SARS-CoV-2 VARIANTS-DEPENDENT INFLAMMASOME ACTIVATION

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.

New Onset of Type 1 Diabetes After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination

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

Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

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.

COVID 19 Induced Hyperglycaemic Complications

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.

IDF2022-0635 Can COVID-19 infection provoke new-onset A-beta+ KPD (ketosis-prone diabetes)? - Insights from an Indian prospective study

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.

Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

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.

Could COVID-19 be a Causative Factor for Hyperglycaemia and Cause Diabetes Mellitus.

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.

SARS-CoV-2 Host Receptors Expression in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic subjects

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.

THE EFFECTS OF VITAMIN D THERAPY ON OUTCOMES FOR HISPANIC PATIENTS HOSPITALIZED FOR COVID-19

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.

MACROPHAGES IN EPICARDIAL ADIPOSE TISSUE AND SERUM NT-proBNP IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE

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.

Historical aspects and current understanding of the connections and implications of viruses and diabetes: A narrative review

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.

TYPE 2 DIABETES IMPAIRS ANTIVIRAL IMMUNITY BY PREVENTING THE INDUCTION OF FASTING METABOLISM

Background and Aims: Type 2 diabetes (T2D) is a major risk factor for developing severe infectious disease, such as COVID-19. The endocrine and immune system closely interact following viral infection, which is deregulated in T2D. Previously, we showed in humans and mice that viral infection causes transient insulin resistance, which can lead to permanent loss of glycemic control in subjects with pre-diabetes. How changes in systemic glycemia benefit the antiviral response, and how this derails in T2D is mostly unknown. Methods: Mice were infected with virulent strains of cytomegalovirus or lymphocytic choriomeningitis virus. Glucose-, insulin- and pyruvate-tolerance tests and hyperinsulinemic euglycemic clamping were used to determine the metabolic state of animals. Conditional knock-out models were used to measure the impact of cytokines on metabolism of specific organs. Dietinduced obesity models were used to determine the impact of hyperglycemia on the antiviral response. Results: Severe viral infection causes pancreatic β-cell hyperfunctionality following their stimulation with the cytokine IFNγ by local T cells. Virus-induced hyperinsulinemia impaired glucose release by the liver and promoted induction of fasting metabolism, because of reduced hepatic glycogenolysis, causing relative, transient hypoglycemia (RHG). RHG was beneficial to the antiviral response by promoting the release of antiviral cytokines by endothelial cells, which impaired viral replication. Obese mice failed to induce fastng metabolsim, resulting in lower antiviral cytokines, higher viral titers and increased pathology. Conclusions: Metabolic adaptations following infection are of major importance for optimal control of viral replication. In context of T2D, these changes cannot be accomplished, thus leading to more frequent and severe infections.

Recurrent severe hypoglycaemia: Think about antibiotic choice

A 64 year-old Caucasian woman was admitted profoundly unwell with lethargy and generalised weakness. She had rheumatoid arthritis, with no history of diabetes or long-term steroid-use. Blood tests revealed pancytopaenia secondary to methotrexate (stopped on admission), acute kidney injury and severe metabolic acidosis. CT demonstrated lung base ground-glass changes. The patient had been double-vaccinated for covid-19 and all covid swabs were negative. Despite receiving Tazocin, respiratory symptoms worsened. High-dose co-trimoxazole was commenced to treat potential Pneumocystis infection from being immunocompromised. Subsequently she developed new confusion. Random blood glucose at midday was 1.2mmol/l. After treatment, hypoglycaemia recurred and persisted despite repeated intravenous dextrose boluses and glucagon injection. Blood glucose only improved with continuous 10% dextrose infusion. Causes were explored -a recent CT scan showed no pancreatic or intra-abdominal pathology;morning cortisol was normal. Literature review revealed very rarely Co-trimoxazole causes hypoglycaemia;hence this was stopped. Hypoglycaemia resolved within 48 hours;confusion improved. When serum glucose was 3.3mmol/l, c-peptide measured was inappropriately high (5175pmol/L). Co-trimoxazole is biochemically similar to sulfonylureas, mimicking their action on pancreatic beta-cells. Endogenous insulin hypersecretion raises c-peptide levels during hypoglycaemia. As Co-trimoxazole is renally excreted, when renal function is impaired it accumulates, with exacerbation of side effects such as protracted hypoglycaemia, especially at higher doses, as in our case. Hypoglycaemia will likely resolve after a 24-48h washout period, especially if renal function improves back to baseline. We recommend awareness of hypoglycaemia risk with co-trimoxazole treatment and blood glucose monitoring for inpatients taking high doses, especially in the setting of renal impairment.

