Glucocorticoid-induced Hyperglycemia Research Articles

NCMP-30. GLUCOCORTICOID-INDUCED HYPERGLYCEMIA IN BRAIN TUMOR PATIENTS: A SINGLE CENTER RETROSPECTIVE STUDY

Abstract BACKGROUND Glucocorticoid (GC) therapies are integral in managing brain tumor-associated cerebral edema and neurological deficits in the neuro-oncology perioperative setting. Despite their effectiveness, GCs can induce significant morbidity, including hyperglycemia. METHODS This single-center retrospective study at the University of North Carolina neurological surgery department examines the incidence and risk factors for glucocorticoid-induced hyperglycemia in brain tumor patients treated with high-dose GCs. Data from clinical databases, electronic medical records, laboratory systems, and pathology information banks will be utilized. Documented glucose measurements, glycated hemoglobin test (HbA1c) and clinical outcomes (mortality, infection, hypoglycemia) in brain cancer patients treated with Glucocorticoid (GC) that developed hyperglycemia will be compared with brain tumor patient with normoglycemia. RESULTS We will document the total number of brain tumor patients referred over the study period, eligibility rates, and the percentage that developed glucocorticoid-induced diabetes (defined as two glucose measurements ≥200 mg/dL within the first week of treatment). Timing of hyperglycemia onset, treatments received, and risk factors for developing glucocorticoid-induced diabetes will also be analyzed. CONCLUSIONS The findings could underscore the necessity for proactive screening for glucocorticoid-induced diabetes in brain tumor patients to mitigate the associated morbidity. This study may guide future research on the benefits of optimized glucose control on clinical outcomes in patients with GC-induced hyperglycemia. Keywords: brain tumor, steroid-induced hyperglycemia, glucocorticoid-induced diabetes, dysglycemia, risk factors, outcomes.

Management of Glucocorticoid-Induced Hyperglycemia in Cancer Patients: A Feasibility Study.

Glucocorticoids are commonly used in the management of patients with hematological and solid malignancies. However, their use may be associated with impaired glycemic metabolism and increased treatment-related morbidity and mortality. This study aimed to examine the feasibility and acceptability of a nurse-led model of care (MOC) for screening and managing glucocorticoid-induced hyperglycemia (GIH) in non-diabetic patients requiring high-dose glucocorticoid (HDG) therapies, as well as patients' and health professionals' experiences with the MOC. This study was a single-site feasibility study. Patients with hematological or oncological malignancies who were >18 years of age, receiving a chemotherapy regimen including HDGs, had no prior diagnosis of diabetes or prediabetes, and were not at the end of life were considered eligible for this study. Participants were recruited from a district hospital's Cancer Centre in Australia. All consenting participants were screened for diabetes and were provided with a blood glucose meter to monitor their blood glucose levels (BGLs) four times a day on the days of glucocorticoid therapy (GT) plus one extra day following GT, for the first four cycles of their treatment, to screen for the presence of GIH. Feasibility and acceptability were assessed using rates of consent, study completion, and staff and patient surveys. Forty-eight percent (35/74) of patients approached consented to participate in the study and had screening tests for preexisting diabetes. None were diagnosed with diabetes. Six out of 35 patients withdrew, and 10/29 patients did not complete the recommended BGL monitoring. Thirteen percent (4/29) of patients developed GIH. The most common reasons for non-participation and study withdrawal were related to the self-monitoring of BGLs. While clinical stakeholders found the MOC feasible and acceptable, the results of this study suggest that alternative methods for encouraging self-monitoring of BGL and monitoring the presence of GIH during high-dose chemotherapy need to be explored to address issues associated with adherence and sustainability.

The Impact of Insulin Degludec on Glucocorticoid-Induced Hyperglycemia in Patients with Diabetes and COVID-19 Infection

The Impact of Insulin Degludec on Glucocorticoid-Induced Hyperglycemia in Patients with Diabetes and COVID-19 Infection

Glucocorticoid-Induced Hyperglycemia: A Neglected Problem.

