The First Reported Case of Lorlatinib-Associated Diabetic Ketoacidosis

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

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

Self-Reported Depression and Anxiety among Graduate Students during the COVID-19 Pandemic: Examining Risk and Protective Factors

Depression and anxiety among students in higher education are well-established public health concerns with rates that have steadily increased over the past several decades. The global COVID-19 pandemic caused a need for rapid transition on campuses to online learning, a disruption of research, and uncertainty about meeting program requirements and employment. Graduate students often feel overlooked at the best of times and the potential for the pandemic to worsen this perception cannot be understated. This study examined the rates of self-reported depressive and anxiety symptoms among graduate students who were located at the national epicenter of the COVID-19 pandemic in the United States in the spring of 2020. Demographic characteristics, loneliness, and coping to determine potential risk and protective factors were also examined. A comprehensive online survey was created including the University of California Los Angeles (UCLA) 3-Item Loneliness Scale, the Patient Health Questionnaire Depression Scale (PHQ-9), and the Generalized Anxiety Disorder scale (GAD-7). Descriptive statistics, Pearson's chi-squared test, Spearman's correlation, and unadjusted and adjusted multivariable logistic ordinal regression models were used to describe the sample and to assess factors associated with depression and anxiety. 341 surveys were analyzed;respondents had a mean age of 31.88, 68% were female, 63% were White, and 23% identified as lesbian/gay/bisexual. Approximately 89% of students reported moderate-severe depression, and 76% moderate-severe anxiety. Risk factors associated with depression (p < 0.05) were being "sometimes' lonely”, "often/always lonely”, and time spent searching COVID-19 information. Emotional support, having children, and perceived emotional/mental health were protective against depression (p < 0.05). Risk factors associated with anxiety were "‘often/always lonely”, identifying as lesbian/gay/bisexual, and time searching COVID-19 information. Coping, having children, being born outside of the U.S., and perceived emotional/mental health were protective against anxiety (p < 0.05). Based on study findings, it is recommended that universities include more focused interventions for graduate students in consideration of their unique personal and professional needs. Graduate students are part of the emerging professional workforce and as such employers are also advised to integrate wellness and mental health programs and interventions into their employee assistance programs.

Longitudinal cohort study to assess the long-term trajectory of healthcare workers' mental health during COVID-19 pandemic

IntroductionEarly evidence following COVID-19 pandemic onset showed substantial impact on Healthcare Workers' (HCWs) mental health. Most research relies on cross-sectional data collected during the pandemic early stages and longitudinal studies are mainly focused on its first year;more recent mental health data on HCWs are not yet available. The aim of this study is to assess the long-term trajectory of HCWs' psychological symptoms and the associated risk factors.Materials and MethodsA longitudinal cohort study was carried out between July 2020 and July 2022 in a large Italian hospital. At T1 (July 2020-July 2021), 990 HCWs took part in the study. For each subject, we administered a set of scales General Health Questionnaire (GHQ-12), Impact of Event Scale (IES-R), General Anxiety Disorder (GAD-7). The same set was re-administered at T2 (July 2021-July 2022). We performed McNemar's test to measure potential changes in symptoms trajectories in time and Generalized Estimating Equation (GEE) to evaluate potential risk factors associated with scorings above the cut-off.ResultsThree hundred and ten subjects participated to the follow-up evaluation. At T2, percentages of overpassing relevant cut-offs were significantly lower (p<0.001) than T1 for all scales (23% vs 48% for GHQ-12;11% vs 25% for IES-R;15% vs 23% for GAD-7). Being a nurse (IES-R OR=3.21, 95%CI 1.92–9.23;GAD-7 OR=2.34, 95%CI 1.25–4.37) or a health assistant (IES-R OR=4.43, 95%CI 1.12–13.6) and having had an infected family member (GHQ-12 OR=1.88, 95%CI 1.01–3.49) resulted as risk factors for psychological distress. Differently from T1, gender and working in COVID-19 area did not show significant associations with psychological symptoms.ConclusionsIn the second year of the pandemic, mental health among HCWs improved compared to the previous year and risk factors for psychological distress were slightly different. Longitudinal studies may help occupational health and safety professionals to address various levels of prevention.

