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Background & Aim: The pro-angiogenic, immunoregulatory and anti- inflammatory properties of MSCs are being exploited for the development of cellular therapies, including the treatment of graft versus host disease (GvHD), inflammatory bowel disease and COVID-19. SNBTS have developed a GMP process to bank umbilical cord MSCs (UC-MSCs) whereby we can reliably bank 100 vials of 10 million P2 UC-MSCs per cord. Each of these vials can be extensively expanded and stored for specific applications. The ultimate aim of the bank is for off-the-shelf clinical use, e.g., in GvHD or as an adjuvant therapy in Islet transplantations. Methods, Results & Conclusion(s): During process development, different basal media and supplements were screened for proliferation and MSC marker expression. Cells grown in promising media combinations were then tested for tri-lineage differentiation (identity), their chemokine/cytokine expression and T-cell inhibition (function) assessed. Medium selected for further GMP development and scale up was ultimately determined by all round performance and regulatory compliance. GMP-like UC-MSCs were shown to have immune-modulatory activity in T-cell proliferation assays at 4:1 or 16:1 ratios. Co-culture of UC-MSCs and freshly isolated leukocytes, +/- the immune activating agent LPS, show a dose dependent survival effect on leukocytes. In particular, neutrophils, which are normally very short lived in vitro demonstrated increased viability when co-cultured with UCMSCs. The survival effect was partially reproduced when UC-MSC were replaced with conditioned medium or cell lysate indicating the involvement of soluble factors. This improved neutrophil survival also correlates with results from leukocyte migration studies that demonstrate neutrophils to be the main cell type attracted to MSCs in in vitro and in vivo. Genetic modification of UC-MSC may improve their therapeutic potential. We have tested gene editing by CRISPR/Cas9 technology in primary UC-MSCS. The CXCL8 gene, highly expressed in UC-MSC, was targeted in isolates from several different donors with editing efficiencies of 78-96% observed. This translated to significant knockdown of CXCL8 protein levels in resting cells, however after stimulation levels of CXCL8 were found to be very similar in edited and non-edited UC-MSCs. This observation requires further study, but overall the results show the potential to generate future banks of primary UC-MSCS with genetically enhanced pro-angiogenic, immunoregulatory and/or anti-inflammatory activities.Copyright © 2023 International Society for Cell & Gene Therapy
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Background: Innate immunity is the first line of defense in response to pathogens, which acts locally and also leads the stimulation of adaptive immunity through at least with IL-1beta secretion. It has been shown that SARSCoV- 2 infection triggered the NLRP-3 inflammasome activation and the IL-1beta secretion. The aim of this study was to analyze and compare the level of IL-1beta secretion that is one of the most important innate immunity cytokines, in monocyte-like cells infected with 6 different variants of the SARS-CoV-2. Method(s): Six SARS-CoV-2 variants (historical (B.1, D614G), Alpha, Beta, Gamma, Delta and Omicron BA.1) were isolated from COVID-19 hospitalized patients. Viral stocks were obtained by inoculation in Vero and Vero-TRMPSS2 cells. THP-1 monocyte-like cells were cultured with RPMI-hepes 10% FBS-0.05 mM 2-mercaptoethanol. A total of 5 x 104 of THP-1 cells was plated per well in 96-wells plate and differentiated with 10nM of PMA for 24h. Differenciated- THP-1 were first primed with LPS 1mug/ml for 2h and infected with different SARS-CoV-2 variants with a MOI 0.1. IL-1beta was measured by luminescence in the supernatant after 24 h of infection. Result(s): We analyzed and compared IL-1beta secretion between SARS-CoV-2 virus 6 sublineages after infection of monocytes like THP-1. We observed that THP-1 cells infected with SARS-CoV-2 variants presented a significantly higher IL-1beta secretion than non-infected cells. Moreover, some SARS-CoV-2 variants led to a stronger IL-1beta secretion, and particularly we observed a significantly higher level of IL-1beta cells infected with Omicron BA.1 sublineage compared to other variants. Indeed, Omicron BA.1 infected cells presented the higher IL-1beta secretion (median 385.7 pg/ml IQR[302.6-426.3]) follows by the Delta variants and the historical variants (median 303.6 [266.3-391.9] and 281.9 [207.2-410], respectively). Alpha, Beta and Gamma variants presented the lowest IL-1beta secretion (median 228.1 [192.5-276.4], 219.1 [185.1-354.2] and 211 [149.8- 228.8]). Conclusion(s): We observed the inflammasome activation for the 6 SARS-CoV-2 sublineages with a variation in level of IL-1beta secretion. Indeed, our results suggested that Omicron BA.1 was more recognized by the innate immune cells than other SARS-CoV-2, which could in part, with its upper respiratory tract tropism, possibly explain its less clinical virulence. Taking together, these results suggest that the innate immunity response and precisely, IL-1beta secretion pathways were activated in a SARS-CoV-2 variants-dependent manner.