Glucocorticoids provide a potent therapeutic response and are widely used to treat a variety of diseases, including coronavirus disease 2019 (COVID-19) infection. However, the issue of glucocorticoid-induced hyperglycemia (GIH), which is observed in over one-third of patients treated with glucocorticoids, is often neglected. To improve the clinical course and prognosis of diseases that necessitate glucocorticoid therapy, proper management of GIH is essential. The key pathophysiology of GIH includes systemic insulin resistance, which exacerbates hepatic steatosis and visceral obesity, as well as proteolysis and lipolysis of muscle and adipose tissue, coupled with β-cell dysfunction. For patients on glucocorticoid therapy, risk stratification should be conducted through a detailed baseline evaluation, and frequent glucose monitoring is recommended to detect the onset of GIH, particularly in high-risk individuals. Patients with confirmed GIH who require treatment should follow an insulin-centered regimen that varies depending on whether they are inpatients or outpatients, as well as the type and dosage of glucocorticoid used. The ideal strategy to maintain normoglycemia while preventing hypoglycemia is to combine basal-bolus insulin and correction doses with a continuous glucose monitoring system. This review focuses on the current understanding and latest evidence concerning GIH, incorporating insights gained from the COVID-19 pandemic.

NCMP-10. DEXAMETHASONE: A TOOL AND A PROBLEM IN GLIOBLASTOMA MANAGEMENT

Abstract Glioblastoma (GBM) patient morbidity and overall survival (OS) are associated with dexamethasone use. We studied dexamethasone-associated hyper-glycemia, leukocytosis, and accompanying complications in the peri-operative period. We also examined the effect of metformin treatment on GBM patient OS. We retrospectively studied 243 GBM patients admitted between 2014-2018. Patients with peri-operative glucose measurements and adequate follow-up to assess for complications were included. Metformin was used for treatment of diabetes or in the management of glucocorticoid-induced hyper-glycemia. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios for multivariate analysis. Dexamethasone dose was associated with hyper-glycemia and leukocytosis post-operatively. Poor glycemic control was associated with increased odds of 30-day any complication on univariate analysis and 30-day any complication and increased length of stay on multivariate analysis. We then demonstrated that metformin improved OS in methylated O6-methylguanine DNA methyltransferase gene (MGMT) promoter tumor patients (652 days, 95% CI 327 – 897, n = 25 vs 394 days, 95% CI 210 – 513, n = 63; P = .049). Non-diabetic MGMT-methylated tumor patients treated with metformin also had an improved median OS of 736 days, 95% CI 365 – 1036, n = 11 vs 395 days, 95% CI 210 – 513, n = 66; P = .01). Overall, peri-operative hyper-glycemia and higher average dexamethasone use are associated with poor glycemic control and leukocytosis. As a result, dexamethasone can increase the risk of peri-operative complications in GBM patients. Avoiding hyper-glycemia by limiting dexamethasone use or using Metformin may decrease the risk of complications and improve OS.

Berberine ameliorates glucocorticoid-induced hyperglycemia: an in vitro and in vivo study.

Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have less side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2mg/kg, i.m.) for 30days and effect of BBR at the doses 100, 200, and 500mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed for evaluating the development of the diabetic model. Echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis was analyzed. In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Type 2 Diabetes Polygenic Score Predicts the Risk of Glucocorticoid-Induced Hyperglycemia in Patients Without Diabetes.

To assess whether increased genetic risk of type 2 diabetes (T2D) is associated with the development of hyperglycemia after glucocorticoid treatment. We performed a retrospective analysis of individuals with no diagnosis of diabetes who received a glucocorticoid dose of ≥10 mg prednisone. We analyzed the association between hyperglycemia and a T2D global extended polygenic score, which was constructed through a meta-analysis of two published genome-wide association studies. Of 546 individuals who received glucocorticoids, 210 developed hyperglycemia and 336 did not. T2D polygenic score was significantly associated with glucocorticoid-induced hyperglycemia (odds ratio 1.4 per SD of polygenic score; P = 0.038). Individuals with increased genetic risk of T2D have a higher risk of glucocorticoid-induced hyperglycemia. This finding offers a mechanism for risk stratification as part of a precision approach to medical treatment.

