Steroid-induced Diabetes Mellitus Research Articles

Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues.

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) and are commonly used as anti-inflammatory and immunosuppressant medications. Chronic GC use has been linked with unwanted complications such as steroid-induced diabetes mellitus (SIDM), although the mechanisms for these effects are not completely understood. Modification of six GC parent molecules with 2-mercaptobenzothiazole resulted in consistently less promoter activity in transcriptional activation assays using a 3xGRE reporter construct while constantly reducing inflammatory pathway activity. The most selective candidate, DX1, demonstrated a significant reduction (87%) in transactivation compared to commercially available dexamethasone. DX1 also maintained 90% of the anti-inflammatory potential of dexamethasone while simultaneously displaying a reduced toxicity profile. Additionally, two novel and highly potent compounds, DX4 and PN4, were developed and shown to elicit similar mRNA expression at attomolar concentrations that dexamethasone exhibits at nanomolar dosages. To further explain these results, Molecular Dynamic (MD) simulations were performed to examine structural changes in the ligand-binding domain of the glucocorticoid receptor in response to docking with the top ligands. Differing interactions with the transcriptional activation function 2 (AF-2) region of the GR may be responsible for lower transactivation capacity in DX1. DX4 and PN4 lose contact with Arg611 due to a key interaction changing from a stronger hydrophilic to a weaker hydrophobic one, which leads to the formation of an unoccupied channel at the location of the deacylcortivazol (DAC)-expanded binding pocket. These findings provide insights into the structure-function relationships important for regulating anti-inflammatory activity, which has implications for clinical utility.

AN AUDIT OF STEROID-INDUCED DIABETES IN PRIMARY BRAIN TUMOUR PATIENTS

Abstract AIMS Dexamethasone is an effective and commonly used treatment in patients with gliomas. However, it can also cause several metabolic side effects, including steroid-induced diabetes mellitus (SIDM), of which prevalence is estimated at 11-56%. We aimed to assess prevalence of SIDM in our local brain tumour population and audited adherence to recently published national guidance for monitoring and management of SIDM. METHOD Retrospective data review of all new primary malignant brain tumour patients seen in clinic over 12 months to assess local prevalence. Patients’ notes audited for 2 months pre- and post-adoption within the department of national guidelines focussing on how to screen and monitor for diabetes when initiating high dose steroids. RESULTS 71 new patients seen over 12 months. 66 patients with high grade and 5 with low grade gliomas. 82% were on steroids at first oncological visit. 14% known diabetic or pre-diabetic. 7% subsequently developed SIDM. 19 patient notes audited over 2 months prior to intervention (Group 1) and 11 post intervention (Group 2). All patients were taking dexamethasone. 40% of Group 1 and 36% of Group 2 had neither HbA1c nor lab glucose checked at baseline. 1 patient in Group 1 developed SIDM. CONCLUSIONS Diabetes mellitus in cancer patients increases risk of infections, cardiovascular comorbidities, and can reduce effcacy of treatment, leading to preventable admissions and decreased survival rates. Prevalence of SIDM in our local population is comparable to published data. Adoption of published guidance improved baseline monitoring but needs to be embedded within acute oncology pathways across the Trust.

Primary mandibular mucormycosis without para nasal sinus involvement following SARS CoV-2 infection – a series of four cases and review of literature

The increased incidence of mucormycosis in post covid-19 is due to steroid induced diabetes mellitus. The commonest presentation is acute invasive fungal sinusitis involving maxillary sinus most commonly followed by invasion to local soft tissues and bone structures. It also involves orbit and brain extending from sinuses. Mandible has no direct communication with any of the para nasal sinuses and involvement is extremely rare and seldom reported. We came across four such cases during post covid-19 mucormycosis epidemic. Poor dentitions, ulcerated mucosa, inoculation during dental procedures are the proposed mode of entry of the fungi into the mandible.

