Corticosteroid-induced Hyperglycemia Research Articles

Corticosteroid-induced hyperglycemia

Glucocorticoids are medications of wide medical use, notably due to their known anti-inflammatory effects. Furthermore, fluctuations in glycemic indexes stand out as risk factors for clinical and surgical complications, mortality and increased hospital stay. The study consists of an integrative and descriptive literature review, through the PUBMED platform with the following keywords: “Hyperglycemia”, “Glucocorticoid” and “Induce”, in the last 12 years and aims to gather and unify information regarding the understanding and clinical and therapeutic management of hyperglycemia induced by the use of corticosteroids and corticogenic diabetes. The fluctuation in glycemic indexes with the use of corticosteroid therapy is an imbalance between the increase in insulin resistance and the inhibition of insulin production and secretion at the pancreatic cellular level. Screening for Diabetes Mellitus in patients on corticosteroid therapy is based on consensus in the literature with a plasma glucose level above 125 mg/dL, any capillary measurement above 200 mg/dL, HbA1c> 6.5% or oral tolerance test glucose above 200mg/dL after 2 hours. The main glycemic target is capillary blood glucose between 108-180 mg/dL and in cases of initiating therapeutic approaches for hospital management of glycemic fluctuations, the use of insulin therapy is chosen. Hyperglycemia induced by the use of corticosteroids is a topic that has been gaining prominence in the medical scenario, despite the lack of studies that uniformly protocol the approach to patients when this scenario is confirmed, with the aim of reducing the risks associated with hospitalization.

Immune dysregulation in Kabuki syndrome: a case report of Evans syndrome and hypogammaglobulinemia

Kabuki syndrome (KS) is a rare multisystemic disease due to mutations in the KMT2D or KDM6A genes, which act as epigenetic modulators of different processes, including immune response. The syndrome is characterized by anomalies in multiple organ systems, and it is associated with autoimmune and inflammatory disorders, and an underlying immunological phenotype characterized by immunodeficiency and immune dysregulation. Up to 17% of KS patients present with immune thrombocytopenia characterized by a severe, chronic or relapsing course, and often associated to other hematological autoimmune diseases including autoimmune hemolytic anemia, eventually resulting in Evans syndrome (ES). A 23-year-old woman, clinically diagnosed with KS and presenting from the age of 3 years with ES was referred to the Rare Diseases Centre of our Pediatric Department for corticosteroid-induced hyperglycemia. Several ES relapses and recurrent respiratory infections in the previous years were reported. Severe hypogammaglobulinemia, splenomegaly and signs of chronic lung inflammation were diagnosed only at the time of our observation. Supportive treatment with amoxicillin-clavulanate prophylaxis and recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin replacement were immediately started. In KS patients, the failure of B-cell development and the lack of autoreactive immune cells suppression can lead to immunodeficiency and autoimmunity that may be undiagnosed for a long time. Our patient's case is paradigmatic since she presented with preventable morbidity and severe lung disease years after disease onset. This case emphasizes the importance of suspecting immune dysregulation in KS. Pathogenesis and immunological complications of KS are discussed. Moreover, the need to perform immunologic evaluations is highlighted both at the time of KS diagnosis and during disease follow-up, in order to allow proper treatment while intercepting avoidable morbidity in these patients.

QLTI-05. HBA1C AND INSULIN COVERAGE FOR NEWLY DIAGNOSED HGG PATIENTS IN THE HOSPITAL

Abstract Corticosteroids are used in the management of patients with high-grade gliomas (HGG). Corticosteroids lead to elevated serum glucose levels, necessitating sliding-scale insulin. A hemoglobin A1c (HbA1c) reflects historical serum glucose levels but it’s unclear if it predicts corticosteroid-induced hyperglycemia. We retrospectively reviewed all newly diagnosed HGG patients who were admitted between Jan 2019 to July 2021 who had an HbA1c performed at the time of their diagnosis. HbA1c is classified into: normal (< 5.6%), elevated (5.7 – 6.4%) and diagnostic (> 6.5%). We identified 86 patients of whom 29 and 16 had elevated and diagnostic HbA1c, respectively. These patients were more likely to require sliding scale insulin at least twice during their hospitalization, 64% vs 13% of those with a normal HbA1c. Only 28% of patients had a history of diabetes. There was no correlation between elevated HbA1c and the likelihood of initiating post-operative therapy, surgical complications, or BMI results. When reviewing age, 39 patients were less than 65, of which 34% had at least an elevated HbA1c. Of those older than 65, 65% had at least an elevated HbA1c. Our analysis suggests there is a predictive value of HbA1c and the need for sliding-scale insulin while receiving corticosteroids in the HGG population, especially in the older population. We recommend screening all new HGG patients with an HbA1c at the time of diagnosis, regardless if they have a history of diabetes. We also recommend monitoring serum glucose less frequently with those who have a normal HbA1c. If the HbA1c is elevated or diagnostic, they should have monitored serum glucose levels with available sliding-scale insulin. If the patient is > 65 years of age, they should be considered a higher risk for having hyperglycemia and HbA1c should be reviewed. Further analysis is being conducted and will be reviewed at a later date.

