Diagnosing gestational diabetes during the Covid-19 pandemic using HbA1c rather than oral glucose tolerance test (OGTT)

The Royal College of Obstetrics and Gynaecology advocated replacing OGTT with HbA1c for gestational diabetes (GDM) screening for women with risk factors during the Covid-19 pandemic. HbA1c >=48mmol/mol/random plasma glucose (RPG) >=11.1mmol/l at booking indicated diabetes, and 41-47mmol/ mol/9-11mmol/ l prediabetes or possible GDM. Testing was repeated at 26 weeks if normal previously, with HbA1c >=39mmol/mol, fasting PG >=5.6mmol/l, or RPG >=9mmol/l diagnostic for GDM. A) At her clinic booking visit at 10 weeks gestation, 36 year-old South Asian female had HbA1c 55mmol/mol/RPG 9.5mmol/l suggesting undiagnosed type 2 diabetes. Initially managed with dietary advice and home blood glucose monitoring, metformin was added when self-monitored glucose above pregnancy targets (fasting and pre-meal <5.3mmol/l or 1 h post meal <7.8mmol/l) but insulin was required later. Metformin and insulin were stopped after delivery at 38 weeks with HbA1c 50mmol/mol three months postpartum, supporting the earlier diagnosis of type 2 diabetes. B) 32 year-old White Caucasian female was screened for GDM on booking at 11 weeks as BMI 38 kg/m2. HbA1c 44mmol/mol and RPG 6.9mmol/l confirmed GDM which was managed by dietary/lifestyle changes with glucose and pregnancy targets achieved until 28 weeks when metformin added. Normal delivery at 40 weeks with HbA1c 40mmol/mol three months postpartum triggered advice on long-term dietary/lifestyle changes and annual HbA1c checks. HbA1c was useful during the pandemic but most centres reverted to OGTT for GDM screening due to a significant fall in diagnoses using HbA1c >=39mmol/mol at 26 weeks. But, HbA1c testing was advantageous at booking to diagnose type 2 diabetes earlier.

GDM diagnosis criteria: Standard and Covid-19 criteria

Aim: Standard diagnosis of gestational diabetes (GDM) is based on the Oral Glucose Tolerance test (OGTT). During the Covid-19 outbreak, due to Covid restrictions, criteria were modified i.e Fasting Blood Glucose >=5.3 and/ or HbA1c >= 39 for diagnosis of GDM. After the lifting of the Covid restrictions, the standard criteria were reimplemented and on analyzing the data, it was highlighted that some of the patients could have tested negative for GDM based on Covid Criteria. Method(s): We analyzed the data of 43 patients based on standard criteria (OGTT and HbA1c) after Covid restrictions, with the following results. Result(s): 11/43(28%) patients who were diagnosed on the basis of standard criteria could have been missed based on Covid criteria. Out of 11 deliveries, 2 babies with weight above 4 kg. There were no admissions to NICU. One patient had postpartum hemorrhage with 670 mL of blood loss. Conclusion(s): This was a retrospective study in which we analyzed the data of 45 pregnant females diagnosed with GDM based on testing using the Covid criteria and compared this to 43 pregnant females who were diagnosed with GDM on the basis of OGTT based on GOLD standard NICE criteria. In addition, we also examined maternal and obstetric outcomes in both groups such as the mode of delivery, the baby's birth weight, the incidence of shoulder dystocia, mean blood loss (MBL), and NICU admission. We understand that Covid GDM diagnosis was a necessity of time. In this study, we want to learn what could have been missed with that diagnostic criteria. For future pandemics, we need to revise our diagnostic criteria to avoid the risk of underdiagnosing GDM and associated complications.