1467-P: Type 2 Diabetes Polygenic Score Predicts the Risk of Glucocorticoid-Induced Hyperglycemia in Patients without Diabetes

Introduction: Glucocorticoids are commonly prescribed medications with a known side effect of hyperglycemia due to their effect on glucose metabolism. However, only 10-50% of patients receiving glucocorticoids develop overt hyperglycemia. It is unknown whether patients with increased genetic risk for type 2 diabetes (T2D) are predisposed to develop hyperglycemia after glucocorticoid treatment. Methods: We accessed electronic health records and genetic data in the Mass General Brigham Biobank. We examined patients with no diagnosis of diabetes or prediabetes who received a glucocorticoid dose equivalent to 10 mg of prednisone or more, and who had glucose levels checked within 7 days of glucocorticoid administration. Hyperglycemia was defined as fasting blood glucose ≥126 mg/dL or random blood glucose ≥200 mg/dL. A T2D global extended polygenic score was constructed through a meta-analysis of T2D genome-wide association studies in the Million Veteran Program, DIAMANTE, and FinnGen. We performed logistic regression to analyze the association between the polygenic score and hyperglycemia, controlling for age, gender, BMI, baseline creatinine, glucocorticoid dose and duration, and the first 10 principal components of genetic ancestry. Results: Out of 552 patients who received glucocorticoids, 216 developed hyperglycemia and 336 did not. The T2D polygenic score was significantly associated with glucocorticoid-induced hyperglycemia (p = 0.032, OR = 1.5 per standard deviation of the polygenic score). Other significant covariates included baseline creatinine (p = 8.0 × 10−4, OR = 2.2 per mg/dL of creatinine) and glucocorticoid dose (p = 9.5 × 10−5, OR = 1.01 per 10 mg of prednisone). Conclusions: Patients carrying a higher burden of genetic variants that confer risk for T2D have an increased risk of hyperglycemia after receiving glucocorticoids. This finding offers a mechanism for risk stratification as part of a precision approach to medical treatment. Disclosure A.J.Deutsch: None. P.H.Schroeder: None. R.Mandla: None. F.Erenler: None. J.M.Mercader: None. M.Udler: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. L.Brenner: None. Funding National Institutes of Health (T32DK007028)

An Old Theme and New Technology: Marked Glucocorticoid-Induced Hyperglycemia in a Hospitalized Patient Uncovered Retrospectively by Her Flash Glucose Monitoring

Abstract Background Glucocorticoid-induced hyperglycemia is a problem-facing endocrinologists and internal medicine specialists in hospital wards. Case History A 63-year-old woman with type 2 diabetes was admitted to the hospital with acute exacerbation of chronic obstructive airway disease. She was treated with a short course of intravenous hydrocortisone followed by oral prednisolone. On discharge, she attended her regular diabetes consultation. Throughout the period, she had her flash glucose monitoring (FGM) sensor in place, and she was monitoring her blood glucose regularly. As part of her diabetes clinic routine, the meter data uploaded and ambulatory glucose profiles were examined. These revealed three distinctly different blood glucose levels before, during, and after glucocorticoid therapy. Glucocorticoid therapy resulted in a marked rise in blood glucose that lasted for a further week before it returned to the pre-treatment levels. This old phenomenon has yet to be demonstrated using the new FGM technology. Conclusions The story (1) asserts the significant impact of glucocorticoid therapy on glycemic control, (2) demonstrates the prolonged impact on glycemic control following discontinuation of glucocorticoids, (3) suggests a lack of adequate monitoring and timely recognition of hyperglycemia in the hospital, and poor management glucocorticoid-induced hyperglycemia either due to failure of conventional monitoring methods or a degree of complacency to appreciate its magnitude.

A Novel Algorithm for the Management of Inpatient COVID-19 Glucocorticoid-Induced Hyperglycemia.