Burden of Hyperglycemia in Patients Receiving Corticosteroids for Severe COVID-19

Although corticosteroid therapy is the standard of care for all patients hospitalized with severe coronavirus disease 2019 (COVID-19), the studies demonstrating the mortality–benefit ratio of corticosteroids were limited to fully evaluate their adverse effects. To determine the severity of corticosteroid-induced hyperglycemia in patients with and without diabetes mellitus, we retrospectively collected data from the medical records of patients hospitalized with COVID-19 before and after corticosteroids were the standard of care. Corticosteroid-induced hyperglycemia was more severe in patients hospitalized with COVID-19 with diabetes than those without diabetes. Additionally, patients with diabetes required higher doses of correctional insulin per day when on corticosteroid therapy, suggesting that intensive point-of-care glucose monitoring could be limited in patients without diabetes mellitus and support cautionary use of corticosteroids in patients with COVID-19 discharged with supplemental oxygen.

Patterns of Glucose Fluctuation are Challenging in Patients Treated for Non-Hodgkin's Lymphoma.

PurposeThis cohort study aimed to determine patterns of glycemic fluctuation and changes in metabolic parameters during and after corticosteroid administration in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP chemotherapy.Patients and MethodsThe study was performed in 20 patients of whom 11 had diabetes and 9 were nondiabetics. Anthropometric parameters were collected, and blood samples were taken four times during the study to analyze metabolic parameters. Capillary glucose was measured seven times a day (fasting, before mean meals, postprandial, and before bedtime) to evaluate the glycemic profile.ResultsIn all 20 patients, acute glucocorticoid administration resulted in the elevation of average glucose levels, dominantly postprandial in the afternoon which correlates with corticosteroid peak action. In 7 out of 11 diabetics, prandial insulin was started during corticosteroid administration and discontinued afterward. Although none of our nondiabetic patients met diabetes criteria, evident is the elevation in average glycemia levels six weeks after corticosteroid administration. Potentially, even transient corticosteroid administration reduces insulin sensitivity and contributes to later glycemic disturbances. HbA1c levels were higher at the end of the study while fructosamine levels were higher during the study.ConclusionPatients and health-care professionals need to be aware of corticosteroid-induced hyperglycemia. We recommend identifying risk factors, measuring glycemia before, during, and after corticosteroid administration, and starting the adequate therapy as soon as possible.

Glucocorticoid-induced hyperglycemia in oncohematological patients

Background Glucocorticoids are a common component of systemic chemotherapy regimens for hematological malignancy. Steroid-induced hyperglycemia remains a common potentially harmful problem that must be considered when using any type of glucocorticoids. Little is known about the impact of hyperglycemia associated with steroid use on treatment morbidity, infectious complications, as well as disease remission and mortality. Objective The aim of the current work is to study glucocorticoid-induced hyperglycemia in patients with hematologic malignancies receiving repeated short-term pulse cycles of glucocorticoids (5–7 days), to estimate its prevalence, to define the risk factors, and to assess treatment response. Patients and methods The prospective study included 30 adult patients with acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia attending the outpatient clinic of Al Hussein Hospital, Al Azhar University during the period between November 2015 and April 2016. During the period of the study, 30 patients received a total of 60 cycles of chemotherapy including corticosteroid. Results Out of the 30 study patients, 15 (50%) were men and 15 (50%) were women with a mean age of 44.17. Corticosteroid-induced hyperglycemia was documented in 12 patients after one or more than one cycle (12/30–40%). Among the 60 cycles, corticosteroid-induced hyperglycemia was documented after 19 cycles (19/60–31%). The age of the patient was found to be the most important factor that affected the occurrence of hyperglycemia after corticosteroid where younger patients were less likely to develop hyperglycemia (P=0.013). Patients with BMI less than or equal to 25 had the lowest chance to develop hyperglycemia after corticosteroid. However, this difference was not statistically significant. The three patients who developed persistent hyperglycemia received hypoglycemic medications. Conclusion About one-third of patients with hematological malignancies receiving glucocorticoids may develop hyperglycemia. To allow for early detection and effective treatment, these patients should be screened for hyperglycemia at least before each cycle and 4–6 h after glucocorticoids intake, especially old obese patients Appropriate guidelines for the diagnosis and treatment of steroid-induced diabetes are needed in order to prevent complications associated with the hyperglycemic state

