The Optimal Method to Predict Hemoglobin A1c from Flash Glucose Monitor Data

In situations where it is difficult for patients to visit hospitals, such as the coronavirus disease pandemic, it is important to more detailly predict hemoglobin A1C (HbA1c) from flash glucose monitor (FGM) data. CGM data over 14 days can be obtained from a FGM sensor;therefore, there are many options for extracting the duration from which glucose levels are derived. Thus, the extracted durations were closely studied to determine which mean glucose levels can predict HbA1c more accurately. Seventy-three outpatients with type 2 diabetes mellitus underwent HbA1c testing, wore a FGM (FreeStyle Libre Pro), and did not change diabetic treatments, on a hospital visit. FGM data over 24 h 13 days (from 00:00 on day 2 to 24:00 on day 14 [FGM attachment: day 1]) were analyzed. The mean glucose levels were calculated corresponding to the following durations: 1 day: day 2 ~ day 14 (n=13), 2 days: days 2-3 ~ days 13-14 (n=12) 12 days: days 2-13 ~ days 3-14 (n=2), 13 days: days 2-14 (n=1) [total 91 durations] (extracted mean glucose levels). Data were analyzed in all patients (n=73), in patients with hypoglycemia in the 13 days (Hypo) group (n=40), and in patients without hypoglycemia in the 13 days (Nonhypo) group (n=33). In all patients, HbA1c was correlated to all 91 extracted mean glucose levels (r=0.76-0.86, p<0.001). HbA1c was the most significantly correlated to the mean glucose levels over 13 days (days 2-14). "Correlation coefficients between HbA1c and extracted mean glucose levels" ("r, HbA1c, EMGL") were also correlated to number of extracted days for the extracted mean glucose levels (r=0.80, p<0.001 [n=91]). In the Hypo group, HbA1c was correlated to all 91 extracted mean glucose levels (r=0.55-0.73, p<0.001). The mean glucose levels over 13 days (days 2-14) were the most significantly correlated to HbA1c. "r, HbA1c, EMGL" correlated to the number of extracted days for the extracted mean glucose levels (r=0.68, p<0.001;Fig. 2). In the Nonhypo group, HbA1c was correlated to all 91 extracted mean glucose levels (r=0.73-0.87, p<0.001). The mean glucose levels over 12 days (days 2-13) were the most significantly correlated to HbA1c. "r, HbA1c, EMGL" correlated to the number of extracted days for the extracted mean glucose levels (r=0.61, p<0.001). The results of the present study are consistent with that of a previous study reporting that the minimum duration needed to estimate time in range over 90 days is 14 days. In the prediction of HbA1c using data from one FGM sensor, prolonged measurement can make the glucose management indicator more accurate. Especially for patients with hypoglycemia, the importance of prolonged measurement may be applicable.

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

Nirmatrelvir/Ritonavir Uptake among Adults with Covid-19, December 2021-October 2022

Background: COVID-19 vaccine booster uptake remains low and preventable COVID-19 deaths continue to occur, making access to oral antivirals for those most at risk of severe COVID-19 outcomes essential. Method(s): We estimated age and gender adjusted prevalence ratios of oral nirmatrelvir-ritonavir (NMV/r) uptake by sociodemographics, clinical characteristics, and prescription eligibility (based on age, underlying medical conditions, body mass index, physical inactivity, pregnancy, or smokers), among participants in a large U.S. national prospective cohort who were infected with SARS-CoV-2 between December 2021 and October 2022. Among participants who reported NMV/r uptake, we also described the proportion who reported (1) taking NMV/r as directed and (2) NMV/r was helpful for reducing COVID-19 symptoms. Result(s): Among 1,594 participants with a SARS-CoV-2 infection as of October 2022, 1,356 were eligible for NMV/r prescription;of whom 209 (15.4% [95%CI:13.5-17.3]) reported receiving NMV/r. NMV/r uptake increased from 2.2% (95%CI:1.0-3.4) between December 2021 and March 2022 to 16.5% (95% CI:13.0-20.0) between April and July 2022 and 28.6% (95%CI:24.4-32.8) between August and October 2022, respectively. Participants >=65 years of age reported the highest uptake of NMV/r (30.2% [95%CI:22.2-38.2]). Black non-Hispanic participants (7.2% [95%CI:2.4-12.0]) and those in the lowest income group (10.6% [95%CI:7.3-13.8]) had lower uptake than white non-Hispanic (15.8% [95%CI:13.6-18.0]) and high-income individuals (18.4% [95%CI:15.2-21.7]), respectively. Participants with type 2 diabetes had greater uptake (28.8% [95%CI:20.4-37.3]), compared to those without it (12.4% [95%CI:4.8-20.0]). Among a subset of 278 participants who had a prior SARSCoV-2 infection, those who had a history of long COVID reported greater uptake (22.0% [95%CI:13.9-30.1]) for a subsequent SARS-CoV-2 infection than those without a history of long COVID (7.9% [95%CI:3.9-11.8]). Among all participants who were prescribed NMV/r (N=216), 89% (95%CI:85-93) reported that they took NMV/r as directed and 63% (95%CI:57-70) stated NMV/r was helpful for reducing COVID-19 symptoms. Conclusion(s): Uptake of NMV/r increased over time coinciding with national efforts to increase awareness and access. However, most individuals who were eligible for NMV/r did not receive it. Lower NMV/r uptake among racial/ethnic minorities and individuals with lower household income suggests a need to improve awareness and address barriers to uptake in these populations.