Steroid Induced Diabetes Mellitus

Glukokortikoid sampai saat ini sering digunakan sebagai terapi imunosupresan dan antiinflamasi pada berbagai kondisi medis. Selain memberikan manfaat secara klinis, glukokortikoid memiliki berbagai efek samping salah satunya terkait diabetes melitus yang diinduksi steroid (SIDM). Diabetes mellitus yang diinduksi steroid dapat merupakan onset baru maupun merupakan suatu perberatan hiperglikemia pada pasien yang telah terdiagnosis DM sebelumnya. Hiperglikemia akut dan kronis akibat steroid dapat berdampak pada pemanjangan rawat inap, komplikasi infeksi, penurunan respon terapi dan peningkatan kematian. Tantangan mengelola diabetes mellitus yang diinduksi steroid sangat bervariasi. Pemehaman mengenai patofisiologi, faktor resiko, diagnosis dan terapi dapat menambah wawasan terkait tatalaksana komprehensif pada DM yang diinduksi steroid.

Glucocorticoid-mediated induction of ZBTB16 affects insulin secretion in human islets and EndoC-βH1 β-cells

Glucocorticoid use is associated with steroid-induced diabetes mellitus and impaired pancreatic β-cell insulin secretion. Here, the glucocorticoid-mediated transcriptomic changes in human pancreatic islets and the human insulin-secreting EndoC-βH1 cells were investigated to uncover genes involved in β-cell steroid stress-response processes. Bioinformatics analysis revealed glucocorticoids to exert their effects mainly on enhancer genomic regions in collaboration with auxiliary transcription factor families including AP-1, ETS/TEAD, and FOX. Remarkably, we identified the transcription factor ZBTB16 as a highly confident direct glucocorticoid target. Glucocorticoid-mediated induction of ZBTB16 was time- and dose-dependent. Manipulation of ZBTB16 expression in EndoC-βH1 cells combined with dexamethasone treatment demonstrated its protective role against glucocorticoid-induced reduction of insulin secretion and mitochondrial function impairment. In conclusion, we determine the molecular impact of glucocorticoids on human islets and insulin-secreting cells and investigate the effects of glucocorticoid targets on β-cell function. Our findings can pave the way for therapies against steroid-induced diabetes mellitus.

Steroid Induced Diabetes Mellitus

Glukokortikoid sampai saat ini sering digunakan sebagai terapi imunosupresan dan antiinflamasi pada berbagai kondisi medis. Selain memberikan manfaat secara klinis, glukokortikoidmemiliki berbagai efek samping salah satunya terkait diabetes melitus yang diinduksi steroid (SIDM). Diabetes mellitus yang diinduksi steroid dapat merupakan onset baru maupun merupakan suatu perberatan hiperglikemia pada pasien yang telah terdiagnosis DMsebelumnya. Hiperglikemia akut dan kronis akibat steroid dapat berdampak pada pemanjangan rawat inap, komplikasi infeksi, penurunan respon terapi dan peningkatan kematian. Tantangan mengelola diabetes mellitus yang diinduksi steroid sangat bervariasi. Pemehaman mengenai patofisiologi, faktor resiko, diagnosis dan terapi dapat menambah wawasan terkait tatalaksana komprehensif pada DM yang diinduksi steroid.

Steroid Induced Diabetes Mellitus: An Overview

Glucocorticoids are often used as immunosuppressant and anti-inflammatory therapy in various medical conditions. In addition to providing clinical benefits, glucocorticoids have various side effects, one of which is related to steroid-induced diabetes mellitus (SIDM). Steroid-induced diabetes mellitus can be a new onset or an exacerbation of hyperglycemia in patients who have previously been diagnosed with DM. Acute and chronic hyperglycemia due to steroids can have an impact on lengthening hospitalization, infectious complications, decreased response to therapy and increased mortality. The challenges of managing steroid-induced diabetes mellitus vary widely. Understanding of pathophysiology, risk factors, diagnosis and therapy can add insight regarding the comprehensive management of steroid-induced DM

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Influence of diabetes mellitus on the biochemical parameters and outcomes of multiple myeloma

ABSTRACTObjective:The incidence of MM in most registries remains stable or showing only a slightly increase. However, prevalence of MM is increasing due to the increase in overall survival in the last two decades. The aim of this study was to observe changes in biochemical parameters during the diagnosis and treatment of MM.Methods:A retrospective analysis was made of the biochemical indicators, survival time, and related adverse events of 196 patients with MM.Results:Of the 196 patients with MM, 26 were diagnosed with DM (DM-MM group) at the first diagnosis, 31 with steroid-induced diabetes mellitus (SID-MM group) during treatment, and 139 without DM (MM group). There was no significant difference between the three groups in the mean age of onset, sex ratio, incidence of hypercalcemia, renal dysfunction, anemia, abnormal lactate dehydrogenase, and median value of D-dimer and fibrinogen during diagnosis and treatment. There was no significant difference in survival time between the SID-MM and MM groups, but there was a significant difference between the DM-MM and MM groups.Conclusion:There was no significant difference between the three groups in the incidence of hypercalcemia, anemia, and renal function impairment. The survival time of patients with DM was shorter than that of patients without DM.

