Pancreatic Diabetes Research Articles

Novel Insights into Postoperative Surveillance in Resected Pancreatic Cystic Neoplasms-A Review.

Pancreatic cystic lesions (PCL) are frequently encountered in clinical practice and some are referred to surgery due to their neoplastic risk or malignant transformation. The management of PCL involves complex decision-making, with postoperative surveillance being a key component for long-term outcomes, due to the potential for recurrence and postoperative morbidity. Unfortunately, the follow-up of resected patients is far from being optimal and there is a lack of consensus on recommendations with regard to timing and methods of surveillance. Here, we summarize the current knowledge on the postoperative surveillance of neoplastic pancreatic cysts, focusing on the mechanisms and risk factors for recurrence, the recurrence rates according to the initial indication for surgery, the final result of the surgical specimen and neoplastic risk in the remaining pancreas, as well as the postsurgical morbidity comprising pancreatic exocrine insufficiency, metabolic dysfunction and diabetes after resection, according to the type of surgery performed. We analyze postsurgical recurrence rates and morbidity profiles, as influenced by different surgical techniques, to better delineate at-risk patients, and highlight the need for tailored surveillance strategies adapted to preoperative and operative factors with an impact on outcomes.

Fibrocalculous Pancreatic Diabetes in a Bangladeshi Girl

Fibrocalculous pancreatic diabetes (FCPD) is atypical but unique variety of diabetes, in which chronic inflammation and pancreatic calcification lead to exocrine and endocrine failure of the pancreas, primarily occurs in tropical countries. At an early age, these diabetic children are at risk of developing disabling and life-threatening complications, putting a major human and economic burden on families and societies. Here, authors report a case of young female patient presenting with the clinical features of FCPD. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 89-91

Difference in impact of flash glucose monitoring in patients with type 1 diabetes mellitus and pancreatogenic diabetes

Difference in impact of flash glucose monitoring in patients with type 1 diabetes mellitus and pancreatogenic diabetes

Clinical characteristics, management and psychological outcomes of patients with diabetes secondary to chronic pancreatitis

Abstract Aims: To determine the clinical characteristics, management, rates of complications and psychological outcomes of patients with diabetes mellitus secondary to chronic pancreatitis (DMsCP) referred to the Belfast Pancreatic Diabetes Clinic.Methods: Clinical and laboratory data were obtained from online health care records (NIECR). Psychological outcomes and a service‐based questionnaire were performed.Results: Baseline characteristics (n=63 patients [male: 41, female: 22]) at initial referral included: mean age 56.2 years (range 19–84); mean duration of chronic pancreatitis 10.7 years (range 1–40); mean duration of diabetes 7.2 years (range 1–40). Previous pancreatic surgery was performed in 19% (12/63) of patients. Initial mean HbA1c was 82mmol/mol (range 41–189); mean HbA1c at six and 12 months follow‐up was 69.9mmol/mol and 70.6mmol/mol, respectively. Rates of microvascular complications included: retinopathy (background and pre‐proliferative) 16%; microalbuminuria 17%; peripheral neuropathy 14%, with no foot ulceration/amputation occurring. Macrovascular disease occurred in 24% of patients. Sixteen (25%) had missed at least one outpatient diabetes appointment over the preceding year. Quality of life (QoL) as measured by the PANQOLI was low with a mean total score of 64.9/103; 59% (16/27) of the service cohort also breached clinical cut‐offs for the presence of both anxiety (GAD‐7) and depression (PHQ‐9).Summary: DMsCP in our cohort was characterised by significant micro‐ and macrovascular complications, sub‐optimal glycaemic control, reduced clinic attendance and impaired QoL as well as a significant component of anxiety and depression. The optimal care for these patients should consist of a collaborative approach that best meets their complex and multifaceted needs. Copyright © 2024 John Wiley & Sons.

A study on fibro-calculous pancreatic diabetes conducted in a tertiary medical institution in Northern Bihar

Fibro-calculous pancreatic diabetes (FCPD), which is seen in tropical areas and is caused by idiopathic nonalcoholic chronic pancreatitis, is characterized by pancreatic calcification and stomach pain. One female patient and nine male patients were identified as having FCPD. Half of the patients were under 30 years old, with an average age of 28.44±7.07. Seven individuals had diabetes for a shorter period of time than five years. Four patients reported with problems related to various infections, while six patients had osmotic complaints due to uncontrolled diabetes. With a mean waist-hip ratio of 0.89 and a mean BMI of 19.42, all of the patients were thinly built. With mean FBS of 231 mg/dl, PPBS of 469 mg/dl, and HbA1c of 11.96, all patients had uncontrolled diabetes. Microvascular issues affected 30% of the patients, while none of the patients experienced macrovascular complications. A rare type of secondary diabetes called FCPD is becoming more widespread in northern states like Bihar.