The Complexities of Managing Hypertriglyceridemia-Induced Pancreatitis in a Critically-Ill COVID-19 Patient

Introduction: Hypertriglyceridemia-induced pancreatitis (HTP) is a variant of pancreatitis requiring unique management. The complications of COVID-19 and its treatments can make HTP therapy more nuanced. This case describes a patient who presented in diabetic ketoacidosis (DKA) with HTP, and COVID-19. The patient developed renal and respiratory failure, necessitating hemodialysis (HD) and extracorporeal membrane oxygenation (ECMO), complicating an otherwise straightforward medical management plan. Case Description: A morbidly obese (BMI 38.9 kg/m2) 43-year-old male presented to an outside hospital with abdominal pain, and vomiting, and was found to have HTP with triglycerides (TG) >2000 mg/dL (<149 mg/dL) and presumed new-onset type 2 Diabetes (HbA1c 10.9%) with DKA. Treatment with fluids, intravenous (IV) insulin infusion and plasmapheresis were initiated. He developed hypoxia after receiving over 17 liters of fluids and was intubated, subsequently developing renal failure and was transferred to our tertiary center for HD and ECMO. On admission, he tested positive for COVID-19, rhabdomyolysis [creatinine kinase 5600 U/L (30-200 U/L)], HTP [TG 783 mg/dL (<149 mg/dL), lipase 461 U/l (7-60 U/L)], glucose 269 mg/dL (not in DKA), transaminitis [AST 184 U/L (4-40 U/L), ALT 61 U/L (4-41 U/L)] and renal failure (GFR 10 ml/min/1.73m2). IV insulin infusion was initiated for hyperglycemia worsened by COVID-19 dexamethasone treatment. Plasmapheresis was performed twice with minimal effect at maintaining a low TG. Fenofibrate was not initiated due to renal failure;Lovaza could not be given via oral gastric tube;Atorvastatin was attempted once rhabdomyolysis resolved, with subsequent worsening of liver function tests. Heparin infusion was initiated for deep vein thrombosis treatment and HTP but was stopped after development of heparin induced thrombocytopenia. The patient developed worsening hypoglycemia requiring cessation of IV insulin, hypotension requiring maximum pressor support, and worsening sepsis leading to his death. Discussion(s): This case illustrates the challenges of managing a patient with HTP and COVID-19. It demonstrates how a normally straightforward treatment algorithm can become increasingly complex when factoring the patient's comorbid conditions. The case highlights the importance of knowing both treatment indications and contraindications for HTP. In this case, HTP may have been the initial diagnosis, straightforward for most endocrinologists, but its treatments and comorbid conditions ultimately made the landscape more challenging, limiting effective management and ultimately leading to this patient's demise.Copyright © 2023

Characterization of secondary bacterial and fungal infections in ICU hospitalized patients with COVID-19: retrospective observational study

Introduction: We aimed to describe the incidence, risk factors, and clinical outcomes of bacterial and fungal co-infections and superinfections in intensive care patients with COVID-19 in a retrospective observational study. Method(s): A retrospective cohort of intensive care patients with confirmed SARS-CoV-2 by PCR was analysed from January to March 2021. This was contrasted to a control group of influenza-positive patients admitted during 2012-2022. Patient demographics, microbiology and clinical outcomes were analysed. Result(s): A total of 70 patients with confirmed SARS-CoV-2 were included;6 (8.6%) of 70 had early bacterial isolates identified rising to 42 (60%) of 70 throughout admission. Blood cultures, respiratory samples, and urinary samples were obtained from 66 (94.3%), 18 (25.7%) and 61 (87.1%) COVID-19 patients. Positive blood culture was identified in 13 patients (18.6%). Bacteraemia resulting from respiratory infection was confirmed in 3 cases (all ventilator-associated). Line-related bacteraemia was identified in 9 patients (6 Acinetobacter baumannii, 4 Enterococcus spp. and 1 Pseudomonas aeruginosa and 1 Micrococcus lylae). No concomitant pneumococcal, Legionella or influenza co-infection was detected. Invasive fungal infections with Aspergillus spp. were identified in 2 cases. Pneumococcal coinfections (7/68;10.3%) were identified in the control group of confirmed influenza infection;clinically relevant bacteraemias (6/68;8.8%), positive respiratory cultures (15/68;22.1%). The rate of hospital- acquired infections was 51.4% for COVID-19 and 27.9% for influenza. Longer intensive care stay, type 2 diabetes, obesity and hematologic diseases were independent risk factors for superinfections in the COVID-19 cohort. Conclusion(s): Respiratory coinfections occurred in influenza but not in COVID-19 patients. The rate of hospital-acquired infections (51.4% for COVID-19;27.9% for influenza) was unexpectedly high in both groups.