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Introduction: Lorlatinib is a third-generation tyrosine kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1). Although 2-10% of patients with non-small cell lung cancer developed hyperglycemia in phase 2 and 3 studies of lorlatinib, only one case has subsequently reported hyperglycemia >500 mg/dL, and no cases of diabetic ketoacidosis (DKA) have been previously reported. Phase 1 trials in neuroblastoma are ongoing. Case Description: A 34-year-old woman with ALK-mutated paraspinal neuroblastoma presented with DKA 14 months after initiation of lorlatinib. Prior to starting lorlatinib, her hemoglobin A1c had been 5.0% (n: < 5.7%). After 12 months of therapy, her A1c increased to 7.8%, prompting the initiation of metformin 500 mg daily. However, two months later she was admitted for DKA with a blood glucose of 591 mg/dL (n: 65-99 mg/dL), CO2 17 mmol/L (n: 20-30 mmol/L), anion gap 18 (n: 8-12), moderate serum ketones, and 3+ ketonuria. Her A1c was 14.8%, C-peptide was 1.2 ng/mL (n: 1.1-4.3 ng/mL), and her glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies were negative. She was also found to be incidentally positive for COVID-19 but was asymptomatic without any oxygen requirement. The patient's DKA was successfully treated with IV insulin infusion, and she was discharged after 3 days with insulin glargine 27 units twice daily and insulin aspart 16 units with meals. One month later, her hemoglobin A1c had improved to 9.4%, and the patient's oncologist discontinued lorlatinib due to sustained remission of her neuroblastoma and her complication of DKA. After stopping lorlatinib, her blood glucose rapidly improved, and she self-discontinued all her insulin in the following 3 weeks. One month later, she was seen in endocrine clinic only taking metformin 500 mg twice daily with fasting and post-prandial blood glucose ranging 86-107 mg/dL. Discussion(s): This is the first reported case of DKA associated with lorlatinib. This case highlights the importance of close glucose monitoring and the risk of severe hyperglycemia and DKA while on lorlatinib therapy. Discontinuation of lorlatinib results in rapid improvement of glycemic control, and glucose-lowering treatments should be promptly deescalated to avoid hypoglycemia.Copyright © 2023
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Background: A major consequence of COVID-19 is long-term metabolic complications (metabolic PASC or Long COVID) following acute disease resolution leading to hyperglycemia, increased risk of diabetes or defects in glucose metabolism. However, the mechanisms underlying the links between COVID-19 and glycometabolic disruptions remain unclear. Method(s): 15 African green monkeys (AGM;Chlorocebus aethiops) were infected with SARS-CoV-2 (Wuhan stain) and divided into two groups: unvaccinated (n=10) and vaccinated (BNT162b2 (Pfizer) 4-days post infection;n=5). Subgenomic SARS-CoV-2 mRNA (sgRNA) reflecting active replication was quantified in nasal and pharyngeal swabs, and blood chemistry analysis was performed longitudinally up to 18 weeks post-infection. We quantified liver glycogen at necropsy using Periodic acid-Schiff staining. Finally, we longitudinally analyzed 96 plasma proteins using a proximity extension assay (Olink). STRING was used to identify enriched protein networks. Comparisons between the two groups over time were performed using PERMANOVA. Result(s): All animals had detectable sgRNA ( >3.64x106) at day 3, and only two were undetectable at week 5. Post-infection BNT162b2 vaccination partially inhibited the SARS-CoV-2 mediated disruption of glucose levels (P=0.001, Fig. 1A). Liver glycogen levels following necropsy correlated positively with blood glucose levels at week 12 (r=0.74, P =0.003). Histopathological analysis revealed no marked evidence of long-term inflammation or fibrosis of pancreatic islets. Using the plasma proteomic data, we identified a signature of 15 SARS-CoV-2-modulated plasma proteins coinciding with early onset hyperglycemia during acute infection (P=0.001, Fig. 1B). These proteins are enriched for biological processes linked to chemotaxis (FDR=1.38E-06), and viral protein interaction with cytokines (FDR=1.01E-12) (Fig. 1C). Of these, CCL25 and glial cell derived neurotrophic factor (GDNF) remained persistently elevated post-acute infection and correlated with blood glucose levels (r=0.57, P=0.0003;and r=0.64, P<0.0001, respectively, Fig. 1D). Conclusion(s): Our AGM model validates phenotypes of metabolic PASC and offers an opportunity to mechanistically study the manifestations of PASC. Our preliminary data suggest that vaccine-preventable early insults by metabolicregulating immune factors may contribute to long-term dysregulated liver and systemic glucose homeostasis during PASC. These immune factors warrant further investigation for their mechanistic links to PASC. (Figure Presented).
