Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review.

OBJECTIVE: Optimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19. METHODS: A systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for "steroid-induced diabetes" or "steroid-induced hyperglycemia." Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality. RESULTS: Initial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19-related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens. CONCLUSION: Few RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.

Adverse events of alpelisib: A postmarketing study of the World Health Organization pharmacovigilance database.

AIMS: To explore and describe the adverse reaction signals in the safety reporting for alpelisib. METHODS: We performed a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database from 1 January 2019 to 30 June 2021. Disproportionality analysis by information components (ICs) were used to evaluate the potential association between adverse events (AEs) and alpelisib. RESULTS: A total of 33 327 reports were extracted, 5695 of them were chosen with alpelisib as the suspected drug. After combining the same ID, 687 cases remained. The 45-64-years group had the most cases (n = 203, 29.55%). There were 129 Preferred Terms with significant signals. Hyperglycaemia (IC025 = 6.74), breast cancer metastatic (IC025 = 5.85) and metastases to liver (IC025 = 4.70) were the AEs with the strongest signal. AEs with the most cases were hyperglycaemia (n = 595), rash (n = 535) and diarrhoea (n = 475). CONCLUSION: We established a comprehensive list of AEs potentially associated with alpelisib. AEs with the most significant signals were hyperglycaemia, breast cancer metastatic, metastases to liver. The AEs with the most cases were hyperglycaemia, rash, diarrhoea, blood glucose increase and nausea.

Impact of COVID-19 therapy on hyperglycemia.

The goal of this study was to analyze the effect of COVID-19 drugs and biologicals on hyperglycemia. A literature search with key terms, such as "COVID-19 drugs and hyperglycemia" and "COVID-19 vaccines and hyperglycemia," was conducted using PubMed through September 2021. The CDC data were referenced for current COVID-19 profile and statistics. The NIH COVID-19 guidelines were referenced for updated treatment recommendations. Micromedex and UpToDate were used for drug and disease information. Current results suggested that corticosteroids (dexamethasone), remdesivir and antivirals (lopinavir and ritonavir) all have the potential to significantly raise blood glucose levels putting patients at elevated risk for severe complications. In contrary, hydroxychloroquine is associated with hypoglycemia, and tocilizumab decreases inflammation which is associated with improving glucose levels. Other anti-cytokine bioactive molecules are correlated with lower blood glucose in patients with and without diabetes mellitus. Ivermectin, used for mild COVID-19 disease, possesses the potential for lowering blood glucose. Covishield, Pfizer-BioNTech, and Moderna have all been associated with hyperglycemia after the first dose. Individualized /personalized patient care is required for diabetic mellitus patients with COVID-19 infection. Improper drug therapy aggravates hyperglycemic conditions and other comorbid conditions, leading to increased morbidity and mortality.

Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial.

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).

Insulin management in hospitalized patients with diabetes mellitus on high-dose glucocorticoids: Management of steroid-exacerbated hyperglycemia.

BACKGROUND: Glucocorticoid (GC)-exacerbated hyperglycemia is prevalent in hospitalized patients with diabetes mellitus (DM) but evidence-based insulin guidelines in inpatient settings are lacking. METHODS AND FINDINGS: Retrospective cohort study with capillary blood glucose (CBG) readings and insulin use, dosed with 50% basal (glargine)-50% bolus (lispro) insulin, analyzed in hospitalized patients with insulin-treated DM given GC and matched controls without GC (n = 131 pairs). GC group (median daily prednisone-equivalent dose: 53.36 mg (IQR 30.00, 80.04)) had greatest CBG differences compared to controls at dinner (254±69 vs. 184±63 mg/dL, P<0.001) and bedtime (260±72 vs. 182±55 mg/dL, P<0.001). In GC group, dinner CBG was 30% higher than lunch (254±69 vs. 199±77 mg/dL, P<0.001) when similar lispro to controls given at lunch. Bedtime CBG not different from dinner when 20% more lispro given at dinner (0.12 units/kg (IQR 0.08, 0.17) vs. 0.10 units/kg (0.06, 0.14), P<0.01). Despite receiving more lispro, bedtime hypoglycemic events were lower in GC group (0.0% vs. 5.9%, P = 0.03). CONCLUSIONS: Since equal bolus doses inadequately treat large dinner and bedtime GC-exacerbated glycemic excursions, initiating higher bolus insulin at lunch and dinner with additional enhanced GC-specific insulin supplemental scale may be needed as initial insulin doses in setting of high-dose GC.

Assessment of the Effectiveness of a Protocol to Manage Dexamethasone-Induced Hyperglycemia Among Hospitalized Patients With COVID-19.