Optimal continuous glucose monitoring metrics for identification of women with gestational diabetes

Aims: Continuous glucose monitoring (CGM) is widely used in pregnant women with pre-gestational diabetes, but optimal targets have not been defined in gestational diabetes. Previous work identified mild hyperglycaemia in pregnant women without gestational diabetes, but with risk factors such as obesity. We aimed to examine CGM metrics and patterns of glycaemia in women with gestational diabetes compared to healthy pregnant women with comparable risk factors. Method(s): We recruited 73 healthy women with >1 risk factor (gestational diabetes excluded using Covid-19 criteria, OGTT) and 200 women with gestational diabetes (NICE and interim-Covid- 19 criteria) from antenatal clinics at 28 weeks' gestation. A Dexcom G6 CGM device was cited on the non-dominant upper arm. Result(s): Women with gestational diabetes had significantly higher weight (mean +/- SEM 95.7 kg +/- 1.3 Vs 85.4 kg +/- 2.2) and BMI (36.0 +/- 0.5 Vs 31.3 +/- 0.7) compared to healthy pregnant women (p < 0.01). Women with gestational diabetes had significantly higher mean CGM-glucose (mean +/- SEM 5.6 +/- 0.01 Vs 5.4 +/- 0.01mmol/l;p < 0.01), significantly altered time-below- range (median(IQR);1.0% (0.2-2.9) vs 2.5% (0.7-5.5);p < 0.05) and time-in- range (95.0% (91.1-97.9) vs 94.5% (87.9-96.2);p < 0.05) but comparable time-above- range to healthy women with risk factors. Diurnal glucose profiles in women with gestational diabetes were comparable to healthy women between 14:00 and 18:00, but demonstrated significant increases in glucose at all other time points during the 24-h cycle (p < 0.01). Conclusion(s): Mean CGM glucose is the most reliable CGM metric to distinguish women with gestational diabetes from healthy pregnant women with risk factors.

Was the diagnosis of gestational diabetes from 34 weeks gestation of pregnancy more prevalent during Covid-19 due to the change in how gestational diabetes was diagnosed?

Aim: During Covid we noticed that more women were being diagnosed with Gestational Diabetes (GDM) from 34 weeks gestation than prior to Covid. It was suspected that this was due to how GDM was diagnosed, from Oral Glucose Tolerance Test (OGTT) prior to Covid to HbA1c with Fasting or Random Blood Glucose (RBG) during Covid. Method(s): An audit of our GDM database was performed, looking at rates of late GDM diagnosis from 2018-present. Result(s): Prior to Covid the late diagnosis rate was 14-15%. In 2020 and 2021 this increased to 27.7%. This year diagnosis is only by OGTT, and the rate has dropped to 21%. There was also a significant rise in the number of women who were being diagnosed from 34 weeks gestation whom had previously been tested for GDM earlier in their pregnancy. In 2018 and 2019 52-56% of these women had previously been tested. In 2020 this increased up to 84% and fell to 74% in 2021. This year the rate has fallen to 67%. In 2018 and 2019 all women had been diagnosed using OGTT's. In 2020 61% of women had previously been tested for GDM by HbA1c and RBG, with this increasing to 84% in 2021. This year only 10% had previously been tested using HbA1 and RBG. Conclusion(s): The sharp increase in late diagnosis of GDM during the Covid seems to be related to the change in diagnostic testing and shows that OGTT is the more accurate way to diagnose GDM and not HbA1c with RBG.

Prevalence of Hyperglycemia in Pregnancy and Related Screening Practices in Rural Dehradun: The First Population-Based Study from Uttarakhand (PGDRD-1).

Aims: Phase I of the Prevalence of Gestational Diabetes Mellitus in Rural Dehradun (PGDRD) project estimates hyperglycemia in pregnancy (HIP) prevalence and identifies gaps in the utilization of community-related services in rural areas of the Dehradun district (western Uttarakhand); a state where notably no prior population-based study has ever been conducted despite being an Empowered Action Group state for more than two decades. Methods: Using a multistage random sampling technique, 1,223 pregnant women locally registered in the rural field practice area of a block were identified. Those requiring HIP screening were subjected to a 2-h 75 g oral glucose tolerance test during the house visit irrespective of their period-of-gestation and last meal timings, diagnosed using the Diabetes in Pregnancy Study Group India (DIPSI) criterion (when indicated). Data were collected by personal interviews using a pretested data collection tool. Statistical Package for Social Sciences version 20.0 was used for analysis. Results: The overall HIP prevalence recorded was 9.7% (95% CI: 8.1-11.5%); the majority (95.8%) were GDM followed by overt DIP (4.2%). Less than 1% of the subjects (0.7%) self-reported pre-GDM. Despite this burden, more than three-fourths were never screened for HIP in their pregnancy. Of those tested, the majority availed secondary healthcare facilities. Few even had to bear expenses in private with a very handful being tested free-of-cost by ANM in the community; findings that altogether sharply contrast to those recommended by national protocols. Conclusion: Despite the high HIP burden, beneficiaries are unable to utilize community-related universal screening protocols as desired.