Hyperglycemia and Hypoglycemia Contributions to Acute Respiratory Distress Syndrome

Purpose of Study Non-diabetic COVID-19 patients with elevated admission fasting blood glucose levels ('hyperglycemia') inexplicably have an increased 28 day mortality and higher inhospital complications including the Acute Respiratory Distress Syndrome (ARDS) but potentially contributing blood glucose changes during ARDS development were not reported (Wang S et al: Diabetologia 2020). Our goal was to determine blood glucose alterations before and during acute lung injury development in a rat model used to study ARDS. Methods Used We sequentially evaluated blood glucose levels for 24 hours and lung lavage protein levels (lung permeability) and lung lavage neutrophil numbers (lung inflammation) at 24 hours to assess acute lung injury ('ARDS') in young (~3 month) and old (~12 month) control and a novel strain of hyperoxia surviving 'resistant' rats before and after administering high and low insulin doses and before and after interleukin- 1/lipopolysaccharide (IL-1/LPS) insufflation. Summary of Results Glucose levels increase rapidly and sequentially in young control, but not young resistant, rats peaking ~2 hours after insufflation. Glucose levels also increase in old control and old resistant rats after insufflation compared to young control and young resistant rats after insufflation. The pattern of glucose levels at 2 hours after insufflation resembles lung lavage proteins and neutrophils at 24 h after insufflation (table 1). Administering high insulin (High In) doses decreases glucose levels ('hypoglycemia') and worsens ARDS while administering low insulin (Low In) doses correct glucose levels and improve ARDS. Conclusions Hyperglycemia develops in both young and old rats developing ARDS and high or low glucose levels parallel worse acute lung inflammation and acute lung injury ('ARDS'). Controlling glucose judiciously with insulin may be beneficial in combatting ARDS caused by SARS-CoV-2 infection and other insults.

Effect of telehealth-based versus in-person nutritional and exercise intervention on type II diabetes mellitus improvement and efficiency of human resources utilization in patients with obesity

Aims: Telehealth became a patient necessity during the COVID pandemic and evolved into a patient preference in the post-COVID era. This study compared the % total body weight loss (%TBWL), HbA1c reduction, and resource utilization among patients with obesity and diabetes who participated in lifestyle interventions with or without telehealth. Method(s): A total of 150 patients with obesity and diabetes who were followed every 4-6 weeks either in-person (n = 83) or via telehealth (n = 67), were included. All patients were provided with an individualized nutritional plan that included a weight-based daily protein intake from protein supplements and food, an activity/sleep schedule-based meal times, and an aerobic exercise goal of a 2000-calorie burn/week, customized to patient's preferences, physical abilities, and comorbidities. The goal was to lose 10%TBWL. Telehealth-based follow-up required transmission via texting of weekly body composition measurements and any blood glucose levels below 100 mg/dl for medication adjustments. Weight, BMI, %TBWL, HbA1c (%), and medication effect score (MES) were compared. Patient no-show rates, number of visits, program duration, and drop-out rate were used to assess resource utilization based on cumulative staff and provider time spent (CSPTS), provider lost time (PLT) and patient spent time (PST). Result(s): Mean age was 47.2 +/- 10.6 years and 74.6% were women. Mean Body Mass Index (BMI) decreased from 44.1 +/- 7.7-39.7 +/- 6.7 kg/m2 (p < 0.0001). Mean program duration was 189.4 +/- 169.3 days. An HbA1c% unit decline of 1.3 +/- 1.5 was achieved with a 10.1 +/- 5.1%TBWL. Diabetes was cured in 16% (24/150) of patients. %TBWL was similar in regards to telehealth or in-person appointments (10.6% +/- 5.1 vs. 9.6% +/- 4.9, p = 0.14). Age, initial BMI, MES, %TBWL, and baseline HbA1c had a significant independent effect on HbA1c reduction (p < 0.0001). Program duration was longer for in-person follow-up (213.8 +/- 194 vs. 159.3 +/- 127, p = 0.019). The mean annual telehealth and in-person no-show rates were 2.7% and 11.2%, respectively (p < 0.0001). Mean number of visits (5.7 +/- 3.0 vs. 8.6 +/- 5.1) and drop-out rates (16.49% vs. 25.83%) were lower in telehealth group (p < 0.0001). The CSPTS (440.4 +/- 267.5 min vs. 200.6 +/- 110.8 min), PLT (28.9 +/- 17.5 min vs. 3.1 +/- 1.6 min), and PST (1033 +/- 628 min vs. 113.7 +/- 61.4 min) were significantly longer (p < 0.0001) for the in-person group. Conclusion(s): Telehealth offered comparable %TBWL and HbA1c decline as in-person follow-up, but with a shorter follow-up, fewer appointments, and no-shows. If improved resource utilization is validated by other studies, telehealth should become the standard of care for the management of obesity and diabetes.Copyright © 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.

