Steroid-induced Hyperglycemia Research Articles

SUN-163 Implementation of a Protocol for the Management of Steroid-Induced Hyperglycemia

Implementation of a Protocol for the Management of Steroid-Induced Hyperglycemia Background: Hyperglycemia is a recognized complication of supra-physiological steroid dosing. Such hyperglycemia can be of concern in hospitalized patients as it is linked with increased length of stay and mortality1. There are no consensus guidelines on optimal treatment of steroid-induced hyperglycemia. The aim of this study was to assess the safety of a weight based insulin algorithm for persons treated with supra-physiological doses of steroids to examine the efficacy of using this algorithm in patients with diabetes treated with prednisone or methylprednisolone. Methods: All participants were admitted to medicine units with a known diagnosis of diabetes mellitus or Hemoglobin A1c over 6.5% who were prescribed at least 7.5mg of prednisone or methylprednisolone daily with two episodes of hyperglycemia (Blood glucose (BG)>200mg/dL) within 24 hours of steroid administration. Patients were excluded if they did not have at least 8 BG values after enrollment in the protocol. Two main analyses were conducted: 1) a comparison between control and protocol groups in terms of the proportion of high BG readings (i.e.BG>200) using generalized estimating equations (GEE) logistic regression and 2) a comparison between pre- and post-protocol BG readings in protocol patients who started protocol more than 48 hours after first steroid administration using Wilcoxon’s exact signed rank test. A result was statistically significant at the p<0.05 level of significance. All analyses were performed using SAS version 9.4(SAS Institute, Cary, NC). Results: A total of 51 patients were analyzed: 25 controls (before implementation of hyperglycemia protocol) and 26 protocol patients (after implementation of hyperglycemia protocol). The mean proportion of high BG readings in the control group was 70% vs. 62% in the protocol group; there was not enough evidence to conclude the proportion of high BG readings differed between the groups (p=0.18). The mean glucose levels had minimal differences between the two groups (mean BG=253mg/dL vs. 232mg/dL, respectively; p=0.10). In the protocol group, pre and post initiation of the protocol, the proportion of high BG readings decreased (p=0.053), ranging from 33% to 62% decrease, with a mean of 44% decrease. There were no episodes of hypoglycemia in those who received the protocol. Conclusion: There was evidence to suggest the proportion of BG>200mg/dL was lower after protocol initiation compared to before protocol initiation (p=0.053). The time to reach euglycemia was not immediate, as a result a more aggressive insulin dosing algorithm will be used for future studies. 1 Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, et al. Steroid hyperglycemia: prevalence, early detection and therapeutic recommendations: a narrative review. World J Diabetes 2015;6:1073–81.

What is the optimal time for measuring glucose concentration to detect steroid-induced hyperglycemia in patients with rheumatic diseases?

ObjectiveCorticosteroids may cause hyperglycemia and diabetes mellitus (DM). Development of DM during long-term steroid use has been well studied; however, data regarding the short-term effects of steroid therapy are scarce. In this study, we aimed to detect the actual time of short-term steroid-induced hyperglycemia in patients without previous impaired glucose metabolism, and the ideal time (which day and in relation to meals) of glucose measurement. MethodsThe 7-point blood glucose (BG) measurements of patients who were commenced moderate to high-dose steroids (≥15 mg/day prednisolone or its equivalent) due to rheumatological diseases during the first 5 days of steroid therapy were recorded. Fasting BG ≥ 7 mmol/L (126 mg/dL) or random BG ≥ 11.1 mmol/L (200 mg/dL) were considered as overt DM in accordance with the 2016 American Diabetes Association guideline, and post-meal BG ≥10 mmol/L (180 mg/dL) was considered as steroid-induced hyperglycemia. ResultsFifteen males (mean age: 44 ± 16 years) and 35 females (mean age: 41 ± 12 years) were recruited to the study. One thousand seven hundred fifty fasting, pre-meal, and 2-hours post-meal BG concentrations were analyzed. Twenty-one (42%) patients developed steroid-induced DM and 39 (78%) developed steroid-induced hyperglycemia. The highest glucose concentrations were detected on the 3rd day of steroid therapy and 2-h after meals (p < .0001). ConclusionIntermediate to high-dose steroid therapy causes hyperglycemia after lunch and dinner on the 3rd day of treatment. This time period should be taken into consideration in the detection and treatment of steroid-induced hyperglycemia.