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Introduction: The association between worse COVID-19 outcomes and diabetes has been well-established in the literature. However, with more cases of new-onset diabetes and pancreatitis being reported with or after COVID-19 infection, it poses the question if there is a causal relationship between them. Case Description: 31 y/o female with COVID-19 infection 4-6 weeks ago with moderate symptoms (not requiring hospital admission or monoclonal ab), presented to ED with bandlike epigastric pain radiating to back, which is worsened with food, associated with nausea, vomiting, polyuria, and fatigue. Workup showed lipase 232, AST 180, ALT 256. Blood glucose was 281 and HbA1c was 12. CT A/P showed post cholecystectomy status, normal pancreas with mesenteric adenitis. MRCP showed hepatic steatosis with trace fluid around the pancreas s/o inflammation, and no evidence of choledocholithiasis or biliary dilatation. She denied alcohol use and autoimmune workup for pancreatitis was unremarkable. Islet cell antibodies were negative. The patient improved with fluid resuscitation and was discharged home on insulin with plans to transition to oral agents outpatient. Discussion(s): Long COVID is defined as a range of conditions or symptoms in patients recovering from COVID-19, lasting beyond 4 weeks after infection. A retrospective cohort study showed increased new-onset diabetes incidence in patients after COVID-19. This was redemonstrated in a systematic review and meta-analysis that showed a 14.4% increased proportion of new diagnoses of diabetes in patients hospitalized with COVID-19. Possible pathophysiology that have been attributed to this include undiagnosed pre-existing diabetes, hyperglycemia secondary to acute illness and stress from increased inflammatory markers during the cytokine storm, the effect of viral infections on the pancreas, and concurrent steroid use in patients with severe respiratory disease. The binding of SARS-CoV-2 to ACE2 receptors is thought to the other mechanism by which COVID can cause pancreatitis and hyperglycemia. Study showed increased lipase and amylase levels in patients with COVID and the increase in serum levels was proportional to the severity of the disease. Patients who died due to COVID-19 were also found to have degeneration of the islet cells. While, several studies have showed new onset diabetes and pancreatitis during an active COVID infections, we need larger cohort studies to comment on its true association or causation, especially in patients with long COVID symptoms. As more cases of new onset diabetes and pancreatitis with COVID-19 are being reported, there may be a need for more frequent blood sugar monitoring during the recovery phase of COVID-19.Copyright © 2023
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Introduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses the greatest threat of our times. SARS-CoV-2 vaccines are one of the most effective strategies against this infection. Diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, and new-onset diabetes as adverse effects of SARS-CoV-2 vaccination have been infrequently described in the literature. We hereby report a rare case of new-onset type 1 diabetes after SARS-CoV-2 vaccination. Case Description: An 18-year-old male presented to the outpatient office for evaluation of breast pain. On routine laboratory tests, he was noted to have fasting blood glucose of 200 mg/dL. On further questioning, he reported some polyuria, nocturia, and a 10-pound weight loss over the preceding month. He received the initial dose of Pfizer-BioNTech SARS-CoV-2 vaccine in May 2022 and the second dose in June 2022, approximately one month before the onset of symptoms. He denied any earlier viral infections and had no personal or family history of autoimmune conditions. On evaluation, his body mass index was 20 kg/m2, but otherwise, he had a normal physical exam, including a breast exam. Over the next few days, his blood