Assessing Mental Health Status among COVID-19 Recovery Patients in Bangladesh- A Pilot Study

The impact of the COVID-19 pandemic has the potential to have long-lasting profound repercussions on the mental health of surviving patients from COVID-19. The main goal of this study is to assess the mental strength among post-COVID-19 recovery patients. A pilot survey study was conducted with 60 participants who willingly completed the questionnaire consisting of PCL-5, GAD-7, PHQ-9, and relevant questions. Univariate, bivariate analysis, and multivariate logistic regression were conducted to find the significant risk and protective factors associated with the mental health of recovery patients. The result found that 48.33% of the patients had PTSD symptoms, 30% identified to have severe anxiety, and 53.33% of them had gone through severe depression. The severity of illness, hospitalization, ignorance by family members, people staying away from them even after recovery were significant risk factors, and eating nutritious food, wearing masks were significant protective factors for PTSD, anxiety, and depression. This study's findings can guide policymakers as well as family members to take proper initiatives towards COVID-19 recovery patients, such as providing counseling, ensuring rehabilitation, reducing social stigma, which may bring consequential relief from psychological illness.

Efficacy of Online-Based Intervention for Anxiety during COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

COVID-19 has caused widespread psychological suffering. Anxiety is one of the several psychological disorders that are escalating globally, yet social distance constraints restrict in-person mental health therapy. Anxiety and other psychological disorders whose treatments are limited due to social distancing continue to grow, so there is an increasing need to use mental healthcare that can be offered remotely, especially in the pandemic era. This study aimed to conduct a systematic review and meta-analysis of the efficacy of online-based interventions for anxiety during COVID-19. This study followed the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA). We collected data from three databases, namely PubMed, CINAHL, and Oxford Library Press, published in 2020–2022. Additionally, we collected data using the snowball technique. This meta-analysis analyzed the pooled mean difference (MD) and its p-value using random-effects models. Critical appraisal and risk of bias were assessed using Cochrane Risk of Bias (Rob) 2. We retrieved 34 RCTs for systematic review and 14 RCTs for meta-analysis, yielding 9159 participants for general anxiety disorder (GAD-7) measurement and 1303 participants for depression anxiety stress scale (DASS-21) measurement. This study shows that online-based interventions significantly reduce GAD-7 score (a pooled MD of 1.30;95% CI: 2.83–4.65;p = 0.00001) and insignificantly reduce DASS-21 (0.05;95% CI: −2.63–2.72;p = 0.97) according to pre- and post-test in intervention group. Additionally, there is a significant difference between the intervention and control groups, where the intervention group performed statistically progressively better than the controls (−7.26;95% CI: −11.58–−2.95;p = 0.001) (−2.08;95% CI: −6.71–2.55;p = 0.001). Online-based interventions have proved effective for reducing general anxiety during the COVID-19 pandemic. Consequently, this meta-analysis can be adapted as a model for mental health services in the new normal.

Parental mental health and associations between living in temporary accommodation and socio-political determinants during the COVID-19 pandemic

576 Figure 1Is the adjusted odds ratio (OR) plot showing the odds of an increased rank of depression severity with living in Temporary Accommodation as the main exposure and each predictior variable given all the other variables were held constant in the model[Figure omitted. See PDF] 576 Figure 2Is the adjusted odds ratio (OR) plot showing the odds of an increased rank of anxiety severity with living in temporary accommodation as the main exposure and each predictior variable given all the other variables were held constant in the model[Figure omitted. See PDF]22.9% and 20.0% of TA parents/caregivers had severe anxiety and moderate anxiety compared to 4.0% and 25.0% of non-TA parents/caregivers, respectively. For parents/caregivers living in TA, the odds of a more severe anxiety rank were 2.46 times higher (95%CI:1.27–4.75). Other significant factors for anxiety were: Very Low Food Security (OR 4.45, 95%CI:3.26–6.08);families ‘finding it very difficult’ financially (OR 1.62, 95%CI:0.96–2.73). [Figure 2]ConclusionFamilies living in TA had a greater odds of poor parental mental health outcomes, which was further compounded by factors including NRPF status, financial insecurity, food insecurity and poor housing environments. Poor parental mental health is an adverse childhood experience (ACE) directly impacting both the health and wellbeing of the parent and child throughout the life course. Targeted policies and tailored community-based mental health strategies, including the co-location of mental health and housing support within settings already accessed by TA families with under 5s, are vitally needed, since this vulnerable group is at higher risk of poorer parental mental health and a higher ACE count, which is exacerbated by the unsuit ble and unsafe TA environment.