Improving screening for cystic fibrosis-related diabetes in a pediatric cystic fibrosis clinic

Background: Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in people with cystic fibrosis (CF), affecting approximately 20% of adolescents and 40% to 50% of adults [1]. CF care guidelines recommend screening for CFRD using the 75-gram 2-hour oral glucose tolerance test (OGTT) yearly beginning at 10 years old. Our CF center had a below-average percentage of eligible patients adequately screened for CFRD (65% total screened [only 36% with recommended OGTT] vs ~63% nationally) because of use of a non-preferred screening method and a wide clinic catchment area.We initiated a quality improvement project to increase the percentage of eligible people with CF appropriately screened according to recommended CF care guidelines. Method(s): We began in 2019 by reviewing current data and processes to understand our baseline, goals, and anticipated barriers. We then established the goals of our project with proposed interventions and obtained institutional reviewboard approval. The three goals of our project were to fully eliminate use of the non-preferred screening method by the end of 2020, streamline local OGTT location options for families that live far from our CF center, and increase the percentage of eligible patients screened via OGTT by 20% by the end of 2020.We accomplished these goals by educating families regarding the recommended CFRD screening by OGTT in our CF newsletter;surveying families on how, when, and where they would like to complete their OGTT;and creating an OGTT informational brochure including three selected locations across our clinic geographical coverage area where OGTT can be reliably obtained. An additional goal was added in January 2022 because our percentage of appropriately screened patients dropped in 2021.We aimed to increase our percentage of eligible patients screened by 10% for the year. We are doing this by changing the location of an outlying OGTT facility after receiving negative feedback from our patients. Result(s):We fully eliminated use of the non-preferred screening method by 2020;all patients screened in 2020 were done by OGTT. We increased our total screening percentage from 65% in 2019 to 86% percent in 2020, despite difficulties created by the COVID pandemic. Our screening percentage dropped to 78% in 2021, but we have worked to offer OGTT at one of our associated pediatric clinic locations to better serve families. Conclusion(s): Using traditional quality improvement methods and processes, we eliminated use of a non-preferred CFRD screening method in our pediatric CF clinic. We have increased our screening rates to above the national average and continue to work on improving the CFRD screening process for our patients and families.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Changes in Diagnosis of Gestational Diabetes Mellitus during the Covid-19 Pandemic at a large Maternity Hospital in Southwest Ireland

Background Targeted screening for Gestational Diabetes Mellitus (GDM) occurs routinely at 24-28 weeks gestation using the oral glucose tolerance test (OGTT). During the COVID-19 pandemic, the Health Service Executive (HSE) and the Royal College of Obstetricians and Gynaecologists recommended discontinuing the OGTT to minimise hospital visits. Fasting plasma glucose (FPG), random plasma glucose (RPG), and glycated haemoglobin (HbA1c) were instead proposed for diagnosing GDM. This study retrospectively compared testing patterns and putative diagnostic rates for GDM in pregnancies using the HSE guidelines pre- and post-pandemic. Methods Pregnancies with complete gestation in the 18 months before (Group1) or 18 months after (Group2) adoption of revised HSE guidance at CUMH (01/05/2020) were included. Women with pre-existing diabetes mellitus were excluded. Results were extracted from databases at the Departments of Clinical Biochemistry and Haematology at CUH. Diagnostic cut-offs for GDM were: OGTT (FPG >=5.1 mmol/L or 2-h plasma glucose >=8.5 mmol/L), FPG (>=5.1 mmol/L), RPG (>=9 mmol/L), and HbA1c (>=39 mmol/mol). Diagnostic rates were compared using Chi-square analysis. The study was approved by the Cork Teaching Hospitals Clinical Research Ethics Committee. Results In Group1, 43.8% of 6,737 pregnancies had an OGTT, compared with 20.5% of 6,743 pregnancies in Group2. After implementing the revised guidelines, OGTT requests were 34.5% and 79.7% lower for primary and secondary care, respectively. Comparing Group1 with Group2, FPG was measured in 46.9 vs 49.8%, RPG in 13.3 vs 11.8%, and HbA1c in 23.7 vs 51.9%. The positive rate for GDM testing was 15.9% in Group1 and 22.0% in Group2 (p<0.00001). Conclusions OGTT use fell significantly with revised HSE guidelines, although only a modest reduction was observed in primary care. HbA1c use in pregnancy doubled during the pandemic. The proportion of pregnancies with biomarkers positive for GDM showed a small but significant increase upon adopting the new diagnostic guidelines.