glucose progressively increased to over 300 mg/dl. HbA1c was noted to be elevated at 8.6%, glutamic acid decarboxylase-65 (GAD-65) antibodies were remarkably high >250 IU/ml (normal 5 IU/ml), C-peptide was 1.51 ng/ml (normal 0.80 - 3.85 ng/ml), blood glucose 156 mg/dl, islet-cell antibody titer was 320 (< 1.25 JDF units) and insulin autoantibodies were negative. He was diagnosed with autoimmune Type 1 diabetes and a basal-bolus insulin regimen was initiated to improve glycemic control. On a one-month follow-up, his insulin requirements remained low but persistent and his glycemic control was acceptable. Discussion(s): Various viruses are known to play a fundamental role in the onset of type 1 diabetes via a variety of effects on pancreatic beta-cells because of either the direct lytic effects of viral replication or the inflammatory response to the virus, which is mediated by autoreactive T cells. The limited release of islet cell antigens induces molecular mimicry and paves the way for long-term autoimmunity and the development of type 1 diabetes mellitus. Our patient did not report any viral illnesses before the onset of his symptoms. He also did not have a family or personal history of autoimmune diseases. His onset of diabetic symptoms coincided temporally with receiving the SARS-CoV-2 vaccine. The detection of a considerable titer of GAD-65 antibodies proved autoimmunity. Clinicians must stay vigilant about this potential side effect of SARS-CoV2 vaccine so that a timely diagnosis can be made.Copyright © 2023
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Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.
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Background: COVID 19 has two-way interaction with Type II Diabetes Mellitus. First, patient with DM are more prone for developing severe COVID 19. Second, moderate to severe COVID 19 can present with new onset DM or may lead to hyperglycaemia and hyperglycaemic complications in Type II DM patients. In this report we present 4 cases of COVID 19 associated Hyperglycaemic Complication (3 with Diabetic Ketoacidosis and 1 with Hyperglycaemic hyperosmolar state). Method(s): Case Series of patients admitted to Thumbay Hospital, Ajman. Result(s): We report 4 cases of COVID 19 patients who presented to us with hyperglycaemic complications. There of them had features of Diabetic Ketoacidosis and one had Hyperglycaemic hyperosmolar state. All were treated with IV Insulin infusion and IV Fluids. COVID 19 infection was managed as per MOH protocol. All patients recovered well and were discharged in stable condition. Discussion(s): COVID 19 is associated with new onset DM or may lead to hyperglycaemic complications in patients with Type II DM. There are three pathophysiological processes which may be responsible for this finding. One, SARS-CoV-2 virus is known to enter the body through angiotensin-converting enzyme (ACE) II receptors in the pulmonary pneumocytes leading to infection and inflammation. Similar ACE-II receptors are also expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys. Direct infection of pancreatic beta-cells with SARS-CoV-2 virus with beta-cell cell injury is likely the underlying mechanism for development of new onset diabetes and hyperglycaemia in existing diabetic patients. Such direct beta cell infection can cause hyperglycaemic complications in asymptomatic or mild COVID 19 as well. Two, moderate to severe COVID 19 is associated with hyperinflammatory immune response leading to marked rise in inflammatory mediators such as C-reactive protein and ferritin. Such hyperinflammatory response can also lead to hyperglyacemia in patients with diabetes mellitus. Three, corticosteroids are mainstay treatment of patients with moderate to severe COVID 19 and would definitely contribute to worsening of hyperglycaemia in these patients. Our patients presented to us with hyperglycaemic complications before initiation of any treatment. It is likely that such a situation would be due to direct infection and destruction of beta cells with SARS-CoV-2 virus infection. Conclusion(s): Type II Diabetes Mellitus patients are high risk of developing hyperglycaemic complications due to COVID 19. This can lead to increased morbidity and mortality. Patients with Type II DM should seek medical attention even if they have mild to asymptomatic COVID 19 to monitor for hyperglycaemic complication which can develop irrespective of severity of stage of illness.
