BACKGROUND: Exocrine pancreatic insufficiency (EPI) can be associated with all types of diabetes. Pancreatic enzyme replacement therapy (PERT) has short and long-term benefits in subjects with EPI, but its effects on diabetes control are uncertain. We aimed to study the effects of PERT initiation on glycemic control in subjects with diabetes and EPI from any cause.
METHODS: In this retrospective study, we compared subjects with EPI and diabetes who were prescribed PERT with subjects with diabetes who had a fecal elastase-1 concentration dosage, but did not receive PERT. The primary outcome was the effect of PERT on hypoglycemia frequency and severity. The secondary outcomes were the effects of PERT on gastro-intestinal disorders, HbA1c and body mass index (BMI).
RESULTS: 48 subjects were included in each group. Overall, PERT did not have any significant effect on hypoglycemia frequency or severity, but hypoglycemia frequency tended to decrease in subjects with chronic pancreatitis. While 19% of subjects experienced mild hyperglycemia after PERT initiation, we did not report any keto-acidosis or any other severe adverse event. Gastro-intestinal disorders improved in 80% of subjects treated with PERT, versus in 20% of control subjects (p = 0.02). Gastro-intestinal disorders improved in 87% of subjects with recommended dosage of PERT, versus in 50% of subjects with underdosage (NS). HbA1c and BMI evolution did not differ between the groups.
CONCLUSIONS: PERT initiation is safe in subjects with diabetes and EPI. It does not globally decrease hypoglycemia severity of frequency, but is associated with a decrease in gastro-intestinal disorders. Trial registration Retrospectively registered. The database was registered with the Commission Nationale Informatique et Libertés (CNIL), registration number: 2203351v0. The study was approved by the local ethics committee CLEP, registration number: AAA-2023-09047.

OBJECTIVE: Studies of a rare homozygous missense mutation identified in two brothers diagnosed with congenital pancreatic lipase deficiency (CPLD) provided the first definitive evidence linking CPLD with missense mutations in the gene of PNLIP. Herein, we investigated the molecular basis for the loss-of-function in the three novel PNLIP variants (c.305G > A, p.(W102∗); c.562C > T, p.(R188C); and c.1257G > A, p.(W419∗)) associated with CPLD.
METHODS: We characterized three novel PNLIP variants in transfected cells by assessing their secretion, intracellular distribution, and markers of endoplasmic reticulum (ER) stress.
RESULTS: All three variants had secretion defects. Notably, the p.R188C and p.W419∗ variants induced misfolding of PNLIP and accumulated as detergent-insoluble aggregates resulting in elevated BiP at both protein and mRNA levels indicating increased ER stress.
CONCLUSIONS: All three novel PNLIP variants cause a loss-of-function through impaired secretion. Additionally, the p.R188C and p.W419∗ variants may induce proteotoxicity through misfolding and potentially increase the risk for pancreatic acinar cell injury.

OBJECTIVE: We evaluated exocrine pancreas functions using a noninvasive indicator in a case-control study conducted on children and adolescents diagnosed with type 1 diabetes mellitus.
METHODS: Sixty-seven patients who participated in a summer camp were enrolled in this study. Nineteen healthy children in the same age group were assigned to the control group. Fecal pancreatic elastase was assayed using the enzyme-linked immunosorbent assay technique. Values higher than 200 µg/g were considered an indication of sufficient exocrine pancreatic functioning, values between 100 µg/g and 200 µg/g were considered mild exocrine pancreatic insufficiency, and values below 100 µg/g were considered severe exocrine pancreatic insufficiency.
RESULTS: The mean concentration of fecal elastase was 158.38 ± 59.67 µg/g. The patients were assigned to three groups according to these values. Thirteen patients (22%) had sufficient fecal elastase levels, whereas 36 patients (62%) had mildly insufficient levels, and nine patients (16%) had severely insufficient fecal elastase concentrations. The levels of fecal elastase, amylase, lipase, and zinc were significantly different between the patients and controls (p < 0.001). Only the duration of diabetes was significantly different between patients with different severities of exocrine pancreatic insufficiency (p = 0.037). Additionally, the group with severe pancreatic insufficiency had more frequent hypoglycemic attacks.
CONCLUSIONS: Exocrine pancreatic insufficiency may develop in children with diabetes, and hypoglycemia attacks are observed more frequently depending on the severity of pancreatic insufficiency.