Autologous Pancreatic Islet Cell Transplantation Following Pancreatectomy for Pancreas Diseases Other Than Chronic Pancreatitis: A 15-y Study of the Milan Protocol.

Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis. This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes. Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms. These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis.

Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

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.

Potential of Clitoria ternatea L. Extract Towards Insulin Receptor Expression and Marker of Inflammation in Diabetes Mellitus Rats Model

Metabolic abnormalities caused by the accumulation of human, environmental, genetic and lifestyle variables can be found in diabetes mellitus (DM). An increase in blood glucose carried on by a reduction in insulin production can also result in DM. Insulin resistance often occurs as a result of obesity and a lack of physical activity and aging. Telang flower extract (Clitoria ternatea L.) is reported to have several qualities such as being able to treat DM, chronic bronchitis, goiter, mucosal disorders and leprosy. This study’s objective was to elucidate anti-dibetic effect of C. ternatea extract (CTE) in rats with diabetic complications related to dyslipidemia. Rats suffering from diabetes will be examined after being given oral doses of Simvastatin 0.9 mg/kg BW, Glibenclamide 0.45 mg/kg BW, and 200, 400, and 800 mg/kg BW CTE, model induced by streptozotocin. The expression of the insulin gene (INS-1) was investigated by qRTPCR, Tumor Necrosis Factor-α (TNF-α), and Interleukin-1β (IL-1β) pancreatic DM rats model using the Immunohistochemistry (IHC) test. Both descriptive and quantitative data were acquired for the data. After utilizing ANOVA to evaluate quantitative data, the Tukey post hoc test was used to analyze the data, the expression of TNF-α and IL-1β was found to decrease while INS-1 expression increased in response to CTE. This effect was attributed to the modulation of TNF-α, IL-1β, and INS-1 expression. These findings suggest that CTE possesses antidiabetic properties.

Enhancing outcome prediction by applying the 2019 WHO DM classification to adults with hyperglycemic crises: A single-center cohort in Thailand

Background and aimsHyperglycemic crisis is a metabolic catastrophe which can occur in any type of diabetes. In 2019, the World Health Organization (WHO) revised the classification of diabetes mellitus (DM) and established two new hybrid forms, latent autoimmune diabetes in adults (LADA) and ketosis-prone type 2 diabetes (T2D). This study aimed to determine clinical outcomes after a hyperglycemic crisis event in people with diabetes classified subtypes by 2019 WHO DM classification. MethodsA five-year (2015–2019) retrospective study of adult patients admitted with hyperglycemic crises was conducted. Types of diabetes were recategorized based on the 2019 WHO DM classification. Clinical characteristics, in-admission treatment and complications, long-term follow-up outcomes, and mortality were collected, analyzed, and compared. ResultsA total of 185 admissions occurred in 136 patients. The mean age was 50.6 ± 18.4 years (49.3 % men). The annual average incidence of hyperglycemic crises was 5.2 events/1000 persons. The proportion of type 1 diabetes, T2D, LADA, ketosis-prone T2D, and pancreatic DM were 15.4 %, 69.1 %, 2.2 %, 11 %, and 2.2 %, respectively. In-hospital mortality was 3.7 % while cumulative mortality totaled 19.1 %. During the 24-month follow-up, ketosis-prone T2D had the highest success of insulin discontinuation (HR 6.59; 95 % CI 6.69–319.4; p < 0.001), while T2D demonstrated the highest mortality compared to others (HR, 2.89; 95%CI 1.15–6.27; p = 0.02). ConclusionThe reclassification of diabetes based on 2019 WHO DM classification helped elucidate differences in long-term outcomes and mortality among DM types. The new classification, which separates ketosis-prone T2D from standard T2D, should be encouraged in clinical practice for precise and individualized management.