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Background COVID-19 as a trigger for A-beta+ ketosis-prone diabetes (KPD) [1,2] in previously normoglycemic individuals presenting with new-onset DKA, has been sparsely studied. Aim To study prospective changes in insulin secretion and insulin resistance in suspected A-beta+ KPD patients presenting with COVID-associated new-onset DKA. Method 22 previously non-diabetic, antibody-negative patients with new-onset DKA and RT-PCR positive COVID-19 (suspected A-beta + KPD), were followed up for one year. They were compared with 20 Type 1A and 18 Type 2 DM patients, with serial assessments (0,6 and 12 months) of insulin secretion rates (ISR) and multi-tissue insulin resistance (IR). 75-g OGTT with serial glucose, insulin and C-peptide estimation (0,15, 30,45, 60,90,120, 150 and 180 minutes) was used to derive IS, while hepatic and peripheral IR was calculated based on study by Ghani et al. [3]. Results At baseline, ISR in suspected KPD (n = 22) was significantly reduced but similar to Type 1A DM(p = 0.15). Serial ISR demonstrated complete recovery in 17 (77%) patients who became insulin independent at one-year follow-up (remission), while 5(23%) patients continued to require insulin (non-remission). KPD patients showed significant hepatic and peripheral IR at baseline compared to Type 1A DM (p < 0.05). The remission group (n = 17) showed significantly enhanced recovery of hepatic and peripheral insulin sensitivity at 6 and 12 months follow-up (all p < 0.01) compared to the non-remission (n = 5) group, with IR in the latter being comparable to Type 2 DM at follow-up (all p > 0.05). Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were factors associated with poorer recovery of beta-cell secretion amongst the KPD patients. Conclusion This is the first prospective study to demonstrate progressive recovery of p-cell secretion in new-onset A-beta + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM.Copyright © 2023 Elsevier B.V.
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Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.
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Since the outbreak of the COVID-19 pandemic, it has been suspected that its causative agent, the SARS-CoV-2 coronavirus, may cause transient or permanent hyperglycemia. This fact has resulted in a new focus of research interest related to the study of potential mechanisms leading to damage of pancreatic insulin-producing cells, as well as the possible impact of the virus on insulin sensitivity, which may manifest as metabolic disturbances in patients with COVID-19 and cause diabetes mellitus. Evidence from the literature suggests that Corona viruses can damage pancreatic (beta-cells by direct or indirect mechanisms and cause changes in insulin secretion and sensitivity. To what extent all these changes are valid claims that SARS-CoV-2 can trigger diabetes mellitus is still not fully proven.Copyright © 2022 Medical Information Center. All rights reserved.
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Background: It is well established that diabetic patients infected with COVID-19- are at higher risk of developing severe symptoms that may lead to death. Such observation argues for the possibility that SARS-CoV-2 may target and infect pancreatic islets. SARSCoV- 2 is thought to enter the cells through the binding of viral spike S1 protein to ACE2. The cellular entry process includes priming of the S protein by TMPRSS2 and ADAM17, which facilitate the binding and promote ACE2 shedding. To date, no conclusive evidence has emerged to address the expression of TMPRSS2 and ADMA17 or the interaction between SARS-CoV-2 and human pancreatic islets. Method(s): Microarray and RNA-sequencing (RNA-seq) expression data from human islets were used to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in diabetic and non-diabetic subjects. Result(s): Pancreatic islets express all three receptors regardless of diabetes status. ACE2 expression was significantly elevated in diabetic islets than non-diabetic. Female donors showed to have higher ACE2 expression compared to males, whereas ADAM17 and TMPRSS2 were not affected by gender. No difference in the expression of the three receptors in young (<=40 years old) compared to old (>=60 years old) islets. Obese donors (BMI>30) showed significantly higher expression levels of ADAM17 and TMPRSS2 as compared to non-obese (BMI<25). Expression of TMPRSS2 was associated positively with HbA1c and inversely with age, while ADAM17 and TMPRSS2 were associated positively with BMI. Muscle and subcutaneous adipose tissues showed similar expression of the three receptors in diabetic and nondiabetic donors. Conclusion(s): ACE2 expression is increased in diabetic human islets. More studies are warranted to understand the permissiveness of human pancreatic beta-cells to SARS-Cov-2 and whether variations of ACE2 expression could explain the severity of COVID-19 infection between diabetics and non-diabetic patients.