Covid-19 pneumonia and diabetic ketoacidosis in a patient with type 2 diabetes

A 78-year- old man presented to the emergency department with acute confusion and urinary incontinence. His past medical history included type 2 diabetes with poor glycaemic control (HbA1c 126 mmol/mol Hb two months prior to admission). On examination he was febrile, tachycardic and clinically dehydrated. A chest x-ray confirmed right basal consolidation. Venous blood gas analysis showed an elevated glucose of 18.1 mmol/L and a raised anion gap metabolic acidosis. Capillary blood ketones were 6.1 mmol/L indicating diabetic ketoacidosis (DKA). Blood tests showed an acute kidney injury and markedly raised inflammatory markers (C-reactive protein 537 mg/L, WCC 11.6mg/l). A diagnosis of covid-19 pneumonia was made following detection of severe acute respiratory syndrome 2 (SARS CoV-2) on polymerase chain reaction (PCR) testing. The patient received treatment for DKA in accordance with the hospital's local clinical guidelines, which resolved rapidly within hours. His pneumonia was treated with intravenous ceftriaxone. The patient's clinical course in hospital was otherwise uncomplicated, but the case highlights the role of covid-19 as a possible precipitant of metabolic emergencies in patients with diabetes. There is increasing evidence describing the complex and multidirectional way in which covid-19 and diabetes interact. It is now well known that diabetes is one of the most important comorbidities associated with severe covid-19 disease. Recent research has suggested potential for the SARS CoV-2 virus itself to have a direct effect on beta cell function. This case illustrates the notion of diabetes being both a risk factor for and a condition that is worsened by covid-19.

BMS e-CON 2021 Conference Proceedings on “Exploring the Newer Modalities in Teaching - Learning and Research in Basic Medical Sciences during COVID-19 Era”

The proceedings contain 194 papers. The topics discussed include: regional variation of human pancreatic islets dimension and its impact on beta cells in Indian population;cytogenetic effects of formalin exposure on buccal mucosa: a cross-sectional observational study;association of sperm DNA fragmentation with serum lipid profile among males with abnormal semen parameters;embryological and clinico-anatomical perspective of ilioinguinal nerve variations in inguinal region;student involved fun activities- a novel strategy to teach functional correlation of brain in anatomy lectures;anti-hyperglycemic activity of ethonalic extract of stem of cissus quadrangularis in streptozotocin induced experimental diabetic rats-blood parameters;attitude and response of first year medical students towards cadaveric dissection in medical colleges of south Karnataka;and unilateral ectopic pelvic kidney - a rare case.

A case of newly diagnosed type 2 diabetes complicated by SARS-CoV-2 infection

Introduction: Covid-19, a novel Coronavirus SARS-COV-2, has caused major morbidity and mortality worldwide most especially in the high-risk population. SARS-COV-2 has caused more unfavorable outcomes and increased insulin resistance in patients with diabetes mellitus. It has been observed that many of these patients require very high doses of insulin to manage hyperglycemia. This will discuss a case of a young male with newly diagnosed type 2 diabetes complicated with Covid-19 infection. Case Description: 38-year-old Hispanic male with no past medical history presented to the emergency department with shortness of breath, cough, and chest congestion. His only medication was azithromycin. He had no family history of diabetes mellitus. There was no acanthosis nigricans on examination and the patient's BMI was 26.7 kg/m 2 . The patient was admitted for severe acute respiratory syndrome and diabetic ketoacidosis. His hba1c level was 13.7%, c-peptide was inappropriately low with a value of 0.31 ng/mL and glucose of 153 mg/dL and GAD-65 and islet cell antibodies were negative. Endocrinology was consulted for diabetic management. The patient was started on basal insulin 5 units at bedtime;however, the dose was increased to 7 to 9 to 12 and then 20 units at bedtime due to uncontrolled sugar levels. The patient was started on short-acting insulin before meals because his glucose ranged from 156 mg/dL to 381 mg/dL. The patient clinically improved and was discharged on hospital day 12. He got discharged on insulin detemir 20 units at bedtime and insulin lispro 8 units before meals. On a visit to the clinic, the patient was weaned off of insulin due to better glycemic control. His hba1c level significantly dropped to 7.2% and his c-peptide level improved to 3.21 ng/mL. He is now been controlled only on metformin 1000mg twice a day. Discussion: There is no definite explanation for why SARS-COV- 2 infection causes new-onset diabetes and worsening insulin resistance. However, there have been some theories attributed to the effects of the SARS-COV-2 coronavirus on angiotensin-converting enzyme 2 (ACE2). ACE2 is present in metabolic organs and tissues including pancreatic beta cells. As a result, an infection with the SARS-COV-2 virus could affect the pathophysiology of glucose metabolism causing increase insulin resistance. Another theory explains that coronavirus could cause ketosis-prone diabetes causing diabetic ketoacidosis in patients with no known history of hyperglycemia. Therefore, Covid-19 has some association with diabetes mellitus management outcomes.