Type 2 Diabetes Mellitus in Patients with a Prior History of Corticosteroid-induced Hyperglycemia

Type 2 Diabetes Mellitus in Patients with a Prior History of Corticosteroid-induced Hyperglycemia

Evaluation of Glycemic Control Obtained from NPH Insulin in Patients Experiencing Corticosteroid-Induced Hyperglycemia

Objective: To compare the safety and efficacy of neutral protamine Hagedorn (NPH) insulin to other antidiabetic regimens in the treatment of corticosteroid-induced hyperglycemia in non-critically ill; hospitalized patients.

Management of Steroid-induced Hyperglycemia

Steroids are widely used as potent anti-inflammatory and immunosuppressive drugs to treat a wide range of diseases. However, they are also associated with a number of side effects including new-onset hyperglycemia in patients without a history of diabetes mellitus or severely uncontrolled hyperglycemia in patients with known diabetes mellitus. This negative effect is believed to be caused by a variety of factors, including increased insulin resistance, increased glucose intolerance, reduced beta-cell mass from beta-cell dysfunction, and increased hepatic insulin resistance leading to impaired suppression of hepatic glucose production. Steroid-induced hyperglycemia is important in clinical practice because it has been associated with deleterious effect on prognosis. However, there is no scientific evidence regarding the consequences of corticosteroid-induced hyperglycemia and clinical studies investigating the effects of prevention and correction of the condition are lacking. Similar to non-steroid-related diabetes, the principles of early detection and risk factor modification apply. Challenges in the management of steroid-induced diabetes stem from wide fluctuations in post-prandial hyperglycemia and the lack of clearly defined treatment protocols. Together with, or after, life style measures, hypoglycemic drug with important insulin sensitizer effects is indicated. Other oral hypoglycemic drugs or insulin therapy can be considered as the drug of choice. These treatments may provide additional long-term survival benefit and improve glycemic control.

Randomized clinical trial of the efficacy and safety of insulin glargine vs. NPH insulin as basal insulin for the treatment of glucocorticoid induced hyperglycemia using continuous glucose monitoring in hospitalized patients with type 2 diabetes and respiratory disease

AimsTo investigate the clinical efficacy and safety of insulin glargine compared with NPH insulin as basal insulin for the management of corticosteroid-induced hyperglycemia in hospitalized people with type 2 diabetes (T2DM) and respiratory disease. Materials and methodsRandomized, two-arm parallel group, clinical trial undertaken from February 2011 to November 2012 on the pneumology ward of the Hospital Regional Universitario de Málaga (Spain), involving 53 participants with T2DM treated with medium/high doses of intermediate-acting corticosteroids. Participants were randomly assigned to receive one single dose of insulin glargine or NPH insulin in three equally divided doses before each meal as basal insulin within a basal–bolus insulin protocol. The intervention lasted six days or until discharge if earlier. ResultsNo significant differences were seen between groups during the study in mean blood glucose (11.43±3.44mmol/l in glargine vs. 11.88±2.94mmol/l in NPH, p=0.624), and measures of glucose variability (standard deviation 3.27±1.16mmol/l vs. 3.61±0.99mmol/l, p=0.273; coefficient of variation 1.55±0.33mmol/l vs. 1.72±0.39mmol/l, p=0.200). Results from CGM were concordant with those obtained with capillary blood glucose reading. The length of hospital stay was also similar between groups (8.2±2.8 days vs. 9.8±3.4 days, p=0.166) There was a non significant trend for lower episodes of mild (4 vs. 8, p=0.351) and severe hypoglycemia (0 vs. 3, p=0.13) in the glargine group. ConclusionsThe results of this study showed that insulin glargine and NPH insulin are equally effective in a basal–bolus insulin protocol to treat glucocorticoid-induced hyperglycemia in people with T2DM on a pneumology ward.

Incretin Based Therapy in the Management of Steroid Induced Diabetes Mellitus

Corticosteroid-induced hyperglycemia is a common medical problem which can cause frequent hospitalizations and therefore relates to an increase in morbidity. Metformin, sulfonylureas, thiazolidinediones and insulin are well known available therapies for the treatment of steroid induced hyperglycemia. Incretin based therapies are a newly developing strategies with a considerable importance in the treatment regimen as well. This review aims at discussing the pathophysiology of steroid induced hyperglycemia in addition to the available therapies used for treatment, focusing on incretin therapies.