OBJECTIVE: Well-controlled glucose levels (ie, 70-180 mg/dL) have been associated with lower mortality from COVID-19. The addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the potential negative consequences of dexamethasone-induced hyperglycemia. METHODS: We developed a protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19. Two of the 4 medical teams managing patients with COVID-19 at a tertiary center in Saudi Arabia used the protocol and the other 2 teams continued to manage hyperglycemia at the discretion of the treating physicians (protocol and control groups, respectively). The glycemic control and clinical outcomes in 163 patients hospitalized with COVID-19 and dexamethasone-induced hyperglycemia between July 5th and September 30th, 2020, were retrospectively compared between the 2 groups. RESULTS: Compared to the control group, the protocol group had higher proportions of patients with well-controlled glucose across all premeals and bedtime glucose readings throughout the hospital stay. The differences in glycemic control between the 2 groups were statistically significant for fasting glucose on days 4, 5, and the discharge day; prelunch glucose on the discharge day; predinner glucose on days 3, 5, and the discharge day; and bedtime glucose on day 1 (all P < .05). After adjusting for age, sex, nationality, body mass index, Charlson score, and diabetes status, patients in the protocol group were more likely to have well-controlled glucose levels compared with those in the control group. Moreover, the in-hospital mortality was significantly lower in the protocol group (12.93%) compared to the control group (29.93%) (P < .01). CONCLUSION: The implementation of a protocol to manage dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19 resulted in more patients achieving well-controlled glucose levels and was associated with lower mortality from COVID-19.

Daily glucose variation influenced by the use of corticosteroids in COVID-19 patients treated in Lima-Peru.

AIM: The pandemic has generated the need for COVID-19 patients to be treated as best as possible; however, the effect of these treatments on glycemic control has not yet been taken into account. This article aims to determine whether the daily variation of glucose is influenced by the use of corticosteroids in COVID-19 patients treated in Lima-Peru. METHODOLOGY: A prospective cohort study was undertook, in which glucose was measured four times a day in 53 patients hospitalized due to COVID-19. These values were associated with the use of corticosteroids and adjusted for other socio-educational variables, all by means of PA-GEE models. RESULTS: Nested multivariate analysis of daily glucose variation found that those using corticosteroids increased the daily average glucose as well as the first and last glucose measurements, this is, at 6am and 10pm, respectively (all p-values <0.026). An increase in glucose levels was also observed in those with diabetes (all p-values <0.001). In contrast, we found that there was a decrease in the last glucose measurement of the day in obese patients (p-value = 0.044). CONCLUSIONS: The patients who used corticosteroids for the treatment of COVID-19 increased the average glucose per day, especially in the first and last measurement.

High-dose vitamin-C induced prolonged factitious hyperglycemia in a peritoneal dialysis patient: a case report.

BACKGROUND: High-dose vitamin C is increasingly used for sepsis and more recently for coronavirus disease 2019 (COVID-19) infections. Proponents argue that the low cost and near perfect safety profile of vitamin C support its early adoption. Yet, adverse events might be underreported and underappreciated. CASE PRESENTATION: We report a 73-year-old non-diabetic white man with end-stage renal disease on peritoneal dialysis admitted to the intensive care unit with septic shock that was suspected to be due to peritonitis. The patient was enrolled in LOVIT (Lessening Organ Dysfunction with VITamin C; ClinicalTrials.gov identifier: NCT03680274), a randomized placebo-controlled trial of high-dose intravenous vitamin C. He developed factitious hyperglycemia, as measured with a point-of-care glucometer, that persisted for 6 days after discontinuation of the study drug, confirmed to be vitamin C after unblinding. He also had short-lived iatrogenic coma because of hypoglycemia secondary to insulin administration. These events triggered a protocol amendment. CONCLUSIONS: Although factitious hyperglycemia has been reported before using certain glucometers in patients treated with high-dose vitamin C, the persistence of this phenomenon for 6 days after the discontinuation of the therapy is a distinguishing feature. This case highlights the importance of monitoring glucose with a core laboratory assay for up to a week in specific populations, such as patients on peritoneal dialysis.

Glycemic Profile of Intravenous Dexamethasone-Induced Hyperglycemia Using Continuous Glucose Monitoring.

BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.

Management of COVID-19 infection in organic acidemias.

The COVID-19 pandemic has affected the health and healthcare of individuals of all ages worldwide. There have been multiple reports and reviews documenting a milder effect and decreased morbidity and mortality in the pediatric population, but there have only been a small number of reports discussing the SARS-CoV-2 infection in the setting of an inborn error of metabolism (IEM). Here, we report two patients with underlying metabolic disorders, propionic acidemia and glutaric aciduria type 1, and discuss their clinical presentation, as well as their infectious and metabolic management. Our report demonstrates that individuals with an underlying IEM are at risk of metabolic decompensation in the setting of a COVID-19 infection. The SARS-CoV-2 virus does not appear to cause a more severe metabolic deterioration than is typical.

Pharmacotherapeutic considerations for the management of diabetes mellitus among hospitalized COVID-19 patients.

INTRODUCTION: Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19. AREAS COVERED: We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes. EXPERT OPINION: The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.