Abstract 6692: Intermittent fasting-remodeled gut microbiota improves anti-tumor immunity in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) has become the third leading cause of cancer-related death in the United States with high resistance to therapies, presentation at late stages and aggressive biology. Immunotherapy has revolutionized cancer therapy by offering survival benefit in many solid malignancies, however, it is still not effective in pancreatic cancer. Host factors are crucial modulators of responses to immunotherapy. The roles of gut microbiome in modulating the immune system and determining cancer outcomes have been well established. Eating patterns can alter the gut microbiota and metabolic output, both of which affect anti-tumor immune responses. Intermittent fasting (IF), a form of dietary restriction which is characterized by limited feeding with unlimited calorie consumption during a certain time window. IF has been shown to affect gut microbiota composition, modulate immunity, and metabolic processes. Despite the well-known beneficial role of fasting in pancreatic conditions, including pancreatitis and diabetes, its effect in the treatment of pancreatic cancer has not been explored. Our study found that IF reverses immunotherapy resistance in PDAC. IF can reshape gut microbiota composition and reprogram the metabolism of host. We found that IF improves anti-tumor immunity through modulating gut microbiota. Depletion of gut microbiota can abrogate the beneficial effect of IF on anti-tumor response, while fecal microbiota transplantation from mice exposed to IF can sensitize the anti-tumor effects of immunotherapy. Using 16S rRNA sequencing, metabolic profiling and transcriptomic sequencing, our findings elucidate the mechanism of IF-remodeled gut bacteria influencing metabolic molecules which drive immune cells activation. Our study suggests that IF-based interventions have potential utility for the prevention and treatment of PDAC. Citation Format: Le Li, Vidhi Chandra, Olivereen Le Roux, Rian Morgan Howell, Virginia Tahan, Nagireddy Putluri, Joseph Petrosino, Arun Sreekumar, Jay K. Kolls, James White, Florencia McAllister. Intermittent fasting-remodeled gut microbiota improves anti-tumor immunity in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6692.

Pancreatitis in cystic fibrosis: Presentation, medical and surgical management, and the impact of modulator therapies.

Patients with Cystic Fibrosis (CF) are at increased risk of acute (AP) and chronic (CP) pancreatitis, and their complications. The extent of remaining healthy pancreatic parenchyma determines the risk of developing future episodes of pancreatitis, as well as pancreatic exocrine or endocrine insufficiency. Pancreatitis may be the presenting symptom of CF, and genetic testing is especially important in pediatrics. AP and recurrent AP are managed with intravenous fluid hydration and pain control, in addition to early refeeding and treatment of complications. With the use of modulator therapy in CF, pancreatic function may be restored to some extent. CP related pain is managed with analgesics and neuromodulators, with surgery if indicated in specific situations including TPIAT as a possible type of surgical intervention. Long-term sequelae of CP in patients with CF include exocrine pancreatic insufficiency treated with pancreatic enzyme replacement therapy, fat-soluble vitamin deficiencies and associated metabolic complications such as bone disease/osteoporosis, pancreatogenic diabetes, and less commonly, pancreatic cancer. We review the presentation and etiologies of pancreatitis in CF patients as well as the management of AP and CP primarily in children.

Use of the Guardian Connect glycemic monitoring system in patients after total duodenopancreatectomy in the early postoperative period on intravenous insulin therapy

BACKGROUND: Among different subtypes of pancreatogenic diabetes mellitus the biggest difficulties of glycemic control arise in patients after total duodenopancreatectomy (TDPE), first of all due to the presence of absolute insulin insufficiency.AIM: Estimating safety and cost-effectiveness Guardian Connect CGM system in early postoperative period in hospitalized patients after TDPE on continuous intravenous insulin therapy (CIVIT).MATERIALS AND METHODS: Glucose measurement results of 26 patients in early postoperative period after TDPE were analyzed. In 12 of them, we used Guardian Connect CGM system. In this group 43 cycles (1 cycle — 6 days, 258 days total) of CGM and 971 glucometer measurements used for CGM calibration were analyzed; in other 14 patients in whom only glucometer was used we analyzed 2496 glycemic values.Cost-effectiveness was calculated over 6 days for CGM and only glucometer use (including cost of CGM, glucometers, disposable materials, clinic wage-costs to medical staff for time required for glucose control).RESULTS: Glucose levels of group #1 were in the target range 5.6 to 10.0 mmol/L (66.7 vs 61.2%, p=0.003) and the range 4.3–11.6 mmol/L (85.2% vs 82.2%, p=0.038) more than in comparison with group #2.The frequency of hypoglycemic episodes (&lt;3.9 mmol/L) was statistically significantly lower in the CGM group (6 vs 54, p&lt;0.001, RO 8.463 [3.579; 20.015], RR 1.746 [1.551; 1.966]).Cost analysis of glucose control using Guardian Connect CGM system for one cycle (6 days) and cost of glucose control using glucose meter for the same period showed that using Guardian Connect CGM system in patients after TDPE on intravenous insulin therapy reduced clinic costs by 21.7% in ICU and by 25.7% in the hospital department.CONCLUSION: Guardian Connect CGM have demonstrated its safety and cost-effectiveness during glucose control in patients in early postoperative period after TDPE on CIVIT.