A Clinical Case of Pheochromocytoma Presenting with Decompensated Diabetes Mellitus and Paroxysmal Hypertension

Introduction: Pheochromocytoma is a rare neuroendocrine tumor that originates from the adrenal medulla, less commonly from extraadrenal chromaffin cells (paraganglioma). In about 90% of cases, the tumor produces abnormal amounts of catecholamines. Pheochromocytomas are usually benign, but in rare cases can be malignant. Typical clinical manifestations are the result of the haemodynamic and metabolic effects of catecholamines and usually include paroxysmal hypertension with the classic triad (headache, excessive sweating, palpitations), carbohydrate disorders, etc. Elevated levels of catecholamine metabolites (metanephrine and normetanephrine) tested in plasma or in 24-hour urine confirm the diagnosis. Surgical removal of the tumor is the only radical treatment. Follow-up of patients postoperatively should be lifelong and performed by a multidisciplinary team in a specialized center of expertise. Case report: A 36-year-old female patient referred to the clinic for decompensated diabetes mellitus. Detailed history revealed paroxysmal hypertension and the classic triad of pheochromocytoma. The diagnosis was confirmed by high urinary metanephrine levels and an abdominal CT scan, showing a tumor in the right adrenal gland with features typical of pheochromocytoma. Surgical removal of the pheochromocytoma and normalization of catecholamine levels led to normalization of blood pressure and reversal of diabetes mellitus. Conclusion(s): Pheochromocytoma is a difficult diagnosis in endocrinology practice as it can mimic many other diseases. Early detection and surgical removal of the tumor are crucial to avoid complications caused by elevated serum catecholamine levels.Copyright © 2022 Medical Information Center. All rights reserved.

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.

Improving cystic fibrosis-related diabetes annual screening in adults with cystic fibrosis

Background: Cystic fibrosis (CF)-related diabetes (CFRD) is associated with decline in lung function and nutritional status. Cystic Fibrosis Foundation (CFF) guidelines recommend annual CFRD screening in patients starting at age 10. A review of our adult program data showed a decline in screening during 2020. We identified barriers, in addition to the COVID pandemic, that contributed to a decline in adherence. In July 2020, our clinic moved to a new location and began offering morning visits. After a quality improvement review, we began offering annual oral glucose tolerance testing (OGTT) within a routine clinic visit along with annual routine labs. Our objective was to use this multidisciplinary approach to increase OGTT screening to 50% within the first year of moving to our new location. Method(s): The CFF Patient Registry was used to compile a list of our nondiabetic patients overdue for annual OGTT. The list was reviewed during our multidisciplinary preclinic conference to identify patients who needed testing. Each patient was re-educated during clinic, and barriers to testing identified through patient interview and questionnaires. Common barriers to testing adherencewere length of testing time, time missed from work, COVID concerns, and needle phobia. The nurse and nurse coordinators made follow-up appointments, incorporating OGTT into next clinic appointment to increase adherence. Patients received phone call reminders for these appointments and the fasting criteria for testing. Result(s): CFF Registry Report data showed a decline in OGTT screening from 26% in 2019 to 21% in 2020.We identified 76 eligible patients who needed OGTT in 2021. Patient interviews were conducted during clinic visits and barriers identified. We offered routine clinic appointments in conjunction with lab appointments to increase screening adherence. We were able to capture seven patients in the first 6 months and 14 in the second 6 months, increasing our OGTT screening rate to 28%. Conclusion(s): Using a multimodal approach in a multidisciplinary team,we increased our OGTT annual screening rate by 7 percentage points. The ability to incorporate recommended screening into routine clinic visits supported adherence and patient satisfaction. Limitations to OGTT screening include continued COVID concerns and transportation to clinic.We plan to continue this quality improvement approach to increase adherence to 50% within this next year by continued consolidation of lab work and OGTT with visits and assisting patients with scheduling lab appointments and transportation to the clinic Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