HYPOGLYCEMIC EFFECT OF SITAGLIPTIN AND AMINOGUANIDINE COMBINATION IN EXPERIMENTAL DIABETES MELLITUS

The aim of the work was to determine the antidiabetic effect of a sitagliptin and aminoguanidine combination in rats with experimental diabetes mellitus.Materials and methods. The study was carried out on male Wistar rats and C57BL/KsJ-db/db mice. According to the models used, it was divided into 4 series, in which alloxan, steroid-induced (dexamethasone) and streptozotocin-nicotinamide-induced diabetes mellitus (DM) were formed, respectively, in rats, and in the 4 series, obese C57BL/KsJ-db/db mice were used. In the 1 and 2 series, the treatment was started prophylactically – 3 h after the alloxan administration and simultaneously with the dexamethasone administration, in the 3rd and 4th series, the treatment was carried out after the pathology had developed – 7 days after the streptozotocin with nicotinamide administration, and in the obese mice – immediately after their distribution according to the groups. The treatment was carried out with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The treatment was continued till the end of the experiment, which was completed with an oral glucose tolerance test (OGTT) after 4 h of fasting. The obtained data were subjected to statistical processing.Results. In the course of the experiments, it was found out that the prophylactic administration of a sitagliptin and aminoguanidine combination, unlike each of the components, prevented the development of alloxan DM. More effectively than the administration of sitagliptin alone, it reduced the severity of steroid-induced DM, which was expressed in a significantly lower level of fasting glycemia (after 4 h of fasting) and postprandial glycemia (during OGTT). Under the conditions of streptozotocin-nicotinamide-induced DM, the studied combination slowed down the progression of the pathology, and in the obese mice, the course therapeutic administration of sitagliptin and its combination reduced the severity of carbohydrate metabolism disorders (fasting glycemia) and increased the rate of glucose utilization.Conclusion. As an iNOS blocker, aminoguanidine enhances the antidiabetic effect of sitagliptin, preventing the development of alloxan diabetes and reducing the severity of steroid-induced DM when administered prophylactically. When administered therapeutically, it reduces the severity of streptozotocin-nicotinamide-induced DM in rats and type 2 DM in mice with a predisposition to obesity.

Steroid-induced diabetes mellitus in pemphigus vulgaris patient at Bali Mandara Hospital: a case report

Background: Pemphigus vulgaris (PV) is a blistering autoimmune disease of the skin and mucous membranes defined histologically by intraepidermal blister due to acantholysis. Systemic corticosteroids and immunosuppressive agents had greatly improved the prognosis of pemphigus. However, steroid use often leads to metabolic complications, such as diabetes mellitus. This case report describes steroid-induced diabetes mellitus in PV, where the side effect of long-term high dosages steroid used and the method to manage it can be used as a study case.
 Case report: A 31-year-old man complained of new blisters from almost the entire body. He had a history of PV 1 year ago and no history of diabetes mellitus in the patient or family. He had a medication history of methylprednisolone 8 mg every 8 hours. Dermatological status showed erythema macules, extensive erosion almost on the entire body, the Nikolsky sign (+), and the Asboe-Hansen sign (+). Blood laboratory result: random blood glucose 451 mg/dl, HbA1c 12.3%. Histopathological examination: suprabasal blister, in which the basal cells still attached to the basement membrane show a “tombstone” appearance. The diagnosis was steroid-induced diabetes in pemphigus vulgaris. He was treated with steroids and insulin.
 Conclusion: Steroid use in PV treatment can lead to metabolic complications, such as diabetes mellitus. Regularly monitoring is needed to prevent complications due to steroid use.