Exploring the role of TLK2 mutation in tropical calcific pancreatitis: an in silico and molecular dynamics simulation study

Tropical calcific pancreatitis (TCP) is a juvenile form of non-alcoholic chronic pancreatitis seen exclusively in tropical countries. The disease poses a high risk of complications, including pancreatic diabetes and cancer, leading to significant mortality due to poor diagnosis and ineffective treatments. This study employed whole exome sequencing (WES) of 5 TCP patient samples to identify genetic variants associated with TCP. Advanced computational techniques were used to gain atomic-level insights into disease progression, including microsecond-scale long MD simulations and essential dynamics. In silico virtual screening was performed to identify potential therapeutic compounds targeting the mutant protein using the Asinex and DrugBank compound library. WES analysis predicted several single nucleotide variants (SNVs) associated with TCP, including a novel missense variant (c.T1802A or p.V601E) in the TLK2 gene. Computational analysis revealed that the p.V601E mutation significantly affected the structure of the TLK2 kinase domain and its conformational dynamics, altering the interaction profile between ATP and the binding pocket. These changes could impact TLK2's kinase activity and functions, potentially correlating with TCP progression. Promising lead compounds that selectively bind to the TLK2 mutant protein were identified, offering potential for therapeutic interventions in TCP. These findings hold great potential for future research. Communicated by Ramaswamy H. Sarma

Inhibition of Toll-like Receptor 4 Using Small Molecule, TAK-242, Protects Islets from Innate Immune Responses.

Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers. Using in vitro models, we investigate how targeting TLR4 mitigates islet damage and immune cell activation during the peritransplant period. The results of this study support the application of TAK-242 as a therapeutic agent to reduce inflammatory and innate immune responses to islets immediately following transplantation into the hepatic portal vein. Therefore, TLR4 may serve as a target to improve islet transplant outcomes in the future.

Association Between Pancreatic Cysts and Diabetes Mellitus in Von Hippel-Lindau Disease.

Pancreatic cysts are frequently observed in patients with von Hippel-Lindau disease (VHL), and they are considered clinically not important. This study aimed to evaluate the association between pancreatic cysts and diabetes mellitus (DM) in patients with VHL. Among patients who were on a patient list at the VHL Center at Kyoto University Hospital as of December 2022, those who had undergone an upper abdominal magnetic resonance imaging study after 2010 were retrospectively evaluated. The presence or absence of DM and high glycated hemoglobin (HbA1c) levels (>6.0%) were assessed. Patients were divided into two groups: those with DM or high HbA1c levels, and those without DM or high HbA1c levels. The area of the whole pancreas, including the pancreatic cysts and tumors, the area of the pancreatic cysts, and the percentage of pancreatic cysts, calculated by dividing the area of pancreatic cysts by the area of the whole pancreas, were measured on T2-weighted magnetic resonance images and compared between the two groups. Thirty-six patients with VHL, comprising 22 men and 14 women, with a mean age of 36.4 years (range, 11-79 years), were identified. Seven patients had DM, and two additional patients had high HbA1c levels. The area of the pancreatic cysts (p = 0.0013) was significantly larger and the percentage of the pancreatic cysts (p = 0.0016) was significantly higher in patients with DM or high HbA1c levels (n = 9) than in patients without DM or high HbA1c levels (n = 27); however, the difference in the area of the whole pancreas was not significant (p = 0.068). Our findings suggest that patients with VHL who have a large area covered by pancreatic cysts are more likely to have DM than those without.

Interactions between the Exocrine and the Endocrine Pancreas.

The pancreas has two main functions: to produce and secrete digestive enzymes (exocrine function) and to produce hormones that regulate blood glucose and splanchnic secretion (endocrine function). The endocrine and exocrine portions of the pancreas are central regulators in digestion and metabolism, with continuous crosstalk between their deeply interconnected components, which plays a role in disease. Pancreatic neoplasms, inflammation, trauma, and surgery can lead to the development of type 3c diabetes when an insult simultaneously damages both acini and islets, leading to exocrine and endocrine dysfunction. In diabetes mellitus patients, pancreatic exocrine insufficiency is highly prevalent, yet little is known about the associations between diabetes mellitus and pancreatic exocrine function. This review aims to provide an overview of the physiology of the pancreas, summarize the pathophysiology and diagnostic work-up of pancreatic exocrine insufficiency, and explore the relationships between exocrine pancreatic insufficiency and diabetes mellitus.