The impact of corticosteroid treatment on hemoglobin A1C levels among patients with type-2 diabetes with chronic obstructive pulmonary disease exacerbation

Corticosteroid-induced hyperglycemia is a known adverse effect. There are no studies on the impact of corticosteroid treatment on hemoglobin A1c (HbA1c) levels in type-2 diabetes patients with chronic obstructive pulmonary disease (COPD) exacerbation. HbA1c levels were evaluated in type-2 diabetes patients with COPD exacerbation on admission to the hospital (group-1) and 3-months later. Demographic, clinical, laboratory variables and total steroid dose were documented. Age- and sex-matched group of type-2 diabetes patients with COPD who were admitted for other reasons (group-2), were asked to participate as a control group. Mann-Whitney and Chi square/Fischer's exact tests were used to compare between the parameters of the two groups. Wilcoxon's signed rank test was used to compare between HbA1c levels at baseline and 3 months later. Multi-variate linear regression analysis was used to find predictors for a change in HbA1c levels in group-1 patients. 23 and 21 patients in groups 1 and 2 respectively, completed the study. There were 39 male (∼89%) patients. Mean age of the patients was 66.2 ± 8.2 years. In both groups, anti-diabetic management was augmented. There was no significant change in the HbA1c levels in group-1 (p = 0.416), however there was a significant decrease in HbA1c levels in group-2 (p = 0.032). Total dose of steroids was a predictor for an increase in HbA1c levels in group-1 patients (p = 0.026). Type-2 diabetes patients who were treated with steroids for COPD exacerbation had no significant change in HbA1c levels. Total dose of steroids was a predictor for an increase in HbA1c levels.

Glucocorticoid‐induced hyperglycemia (糖皮质激素诱导的高血糖)

Corticosteroid-induced hyperglycemia is a common medical problem that can lead to frequent emergency room visits, hospital admissions and prolonged hospital stay, in addition to the well known morbidity associated with hyperglycemia. However, the diagnosis and treatment of corticosteroid-induced hyperglycemia is surprisingly undervalued by most professionals, probably because of the lack of quality studies to determine specific strategies of action. In the present review, we discuss the pathophysiology of corticosteroid-induced hyperglycemia, focusing on diverse patterns of hyperglycemia induced by the different formulations, and provide clues for diagnosis based on the duration of treatment and the administration schedule of corticosteroids. We propose a treatment strategy based on both the pathophysiology of the process and the mechanism of action of different corticosteroids, and take into account dosing and administration timing to predict the duration of therapy. Finally, we propose treatment goals that differ slightly between the transient and continuous use of corticosteroids based on evidence from clinical practice guidelines of diabetes care both in ambulatory and hospital settings.

Corticosteroid-induced hyperglycemia

Corticosteroid-induced hyperglycemia

Risk of Corticosteroid-Induced Hyperglycemia Requiring Medical Therapy among Patients with Inflammatory Eye Diseases

To identify the incidence and risk factors for corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases. Retrospective cohort study. Patients with ocular inflammation followed at 5 United States tertiary centers that initially were neither diabetic nor taking hypoglycemic medications. Eligible patients who used oral corticosteroids during follow-up were identified and followed longitudinally for initiation of hypoglycemic medication over 1 year after beginning corticosteroids. The remaining eligible patients were followed for 1 year after their initial visit. Survival analysis was used to calculate the risk of hyperglycemia requiring medical therapy and to identify potential risk factors. Initiation of hypoglycemic medications. Among 2073 non-diabetic patients treated with oral corticosteroids, 25 (1.21%) initiated hypoglycemic therapy compared with 5 of 2666 patients (0.19%) not treated with oral corticosteroids (relative risk [RR], 4.39; 95% confidence interval [CI], 1.68-11.5). The RR tended to be higher in association with higher initial doses (for initial doses <40 mg of prednisone per day: RR, 3.23; 95% CI, 1.08-9.64; for initial prednisone dose ≥40 mg/d: RR, 5.51; 95% CI, 2.01-15.1). Other risk factors for the initiation of hypoglycemic therapy included older age (RR [per each additional 10 years], 1.46; 95% CI, 1.15-1.85; P = 0.002) and African-American race (RR, 2.94; 95% CI, 1.34-6.43; P = 0.007). These results suggest that the absolute risk of corticosteroid-induced hyperglycemia that is detected and treated with hypoglycemic therapy in the tertiary ocular inflammation setting is low (an excess cumulative risk on the order of 1% within 1 year), although on a relative scale it is approximately 4.4-fold higher than in patients not treated with oral corticosteroids. Older age and African-American race also were risk factors. Physicians who use systemic corticosteroids for ocular inflammatory diseases should be aware of this risk, and should consider surveillance for hyperglycemia among high-risk patients. However, given the low absolute risk, routine laboratory monitoring or referral for monitoring may not be necessary for low-risk patients.