The data on exocrine pancreatic insufficiency (EPI) following gastric resectional surgery is variable, ranging from 26% to as high as 100%. This study aimed to document symptomatic EPI following gastric resectional surgery and to objectively document EPI, by fecal elastase (FE) testing. This was a cross-sectional study among patients undergoing gastric resection for adenocarcinoma of the stomach, at the Upper Gastrointestinal Surgical Unit at the Christian Medical College Hospital, Vellore, India. A detailed questionnaire was administered to the patients in the postoperative period, to evaluate clinical symptoms of EPI. Further, study participants were tested for FE pre- and postoperatively. Of the 60 patients in this study, the postoperative questionnaire administered to all patients during follow up. None showed symptoms suggestive of EPI. Pre- and post-operative FE testing were feasible in 27 of the 60 patients, which showed a 33% incidence of EPI. None of the patients had clinical symptoms of EPI, following gastric resectional surgery, on short-term follow-up. However, more than a third of the patients tested developed asymptomatic EPI after gastric resectional surgery, based on FE testing. This may be explained by the fact that in the early postoperative period, EPI following gastric resectional surgery perhaps has a mild, subclinical presentation. Therefore routine pancreatic supplementation after gastric resectional surgery may not be necessary. However, one needs to carefully look for worsening of symptoms of EPI on long-term follow-up, which may necessitate appropriate investigations followed by pancreatic enzyme replacement therapy.

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Exocrine pancreatic insufficiency (EPI), which leads to malabsorption and poor weight gain, is seen in 85% of patients with cystic fibrosis (CF). EPI is treated with pancreatic enzyme replacement therapy taken with each meal. The highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator, ivacaftor, restores CFTR function in patients with responsive mutations. It is a widely held view that EPI in CF is irreversible due to the complete destruction of pancreatic ducts and acinar cells. We describe three pediatric CF patients with EPI who were started on ivacaftor, and subsequently showed evidence of restored exocrine pancreatic function with clinical and biochemical parameters.

We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at-risk children with a first-degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study.
Fecal elastase-1 (FE-1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty-eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody-negative children (non-progressors) followed similarly were age and gender-matched with the progressors. An adjusted linear mixed model compared FE-1 concentrations in progressors and non-progressors.
Baseline FE-1 did not differ between progressors and non-progressors, or by HLA DR type or proband status. FE-1 decreased over time in progressors in comparison to non-progressors (Wald statistic 5.46, P = .02); in some progressors the fall in FE-1 preceded the onset of IA.
Pancreatic exocrine function decreases in the majority of young at-risk children who progress to IA and T1D.

Type 1 and type 2 diabetes are often accompanied by mostly mild forms of exocrine pancreatic insufficiency. Despite high prevalence, little is known about the clinical consequences of exocrine pancreatic insufficiency and its optimal (nutritional) treatment. Even less is known if and to what extent exocrine pancreas insufficiency also affects glycemic control in diabetes. This article aims for summarizing current clinical knowledge on screening, diagnosis, and treatment and gives an overview on the pathophysiology of exocrine pancreatic insufficiency in diabetes.
Recent studies reveal novel insights into the close interaction of acinar, ductal, and endocrine cells and the gut-pancreas axis. Exocrine pancreatic insufficiency is a clinically relevant, frequent but poorly understood disorder in both type 1 and type 2 diabetes.

BACKGROUND: Bariatric surgery is the most effective treatment modality in morbidly obese patients. Compared to Roux-en Y gastric bypass (RYGB), sleeve gastrectomy (SG) has better metabolic and nutritional outcomes after surgery. Exocrine pancreatic insufficiency (EPI) can be seen after RYGB but there is not any knowledge about EPI-SG association.
OBJECTIVE: To assess exocrine pancreatic functions before and after the SG procedure.
METHODS: This is a single-center, prospective and case-control study. Forty morbidly obese patients were included in the study. Their pre-operative and post-operative, third month fecal samples were collected. Exocrine pancreatic insufficiency was determined by using fecal elastase-1 and diagnosed when fecal elastase-1 levels were < 200 μg/g.
RESULTS: The mean fecal elastase-1 level was 256.25 ±137.16 μg/g and the mean post-surgical fecal elastase-1 level was 437.7 ±212.43 μg/g (p = 0.001). In the pre-operative period, half of patients had FE levels under 200 μg/g. In the third month after surgery, only 4 patients had fecal elastase-1 levels under 200 μg/g. Comparison of fecal elastase-1 between pre-surgery and post-surgery revealed a significant difference (p = 0.001).
CONCLUSIONS: This is the first study to investigate EPI-SG association. Surgery-associated morbidity and mortality are the leading limitations of bariatric surgery procedures. Exocrine pancreatic insufficiency is one of them; prior studies demonstrate its increased frequency after RYGB. Our study revealed that SG relieves exocrine pancreatic insufficiency.

The exocrine structure is significantly affected by diabetes because of endocrine structure-function disorder within the pancreas. Exocrine pancreatic dysfunction (EPD) is the general name of the malabsorption process resulting from inadequate production, release, decreased activation, and/or insufficient degradation of enzymes required for digestion from pancreatic acinar cells. It is important to diagnose patients early and correctly, since there may be both macro- and micro-nutrient deficiency in EPD. In this paper, EPD, the diabetes-EPD relationship, and the predictive, effective factors affecting the emergence of EPD are briefly explained and summarized with contemporary literature and our experienced based on clinical, lab, and radiological findings.