Rates of Hypoglycemia with Reduced- vs. Standard-Dose Insulin for Hyperkalemia Treatment in Renal Insufficiency

Objective: The primary objective was to assess the difference in rates of hypoglycemia (blood glucose (BG) <=70 mG/dL) when using reduced-dose (5 units) vs. standard-dose (10 units) of IV regular insulin for hyperkalemia treatment in renal insufficiency. Secondary objectives include the efficacy of insulin dose on potassium reduction and evaluating the difference in rates of severe hypoglycemia (BG <=54 mG/dL) between the groups. Method(s): This was a retrospective chart review of patients with renal insufficiency treated with IV regular insulin for hyperkalemia at a tertiary care teaching hospital from June 2020 to June 2021, with institutional review board approval. Inclusion criteria encompassed patients aged 18 years and older with elevated baseline potassium (>=5.5 mEq/L), estimated glomerular filtration rate < 30 mL/min/1.73m2, end stage renal disease, or presence of acute kidney injury, having received either 5 or 10 units of IV regular insulin for hyperkalemia, and had documented glucose and potassium levels after insulin administration. Patients who were pregnant, had diabetic ketoacidosis, or a baseline BG <=70 mG/dL were excluded. Data collection included patient demographics, diabetes history, relevant labs at time of elevated potassium, doses of insulin and dextrose administered for hyperkalemia treatment, presence of coronavirus-19 infection, glucose levels within 6 hours and first potassium level within 24 hours following insulin administration, concurrent use of potassium-lowering agents, insulin outside of hyperkalemia treatment, or steroids, and mortality. Result(s): Out of 409 patients included, 92 were in the 10-unit group and 317 in the 5-unit group. The rate of hypoglycemia in the 5-unit arm vs. the 10-unit arm was 6.9% vs. 8.7% (p=0.649), respectively. The rate of severe hypoglycemia between the 5-unit arm and the 10-unit arm was 3.2% vs 5.4% (p=0.682), respectively. The percent normalization of potassium was not statistically different between the 5-unit group and the 10-unit group (59% vs. 68%;p=0.115), with the same mean reduction in potassium from baseline (0.8 mEq/L (p=0.947)). Administration of concurrent treatments for hyperkalemia was similar between the groups, with dialysis being the only one with statistical significance in normalization of potassium. Patient characteristics that could have an impact on risk of hypoglycemia were studied and analyzed, including pre-treatment BG, history of diabetes mellitus, insulin naive, and patient weight. In patients with hypoglycemia (n=30) vs. those without hypoglycemia (n=379), there was a significantly different mean pre-treatment BG (113 mG/dL vs. 178 mG/dL, p<0.001). Discussion/Conclusion: There was no significant difference in rates of hypoglycemia and severe hypoglycemia between the 5-unit vs. 10-unit groups. There was no significant change in potassium normalization between the two insulin doses. Because of the small number of hypoglycemia events, larger studies are needed to better understand if 5 units of regular insulin is a safer option for the treatment of hyperkalemia in renal insufficiency.Copyright © 2023

Lifestyle and Affective Emotions in Patients with Type 2 Diabetes Mellitus, With or Without COVID-19 History

Background: The management of patients with T2DM is often complicated by psychological disorders including distress, depression, and anxiety, which might negatively impact diabetic patients' life quality and coping mechanisms with their disease. Patients with T2DM are more likely to experience severe or fatal COVID-19 infection. A cross-sectional study on patients with diabetes mellitus during the COVID-19 pandemic found that more than 90% of the participants had features of ongoing mental suffering. Objective(s): To compare lifestyle, positive & negative affective emotions in patients with T2DM, with or without COVID-19 history. Method(s): Using a cross-sectional design, we conducted a study in a primary care facility in Campeche, Mexico. Sixty participants with T2DM were included, thirty per group (COVID-19 history or not). IMEVID questionnaire designed to measure lifestyle in subjects with T2DM was applied. PANAS, a 20-item questionnaire assessed positive affects (10 items) and negative affects (10 items) experienced by the participants in the previous month. Result(s): The most frequent lifestyle was unhealthy with 68%. About both positive and negative affects, were classified as low with 68.3 and 66.7% respectively. Conclusion(s): In this study, no significant relation was observed between the lifestyle and the positive and negative affects of T2DM patients with and without a history of COVID-19. Although several risk factors identified for COVID-19 related mortality in people with T2DM cannot readily be modified, been able to identify unhealthy lifestyle in this cohort allow to intervene early to avoid worst outcomes in subjects infected with COVID-19 and they have uncontrolled T2DM. Keywords: Diabetes mellitus, lifestyle, positive affects, negative affects, and COVID-19 Abbreviations: T2DM: Type 2 Diabetes Mellitus, IMEVID: Instrumento para medir el estilo de vida en diabeticos (Instrument to measure lifestyle in diabetics), PANAS: Positive and Negative Affect Schedule Funding and Conflicts of Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Copyright © 2023