GLUCOSE EXCHANGE DISORDERS IN PATIENTS TAKING GLUCOCORTICOSTEROIDS: FEATURES OF CLINICAL MANIFESTATIONS AND CORRECTION

The review deals with the problem of carbohydrate metabolism disorders in patients undergoing corticosteroid therapy, relevant for specialists in various fields. The article describes the epidemiology and risk factors for the development of carbohydrate metabolism disorders when using glucocorticosteroids. Contemporary information is provided about the diagnostics, prevalence and pathogenesis of steroid-induced hyperglycemia. A particular attention is paid to current data on various disorders of carbohydrate metabolism in patients with a therapeutic profile. Main approaches to the correction of glycemia in the steroid-induced disorders of carbohydrate metabolism using modern therapy are considered elucidated.Conclusion.The widespread use of glucocorticosteroids, significant prevalence of the steroid-induced disorders of carbohydrate metabolism, features of the pathogenetic mechanisms of steroid-induced diabetes mellitus determine the need to create algorithms for the diagnosis and treatment of these conditions. A conclusion is made that rational glucose-lowering therapy that takes into account the pathogenetic and clinical aspects of the steroid-induced disorders of carbohydrate metabolism, can reduce the rate of macro- and microvascular complications.Conflict of interest: the authors declare no conflict of interest.

The monitoring and incidence of hyperglycaemia in inflammatory bowel disease patients treated with intravenous steroids

To improve detection and establish the frequency of steroid-induced hyperglycaemia among inpatients with a flare of inflammatory bowel disease (IBD) receiving intravenous hydrocortisone by improving capillary blood glucose (CBG) monitoring in line with locally adapted Joint British Diabetes

Immune-mediated graft dysfunction in liver transplant recipients with hepatitis C virus treated with direct-acting antiviral therapy.

Interferon treatment of hepatitis C virus (HCV) infection after liver transplantation (LT) can result in immune-mediated graft dysfunction (IGD). The occurrence of, risk factors for, and outcomes of IGD with direct-acting antiviral (DAA) therapy have not been reported. We conducted a multicenter study of HCV+LT recipients who did or did not develop DAA-IGD (1 case: 2 controls-33 vs 66). Among all treated between 2014 and 2016, DAA-IGD occurred in 3.4% (33/978). IGD occurred only after treatment completion (76.0 [IQR, 47.0;176]). Among those treated, 48% had plasma cell hepatitis, 36% acute cellular rejection, 6% chronic rejection, and 9% combined findings. Median time to liver enzyme resolution was 77.5days (IQR, 31.5;126). After diagnosis, hospitalizations, steroid-induced hyperglycemia, and infection occurred in a higher percentage of cases vs controls (33% vs 7.5%, 21% vs 1.5%, 9% vs 0%; all P<.05). Only one IGD patient died and none required retransplant. A multivariate regression analysis found that liver enzyme elevations during and soon after DAA therapy completion correlated with subsequent IGD. In conclusion, while DAA-IGD is uncommon, liver enzyme elevations during or after DAA therapy may be a sign of impending IGD. These indicators should guide clinicians to diagnose and treat IGD early before the more deleterious later clinical presentation.

Management of hyperglycaemia and steroid (glucocorticoid) therapy: a guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care group.

Glucocorticoids (steroids) are widely used across many medical specialities for their anti-inflammatory and immunosuppressive properties. However, one of their major side effects is the development of hyperglycaemia. It is well recognized that high glucose levels in people with diabetes in hospital are associated with harm and increased lengths of hospital stay. The use of glucocorticoid (steroid) treatment in people with pre-existing diabetes will undoubtedly result in worsening glucose control, and this may be termed 'steroid-induced hyperglycaemia', and will warrant temporary additional, and more active, glycaemic management. A rise in glucose may occur in people without a known diagnosis of diabetes, and this may be termed 'steroid-induced diabetes'. There is a lack of evidence to guide how people with hyperglycaemia should be managed, and much of the guidance given here is a consensus based on best practice collated from around the United Kingdom. Where evidence is available, this is referenced. These guidelines on the management of people with diabetes treated with steroids has been adapted specifically for Diabetic Medicine. The full version of the guidelines can be found on line at: www.diabetes.org.uk/joint-british-diabetes-society or https://abcd.care/joint-british-diabetes-societies-jbds-inpatient-care-group.