ELEVATED ANION GAP AS A MARKER OF SEVERE SARS-COV-2 INFECTION IN PREGNANT PATIENTS WITHOUT DIABETES: A CASE SERIES

SESSION TITLE: Biological Markers in Patients with COVID-19 Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: In December 2019, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a global pandemic. The literature has been slowly growing in the subgroup of pregnant women but the metabolic derangements of pregnancy and SARS-CoV-2 have not been well described. METHODS: In this case series, we review 9 patients with severe SARS-CoV-2 infections admitted to the medical ICU at a single institution between 2020-2022, during the delta variant wave. RESULTS: Of the nine critically ill patients, the mean age was 32 ± 6.4 years with fetal age on admission of 27 ±2.81 weeks and 29 ±2.91 weeks at delivery. Average CRP of 114 ± 25 mg/L. In eight of 9 patients (89%), there was an anion gap metabolic acidosis (AGMA) on admission. The average albumin-corrected anion gap was 18±1.93. 75% of patients had mild ketonuria based on urinalysis. However, 50% had documented symptoms of nausea, vomiting, or diarrhea. While betahydroxybutyrate was checked in 2 patients, neither were abnormal. One had lactic acidosis, but none required vasopressors at time of identification. No renal failure or diabetes was noted and only two had abnormal glucose tolerance tests. At delivery, average PEEP was 10± 4 cmH2O with an average respiratory rate of 28 ± 4 breaths per minute. All patients with AGMA delivered early resulting in preterm delivery. 75% of the fetuses showed signs of distress at the time of delivery, which was the primary indication for delivery in 37.5% of deliveries. 37.5% of deliveries were due to significant maternal hypoxia. The only patient without AGMA did not deliver early. CONCLUSIONS: After excluding renal failure, toxin ingestion, and lactic acidosis, only ketosis can weakly explain the AGMA. There have been several studies that highlighted the association between COVID and ketone production. In pregnancy, placental production of glucagon and human placental lactogen and subsequent insulin resistance increases susceptibility to ketosis. A recent study posited that COVID could cause placental abnormalities. Therefore, pregnant women may be more susceptible to significant ketosis because of COVID infection. In one of our cases, the combination of hypoxia and acidosis could not be managed safely by the ventilator and resulted in early delivery. CLINICAL IMPLICATIONS: Ketosis and an elevated anion gap could be a marker for more severe outcomes in pregnant patients with COVID. This case series highlights the challenges of managing the metabolic demands of critically ill pregnant patients infected with SARS-CoV-2. DISCLOSURES: No relevant relationships by Calli Bertschy no disclosure on file for Joey Carlin;No relevant relationships by Jessica Ehrig No relevant relationships by Shekhar Ghamande no disclosure on file for Jordan Gray;No relevant relationships by Abirami Subramanian

Evolution of dry powder inhaled colistimethate sodium (Colobreathe®) in a large adult cystic fibrosis centre

Objectives: Colobreathe® is a dry powder formulation of colistimethate sodium developed to reduce treatment burden for people with cystic fibrosis. In our centre initial experience revealed 45% discontinued this therapy within 12 months, of which 83% were due to tolerance or device issues. Capsuleswere reformulated in 2017 to address some of these issues. We aimed to assess the prescription rates of Colobreathe® over 3 time periods to assess whether prescription practices and tolerance changed. Methods: A retrospective review of antibiotic challenges in the one-year periods from Dec 2013, 2016 and 2020 was conducted. Key end points included tolerance of test dose and continued use at 1 and 3 months. The proportion of antibiotic challenges that were Colobreathe® at each time point was compared. Results: Therewas a significant difference in the proportion of all antibiotic challenges whichwere for Colobreathe® across the 3 periods (2013–65/186 (35%), 2016–8/136 (6%), 2020–22/55 (40%), p < 0.001). The majority of patients at all 3 time points had previously nebulised colistimethate sodium (98%, 88% and 100%, respectively). All patients had a successful test dose during each time period. Therewas no difference in the proportion of patients who commenced long-term prescription following a 1-month review at the 3 time periods (75%, 75% and 73% respectively, p = 0.97). Of those who received a long-term prescription, continuation rates were similar at 3 months (82%, 100% and 93%, respectively). Conclusions: There was a marked reduction in inhaled antibiotic challenges in 2020, likely due to COVID. There was a significant change in prescription of Colobreathe® over the 3 time frames. Colobreathe®waswell tolerated at initial challenge and continuation rates after a month appear to be consistent. A number of factors likely influenced prescription practices, including early experience and potentially changing airway physiology following CFTR modulation introduction.