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Background: Diabetes mellitus (DM) represents one of the most common metabolic diseases in the world, with rising prevalence in recent decades. Most cases are generally classified into two major pathophysiological categories: type 1 diabetes mellitus (DM1), which progresses with absolute insulin deficiency and can be identified by genetic and pancreatic islet autoimmunity markers, and type 2 diabetes mellitus (DM2), which is the most prevalent form and involves a combination of resistance to the action of insulin with an insufficient compensatory response of insulin secretion. In the last two decades, in parallel with the increase in childhood obesity, there has also been an increase in the incidence of DM2 in young people in some populations. Other forms of diabetes may affect children and adolescents, such as monogenic diabetes (neonatal diabetes, MODY – maturity onset diabetes of the young, mitochondrial diabetes, and lipoatrophic diabetes), diabetes secondary to other pancreatic diseases, endocrinopathies, infections and cytotoxic drugs, and diabetes related to certain genetic syndromes, which may involve different treatments and prognoses. DM1 is considered an immuno-mediated disease that develops as a result of gradual destruction of insulin-producing pancreatic beta cells that eventually results in their total loss and complete dependence on exogenous insulin. Clinical presentation can occur at any age, but most patients will be diagnosed before the age of 30 years
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The proceedings contain 228 papers. The topics discussed include: congenital adrenal hyperplasia is associated with increased risk of poor cardiometabolic health;adrenal insufficiency in peroxisomal disorders;patient and parent perspectives on testicular adrenal rest tumors in congenital adrenal hyperplasia;never say never! delayed diagnosis of a rare form of congenital adrenal hyperplasia;prevalence of adrenal insufficiency in pediatric patients with acute recurrent and chronic pancreatitis who undergo a total pancreatectomy with islet auto transplantation (TPIAT);the utility of a random cortisol level in determining neonatal central adrenal insufficiency;neural correlates of obesity and inflammation in youth with congenital adrenal hyperplasia due to 21-hydroxylase deficiency;glucocorticoid dosage and dexamethasone treatment are associated with increased markers of depression in youth with classical congenital adrenal hyperplasia;and new onset primary adrenal insufficiency and autoimmune hypothyroidism in a pediatric patient presenting with MIS-C due to COVID- 19 infection.
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Introduction: WHO declared a pandemic of COVID-19 in March 2020. This study analyses the impact of COVID-19 on beta-cell replacement therapy in the UK. Method(s): Pancreas and islet donation and transplant activity in the period March 2020/2021 was compared with the same period the previous year. Result(s): 2,180 patients had a functioning graft during March 2020/2021. 5.8%(n=126) tested positive for COVID-19 and two died (1%). In this period there was a 43% reduction in solid organ donors n=1,615, compared with the previous year, n=2,840. Of the 625 solid organ donors with a pancreas offered, 32% had the pancreas retrieved compared with 51% the previous period. 97 whole pancreas and islet transplants were performed in the UK down 54% from the prior period. Of the 84 pancreas transplant recipients;four tested positive for COVID-19 but none died, and two grafts failed within the first week from vascular thrombosis (neither were COVID-19 positive). Of the 13 SIK and islet alone transplant recipients, two tested positive for COVID-19 but neither died. Of these SIK transplants, one is known to have failed within a month and this is equivalent to that seen in the previous time period. To our knowledge, no patient receiving beta cell replacement therapy died of COVID during the first year of the pandemic despite immunosuppression. Conclusion(s): In the UK, pancreas, and islet transplantation have continued during the pandemic at a lower rate. Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior. Take-home message: Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior.