DIABETIC KETOACIDOSIS IN A NEW ONSET ELDERLY TYPE 1 DIABETES AFTER SARS-CoV-2 VACCINATION: ASSOCIATION OR COINCIDENCE?

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.

A Prospective Characterization of Metabolic and Metabolomic Profiles of COVID-19–Associated New-Onset Diabetes Patients Presenting with DKA from India

Background: Recent evidence suggests a bidirectional relationship between COVID-infection and new-onset diabetes (NOD) presenting with DKA. Methodology: This one-year prospective study comprised of 29 COVID-negative DKA (controls) and 52 COVID-positive-DKA patients (18 NOD, 15 T1DM ,T2DM) . NOD were previously normoglycemic and negative for GAD/IA-2/ZnT8 autoantibodies. After 75g- OGTT with estimation of glucose, C-peptide, FFA and insulin at 0,15, 30,45, 60,90 ,120, 150 and 180minutes, Insulin secretion rate (ISR) [C-peptide-deconvolution] , Hepatic insulin sensitivity [AUC-glucose × AUC-insulin during first 30-minutes of OGTT ], Peripheral insulin sensitivity [ dG/dt ÷ mean plasma insulin concentration;dG/dt rate of decline in plasma glucose concentration]were calculated alongwith Metabolomics and Adipose tissue gene expression. All tests were performed at admission and 4, 8, and 12-months of followup. Results: At baseline, ISR in NOD was significantly reduced than controls (p=0.001) but similar to T1DM (p=0.15) . Nearly 83% (n=17) of NOD with DKA had near-complete recovery of ISR on follow-up compared to T1DM (all p<0.01) ,with non-remitters (n=3) having significantly worse admission Hba1c and IL-6 (all p<0.01) . NOD had significantly increased hepatic and peripheral insulin resistance compared to T1DM (all p<0.05) ,but similar to T2DM (all p>0.05) . Their Metabolomics revealed increased inflammatory phosphatidylcholines, that correlated with peripheral glucose uptake (p<0.01) ,while RNA sequencing showed significantly enhanced WNT5A , TLR4 (Toll-like Receptor-4) and RETN (resistin) than T1DM and T2DM (both p=0.001) . Conclusion: Our study provides novel insights into COVID-associated NOD with DKA. Majority have near-complete recovery of insulin secretion while simultaneous multi-tissue insulin resistance and inflammatory adipose tissue profiles persist as drivers of hyperglycemia.

Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination.

PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been reported to trigger immune side effects. Type 1 diabetes as a manifestation of autoimmune/inflammatory syndrome induced by adjuvants has been reported in a limited number of cases after vaccinations. A few type 1 diabetes cases after SARS-CoV-2 vaccination have been reported. This study aims to report type 1 diabetes cases associated with the mRNA-based SARS-CoV-2 vaccination. METHODS: We report four cases of type 1 diabetes mellitus after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, one subject had autoimmune thyroid disease. All patients had autoantibodies against glutamate decarboxylase. RESULTS: In the presented case series, type 1 diabetes developed a few weeks after BNT162b2 vaccination. After developing type 1 diabetes, the insulin dose requirements of all patients decreased rapidly, and the need for insulin therapy in three patients disappeared during follow-up. Acute deterioration of glucose regulation in a patient followed by BNT162b2 administration may be due to vaccine-induced autoimmune diabetes. CONCLUSION: Vaccination with BNT162b2 may trigger type 1 diabetes.