Hyperglycemia in hospitalized patients with coronavirus disease 2019 (COVID-19) is linked to increased morbidity and mortality. This article reports on a novel insulin titration protocol for the management of glucocorticoid-induced hyperglycemia in hospitalized patients with COVID-19. Sixty-five patients with COVID-19 and glucocorticoid-induced hyperglycemia admitted after the protocol implementation were matched 1:1 to patients admitted before the treatment protocol rollout for analysis. In a large, diverse health system, the protocol achieved reductions in hypoglycemic events without increasing hyperglycemia or insulin use.

1058. Development of a Steroid Stewardship Bundle to tackle the Glucocorticoid-Induced Hyperglycemia in COVID-19 patients: Results of SUPER Diabetes Study.

Abstract Background Glucocorticoid therapy in COVID-19 patients poses a greater risk of hyperglycemia, leading to an unexpected detrimental effect on treatment outcomes. The Steroid Use in Patients Exhibiting Risk (SUPER) to Diabetes -SUPER Diabetes- study aimed to implement a steroid stewardship bundle to encounter the incidence of Glucocorticoid-Induced Hyperglycemia (GCIH) in COVID-19 patients and to evaluate the effectiveness of the Steroid Stewardship Program. Methods This interventional study included 600 COVID-19 confirmed patients admitted between April 2021and March 2022 in a secondary care hospital in India (stewardship cohort). A six-item Steroid Appropriate Index (SAI) assessed the need for steroid therapy using the parameters like the severity of disease, the onset of symptoms, weight of the patient, CT Thorax score, the preferred route of administration, and the comorbid disorders. This created a steroid stewardship bundle with the following parameters: (1) appropriate selection of the corticosteroid; (2) repeat blood sugar monitoring every 8 hours until discharge from hospital; (3) appropriate duration of therapy (4) proper de-escalation of dose/intravenous to oral switch. The patients were followed until discharge/death to track the incidence of hyperglycemia. The analysis of the effectiveness of SAI and the stewardship bundle was done by comparing this with the clinical outcomes among 300 COVID-19 confirmed patients admitted before implementing the scale (retrospective cohort). Results The majority of the patients included in the stewardship cohort were males (367; 61.1%), and the mean age was 47.3± 17.1 years. The incidence of new-onset of hyperglycemia or a worsened glycemic profile, i.e., Glucocorticoid-Induced Hyperglycemia (GCIH), was more among the retrospective cohort when compared with the stewardship cohort (32.1% vs 6.3%), p< 0.001). The study also revealed that history of diabetes (p< 0.001), age (p=0.002), number of medicines used for treatment (p< 0.001), and the frequency of monitoring of diabetes (p< 0.001) are significantly associated with GCIH. Conclusion Implementing the steroid stewardship bundle significantly improved the appropriate selection and use of corticosteroids, decreasing the incidence of associated adverse events. Disclosures All Authors: No reported disclosures.

Glucocorticoid-induced hyperglycemia (GIH) in pemphigus vulgaris patient at Bangli District General Hospital: A case report

Background: Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous blistering and erosion. This is rare, but greatly affects the patient’s life quality and often cause complication of disease and therapy. Hyperglycemia is a complication due to steroid use called glucocorticoid-induced hyperglycemia (GIH). This case report describes hyperglycemia in PV treatment, which later can be a consideration of PV management.
 Case: A 44-year-old male patient complained of painful lesions on almost the whole body with a form of bullae, erosion, crusting, brittle, the Nikolsky sign (+), and Asboe-Hansen sign (+). The patient was diagnosed with PV. After he had supportive therapy and high-doses of methylprednisolone, his blood sugar is increased. Patients diagnosed by hyperglycemia state due to steroid use, then given insulin as therapy. The patient diagnosed with PV based on history taking and physical examination, but the histopathologic examination wasn’t done due to lack of modality at the hospital. The steroid was given as an immunosuppressive. Be the main therapy for PV, steroids lead hyperglycemia due to disruption of glucose metabolism, thereby increasing insulin resistance in tissues. The diagnosis of hyperglycemia due to steroid use is made in a patient with a normal sugar level before PV therapy. It occurred within the first 1-2 days of therapy. In these patients, diagnosis confirmed by increasing pre-prandial, 2 h post-prandial, and any-time glucose level, after two days methylprednisolone administration. Collaboration with internal medicine colleagues is needed.
 Conclusion: PV treatment with steroids can induce hyperglycemia, which is dangerous. The understanding mechanism is needed to make early detection and provide therapy properly.