Diazoxide in the Treatment of Asymptomatic Refractory Hypoglycemia in End Stage Renal Disease

Introduction: Diabetic patients with end-stage renal disease (ESRD) treated with insulin or any other diabetic agent show high variations in their glucose metabolism, lower insulin clearance level, and uncertain accuracy of glycemic control measurements. Therefore, these patients are at a greater risk of developing hypoglycemia. Diazoxide use in the treatment of spontaneous and refractory hypoglycemia in this population has not been well documented. We report a case of a young diabetic male that has been successfully treated with diazoxide for his asymptomatic refractory hypoglycemic episodes. Case Description: A young man with type 2 diabetes mellitus complicated by diabetic nephropathy, on hemodialysis for ESRD, presented with shortness of breath due to COVID pneumonia. After resolution of his infection, he was noted to have recurrent asymptomatic hypoglycemic episodes, although he has been off his diabetes medications for the past few years due to worsening of his kidney function. His oral intake was adequate and there was no concern for malnutrition, or any substance use. From the testing performed, we were able to exclude exogenous insulin or insulin secretagogues use and the presence of insulin antibodies. Insulin and noninsulin (insulin-like growth factor) mediated mechanisms were also ruled out. Since he was having recurrent and refractory asymptomatic hypoglycemic episodes and to minimize the need for supplemental dextrose containing fluids, he was started on diazoxide at 3 mg/kg/day. Knowing the risk of fluid retention with diazoxide, this patient on hemodialysis tolerated it well. Diazoxide helped reduce his episodes of hypoglycemia and he was then safely discharged on it. Discussion(s): In ESRD, hypoglycemia can be explained by the impaired contribution of the kidneys to gluconeogenesis and glucose release, as well as the higher insulin levels caused by insulin resistance and decrease in insulin clearance. When his hypoglycemia persisted even after the resolution of his infection, further testing and work-up was done and other causes of hypoglycemia were ruled out. Generally, diazoxide is used as a treatment to manage the symptoms of hypoglycemia in congenital hyperinsulinism, insulinomas and post bariatric surgery cases of hyperinsulinemic hypoglycemia. However, it has not been the optimal treatment when it comes to treating hypoglycemia in ESRD patients because of its side effects;specifically, fluid retention, and electrolyte imbalances. In our case, the patient was treated with diazoxide as a last resort, despite its known side effects and the limited documentation of its use in ESRD patients. Actually, a few other case reports, have also shown promising results with the use of diazoxide for that purpose with no or minimal side effects. However, there are not enough studies that have shown the benefits or risks of long-term treatment of diazoxide in ESRD patients, an area of growing interest.Copyright © 2023

Glycemic Control Improvement amongst Patients with Diabetes Mellitus during a COVID-19 Lockdown in Jordan

Aims: The purpose of this study is to evaluate the effects of lockdown measures by the Jordanian government to contain the spread of the novel corona virus (COVID-19) on glycemic control of patients with diabetes mellitus. Method(s): This cross-sectional study was conducted in Jordan University Hospital. A total of 264 patients with type 2 or type 1 diabetes mellitus were sampled. The authors evaluated the extent of glycemic control reached by patients with type 2 or type 1 diabetes mellitus by measuring change in glycosylated hemoglobin (A1C) values, in addition to the number of hypoglycemic episodes experienced by patients during lockdown. The authors conducted a questionnaire via telephone interviews to record information about drug adherence and availability, diet, physical activity, and telephone consultations. A paired sample t-test was used to compare values before and after lockdown. Result(s): A significant reduction in HbA1C values was found during lockdown (p=0.038), with only 33.6% of patients experiencing one or more hypoglycemic episodes;both factors suggest controlled blood glucose levels. Medication adherence was found to be the main reason for improvement, with 74.8% of our population being strongly adherent to their medications. Conclusion(s): In Jordanian patients with diabetes mellitus, glycemic control was significantly improved during COVID-19 lockdown and this was found to be associated with strong medication adherence.Copyright © 2023 University of Jordan,Deanship of Scientific Research. All rights reserved.