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Introduction In the era of the COVID-19 pandemic, several cases of new onset diabetes associated with COVID-19 have been reoprted. Additionally, patients with diabetes, a high-risk population, are prioritised for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The vaccine against the (SARS-CoV-2) could represent a new environmental trigger for autoimmune disorders such as Graves' disease, immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain-Barré syndrome, systemic lupus erythematosus and type 1 diabetes. case We report a case of diabetic ketoacidosis in a new onset Type 1 diabetes in an elderly female following SARSCoV- 2 vaccination. A 69-year-old female with a history of treated TB abdomen in 2015 with no history of diabetes received her second dose of SARS-CoV-2 vaccination (COMIRNATY) on 21st August 2021. Two weeks following vaccination, she developed osmotic symptoms, reduce appetite and lethargy. Her random blood glucose (RBS) was 41 mmol/L, serum ketone 4.4 mmol/L, pH of 7.29 mmHg, bicarbonate 12.5 mmol/L and serum osmolarity of 298 mOsm/kg. She was treated for DKA with intravenous insulin infusion and hydration with resolution of DKA within 12 hours. Anti-Glutamic Acid Decarboxylase and anti-Islet Cells antibodies were positive with low fasting C-peptide of 102 pmol/L. She was discharged well with basal bolus insulin. Four months later, HbA1c reduced from 15.6% to 7.7% with a random C-peptide of 152 pmol/L. Conclusion The occurrence of hyperglycaemia crisis following SARSCoV- 2 vaccine in patients with pre-existing diabetes is known but the occurrence of new onset autoimmune diabetes following vaccination is rare. Further studies are needed to better understand the underlying pathogenesis of autoimmune diabetes following SARS-CoV-2 vaccine.
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BACKGROUND: The SARS-CoV-2 novel coronavirus that causes COVID-19 has been shown to more severely affect individuals with underlying conditions, such as metabolic syndrome or diabetes. This is a reason why SARS-CoV-2 more severely affects populations at risk for these conditions, notably the Hispanic population. Vitamin D has been shown to be a positive immunomodulatory actor, shown to upregulate production of CAMP (cathelicidin antimicrobial peptide) and its effect on mitigating the severity of respiratory illnesses has been widely studied. Additionally, given vitamin D's role in the functional regulation of pancreatic beta cells, this study aims to determine whether vitamin D plays a significant role in providing better outcomes for Hispanic patients with diabetes. Data will be gathered for patients treated at University Medical Center in El Paso, where the majority of the population treated is Hispanic, allowing us the opportunity to observe phenomena unique to this population. METHODS: We collected data from the charts of 1,478 Hispanic patients who were hospitalized for COVID-19 at University Medical Center El Paso. Comparisons were made between patients who received VItamin D therapy (705) and those who did not (773). The main outcome that was assessed was mortality, as well as secondary outcomes such as length of hospital stay, need for supplemental oxygen upon discharge, and ICU admission. Further comparisons were made between patients who suffer from diabetes and those who do not. RESULTS: Our preliminary results by way of a univariate analysis show that patients who were given Vitamin D therapy during their hospitalization had significantly lower rates of mortality (p<0.001). Patients in the group that received Vitamin D therapy were 38% less likely to die during their hospital stay (p<0.001). We also discovered that patients admitted to UMC El Paso were significantly more likely to be given Vitamin D therapy if they presented with respiratory and GI symptoms (p<0.001). A multivariate analysis on the relationship between previous history of diabetes and the efficacy of Vitamin D therapy is pending. CONCLUSIONS: Our results show that Vitamin D therapy as a part of the treatment protocol for COVID-19 can significantly reduce mortality during hospitalization. As a result of the unique composition of our patient population, these findings can help build standards of practice that are applicable to the specific needs of Hispanic patients throughout the course of the pandemic. Because patients in the Hispanic population are more susceptible to severe symptoms due to their predisposition to comorbid conditions like diabetes, using protocols informed by evidence has the potential to prevent mortality on a large scale.