Management of Glucocorticoid-Induced Hyperglycemia.

Glucocorticoids are potent immunosuppressive and anti-inflammatory drugs used for various systemic and localized conditions. The use of glucocorticoids needs to be weighed against their adverse effect of aggravating hyperglycemia in persons with diabetes mellitus, unmask undiagnosed diabetes mellitus, or precipitate glucocorticoid-induced diabetes mellitus appearance. Hyperglycemia is associated with poor clinical outcomes, including infection, disability after hospital discharge, prolonged hospital stay, and death. Furthermore, clear guidelines for managing glucocorticoid-induced hyperglycemia are lacking. Therefore, this consensus document aims to develop guidance on the management of glucocorticoid-induced hyperglycemia. Twenty expert endocrinologists, in a virtual meeting, discussed the evidence and practical experience of real-life management of glucocorticoid-induced hyperglycemia. The expert group concluded that we should be proactive in terms of diagnosis, management, and post-steroid care. Since every patient has different severity of underlying disease, clinical stratification would help understand patient profiles and determine the treatment course. Patients at home with pre-existing diabetes who are already on oral or injectable therapy can continue the same as long as they are clinically stable and eating adequately. However, depending on the degree of hyperglycemia, modification of doses may be required. Initiating basal bolus with correction regimen is recommended for patients in non-intensive care unit settings. For patients in intensive care unit, variable rate intravenous insulin infusion could be temporarily used, but under supervision of diabetes inpatient team, and patients can be transitioned to subcutaneous insulin once stable baseline assessment and continual evaluation are crucial for day-to-day decisions concerning insulin doses. Glycemic variability should be carefully monitored, and interventions to treat patients should also aim at achieving and maintaining euglycemia. Rational use of glucose-lowering drugs is recommended and treatment regimen should ensure maximum safety for both patient and provider. Glucovigilance is required as the steroids taper during transition, and insulin dosage should be reduced subsequently. Increased clinical and economic burden resulting from corticosteroid-related adverse events highlights the need for effective management. Therefore, these recommendations would help successfully manage GC-induced hyperglycemia and judiciously allocate resources.

Glycemic variability assessed by continuous glucose monitoring in hospitalized patients with community-acquired pneumonia

BackgroundGlycemic variability (GV) has only been sparsely studied in patients with community-acquired pneumonia (CAP). This study aimed to quantify in-hospital GV in CAP patients, including determining the impact of type 2 diabetes mellitus (T2DM) and glucocorticoid (GC) treatment on GV.MethodsThis is a prospective cohort study of CAP patients (N = 40) with or without T2DM and treated or not with GCs. The primary endpoint was GV measured as glucose standard deviation (SD), coefficient of variation (CV), and postprandial glucose excursions (PPGE) based on continuous glucose monitoring (CGM). Analysis of glucose data was split into daytime and nighttime when possible.ResultsPatients included had a mean age of 74 (range 55 to 91) years. SD (95%CI) increased by a factor of 1.93 (1.40 to 2.66) and 2.29 (1.38 to 3.81) in patients with T2DM and not treated with GCs during the daytime and the nighttime, respectively (both P < 0.01), and by a factor of 1.42 (1.04 to 1.97) in patients treated with GCs but without T2DM during the daytime (P = 0.031) compared to patients without T2DM and not treated with GCs. CV (95%CI) increased by 5.1 (0.0 to 10.1) and 8.1 (1.0 to 15.2) percentage points during the daytime and the nighttime, respectively, in patients with T2DM and not treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.046 and P = 0.026, respectively). PPGE (95% CI) increased during lunch by 2.5 (0.7 to 4.3) mmol/L (45 (13 to 77) mg/dL) in patients with T2DM and treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.018).ConclusionsCAP patients receiving GCs, especially those with T2DM, are at great risk of developing high GV and therefore require clinical attention to mitigate GV. This applies particularly during the daytime. Results support the 1 to 2-h post-lunch screening procedure for glucocorticoid-induced hyperglycemia in patients without diabetes. SD was positively correlated with hospital length of stay.