Hiv and Chronic Comorbidities: Medication Adherence and Clinical Endpoint Covariation

Background: Evidence suggests negative monthly medication adherence trends during the COVID-19 era for patients with HIV (PWH) and multiple chronic conditions. However, it is unknown whether observed trends are associated with changes in outcomes of HIV care before and during the COVID-19 era. Method(s): Adult PWH with type 2 diabetes, hypertension, and/or hypercholesterolemia were identified in a US mid-Atlantic integrated health system. Multivariable population-averaged panel general estimating equations were used to assess the relationship between medication adherence [i.e., accepted dichotomous thresholds for optimal proportion of days covered (PDC)] for four medication groups: antiretrovirals [ART], diabetes medications [DMs], renin-angiotensin antagonists [RASMs], and statins [SMs] and their related clinical endpoints [i.e., viral load (VL;copies/mL), HbA1c, systolic and diastolic blood pressure (SBP, DBP;mmHg), and total cholesterol (TC;mg/dl)] during a 37-month longitudinal observation period [9/2018-9/2021]. Covariates included demographics, number of medication groups, COVID-19 era (starting 3/1/2020), and a COVID-19/PDC interaction term. Result(s): The cohort [n=543] was predominantly 51-64y [59.30%], Black [73.11%], male [69.24%], and privately insured [65.38%]. All patients were prescribed ART with 75.32% co-prescribed SMs;followed by RASMs [42.73%];and DMs [25.60%]. ART PDC>=0.9 was associated with decreased odds of VL>=200 copies/mL [aOR=0.77, 95% CI: 0.63-0.94]. For DMs, RASMs and SMS, PDC>=0.8 was not associated with the clinical endpoints of HbA1c>=7.0% [aOR=0.99, 95% CI: 0.94-1.04], SBP>=130 mmHg [aOR=1.03;95% CI: 0.93-1.14], DBP>=80 mmHg [aOR=1.05, 95% CI: 0.94-1.16] or TC>=200 mg/dl [aOR=1.00, 95% CI: 0.96-1.04], respectively. The COVID-19 era [3/2020 to 9/2021] was associated with increased odds of SBP>=130 [aOR=1.22, 95% CI: 1.01-1.48], but not for DBP>=80 mmHg [aOR=1.05, 95% CI: 0.85-1.28], VL>=200 copies/ mL [aOR=1.01, 95% CI: 0.67-1.52], HbA1c>=7.0% [aOR=0.99, 95% CI: 0.88-1.11], and TC>=200 mg/dl [aOR=0.95, 95% CI: 0.86-1.04]. No interactions between COVID-19 era and PDC on clinical endpoints were observed. Conclusion(s): ART adherence was associated with viral suppression in PWH, but there were no observed associations between DM, RASM, and SM adherence and their respective clinical endpoints. With the exception of a direct relationship between the COVID-19 start date and SBP, the COVID-19 era was not associated with variations in VL, HbA1c, DBP, and TC clinical endpoints.

New Onset Diabetes and Acute Pancreatitis- A Sequela of Long COVID?

Introduction: The association between worse COVID-19 outcomes and diabetes has been well-established in the literature. However, with more cases of new-onset diabetes and pancreatitis being reported with or after COVID-19 infection, it poses the question if there is a causal relationship between them. Case Description: 31 y/o female with COVID-19 infection 4-6 weeks ago with moderate symptoms (not requiring hospital admission or monoclonal ab), presented to ED with bandlike epigastric pain radiating to back, which is worsened with food, associated with nausea, vomiting, polyuria, and fatigue. Workup showed lipase 232, AST 180, ALT 256. Blood glucose was 281 and HbA1c was 12. CT A/P showed post cholecystectomy status, normal pancreas with mesenteric adenitis. MRCP showed hepatic steatosis with trace fluid around the pancreas s/o inflammation, and no evidence of choledocholithiasis or biliary dilatation. She denied alcohol use and autoimmune workup for pancreatitis was unremarkable. Islet cell antibodies were negative. The patient improved with fluid resuscitation and was discharged home on insulin with plans to transition to oral agents outpatient. Discussion(s): Long COVID is defined as a range of conditions or symptoms in patients recovering from COVID-19, lasting beyond 4 weeks after infection. A retrospective cohort study showed increased new-onset diabetes incidence in patients after COVID-19. This was redemonstrated in a systematic review and meta-analysis that showed a 14.4% increased proportion of new diagnoses of diabetes in patients hospitalized with COVID-19. Possible pathophysiology that have been attributed to this include undiagnosed pre-existing diabetes, hyperglycemia secondary to acute illness and stress from increased inflammatory markers during the cytokine storm, the effect of viral infections on the pancreas, and concurrent steroid use in patients with severe respiratory disease. The binding of SARS-CoV-2 to ACE2 receptors is thought to the other mechanism by which COVID can cause pancreatitis and hyperglycemia. Study showed increased lipase and amylase levels in patients with COVID and the increase in serum levels was proportional to the severity of the disease. Patients who died due to COVID-19 were also found to have degeneration of the islet cells. While, several studies have showed new onset diabetes and pancreatitis during an active COVID infections, we need larger cohort studies to comment on its true association or causation, especially in patients with long COVID symptoms. As more cases of new onset diabetes and pancreatitis with COVID-19 are being reported, there may be a need for more frequent blood sugar monitoring during the recovery phase of COVID-19.Copyright © 2023

Performance of a Computerized Insulin Infusion Protocol in 359 Critically Ill Patients with COVID-19