Health Disparities among People with and without Diabetes during COVID-19: An 18-Month Evaluation

This study describes the mental health of US adults with and without diabetes (ND) over an 18-month period of the COVID-pandemic. A 12-month web-based survey was administered in May 2020 (N = 2,176) to June 2021 and November 2021 (18MO;N = 1,192) including demographics, pandemic experiences, depression (PHQ-8) and anxiety (GAD-7) symptoms, perceived stress (PSS) , and resilience (BRS) . Mean age of 18MO Completers (55%) was 53 years (SD = 16.4) , primarily female (80%) , White (91%) , with an annual household income of ≥ $60,000 (58%) . 165 had type 2 diabetes (T2D;14%) , 83 had prediabetes (7%) , and 56 had type 1 (T1D;5%) . Completers were more likely to be White, educated (45% post-master's degree) , and homeowners with fewer medical and emotional comorbidities at baseline than non-completers (all p<.05) . At 18MO, mean PHQ-8 score was 5.2 (SD = 5.3;mild) , GAD-7 was 4.1 (SD = 4.8) , PSS was 13.2 (SD = 5.5) . All improved from baseline (p<.001) . Ages 18-30 had the highest scores on anxiety (M = 6.1;SD = 5.4) and perceived stress (M = 16.5;SD = 8.3) compared to other age groups (p<.001) . At 18MO, rates of COVID-infection (9.1%;p<.001) , knowing someone with COVID- (86.7%) , loss from COVID- (40.7%) and pandemic burnout (M = 2.6, SD = 2.1) were increased. Greatest burnout was reported by women (M = 2.9, SD = 2.1) , 18-30 y.o.s (M = 3.5, SD = 2.0) and T1Ds (M = 3.5, SD = 1.7) , all p<.05. Financial disparities persisted at all time points. At 18MO, women (15.98%) and Latinos (28.57%) reported difficulty paying monthly bills (p<.001) . Asian/American Indian/Multiracial (23.73%) subgroup reported worsening financial situations compared to Whites (p<.001) . 51-64 y.o.s reported difficulty paying bills (20.4%) , less financial optimism (13.4%) and worsening financial situation (21.45%) compared to other age groups (p<.001) . Over 18 months, mental health outcomes improved slightly while gender, age, ethnic and racial disparities persisted as personal exposure to COVID-and pandemic burnout increased.

Household Food Insecurity, Stress, and Anxiety among Youth and Young Adults with Diabetes

Although household food insecurity (HFI) has been associated with depressive symptoms in youth and young adults (YYA) with youth-onset diabetes, little is known about the association of HFI with other mental health comorbidities. We examined the association of HFI with stress and anxiety symptoms among YYA with diabetes using cross-sectional data from the SEARCH Food Security Cohort study (assessments conducted 2018-2020;n = 1030, age =23.8± 0.3, female =58.8%, type 1 diabetes (T1D) = 881, type 2 diabetes (T2D) =149) . HFI was defined as 3+ affirmations on the USDA Household Food Security Survey Module. The Generalized Anxiety Disorder (GAD-7) and Cohen's Perceived Stress Scale (PSS-14) were used to assess outcomes of anxiety (score range 0-21) and stress (score range 0-56) , higher scores indicating greater anxiety or stress. Linear regression models were adjusted for age, sex, race/ethnicity, site, diabetes duration, parental education, income, and whether assessment was completed pre/post the coronavirus pandemic. Analyses were stratified by diabetes type. HFI was present in 17.3% of T1D and 35.6 % of T2D. Moderate/severe anxiety symptom scores (range 10-21) were found in 27.5 % (mean=6.9, s.d. =5.5) of T1D and 40.9% (mean=8.4, s.d. =6.5) of T2D. Mean stress scores were 26.7 (s.d.=6.3) for T1D and 27.9 (s.d.=6.3) for T2D. In T1D, HFI was associated with higher anxiety (β=4.8, p=<0.0001) and stress (β=4.9, p=<0.0001) symptom scores compared to those with food security adjusted for covariates. Among T2D, HFI was associated with greater anxiety symptoms (β=2.8, p=0.0247) but no association was observed with stress. These findings suggest that assessing and alleviating HFI may help improve stress and anxiety among YYA with diabetes, and further study is warranted to determine associations over time.