Oleic acid-induced acute lung injury in Ob/Ob mice fed with high-fat-diet exacerbate bile acid uptake and liver injury that was reversed by antagonizing their entry

Background and aims: Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. Many studies suggest that people with obesity are at increased risk of severe COVID-19, however, mechanism on liver-lung axis remains unknown. We aimed to evaluate whether bile acid (BAs) trafficking interfere with acute lung injury (ALI) in animal model with obesity. Method: Leptin deficient (ob/ob) mice fed with high-fat-diet (Ob/Ob HFD) were i.p injected with oleic acid (OA) to induce ALI. To modulate BAs uptake, mice were i.p treated with neutralizing antibody for sodium taurocholate co-transporting polypeptide (NTCP;BAs-transporter). Broncho-alveolar lavage fluid (BALF), lungs, livers and serum were obtained from mice and assessed for inflammatory (HandE staining, ALT and pro-inflammatory panel of cytokines), fibrosis (Sirius red staining, a-smooth muscle actin, collagen and fibronectin) and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test (GTT) and fasting blood sugar (FBS)) profiles. In addition, alveolarcapillary membrane injury of surfactant D (SP-D) and the receptor for advanced glycation end-products (RAGE). BAs trafficking were assessed in primary lung cells and their impact on proliferation and apoptosis were evaluated. Results: Compared to WT-littermates, OA-induced lung injury and was worsened in the in the Ob/Ob HFD in the histopathology outcome. In addition, BALF of the Ob/Ob HFD showed elevated levels of BAs (3- fold;P = 0.002) associated with increased GM-CSF, INF-g, IL-1, IL-6 and IL-8 (p < 0.01). Moreover, Ob/Ob HFD with OA showed elevated serum levels in liver enzymes, lipids, glucose and metabolic markers (p < 0.01). In addition, Ob/Ob HFD livers showed an exacerbated fibrosis profile. NTCP neutralizing antibody in Ob/Ob HFD while inhibited BAs uptake/trafficking in both primary alveolar type II (BALF showed 4-fold increase in BAs) and primary hepatocytes (serum showed 3-fold increase in BAs). SP-D, RAGE and serum metabolic markers were suppressed to normal in line with enhance lung and liver histology and maintaining cell viability. Conclusion: Modulation of BAs trafficking from the liver of obese mice to the lungs could be an important step in the pathogenesis of ALI. Antagonizing BAs uptake may suggest a therapeutic strategy in improving liver-lung axis.

An Unusual Case of Autoantibody-Negative KetosisProne Diabetes (KPD) Secondary to Marked Insulin Resistance

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.

Gestational Diabetes during the Pandemic: Screening Methods and Outcomes in First-time GDM