POSC15 Addressing Glucocorticoid-Induced Hyperglycemia in COVID -19 Patients: The Expanding Role of Steroid Stewardship

To characterize the incidence of Glucocorticoid-Induced Hyperglycemia (GCIH) in COVID -19 patients and to evaluate the effectiveness of a Steroid Stewardship Program in countering this effect. This prospective, interventional study included 100 COVID-19 confirmed patients admitted between March 12 – May 12, 2021 who are categorized into B & C as per the guidelines of the Directorate of Health Services, Kerala, India. A five-item Steroid Appropriate Index (SAI) was prepared based on the onset of symptoms, weight of the patient, CT Thorax severity score, the preferred route of administration, and the underlying diseases for choosing the appropriate doing of the preferred corticosteroid. The demographic profile of these patients was collected and they were followed up till discharge/death to track the incidence of worsening of hyperglycemia or new onset of diabetes. The effectiveness of SAI was analyzed by comparing the data of treatment and clinical outcome among 100 COVID-19 confirmed patients admitted before and after implementation of the scale. The majority of the patients were males (57) and the mean age was 45.7± 16.6 years. The incidence of new-onset of hyperglycemia i.e., GCIH was more among the retrospective cohort when compared with the SAI cohort (7% vs 26%, p< 0.001). The study also revealed that history of diabetes (p<0.001), age (p=0.002), number of medicines used for treatment (p<0.001) are significantly associated with glucocorticoid-induced hyperglycemia. The appropriate selection of corticosteroids based on real-world scenarios can decrease the incidence of adverse events associated. Implementation of steroid appropriate index and proper monitoring can be an aid for the same.

Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice With Histone Acetylation in Dpp-4 Promoter.

Glucocorticoid causes hyperglycemia, which is common in patients with or without diabetes. Prolonged hyperglycemia can be experienced even after the discontinuation of glucocorticoid use. In the present study, we examined the time course of blood glucose level in hospital patients who received transient glucocorticoid treatment. In addition, the mechanism of prolonged hyperglycemia was investigated by using dexamethasone (Dexa)-treated mice and cultured cells. The blood glucose level in glucose tolerance tests, level of insulin and glucagon-like peptide 1 (GLP-1), and the activity of dipeptidyl peptidase 4 (DPP-4) were examined during and after Dexa loading in mice, with histone acetylation level of the promoter region. Mice showed prolonged hyperglycemia during and after transient Dexa loading accompanied by persistently lower blood GLP-1 level and higher activity of DPP-4. The expression level of Dpp-4 was increased in the mononuclear cells and the promoter region of Dpp-4 was hyperacetylated during and after the transient Dexa treatment. In vitro experiments also indicated development of histone hyperacetylation in the Dpp-4 promoter region during and after Dexa treatment. The upregulation of Dpp-4 in cultured cells was significantly inhibited by a histone acetyltransferase inhibitor. Moreover, the histone hyperacetylation induced by Dexa was reversible by treatment with a sirtuin histone deacetylase activator, nicotinamide mononucleotide. We identified persistent reduction in blood GLP-1 level with hyperglycemia during and after Dexa treatment in mice, associated with histone hyperacetylation of promoter region of Dpp-4. The results unveil a novel mechanism of glucocorticoid-induced hyperglycemia, and suggest therapeutic intervention through epigenetic modification of Dpp-4.