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KPD is classically regarded as an atypical form of diabetes caused by near-complete beta-cell failure. A 37-year-old Egyptian man (BMI: 27.7 Kg/m2) presented with hyperglycemia (362 mg/dL) and DKA (arterial pH 7.20, ketonemia 5.0 mmol/L, ketonuria 80 mg/dL) . He was afebrile, with recent polyuria, polydipsia and weight loss. HbA1c was 107 mmol/mol (11.9%) and blood tests excluded diabetes secondary to endocrinopathies. SARS-CoV-2 RT-PCR test was negative. IV insulin infusion (0.1 IU/kg/h) and IV fluid therapy were started. He was shortly transitioned to a sc basal-bolus insulin regimen (0.7 IU/kg/day) . Mixed-meal tolerance test (MMTT) revealed a peak 120-min stimulated C-peptide of 12.3 ng/mL, suggesting marked insulin resistance. Islet autoantibodies (ICA, IAA, GADA, IA-2A, ZnT8A) and insulin receptor autoantibodies (IgG/IgM) were negative. HLA genotyping detected the following haplotypes: DRB1∗01, ∗04;DQA1∗01:01P, ∗03:01P;DQB1∗03:02P, ∗05:01P. Insulin dose was gradually reduced and insulin therapy was discontinued after 4 months in favor of metformin (2550 mg/day) plus sc semaglutide (up to 1 mg/week) . After one year, MMTT revealed a peak 60-min stimulated C-peptide of 8.25 ng/mL. During the 18-month follow-up period, fasting capillary beta-hydroxybutyrate values were <0.2 mmol/L and HbA1c remained <48 mmol/mol (<6.5%) , indicating disease remission. This case suggests the existence of an autoantibody-negative KPD subtype driven by marked insulin resistance rather than by insulinopenia.
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Coronary artery disease (CAD) is widely considered a chronic inflammatory disorder, and dysfunction of epicardial adipose tissue could be an important source of the inflammation. Amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a known marker of cardiovascular disorders of cardiac origin. Recent studies show that inflammatory stimuli may influence its secretion. Our purpose was to evaluate NT-proBNP serum concentration in relation to immune cell ratios in epicardial adipose tissue (EAT), and cytokine levels in the patients with stable CAD. Patients with stable CAD and heart failure classified into classes II-III, according to the New York Heart Association (NYHA) scale, scheduled for the coronary artery bypass graft (CABG) surgery, were recruited into the study (n = 10;59.5 (53.0-65.0) y. o.;50% males). The EAT and subcutaneous adipose tissue (SAT) specimens were harvested in the course of CABG surgery. Immunostaining with anti-CD68, anti-CD45, anti-IL-1β and anti-TNFα monoclonal antibodies was performed to evaluate cell composition by differential counts per ten fields (400 magnification). Fasting venous blood was obtained from patients before CABG. Blood was centrifuged at 1500g, aliquots were collected and stored frozen at -40 °С until final analysis. Concentrations of NT-proBNP, IL-1β, IL-6, IL-10, TNFα were determined in serum samples by enzyme-linked immunosorbent assay (ELISA). We have found increased production of IL-1β and TNFα cytokines in EAT compared to SAT. Concentrations of NT-proBNP exceeded 125 pg/ml in 4 patients, and correlations between the CD68+ macrophage counts in both EAT and SAT samples (rs = 0.762;p = 0.010 and rs = 0.835;p = 0.003, respectively). NT-proBNP levels showed positive relations with CD45+ leukocyte counts (rs = 0.799;p = 0.006), and with IL-1β+ cell numbers (rs = 0.705;p = 0.023) in EAT samples only. As for the serum biomarkers, NT-proBNP levels showed negative correlation with fasting glucose levels (rs = -0.684;p = 0.029), and positive correlation with serum IL-6 concentrations (rs = 0.891;p = 0.001). Increased serum concentrations of NT-proBNP in CAD patients correlate with accumulation of macrophages in EAT, which is associated with increased production of IL-1β in EAT and correlates with some metabolic parameters.
RESUMO
The continued increase in diabetes indicates it to be a significant global challenge to the health and wellbeing of people. Hyperglycemia is linked to chronic inflammatory processes and diabetes-related vulnerability to infection. There is historic evidence linking viruses and microbes with diabetes and in some instances considered the causative agent. The viral infection causes inflammation and autoimmune destruction of beta cells, which, in turn, give rise to hyperglycemia, finally leading to diabetes. This review considers the historic aspects of viruses and diabetes, immune dysfunction with hyperglycemia, bidirectional relations between COVID-19 virus and diabetes, and new-onset diabetes in COVID-19.