Objective: To study the impact of national recommendations on the method of screening used for GDM during the COVID-19 pandemic, and evaluate differences in maternal and fetal outcomes among women with first-time GDM (ftGDM). Design: A retrospective observational study in a single Tertiary London Hospital. During the pandemic, the RCOG recommended an amended GDM screening protocol to reduce hospital attendance and risk of virus transmission (fasting blood glucose level ≥5.3 and/or HbA1c ≥39 at 28 weeks of gestation). Our Trust did not adopt this due to concerns regarding its sensitivity. We adopt a 2-step approach to universal GDM screening using a 50g glucose challenge test, and refer those screening positive for a full oral glucose tolerance test. Method: Outcomes were reviewed for women with ftGDM delivering a singleton at ≥24 weeks gestation between 01/04/20 -28/ 5/21. Our primary aim was to determine the impact of the change in COVID-19 GDM screening policy, had it been implemented. Our secondary outcomes included GDM management method, maternal and perinatal complications. We excluded women with a booking HbA1c ≥42 (indicative of pre-diabetes) and those who had bariatric surgery. Demographic and outcome data were obtained from electronic databases. Results: 247 women were diagnosed with ftGDM using local screening methods. Only 23 of these women had a HbA1c ≥39 at time of diagnosis and a further 12 had FBG ≥5.3. There was no significant difference in age or ethnicity between the two groups. The locally diagnosed group had a statistically significantly lower booking BMI (P<0.001) and were less likely to require pharmacological management of GDM (P<0.001). There were no significant differences in rates of induction of labour, gestation at delivery, birth weight or any perinatal adverse outcome. However, the women in the Covid-19 GDM screening group were significantly more likely to be delivered by Emergency Caesarean Section (p = 0.03) and have gestational hypertensive disease (p = 0.025). Conclusions: If we had implemented RCOG HbA1c screening, we would have not diagnosed 207 women with GDM, 41% of whom required pharmacological treatment. It is not surprising that women with higher HbA1c values had higher rates of maternal complications, due to the well-established association between maternal hyperglycaemia and adverse obstetric outcomes. As such, it is imperative that more sensitive screening protocols such as the 50g screen are considered in any future pandemics, such that women with GDM can be identified and maternal hyperglycaemia treated to benefit in-utero fetal programming.

Breathing Curriculum for Stress Reduction in High School Students: A Feasibility Randomized Controlled Trial

Methods: This cluster-randomized pilot compared 5-minute slow DB with treatment-as-usual among four 12th-grade public high school classes. Students individually participated in the curriculum after school during COVID-19-related hybrid teaching, with DB 3 times/week and breath science education once/week. Feasibility was based on overall compliance and qualitative assessments. Preliminary effectiveness was measured with the State-Trait Anxiety Inventory (STAI) and a timed-exhale carbon dioxide tolerance test (CO2TT). Descriptive statistics and repeated analysis of variance were performed to quantify and compare cross-sectional and temporal outcomes between classes and time periods. Human subjects research approval was granted through WCG-IRB. Results: Forty-two students consented to participate. Intervention and effectiveness assessments' compliance varied from 29-91% across classes and weeks, and decreased on average 40% from baseline to follow-up. Compliance of ease/ tolerability assessments ranged from 41% to 86%, and averaged 55% for open-ended assessments. Usefulness, ease and tolerability ratings for the DB ranged from 1.63±0.74 to 2.88±0.35 on scales of 0-3 (“not at all” - “very much”);and from 2.24±0.84 to 2.60±0.55 for effectiveness assessments. Students reported enjoying the DB, CO2TT, and breath science;some found the extended exhales challenging and the curriculum and assessments time-consuming. Outcome measures demonstrated trends towards improvements (e.g., improved STAI and CO2TT before-to-after breathing exercises), but were not statistically significant. Background: Nearly 1 in 3 US adolescents meet the criteria for anxiety, an issue that has worsened with the COVID-19 pandemic. We developed a video-based, 5-week, slow diaphragmatic breathing (DB) stress-reduction curriculum for high school students and evaluated its feasibility and preliminary effectiveness. Conclusion: Implementation of this 5-week slow breathing curriculum was feasible and tolerable to this cohort. Compliance, tolerability, and effectiveness may be improved with in-class participation. Future research on simple and accessible slow-breathing exercises is warranted to address today's adolescent stress-management crisis.

