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Trends in Endocrinology and Metabolism:... Nov 2021The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute... (Review)
Review
The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we take a closer look into potential pathological interactions. We provide an overview of the current knowledge and understanding of SARS-CoV-2 infection of the pancreas with a special focus on pancreatic islets and propose direct, indirect, and systemic mechanisms for pancreas injury as result of the COVID-19-diabetes fatal bidirectional relationship.
Topics: Acinar Cells; Angiotensin-Converting Enzyme 2; COVID-19; Diabetes Mellitus; Glucagon-Secreting Cells; Humans; Insulin-Secreting Cells; Islets of Langerhans; Pancreas; Receptors, Coronavirus; SARS-CoV-2; Serine Endopeptidases; Viral Tropism
PubMed: 34373155
DOI: 10.1016/j.tem.2021.07.004 -
Diabetologia Jul 2023'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This... (Review)
Review
'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This review focuses on 'starting the clock', i.e. the initiation of pre-symptomatic islet autoimmunity/the first appearance of islet autoantibodies. In particular, this review addresses why susceptibility to developing islet autoimmunity is greatest in the first 2 years of life and why beta cells are a frequent target of the immune system during this fertile period. A concept for the development of beta cell autoimmunity in childhood is discussed and three factors are highlighted that contribute to this early predisposition: (1) high beta cell activity and potential vulnerability to stress; (2) high rates of and first exposures to infection; and (3) a heightened immune response, with a propensity for T helper type 1 (Th1) immunity. Arguments are presented that beta cell injury, accompanied by activation of an inflammatory immune response, precedes the initiation of autoimmunity. Finally, the implications for strategies aimed at primary prevention for a world without type 1 diabetes are discussed.
Topics: Female; Humans; Diabetes Mellitus, Type 1; Islets of Langerhans; Autoimmunity; Autoantibodies; Insulin-Secreting Cells; Genetic Predisposition to Disease
PubMed: 37231274
DOI: 10.1007/s00125-023-05927-2 -
Current Opinion in Gastroenterology Sep 2019To review the current management of walled-off pancreatic necrosis (WOPN). (Review)
Review
PURPOSE OF REVIEW
To review the current management of walled-off pancreatic necrosis (WOPN).
RECENT FINDINGS
The management of WOPN has evolved. Many collections do not require intervention and may resolve over time. Nutritional support and treatment of infection are two critical components of medical management. For collections requiring drainage, minimally invasive endoscopic therapies now play a primary role. Endoscopic transmural puncture with stent placement may provide access for drainage and decompression. More complex collections may require transluminal instrumentation with lavage, debridement, and necrosectomy. Concurrent pancreatic duct injuries including strictures, leaks, and disconnections are very common. Addressing the pancreatic ductal injury is a key component in the long-term success of management strategies. Providing high-level care for patients requires a multidisciplinary approach with providers specialized in the management of severe acute pancreatitis and associated complications.
SUMMARY
Minimally invasive management strategies improve the outcomes for patients with WOPN. Close follow-up, medical therapy, and nutritional support are required for most patients. Endoscopic transmural drainage and necrosectomy are the primary approaches for collections requiring intervention. Protocols for endoscopic drainage are being refined to reduce side effects and decrease the number of interventions required for resolution.
Topics: Combined Modality Therapy; Debridement; Drainage; Endoscopy; Humans; Infections; Necrosis; Nutritional Support; Pancreatic Ducts; Pancreatitis, Acute Necrotizing; Stents; Therapeutic Irrigation
PubMed: 31313686
DOI: 10.1097/MOG.0000000000000564 -
Abdominal Radiology (New York) Aug 2022Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic... (Review)
Review
Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.
Topics: Acute Disease; Biopsy; Drainage; Endoscopy, Gastrointestinal; Humans; Pancreas; Pancreatic Ducts; Pancreatitis; Treatment Outcome
PubMed: 34410433
DOI: 10.1007/s00261-021-03244-z -
Nutrition in Clinical Practice :... Oct 2019Nonalcoholic fatty pancreas disease (NAFPD) describes a phenotype of pancreatic steatosis (PS) that is not caused by alcohol consumption, viral infections, toxins, or... (Review)
Review
Nonalcoholic fatty pancreas disease (NAFPD) describes a phenotype of pancreatic steatosis (PS) that is not caused by alcohol consumption, viral infections, toxins, or congenital metabolic syndromes but is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, or increasing age. NAFPD is a relatively new disease entity, as the clinical significance of fatty infiltration of pancreas has gained attention recently. Clinical consequences of NAFPD remain largely unknown despite clinical associations. This review aims to study similarities and differences between hepatic and PS and explore recent advances in NAFPD.
Topics: Humans; Insulin Resistance; Lipid Metabolism Disorders; Malnutrition; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Pancreas; Pancreatic Diseases; Risk Factors
PubMed: 31535735
DOI: 10.1002/ncp.10397 -
Frontiers in Endocrinology 2021Vitamin A (VA), which is stored in several forms in most tissues, is required to maintain metabolite homeostasis and other processes, including the visual cycle, energy... (Review)
Review
Vitamin A (VA), which is stored in several forms in most tissues, is required to maintain metabolite homeostasis and other processes, including the visual cycle, energy balance, epithelial cell integrity, and infection resistance. In recent years, VA molecules, also known as retinoids, have been extensively explored and used in the treatment of skin disorders and immune-related tumors. To date, several observational and interventional studies have explored the relationship between VA status and the pathogenesis of diabetes. In particular, VA micronutrients have been shown to regulate pancreatic development, β-cell function, pancreatic innate immune responses, and pancreatic stellate cells phenotypes through multiple mechanisms. However, there are still many problems to be proven or resolved. In this review, we summarize and discuss recent and available evidence on VA biological metabolism in the pancreas. Analysis of the effects of VA on metabolism in the pancreas will contribute to our understanding of the supportive physiological roles of VA in pancreas protection.