Molecular mechanism of glucocorticoid-induced hyperglycemia

Glucocorticoids are widely used as strong anti-inflammatory and immunosuppressive drugs to treat various diseases. However, the use of glucocorticoids can cause several side effects, such as hyperglycemia. This review aims to discuss the effect of glucocorticoids on increasing glucose in molecular levels based on literature studies. A literature searching was carried out on the PubMed, Science Direct, and Google Scholar databases published in 2010-2020. Glucocorticoids can cause an increase in blood glucose levels by several mechanisms. In the liver, glucocorticoids increase endogenous plasma glucose and stimulate gluconeogenesis. Glucocorticoids increase the production of non-esterified fatty acids which affect the signal transduction of insulin receptor substrate-1 in skeletal muscle. In adipose, glucocorticoids increase lipolysis and visceral adiposity through increased transcription and expression of protein adipose triglyceride lipase and hormone-sensitive lipase. In pancreatic beta cells, glucocorticoids directly inhibit the beta cell response to glucose through the role of protein kinase B and protein kinase C. At the molecular level, glucocorticoids can cause hyperglycemia through mechanisms in the liver, skeletal muscle tissue, adipose tissue, and pancreatic beta cells.

Overview and Management of Glucocorticoid-Induced Hyperglycemia in Pulmonary Diseases: Insight into the COVID-19 Pandemic

Background: Glucocorticoids are potent anti-inflammatory agents that have become an integral component of the standard of care for numerous pathologies. Their wide-ranging uses and efficacy in different treatment pathways are not without important adverse events to consider. Glucocorticoid-induced hyperglycemia remains a prominent issue but the optimal management is understudied. Pulmonary diseases represent a large disease group in which glucocorticoids have shown clinical benefits. Glucocorticoid-induced hyperglycemia in pulmonary disease has been associated with adverse patient outcomes. The coronavirus disease 2019 (COVID-19) pandemic has now introduced a novel indication for glucocorticoids and has further highlighted that hyperglycemia results in increased mortality. Methods: Here we review literature-based epidemiology, clinical outcomes, and treatment of glucocorticoid-induced hyperglycemia in chronic obstructive pulmonary disease, asthma, and most recently, COVID-19. Lastly, we provide a comprehensive review of the outcomes related to hyperglycemia, implications of glucocorticoid treatment, and treatment approaches to hyperglycemia in the COVID-19 pandemic. Conclusion: Management of people with diabetes requiring glucocorticoid therapy can be complex and require aggressive treatment. Awareness of the prevalence of hyperglycemia, attention to insulin and glucocorticoid action profiles, and treatment options can assist in improving glycemic outcomes.

Basal-bolus insulin therapy fails to control glucocorticoidinduced hyperglycemia in patients with severe COPD exacerbation

Basal-bolus insulin therapy fails to control glucocorticoidinduced hyperglycemia in patients with severe COPD exacerbation

Outcomes of Hospitalized Patients with Glucocorticoid-Induced Hyperglycemia-A Retrospective Analysis.

Background: Glucocorticoid (GC)-induced hyperglycemia is a frequent side effect in hospitalized patients. Guidelines recommend treat-to-target treatment between 6–10 mmol/L (108–180 mg/dL) with insulin, but data on outcome is scarce. We investigated the 30-day outcome in hospitalized patients receiving GCs. Methods: All patient records of hospitalized patients between January 2014 and April 2018 were screened for GC administration and consecutive hyperglycemia. The primary combined endpoint consisted of death, cardiovascular events, and infections until 30 days after admission. Hypoglycemia was a secondary outcome. Results: Of the 2424 hospitalized patients (9.6% of all hospitalized patients) who received systemic GCs and met inclusion criteria, the overall incidence for GC-induced hyperglycemia was 812 (33.5%), and 89 (3.7%) had at least one documented hypoglycemia during their hospital stay. Compared to patients with normoglycemia, GC-induced hyperglycemia had an adjusted-odds ratio of 1.68 (95% CI 1.25–2.26) for the combined primary endpoint. Hypoglycemia even had an odds ratio of 1.95 (95% CI 1.2–3.17). Conclusions: Mortality, cardiovascular events, and rate of infections were markedly higher in patients with GC-induced hyperglycemia as compared to patients with normoglycemia. Importantly, hypoglycemia was associated with a doubled risk for adverse outcome. Future studies should evaluate whether optimized glucose control by minimizing the risk for hypoglycemia has a beneficial effect on clinical outcomes in patients with GC-induced hyperglycemia.