Objective: People with diabetes and uncontrolled hyperglycemia are at high risk of COVID-19 complications and as such, many patients admitted to the ICU with COVID-19 have diabetes or stress hyperglycemia. It is suggested that quick and adequate control of hyperglycemia without increasing the risk of hypoglycemia is imperative to improve outcomes in these patients. Control of wide fluctuations of glycemic variances in these patients may often require modifications of existing strategies of glycemic management. Use of a computerized insulin infusion protocol (CIIP) in these settings could be largely beneficial in getting early and sustained glycemic control. We report our experience with the Lalani Insulin Infusion Protocol (LIIP), a novel CIIP with dynamic and adaptive glycemic targets in accordance with the patient's glycemic state, in critically ill COVID-19 patients with hyperglycemia treated with IV insulin. Method(s): We conducted a retrospective analysis of 359 critically-ill COVID-19 patients in whom LIIP was used (8/18/2020 to 08/31/2022) at six HonorHealth Hospitals in the Phoenix metropolitan area. Primary endpoints of the analysis included Time to Euglycemia (min), % of time in euglycemia (70-180 mg/dl), % of time in hyperglycemia (>180 mg/dl), and % of time in hypoglycemia (<70 mg/dl). We also report the average length of stay (ALOS) in the hospital and ICU as well as the discharge dispositions of these patients. Result(s): Of the 359 critically ill COVID-19 patients who received IV insulin directed by LIIP, 167 patients had diabetes, 266 patients were treated with steroids, 226 patients had compromised renal function (eGFR< 60), 40 patients had sepsis, and 5 patients had cardiovascular comorbidities. The following glucometrics were observed: average Time to Euglycemia from baseline glucose values was 278 minutes, average % time in euglycemia was 83.01%, average % time in hyperglycemia was 16.77%, and average % time in hypoglycemia was 0.22%. Of the 359 patients, there were 166 deaths (46.2%), 91 patients were discharged to home (25.4%), and 102 patients were discharged to an interim facility (28.4%). The hospital ALOS was 15.02 days and ICU ALOS was 9.50 days. Discussion/Conclusion: For HonorHealth hospitals, LIIP was a safe and effective method of quickly achieving and maintaining euglycemia in critically ill patients with COVID-19, while maintaining low hypoglycemia incidence. Herein the patients reported had varying degrees of comorbidities and treatments, including steroids and vasopressors;however, no modifications in glycemic management strategy or nursing workflow were necessary during the use of LIIP due to its adaptive formula which individualizes IV insulin rates for each patient.Copyright © 2023

Presentation of Takotsubo Cardiomyopathy in a Patient with Coronavirus-19 Disease

Case Report: It is well documented that Coronavirus Disease 19 (COVID-19) patients who suffer cardiac injury have a higher mortality rate, however the exact mechanism of cardiac injury and potential complications are still unknown. Takotsubo Cardiomyopathy (TCM), which was first described in 1990 in Japan, is characterized by a transient systolic and diastolic left ventricular dysfunction with a range of wall motion abnormalities predominantly affecting women often following an emotional or physical trigger. Though TCM is seen less commonly as a cardiac complication of COVID-19, with increasing rates of cardiovascular events due to COVID-19, TCM should be taken into consideration as a potential diagnosis for a COVID-19 positive patient. Case Description: The case of a 75-year old female with a history significant for hypertension, type 2 diabetes mellitus, hyperlipidemia, and gastroesophageal reflux disease presented to the Emergency Department after a ground level fall and subsequent left hip pain. Upon primary survey, EKG showed persistent sinus tachycardia in the 130-150s, with intermittent borderline dynamic changes and a troponin that was mildly elevated at 0.10, and an initial false negative COVID-19 test. Preoperative echocardiogram showed normal left ventricle size, no regional wall abnormalities, and a left ventricular ejection fraction (LVEF) of 60-65%. In post-operative care, EKG illustrated dynamic changes in the form of ST elevation in the lateral precordial leads, as well as an increase in the cardiac troponins, from 0.07 to 3.51. A subsequent echocardiogram illustrated a drop in her ejection fraction from 60-65% to 30-35%, with evidence of left ventricular systolic dysfunction that was not noted on previous echocardiograms. Following the Mayo clinic diagnostic criteria, this patient met the diagnostic criteria for TCM, as evident by new electrocardiograph findings, non-obstructive cardiac catherization findings, echocardiogram findings illustrating transient left ventricular systolic dysfunction, modest elevations in cardiac troponins as well as the patient being a post-menopausal female. Subsequent echocardiogram on 2 week follow up showed a rebound in her ejection fraction to 50-55%. Discussion(s): Possible outcomes of TCM include cardiogenic shock, respiratory failure, and death. It is imperative that clinicians consider TCM as a possible diagnosis when treating COVID-19 patients that may be exhibiting cardiac complications. Frequent ECG monitoring and a vigilant differential should include TCM in patients presenting with COVID-19.

Antibiotics in Paediatrics: A Boon or a Bane?