Topics: Animals; Glucose; Homeostasis; Humans; Lipid Metabolism; Pancreas; Vitamin A
PubMed: 33679618
DOI: 10.3389/fendo.2021.620941 -
Islets Jul 2021The link between COVID-19 infection and diabetes has been explored in several studies since the start of the pandemic, with associations between comorbid diabetes and... (Review)
Review
The link between COVID-19 infection and diabetes has been explored in several studies since the start of the pandemic, with associations between comorbid diabetes and poorer prognosis in patients infected with the virus and reports of diabetic ketoacidosis occurring with COVID-19 infection. As such, significant interest has been generated surrounding mechanisms by which the virus may exert effects on the pancreatic β cells. In this review, we consider possible routes by which SARS-CoV-2 may impact β cells. Specifically, we outline data that either support or argue against the idea of direct infection and injury of β cells by SARS-CoV-2. We also discuss β cell damage due to a "bystander" effect in which infection with the virus leads to damage to surrounding tissues that are essential for β cell survival and function, such as the pancreatic microvasculature and exocrine tissue. Studies elucidating the provocation of a cytokine storm following COVID-19 infection and potential impacts of systemic inflammation and increases in insulin resistance on β cells are also reviewed. Finally, we summarize the existing clinical data surrounding diabetes incidence since the start of the COVID-19 pandemic.
Topics: Bystander Effect; COVID-19; Cytokine Release Syndrome; Diabetes Mellitus; Humans; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Pandemics; SARS-CoV-2
PubMed: 33970787
DOI: 10.1080/19382014.2021.1909970 -
The Journal of Clinical Endocrinology... Aug 2023Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet β cells, and genetic and environmental factors are thought to trigger autoimmunity....
Type 1 diabetes (T1D) is usually caused by immune-mediated destruction of islet β cells, and genetic and environmental factors are thought to trigger autoimmunity. Convincing evidence indicates that viruses are associated with T1D development and progression. During the COVID-19 pandemic, cases of hyperglycemia, diabetic ketoacidosis, and new diabetes increased, suggesting that SARS-CoV-2 may be a trigger for or unmask T1D. Possible mechanisms of β-cell damage include virus-triggered cell death, immune-mediated loss of pancreatic β cells, and damage to β cells because of infection of surrounding cells. This article examines the potential pathways by which SARS-CoV-2 affects islet β cells in these 3 aspects. Specifically, we emphasize that T1D can be triggered by SARS-CoV-2 through several autoimmune mechanisms, including epitope spread, molecular mimicry, and bystander activation. Given that the development of T1D is often a chronic, long-term process, it is difficult to currently draw firm conclusions as to whether SARS-CoV-2 causes T1D. This area needs to be focused on in terms of the long-term outcomes. More in-depth and comprehensive studies with larger cohorts of patients and long-term clinical follow-ups are required.
Topics: Humans; COVID-19; Diabetes Mellitus, Type 1; SARS-CoV-2; Pandemics; Islets of Langerhans
PubMed: 36950864
DOI: 10.1210/clinem/dgad165 -
Scientific Reports Apr 2023In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia...
In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2A, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3 T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.
Topics: Humans; Enterovirus; Diabetes Mellitus, Type 1; Pancreas; Enterovirus Infections; Pancreas, Exocrine; Antigens, Viral; Islets of Langerhans
PubMed: 37117225
DOI: 10.1038/s41598-023-33011-7 -
Frontiers in Endocrinology 2022Type 2 diabetes mellitus, obesity and metabolic syndrome are becoming more prevalent worldwide and will present an increasingly challenging burden on healthcare systems.... (Review)
Review
Type 2 diabetes mellitus, obesity and metabolic syndrome are becoming more prevalent worldwide and will present an increasingly challenging burden on healthcare systems. These interlinked metabolic abnormalities predispose affected individuals to a plethora of complications and comorbidities. Furthermore, diabetes is estimated by the World Health Organization to have caused 1.5 million deaths in 2019, with this figure projected to rise in coming years. This highlights the need for further research into the management of metabolic diseases and their complications. Studies on circadian rhythms, referring to physiological and behavioral changes which repeat approximately every 24 hours, may provide important insight into managing metabolic disease. Epidemiological studies show that populations who are at risk of circadian disruption such as night shift workers and regular long-haul flyers are also at an elevated risk of metabolic abnormalities such as insulin resistance and obesity. Aberrant expression of circadian genes appears to contribute to the dysregulation of metabolic functions such as insulin secretion, glucose homeostasis and energy expenditure. The potential clinical implications of these findings have been highlighted in animal studies and pilot studies in humans giving rise to the development of circadian interventions strategies including chronotherapy (time-specific therapy), time-restricted feeding, and circadian molecule stabilizers/analogues. Research into these areas will provide insights into the future of circadian medicine in metabolic diseases. In this review, we discuss the physiology of metabolism and the role of circadian timing in regulating these metabolic functions. Also, we review the clinical aspects of circadian physiology and the impact that ongoing and future research may have on the management of metabolic disease.
Topics: Animals; Circadian Rhythm; Diabetes Mellitus, Type 2; Humans; Metabolic Diseases; Obesity; Pancreas
PubMed: 36034454
DOI: 10.3389/fendo.2022.920261