The Efficacious and Safe Treatment for Steroid-Induced Hyperglycemia

The Efficacious and Safe Treatment for Steroid-Induced Hyperglycemia

080 Screening for diabetes and steroid-induced hyperglycaemia in patients with rheumatoid arthritis is done poorly

080 Screening for diabetes and steroid-induced hyperglycaemia in patients with rheumatoid arthritis is done poorly

Management of dexamethasone-induced hyperglycemia in patients undergoing chemotherapy in an outpatient setting: a best practice implementation project.

The objective of this project was to implement best practice in an outpatient clinical setting in order to increase both nursing staff and patients' knowledge and awareness on the importance of blood sugar management during chemotherapy and to show that through compliance with best practice, the incidence of dexamethasone-induced hyperglycemia during chemotherapy can be minimized. Steroid-induced hyperglycemia is a commonly neglected symptom in cancer treatment, contributing to poor patient prognosis and extended hospital stay. Evidence shows that controlled blood sugar during chemotherapy is associated with improved patient outcomes and better tolerance to cancer treatment. For the purpose of this paper steroid-induced hyperglycemia will be referred to as dexamethasone-induced hyperglycemia. This project utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System (JBI-PACES) and Getting Research into Practice (GRiP) audit tools to promote compliance in the clinical setting. Thirty patients participated in the audit, which was executed by nursing staff in the Medical Oncology Outpatient Unit at the Cancer Ambulatory and Community Health Support Department at the Canberra Hospital. The baseline audit revealed large gaps between best practice and current practice. This underlined the need for more education for both nursing staff and patients. Other barriers such as the absence of assessment and documentation by the clinicians and the minimum number of potential referrals to the diabetes educator were addressed by encouraging patients to speak about their diabetes, and also in the development of a simplified referral process in order to have patients reviewed by the Diabetes Educator in a timely manner. There were significant improvements after more information sessions were held and more resources made available to both nursing staff and patients, but there were also minimal to zero compliance drop on parts of the follow-up audit. In an attempt to improve patient outcome during chemotherapy, the project has succeeded in changing the attitude towards blood sugar control, and in increasing knowledge and awareness of dexamethasone-induced hyperglycemia among nursing staff and patients. However, there is room for improvement, based on the results of the implementation project. Future audits are planned to ensure sustainability.

Steroid-Induced Hyperglycemia Successfully Treated With Once-Weekly Dulaglutide in an Old Patient With Type 2 Diabetes

Glucocorticoids induce hyperglycemia in case of pancreatic alpha- and beta-cell dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RA) may prevent steroid-induced hyperglycemia by improving hyperglucagonemia and insulin secretion. An 85-year-old man was treated with oral prednisolone for chronic hypersensitivity pneumonitis, and his glycemic control deteriorated after the initiation of steroid therapy. After the administration of dulaglutide injection, his glycemic control was improved and we could discontinue insulin therapy. Both fasting and postprandial plasma glucagon levels were significantly suppressed by a GLP-1RA, dulaglutide. GLP-1RAs therapy may be a useful strategy for the treatment of steroid-induced hyperglycemia. J Endocrinol Metab. 2018;8(1):10-12 doi: https://doi.org/10.14740/jem491w

Steroid-induced diabetes in the paediatric population

Steroid-induced diabetes is arare disease in the paediatric population. High doses of corticosteroids are used in diseases such as acute lymphoblastic leukaemia (ALL), lymphomas, or connective tissue diseases. Post-steroid hyperglycaemia arises as aresult of increased gluconeogenesis and increased glycogen synthesis. Steroid-induced diabetes most often is asymptomatic; therefore it is important to monitor the glycaemic level in patients receiving systemic glucocorticoids. So far, no separate guidelines for steroid-induced diabetes have been developed, so the criteria for diagnosing drug-related diabetes mellitus do not differ from the criteria for diagnosing type 2 diabetes. Hyperglycaemia adversely affects the immune system: it impairs the function of granulocytes, immunoglobulins, and also causes T-lymphocyte apoptosis. A hyperglycaemic environment favours the development of bacterial and fungal infections. Numerous studies confirm that hyperglycaemia increases the risk of infection and severity of infection. There have also been reports of adverse effects of steroid-induced hyperglycaemia in the course of treatment for the underlying disease in the adult population. Reports related to the paediatric population are not as numerous. There are studies that have proven anincreased risk of infection in paediatric patients with ALL and steroid-induced diabetes, as well as studies that proved an unfavourable effect of diabetes on survival in children with ALL and as well the studies that proved that risk of life-threatening infection and survival does not differ statistically in the group of patients with hyperglycaemia and in the group of patients who did not develop diabetes.