SARS-CoV-2 Infection Is Not Associated with Presence of Islet Autoantibodies in Children: Autoimmunity Screening for Kids (ASK)

Viral infections may trigger islet autoimmunity leading to type 1 diabetes (T1D) . We hypothesized SARS-CoV-2 infection is associated with presence of islet autoantibodies (IAb) in children. Between 8/2020 and 12/2021, ASK screened 47general population Colorado children aged 1-17 y for IAb to GAD, insulin, IA-2 and ZnT8 as well as antibodies to SARS-CoV-2 receptor binding domain (CoV-2 RBDAb) - a sensitive and specific marker of infection. Of those, 4172 (89%) have not previously received SARS-CoV-2 vaccine. During the study period, prevalence of CoV-2 RBDAb increased in unvaccinated from 1% to 58% and up to 100% among vaccinated. Among all children, the prevalence increased from 1% to 72% - an estimate of herd immunity (Figure) . Among the unvaccinated, prevalence of multiple or single high-affinity IAb did not differ between children positive vs. negative for CoV-2 RBDAb, respectively 1.23% (16/1297) vs. 1.00% (29/2875) , p=0.52. In multivariate logistic regression, presence of IAb was not associated with presence of CoV-2 RBDAb (OR=1.40, p=0.31) , adjusting for age, sex, race/ethnicity, and family history of T1D. While we found no association between past SARS-CoV-2 infection and islet autoimmunity, a confirmation in a larger population is warranted. Longer follow-up will help assess whether SARS-CoV2 infection accelerates progression from islet autoimmunity to diabetes.

DIABETES AUTOANTIBODIES STATUS IN NEWLY DIAGNOSED CHILDREN AND YOUTH WITH TYPE 1 DIABETES MELLITUS DURING COVID-19 PANDEMIC AT SINGLE SETTING (2020-2021)

Background and Aims: Four pancreatic islet cell autoantibodies (Abs) mostly associate with Type 1 diabetes (T1D) - glutamic acid decarboxylase antibodies (anti-GAD65), tyrosine phosphatase antibodies (IA 2-Ab), insulin autoantibody (anti- IAA) and zinc transporter 8 antibody. Aim: To evaluate the frequency of positive islet autoantibodies at T1D diabetes onset in youth at Varna's diabetes center during COVID-19 pandemic (2020-2021). Methods: A total of 66 newly-diagnosed patients were tested for anti-GAD65, anti-IA2 and anti-IAA (2020-2021) by ELISA. Results: The mean age of the participants was 9.0±4.3 years (52% boys), 63.6% were prepubertal. At the onset of T1D, 83.3% were with at least one positive diabetes related autoantibody while 16.7 % were with negative Abs (p < 0.0001). At diagnosis, 6.1% of patients were with 3 positive Abs, 39.3% had 2 Abs and 37.9% had 1 positive Ab. of all positive, 89.1% had anti- GAD65, followed by 60% anti-IA2, and 16.4% anti-IAA positive, resp. (p < 0.01). of all participants, 81.8% had low level of C-peptide. Weak significant correlations were found between positivity for Abs, gender (r = -0.325, p = 0.008) and age (r = 0.259, p = 0.036);as well as between C-peptide levels and age (r = 0.483, p < 0.001), anti-GAD65 (r = -0,210, p = 0.018), and anti-IA2 (r = -0.259, p = 0.036). Four patients were positive for COVID-19 at diagnosis. All of them had low C-peptide levels and at least one positive Ab. Conclusions: Most frequent diabetes associated antibody at our setting was anti-GAD65, followed by anti-IA2 and anti- IAA as reported worldwide. No Abs differences were found between those who were COVID-19 positive at diagnosis, compared to the rest, although the numbers were too small to conclude.