The Influence of Hyperglycemia and Other Clinical Variables on Rehabilitation and Hospital Length of Stay After Neurosurgery in Patients With Cancer

Our study was designed to address whether steroid-induced hyperglycemia after neurosurgery affects rehabilitation and hospital length of stay (LOS) in patients with cancer. We reviewed the medical records of 290 post-neurosurgery patients at our cancer center in 2002. Of the 267 nondiabetic patients and 23 diabetic patients (P < .001), 2 and 8, respectively, had hyperglycemia which is defined as casual plasma glucose concentrations of ≥200 mg/dL on 2 different days. In all patients studied, hyperglycemia does not predict longer hospital stay or needs for rehabilitation. The frequency of corticosteroid-induced hyperglycemia in post-neurosurgery patients with cancer was low.

Poster 21: An Adult Steroid Induced Hyperglycemia Protocol for the Screening and Management of Corticosteroid-Induced Hyperglycemia

Objective: To develop a protocol for managing hyperglycemia in cancer patients who are receiving steroids and to evaluate in a retrospective cohort if this protocol improved outcomes. Design: Retrospective cohort. Setting: Inpatient rehabilitation unit in a university affiliated tertiary care hospital in Hamilton, ON, Canada. Participants: Patients undergoing inpatient rehabilitation related to their cancer who are treated with steroids as part of their treatment program. Interventions: A newly developed screening and treatment protocol was compared with usual treatment before the development of the protocol in a retrospective cohort. Main Outcome Measures: Prevalence of severe hyperglycemia, length of stay, and workload, was compared for those treated before initiation of the protocol and those after initiation of the protocol. Results: It was possible to get concensus for a protocol between physiatry, pharmacy, diabetic care teams, and oncologists. The protocol was tried successfully on an inpatient rehabilitation ward. The data for efficacy of the implementation of the protocol will be discussed at the meeting. Conclusions: Currently there is no agreed on protocol for the screening and managment of steroid induced hyperglycemia. We developed a protocol and tested it in an inpatient rehabilitation ward and have assessed efficacy of this protocol for review.

Annual meeting of the Society of Neurosurgical Anesthesia and Critical Care. Atlanta, Georgia, October 20, 1995.

Annual meeting of the Society of Neurosurgical Anesthesia and Critical Care. Atlanta, Georgia, October 20, 1995.

Insulin-like growth factor-I fails to reverse corticosteroid-induced protein catabolism in growing piglets.

Corticosteroids such as dexamethasone (DEX) increase leucine turnover and oxidation in humans and animals, indicating whole body protein catabolism. Recently, interest has been growing in the use of recombinant polypeptides such as GH and IGF-I in reversing various states of catabolism. The aim of our study was to investigate whether IGF-I reverses corticosteroid-induced protein catabolism in rapidly growing piglets. Also, we wanted to determine whether IGF-I attenuates corticosteroid-induced hyperglycemia. To study these questions, we performed leucine kinetic studies and measured blood glucose in eight piglets under postabsorptive conditions. We did three studies in each piglet: baseline, DEX treatment (5 mg/kg/d for 4 d), and DEX plus IGF-I treatment (25 micro g/kg/h for 6 h). DEX increased leucine turnover by 18 +/- 14% (mean +/- SD, p < 0.05), and oxidation by 132 +/- 64% (p < 0.01) over baseline values. Adding IGF-I to DEX treatment failed to reverse these changes in leucine kinetics. Turnover again increased by 18 +/- 8% (p < 0.01), and oxidation by 107 +/- 68% (p < 0.05) over baseline values. Nonoxidative leucine disposal, an indicator for protein synthesis, did not significantly differ after treatment with DEX or with DEX plus IGF-I. Blood glucose values increased over baseline values after DEX treatment, and approached baseline values after DEX plus IGF-I. We conclude that IGF-I attenuates corticosteroid-induced hyperglycemia, but does not reverse corticosteroid-induced protein catabolism in growing piglets.