The Efficacious and Safe Treatment for Steroid-Induced Hyperglycemia

The Efficacious and Safe Treatment for Steroid-Induced Hyperglycemia

Steroid-Induced Hyperglycemia Successfully Treated With Once-Weekly Dulaglutide in an Old Patient With Type 2 Diabetes

Steroid-Induced Hyperglycemia Successfully Treated With Once-Weekly Dulaglutide in an Old Patient With Type 2 Diabetes

Improving outcomes for pregnant women with diabetes

Improving outcomes for pregnant women with diabetes

A Case of Acquired Hepatocerebral Degeneration Presenting as Hemichorea Post-Liver Transplant

Acquired hepatocerebral degeneration (AHCD) is a rare but morbid neurological manifestation of decompensated cirrhosis. Portosystemic shunting leads to manganese deposition in the basal ganglion which is identified as bilateral hyperintense signals on T1-weighted MRI. The resulting neuronal loss leads to involuntary movements, cognitive dysfunction, Parkinsonism, or cerebellar ataxia in the absence of hepatic encephalopathy. We present a case of AHCD with several unique features: 1) initial presentation post-liver transplant (OLT), 2) no clinical or radiographical evidence of portosystemic shunting, and 3) unilateral basal ganglia hyperintensity. A 57-year-old man with hypertension and chronic kidney disease (stage III) underwent OLT for hepatitis C and alcoholic cirrhosis 3 years prior to presentation. His post-transplant course was complicated by continued alcohol abuse, steroid-induced hyperglycemia, and acute cellular rejection without fibrosis 4 months prior. Prescriptions included tacrolimus, mycophenolate mofetil, prednisone, nifedipine, and insulin with questionable adherence. He had no personal or family history of movement disorders. His chief complaint was one month of progressive, uncontrollable right-sided arm and leg movements in a writhing, non-rhythmic pattern. He was afebrile. Physical exam was notable for right-sided hemichorea with normal strength, finger-to-nose test, reflexes, and sensation. He displayed no altered-mental status, asterixis, nystagmus, hepatosplenomegaly or ascites. Labs were notable for total bilirubin 1.3 mg/dL, Alk Phos 43 U/L, AST/ALT 117/65 U/L, blood alchohol level 103 mg/dL. INR 1.0 and platelets 141 x103/μL. Electrolytes, glucose and creatinine were normal. HgbA1c 6.0%. Tacrolimus level undetectable. Serum iron, zinc, lead, and manganese levels were normal. MRI brain notable for T1 hyperintensities in the left globus pallidus without evidence of hemorrhage or acute ischemia (Figure 1). He was treated with haloperidol 1mg twice daily which mildly suppressed the hemichorea and allowed discharge with close neurology follow-up. Symptoms of ACHD often improve with resolution of portosystemic shunting post-OLT. However, we present a case of new onset ACHD in a post-transplant patient without evidence of portosystemic shunting. This illustrates that ACHD remains a poorly understood disorder that should be considered in patients with typical findings and a history of cirrhosis, even after liver transplantation.Figure: T1 weighted magnetic resonance imaging (MRI) of the brain without contrast in axial view (A) and sagittal view (B) of hyperintensity in the left globus without evidence of hemorrhage or acute ischemia.

Optimizing the Treatment of Steroid-Induced Hyperglycemia.

