 extracting direct, within-study comparisons of risk factors on the rate of new-onset PD and DM in AP patients. When PD and DM event rates could not be separated, we reported results for this composite outcome as PD/DM. Meta-analysis was performed using the random-effects model to calculate pooled odds ratios (OR) with 95% confidence intervals (CI).

Of the 61 studies identified, 50 were included in the meta-analysis, covering 76,797 participants. The studies reported on 79 risk factors, and meta-analysis was feasible for 34 risk factor and outcome pairs. The odds of developing PD/DM was significantly higher after severe and moderately severe AP (OR: 4.32; CI: 1.76-10.60) than mild AP. Hypertriglyceridemic AP etiology (OR: 3.27; CI: 0.17-63.91) and pancreatic necrosis (OR: 5.53; CI: 1.59-19.21) were associated with a higher risk of developing PD/DM. Alcoholic AP etiology (OR: 1.82; CI: 1.09-3.04), organ failure (OR: 3.19; CI: 0.55-18.64), recurrent AP (OR: 1.89; CI: 0.95-3.77), obesity (OR: 1.85; CI: 1.43-2.38), chronic kidney disease (OR: 2.10; CI: 1.85-2.38), liver cirrhosis (OR: 2.48; CI: 0.18-34.25), and dyslipidemia (OR: 1.82; CI: 0.68-4.84) were associated with a higher risk of developing DM.

Severe and moderately severe AP, alcoholic and hypertriglyceridemic etiologies, pancreatic necrosis, organ failure, recurrent acute pancreatitis and comorbidities of obesity, chronic kidney disease liver disease, and dyslipidemia are associated with a higher risk of developing PD or DM.

https://www.crd.york.ac.uk/prospero/, identifier CRD42021281983.

Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.