Improving health outcomes in COVID19: Use of flash glucose monitoring in diabetic ketoacidosis

Introduction: COVID-19 has been linked to an increased risk of new-onset diabetes mellitus and increased incidence of diabetic ketoacidosis (DKA) either as a new presentation or with pre-existing diabetes. Various mechanisms such as impaired insulin secretion, impaired glucose disposal or increased counter regulatory responses are proposed.2 Case report: A 57-year-old man diagnosed with COVID-19 one month prior presented with epigastric pain, shortness of breath and weight loss. Investigations confirmed DKA (pH 7.22, bicarbonate 2.6 mmol/L, blood glucose 11.6 mmol/L, blood ketones 5.8 mmol/L) with HbA1c of 95 mmol/mol. Initial treatment was started as per national DKA guidelines. Upon discharge, the patient was prescribed a basal-bolus regime (total 30 units of insulin) and a FreeStyle Libre flash glucose monitoring (FGM) device. Rapid improvement in blood glucose levels was observed, with regular down titration of insulin and complete discontinuation after 24 days. HbA1c was 37 mmol/mol 96 days later. C-peptide normalised at 3 months for paired glucose at 837 pmol/L. Discussion: The use of diabetes technology (FGM device) with remote monitoring of blood glucose was instrumental in the safe and effective management of this patient. Given that the available literature suggests transient beta-cell dysfunction in the majority of COVID-19 patients resulting in DKA,3 we propose that patients who have been diagnosed with COVID-19 presenting with DKA should be discharged with insulin and FGM from secondary care. This enables remote insulin titration with ease, de-escalation of treatment with confidence and avoiding hypoglycaemia in the recovery phase of the illness in those with transient beta-cell dysfunction due to COVID-19.

Covid-19 Induced Diabetes: Disclosing Truth behind the Potential Attention Seeker

Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), the zoonotic virus answerable for the current global health crisis is ringing its dangerous bells on its post disease status. COVID-19 is causing multiple organ damage probably with its entry site. Insulin-Dependent Diabetes (IDDM) also known as Type I Diabetes is a multifactorial disease that typically occurs as a result of the interaction of genetic, environmental and immunologic factors.The mechanisms behind the development of Diabetes and associated consequences are complicated. The morphological mass of Insulin producing β-cells in the pancreatic islets of Langerhans and the functional status determine plasma Insulin levels. Insufficient Insulin levels may develop as a result of a lack of β-cell function resulting in hyperglycemia and Diabetes. Angiotensin-Converting Enzyme 2 (ACE2) receptor, the binding agent which allows Corona virus to enter and migrate to various organs such as lungs, heart, liver, pancreas, and kidneys is assumed to be responsible for this damage. The over expression of ACE2 receptor on pancreatic endocrine cells paves a way for extensive damage to Islets of Langerhans causing Insulin resistance and deficiency. Another common assumption among the researchers and health care professionals are the dreadful relationship shared by viruses and Diabetes which can exacerbate or provoke autoimmunity leading to β-cell auto-oxidation. The metabolic complications like Diabetic Ketoacidosis (DKA) and Hyper osmolar hyperglycemia are predominantly seen in various regions of the world in people with Pre-Diabetes and non-diabetics. However, this review explored the probable truth behind COVID-19 induced new-onset Diabetes mellitus and its complications.