To review therapeutic strategies for the management of patients with steroid-induced hyperglycemia. A literature search of MEDLINE/PubMed (1990 to June 2017) was conducted using the search terms steroid, glucocorticoid, corticosteroid, hyperglycemia, and diabetes as well via review of literature citations. Relevant clinical trials and case studies focusing on pharmacological interventions in humans were reviewed for inclusion. Articles discussing islet cell transplant were excluded. Hyperglycemia is a predictable adverse effect of glucocorticoid therapy, which is associated with negative outcomes, including an odds ratio of 1.36 for developing new-onset diabetes. A variety of strategies have been utilized for managing patients who are at risk of complications caused by steroid-induced hyperglycemia. Agents such as sulfonylureas, thiazolidinediones, meglitinides, metformin, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptidase-1 agonists, and insulin have been evaluated in case studies and small clinical trials with varying degrees of success. Since there are limited clinical data available to guide therapy, strategies that minimize the risk of adverse effects should be selected for the management of steroid-induced hyperglycemia. Therapies that may be safe and effective given current information include DPP-4 inhibitors, metformin, and weight-based neutral protamine Hagedorn insulin.

Outpatient management of steroid-induced hyperglycaemia and steroid-induced diabetes in people with lymphoproliferative disorders treated with intermittent high dose steroids

High dose steroids (HDS) are used in the treatment of haematological malignancies. The reported risk of steroid-induced diabetes (SID) is high. However, screening is not consistently performed. We implemented a protocol for detection and management of SID and steroid-induced hyperglycamia (SIH) in haematology outpatients receiving HDS.Eighty-three people were diagnosed with a lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three people without known diabetes were screened by HbA1c and random venous plasma glucose. All patients (n=34) subsequently prescribed HDS checked capillary blood glucose (CBG) pre-breakfast and pre-evening meal. Treatment algorithms used initiation and/or dose titration of gliclazide or human NPH insulin, aiming for pre-meal CBG 5–11mmol/l. Type 2 diabetes was identified in 4/53 people screened (7.5%). Of 34 people treated with HDS, 17 (44%) developed SIH/SID. All 7 people with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without known diabetes, 8 (30%) developed SID and 1 required insulin. Pre-treatment HbA1c was higher in people who developed SID compared to those that did not (p=0.002). This is the first report of a SID/SIH detection and treatment protocol for use in people with lymphoproliferative disorders receiving intermittent HDS, demonstrating its feasibility and safety.

Steroid-induced hyperglycaemia in hospitalised patients – assessing the current knowledge and practice of monitoring and diagnosis

To assess the current knowledge and practice for monitoring and diagnosis of steroid-induced hyperglycaemia (SIH) in hospitalised patients. This study was undertaken on six wards with high frequency of steroid use – oncology, respiratory and neurology – at a large tertiary care centre in the

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy.

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs.

Early Hyperglycemia after Initiation of Glucocorticoid Therapy Predicts Adverse Outcome in Patients with Acute Graft-versus-Host Disease

Because of first-line treatment with high-dose glucocorticoids (GC), steroid-induced hyperglycemia develops frequently in patients with acute graft-versus-host disease (aGVHD), potentially affecting their outcome. We performed a retrospective analysis on 104 patients who received systemic GC for aGVHD and investigated the consequences of aberrant glucose metabolism. In particular, we focused on glucose parameters early after initiation of GC. With a median of 50 (range, 4 to 513) blood glucose measurements during GC treatment, increasing mean, median, and maximum glucose levels and the need for insulin treatment were associated with decreased overall survival (OS) in simple and multiple survival analysis. Early hyperglycemia, as defined by mean blood glucose levels >125 mg/dL during the first 3 days of GC therapy, was also found to be highly associated with adverse outcome (hazard ratio [HR], 2.5 for death; 95% confidence interval [CI], 1.3 to 4.8, and HR of 3.5 for death due to nonrelapse mortality, 95% CI, 1.7 to 7.5, in a competing risk analysis). A score based on early hyperglycemia and nonresponse to GC within 7 days allowed the identification of 3 risk groups: patients with both risk factors had an inferior OS at 5 years of 4.1% compared with 75.4% in patients with none. Patients with 1 risk factor had a 5-year OS rate of 32.0% (P = .0002 for trend). Early hyperglycemia after GC initiation is a prominent risk factor for adverse outcome in patients with aGVHD. A score based solely on early hyperglycemia and lack of response to GC can predict survival in these patients.