Antibiotics play an essential role in antimicrobial therapy. Among all the medications in children, the most commonly prescribed therapy is antibiotics and is currently the indispensable means to cure transmissible diseases. Several categories of antibiotics have been introduced into clinical practice to treat microbial infections. Reducing the unnecessary use of antibiotics is a global need and priority. This article aims to provide better knowledge and understanding of the impact of the early use of antibiotics. This article highlights the proper use of antibiotics in chil-dren, detailing how early and inappropriate use of antibiotics affect the gut microbiome during normal body development and consequently affect the metabolism due to diabetes mellitus, obe-sity, and recurrence of infections, such as UTI. Several new antibiotics in their development stage, newly marketed antibiotics, and some recalled and withdrawn from the market are also briefly discussed in this article. This study will help future researchers in exploring the latest information about antibiotics used in paediatrics.Copyright © 2023 Bentham Science Publishers.

Hypoglycemic Therapy and the Course of Post-Covid Syndrome, is There a Connection?

Diabetes mellitus (both type 1 and type 2) is considered one of the risk factors for severe COVID-19 and death from this infection. Past infection with COVID-19 leads to deterioration in the control of existing diabetes mellitus, progression of pre-diabetes to diabetes, an increase in the number of new cases of diabetes and an increase in the proportion of glucocorticoid-induced diabetes, which significantly aggravates the course of post-COVID syndrome for this category of patients. Antihyperglycemic drugs may influence the pathogenesis of COVID-19, which may be of relevance for the treatment of patients with type 2 diabetes mellitus and post-COVID syndrome. The review also presents our own data on the effect of various regimens of oral hypoglycemic agents on post-COVID syndrome in people with type 2 diabetes mellitus. The observation showed that the use of dipeptidyl peptidase-4 inhibitors as part of a treatment strategy in patients with type 2 diabetes mellitus with a past COVID-19 infection was associated with a decrease in the duration and severity of post-COVID symptoms.Copyright © 2023 The Russian Archives of Internal Medicine. All rights reserved.

New Onset Autoimmune Disease More Common after Covid-19

Background: Viral infections including SARS-CoV-2 may trigger autoimmune disease through T-cell-mediated autoimmune response through molecular mimicry-cross-reactive T-cell recognition or bystander T-cell activation. Autoantibodies have been detected in patients with COVID-19 and some human proteins have homologous regions with SARS-CoV-2 peptides that could function as autoantigens. While there are scattered reports of various autoimmune diseases diagnosed after COVID-19, the risk is not known. Method(s): TriNetX (a global federated health research network providing access to electronic medical records across 72 large healthcare organizations) was utilized to define a cohort of adults 18 years or older seen on or after January 1, 2020 with at least one follow-up visit after an index date. Exposure was defined as COVID-19 diagnosis by ICD10 code or positive laboratory test. Controls did not have COVID-19 (by the same criteria) and were propensity score-matched to patients who had COVID-19 by age and female sex. Index date was the date of COVID-19 diagnosis or first provider visit for any reason during the study period for controls. Outcomes (see table) were assessed starting one month after index date (to exclude prior undiagnosed autoimmune disease) until one year after. Patients with a specific outcome prior to the index date or within one month after the index date were excluded from the analysis for that outcome. Incidence by COVID-19 exposure status and risk ratios for each outcome were assessed. Result(s): 4,016,472 patients were included (2,008,236 in both groups). Overall, mean (SD) age was 49.2 (17.9) and 57.7% were female. Patients who had COVID-19 were more likely to be white (63 vs 56.9%;p< 0.001). Rheumatoid arthritis, psoriasis and type 1 diabetes mellitus had the highest incidence after COVID-19 (0.24, 0.22 and 0.19%, respectively). While the incidence of most of the autoimmune diseases assessed were low in both groups, the risk ratios for all but one condition (Grave's) showed statistically significant higher risk in patients after COVID-19 than in those without COVID-19 (see table). Risk ratios were highest for polyarteritis nodosa (4.43, 3.27-6.01), reactive arthritis (3.56, 2.05-6.2) and ANCA-associated vasculitis (3.36, 2.6-4.34). Conclusion(s): Autoimmune diseases were more likely to be diagnosed within the first year after COVID-19 than in age-, sex-matched controls. Future work will assess the validity of autoantibodies in predicting autoimmune disease after COVID-19. (Table Presented).

Diabetes mellitus and COVID-19: A bidirectional relationship?.

The COVID-19 pandemic has generated a public health emergency around the world. The risk, severity, and mortality of the disease has been associated to chronic diseases, such as diabetes mellitus. There are multiple patho-physiological explanations that relate these two entities. The possibility of a bidirectional relationship between COVID-19 and diabetes mellitus type 1 and 2 has been raised. Most studies agree that diabetes mellitus of any etiology is associated with a negative outcome of the infection. Also, CO-VID-19 can cause a worsening of glycemic control and can be a trigger for the development of diabetes mellitus type 1.Copyright © 2023 Universidad de Antioquia.