Type 1 Diabetes onset and COVID-19 infection in a child with Sanjad Sakati Syndrome: a case from Kuwait

Background: Sanjad Sakati Syndrome (SSS) is an autosomal recessive multisystem disorder characterized by congenital hypoparathyroidism, prenatal and postnatal growth and mental delay, dysmorphic features, and hypocalcemia seizures. It has not been linked with autoimmune disorders such as Type 1 Diabetes (T1D). Viral infections may play a role in triggering the development of T1D. Contracting SARS-CoV-2 virus may induce an autoimmune response by damaging the pancreatic β cells and accelerate the onset of T1D. To the best of our knowledge, no case studies of SSS has been reported to develop T1D were reported. Aim: To present a child with SSS who was newly diagnosed with T1D and SARS-CoV-2 infection (COVID-19). Method: Data on the patient were extracted from the Childhood Onset Diabetes electronic Registry (CODeR) in Kuwait. Results: The child was diagnosed early in life with SSS by tubulin-specific chaperone E (TBCE) gene mutation. The child is under multidisciplinary care and managed by alphacalcidol treatment. In May 2021, she presented with a history of fever, cough, polyuria, polydipsia, and poor appetite which lasted for 6 days. On investigations, random blood sugar level was 22 mmol/l and HbA1c level was 10%. There was no evidence of diabetic ketoacidosis. Autoantibodies to glutamic acid decarboxylase (GAD) and thyroperoxidase antibodies (TPO) were positive, with normal thyroid function results. Serum insulin and c-peptide levels were low (0.93 miu/ml, 28 pmol/l respectively). Thus, T1D diagnosis was made, and insulin therapy was started. No family history of diabetes was reported. On admission, the child tested positive for SARS-CoV-2 PCR and had positive contacts with family members with COVID-19 infection. As per WHO COVID-19 infection severity criteria, the child’s condition was classified as mild. She was discharged home with no short-term sequelae of COVID-19 infection;diabetes and dietary education was provided. Discussion: To the best of our knowledge, this is the first case reported in literature of a patient with SSS who presented with T1D onset along with COVID-19 infection. Viral infections such as SARS-CoV-2 virus may trigger the development of autoimmune diseases such as T1D. Exploring the relationship between COVID-19 infection and T1D onset is needed for better understand the effect of COVID-19 infection and outcome on pediatric patients with comorbidities. Further explorations are also needed to study the relationship of SSS and autoimmune disorders as well;to fully appreciate the impact on such patients.

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.

New onset diabetes in a boy with multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection

Introduction: Case report Objectives: During the past year, COVID-19 infection was recognized as a potential trigger for new onset diabetes in children. A rare but severe complication of COVID-19 infection in children and adolescents is multisystem inflammatory sindrome in children (MIS-C). We describe a case of newly diagnosed diabetes mellitus (DM) in a tenyear old patient during the course of MIS-C. Methods: Case report Results: A ten-year-old previously healthy male presented with vomiting and painful and enlarged lymph nodes. He was febrile to 39.4°C and tachycardic to 124 beats/minute. Initial laboratory evaluation was notable for acute infection, but the child also had hyperglycemia, ketonuria, glycosuria. Empiric antibiotic therapy was started, but he was persistently febrile, had lymphadenopathy with redness of the surrounding skin and developed conjunctival injection and a discrete livid erythema on the trunk. His follow up labs showed leukopenia with lymphocytopenia and neutrophilia, anemia and thrombocytopenia and upsurge of inflammation markers. Other possible causes of his condition were excluded and he tested positive for anti-SARS-CoV-2 IgM and IgG via immunochromatographic assay. Criteria for MIS-C was met, and intravenous immunoglobulin treatment was started which yielded immediate recovery. During the acute course of MIS-C his blood glucose levels were up to 15.5 mmoL/L, with no disturbances in acid-base status. Since high glucose levels and glucosuria persisted beyond resolution of the MIS-C, and HbA1c was elevated (7.8%), the patient was started on intensified therapy with insulin analogues. Islet-cells autoantibodies were only marginally elevated (GAD-65 1.9 and IA-2A 1.8 kIU/L) and C-peptide was normal. Conclusions: In pediatric population inflammatory syndromes like MIS-C can raise the risk for diabetes development or presentation. Therefore it is important to monitor glycemia during the course of MIS-C and also during post-inflammatory follow-up.