A313 DISCONNECTED PANCREATIC DUCT SYNDROME: A RETROSPECTIVE OBSERVATIONAL STUDY REVIEWING AN IMPORTANT BUT OVERLOOKED COMPLICATION OF NECROTIZING PANCREATITIS

Abstract Background Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis (ANP) characterized by a complete disruption of the main pancreatic duct, leading to the loss of continuity between the pancreatic duct and the gastrointestinal tract (figure 1). Due to unopposed leakage of residual pancreatic fluid, patients with DPDS often experience a prolonged disease course with significant morbidity, including complications such as pancreatic fistulas. However, information about the epidemiology, clinical characteristics, and outcomes of DPDS remains scarce. Aims To assess clinical outcomes, diagnostic delay, burden of endoscopic and surgical interventions, and complications related to DPDS. Methods A retrospective review was conducted for all patients diagnosed with DPDS who underwent either endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) at our tertiary center between January 2010 and December 2022. Results Fifteen patients with DPDS following ANP were identified. The median age of patients at DPDS diagnosis was 56 years (range 33-86 years), with 47% being female. The most common etiology of ANP was biliary (40%), followed by idiopathic (33%) and alcoholic (27%). The median time between ANP diagnosis and DPDS diagnosis was 265 days (range 86-2023 days). Patients underwent a median of 3 (1-9) endoscopic interventions and 1 (0-5) surgical intervention between the initial ANP episode and DPDS diagnosis. 40% of patients experienced intra-abdominal sepsis secondary to infected pancreatic fluid collections. 20% developed pancreatic fistulas (two small bowel fistulas and one cutaneous fistula). 20% developed new-onset diabetes, and 13% had significant worsening of pre-existing diabetes. No mortalities were reported. Conclusions There is a significant delay in diagnosing DPDS following ANP, and a substantial burden of endoscopic interventions is required. Frequent complications of DPDS were pancreatic fistulas, recurrent pancreatic fluid collections, and pancreatogenic diabetes. Developing a predictive model for assessing the risk of DPDS development following ANP could aid in earlier diagnosis and potentially reduce morbidity and complications associated with DPDS. Figure 1. Contrast enhanced CT demonstrating typical finding in DPDS in coronal (A) and axial (B) views. CT demonstrates 3cm area of necrosis involving pancreatic neck/body (asterisk) with viable upstream parenchyma in the remainder of the body and tail (white arrow). Pancreatic head/uncinate parenchyma and main duct appear intact (black arrow). B, the distal pancreatic duct is not dilated. DPDS, disconnected pancreatic duct syndrome. Funding Agencies None

Pancreatic enzyme replacement therapy in subjects with exocrine pancreatic insufficiency and diabetes mellitus: a real-life, case–control study

BackgroundExocrine 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.MethodsIn 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).Results48 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.ConclusionsPERT 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

Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.

In Type 1 and Type 2 diabetes, pancreatic β-cell survival and function are impaired. Additional etiologies of diabetes include dysfunction in insulin-sensing hepatic, muscle, and adipose tissues as well as immune cells. An important determinant of metabolic health across these various tissues is mitochondria function and structure. This review focuses on the role of mitochondria in diabetes pathogenesis, with a specific emphasis on pancreatic β-cells. These dynamic organelles are obligate for β-cell survival, function, replication, insulin production, and control over insulin release. Therefore, it is not surprising that mitochondria are severely defective in diabetic contexts. Mitochondrial dysfunction poses challenges to assess in cause-effect studies, prompting us to assemble and deliberate the evidence for mitochondria dysfunction as a cause or consequence of diabetes. Understanding the precise molecular mechanisms underlying mitochondrial dysfunction in diabetes and identifying therapeutic strategies to restore mitochondrial homeostasis and enhance β-cell function are active and expanding areas of research. In summary, this review examines the multidimensional role of mitochondria in diabetes, focusing on pancreatic β-cells and highlighting the significance of mitochondrial metabolism, bioenergetics, calcium, dynamics, and mitophagy in the pathophysiology of diabetes. We describe the effects of diabetes-related gluco/lipotoxic, oxidative and inflammation stress on β-cell mitochondria, as well as the role played by mitochondria on the pathologic outcomes of these stress paradigms. By examining these aspects, we provide updated insights and highlight areas where further research is required for a deeper molecular understanding of the role of mitochondria in β-cells and diabetes.

A noteworthy rarity: fibrocalculous pancreatic diabetes as an uncommon aetiology of diabetes

No abstract available