Association of Maternal Nutritional Status with COVID-19 Infection and its Effects on Pregnancy Outcomes- A Retrospective Study

Introduction: Need is felt to perform research for assessing the impact of maternal nutrition status on severity of Coronavirus Disease 2019 (COVID-19) in pregnancy and effect of COVID-19 on maternal outcomes as it has not been established. Aim: To evaluate association of maternal nutritional status and pregnancy outcomes with COVID-19 infection in pregnancy. Materials And Methods: A retrospective study was conducted among 260 antenatal patients admitted in COVID-19 level 3 hospital (Teerthanker Mahaveer Medical College and Research Centre), Moradabad, Uttar Pradesh, India, from April 2020 to May 2021 with COVID-19 infection. Records were studied for the effect of maternal nutrition status along with COVID-19 and outcome of pregnancy in terms of anthropometric markers (body mass index), nutritional markers (haemoglobin, total serum proteins) and biochemical markers (oral glucose tolerance test, vitamin D). Pregnancy outcomes were assessed in terms of severity of symptoms, Intensive Care Unit (ICU) admission, labor outcome and obstetric complications. Data were tabulated and examined using the Statistical Package for Social Sciences (SPSS) version 20.0. Results: Mean age of the patients enrolled was 21.4±5.6 years. A statistically significant association was seen with high body mass index (88.24%), hyperglycaemia (82.35%), hypoproteinaemia (6.01±0.47) and hypoalbuminaemia (0.93±0.24). Statistically significant association between adverse pregnancy outcomes in terms of bleeding per vaginum (11.76%), preterm labour (54.92%), gestational diabetes mellitus (82.35%), hypertension (29.41%), Intrauterine Device (IUD) baby (35.29%) with increasing severity of COVID-19 infections. C onclusion: COVID-19 adversely affects the maternal obstetric outcome. Maternal nutrition status factors associated with severity of COVID-19 were body mass index, deranged blood sugar levels and protein levels.

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.

Service evaluation to determine the reason for increased gestational diabetes (GDM) referrals following SARS-CoV- 2 pandemic

Aims: England and Wales report on average, 700,000 annual pregnancies. From these 5% are complicated with hyperglycaemia with 87.5% of these Gestational diabetes (GDM). Pregnant women living with obesity are at higher risk of developing GDM. There is a linear relationship between glucose and adverse pregnancy outcomes. We noted a marked increase in the number of referrals with GDM to our service in 2021. The aim of this study was to compare the incidence of GDM and the characteristics of women under our service in 2021 to the pre-pandemic data from 2019. Methods: Data were collected retrospectively, analysing the data of women with GDM during the time period of 1st May to 31st July 2019 and compared to the same period from 2021. Results: The number of positive OGTT results increased by 209% in 2021 (n = 107 vs 51). In 2021 there was a 66% increase in the number women with GDM with a Body Mass Index (BMI)≥30kgm2 (36 to 60). The average BMI of this group increased from 34.9kg/m2 in 2019 to 36.5 in 2021 although this failed to reach statistical significance. Conclusion: The local incidence of GDM is higher in 2021 compared to 2019. This is driven by an increase in the number of women diagnosed with GDM with a BMI≥30. We hypothesize that this may be a result of sedentary lifestyle brought on by the lock downs because of the pandemic. Further work may be warranted in this area using a larger sample size derived nationally.

Lactose tolerance test as an alternative to hydrogen breath test in the study of lactose malabsorption.

Objectives: Lactose malabsorption is generally assessed by hydrogen breath testing (HBT). However, this test is not recommended in patients with high baseline hydrogen concentrations (H2B). In addition, breath testing is not recommended in the current situation created by the COVID-19 pandemic, due to the potential infectiveness of the samples. The objective is to assess concordance between HBT and lactose tolerance test (LTT) depending on H2B concentrations. Methods: A total of 430 patients (40 years, Q1-Q3 = 28-54 years; 66.7% women) suspected of lactose malabsorption were included in the study. Breath and heparinized blood samples were collected at baseline and sequentially after the intake of 50 g of lactose, to measure hydrogen in breath and glycemia in blood, respectively. Results: H2B was <10 ppm in 69.5% of subjects; 10-20 ppm in 14.7%; and >20 ppm in 15.8% of subjects. In patients with H2B <20 ppm, concordance between HBT and LTT was moderate and consistently improved when the cut-off in LTT was set at 15 mg/dL. The increase in hydrogen and glucose correlated negatively (r=-0.389; p<0.05). The increase in glycemia during LTT was not influenced by H2B levels obtained in HBT. Conclusions: LTT emerges as an alternative to HBT to assess lactose malabsorption in the presence of high H2B levels or when breath testing is not recommended by the circumstances. The best concordance was obtained when the cut-off for LTT was set at 15 mg/dL.