Effect of high density lipoprotein cholesterol (HDL-C) on renal outcome in patients with nephrotic syndrome complicated with steroid-induced diabetes mellitus(SIDM)

ObjectiveWe aimed to investigate the renal prognosis of patients with idiopathic nephrotic syndrome (INS) complicated with steroid-induced diabetes mellitus (SIDM), the association of high-density lipoprotein cholesterol (HDL-C) before glucocorticoid treatment with renal prognosis, and the risk for persistent diabetes among patients with INS who had withdrawn from steroid therapy.Materials and methodsWe retrospectively analyzed 239 patients with INS complicated with SIDM at the National Clinical Research Center of Kidney Diseases, Jinling Hospital, from January 2008 to December 2019. The primary endpoint was the composite renal outcome defined as the development of end-stage renal disease (ESRD) or a 50% decrease in estimated glomerular filtration rate (eGFR) for more than 24 months after glucocorticoid withdrawal. The secondary endpoint was persistent diabetes, defined as fulfilling the criteria for diagnosing diabetes or using antidiabetic medications for at least 24 months after glucocorticoid withdrawal.ResultsAfter glucocorticoid withdrawal for over 24 months, 35 (14.6%) patients reached the composite renal endpoint: end-stage renal disease (n = 14) or a 50% decrease in eGFR (n = 21). Before glucocorticoid therapy, a level of HDL-C greater than 1.45 mmol/L worsened renal survival in patients with INS complicated with SIDM. The log10 the level of HDL-C before glucocorticoid treatment was an independent risk factor for the renal outcome. A prediction model was generated: Hazard ratio (renal outcome) = 0.94 * hypertension before glucocorticoid therapy + 2.29 * log10 level of HDL-C before glucocorticoid treatment + 0.90 * the grade of interstitial tubule injury (AUROC, 0.75; 95% CI, 0.63 to 0.87; P < 0.01). Meanwhile, a level of fasting plasma glucose (FPG) before glucocorticoid treatment greater than 5.2 mmol/L enhanced the likelihood of persistent diabetes for at least 24 months after glucocorticoid withdrawal.ConclusionsIncreased level of HDL-C before glucocorticoid therapy was independently associated with a higher risk for renal outcome and thus may be useful in the renal prognosis of patients with INS complicated with SIDM.

Comparative study of adverse drug reactions of corticosteroids

Background: In Dermatology, corticosteroids (CSs) are widely prescribed in either topical or systemic formulations in various potencies to tailor therapy according to severity of the underlying condition, area of involvement, and patient’s age. CSs, however, are associated with a number of serious adverse effects, particularly with long-term usage. Aims: To study the relationship of adverse drug reactions (ADR) of long-term glucocorticoids (GC) with age, sex, smoking, alcoholism, underlying dermatologic conditions and co-existing medical disorders. To study CSs in relation to musculoskeletal system, metabolic & blood sugar levels and eye complications. To compare the ADR in cases on Oral mini pulse therapy (OMP) and Daily glucocorticoid (DGC) therapy groups. Methods: This was a hospital based prospective study done on 130 patients on OMP or Daily glucocorticoid therapy for more than 1 month duration, over a period of 2 years. Results: Cushingoid features and weight gain were observed in both groups. Bone changes, diabetes mellitus and hypertension were seen in patients on DGC therapy. Bone changes were seen in 17 (18.88%), Steroid induced Diabetes Mellitus (SDM) in 27(30%), Hypertension in 12(13.3%), Lipid abnormalities (in the form of raised cholesterol and triglyceride levels) in 7 (7.77%), Cataract in 12(13.33%) and glaucoma was seen in 1(1.11%) out of 90 patients on Daily glucocorticoid therapy.1 patient each out of 40 in the OMP group developed cataract and hypertension. Conclusion: In conditions like vitiligo, alopecia areata and lichen planus particularly in children, it is preferable to give OMP. In pemphigus group of disorders while using daily GC therapy, continuous monitoring and ADR prevention measures should be considered for patient's benefit.

Steroid-induced diabetes mellitus in children: A case series from Nigeria

Steroid-induced diabetes mellitus in children: A case series from Nigeria

Steroid-induced diabetes mellitus in pemphigus vulgaris patient at Bali Mandara Hospital: a case report

Background: Pemphigus vulgaris (PV) is a blistering autoimmune disease of the skin and mucous membranes defined histologically by intraepidermal blister due to acantholysis. Systemic corticosteroids and immunosuppressive agents had greatly improved the prognosis of pemphigus. However, steroid use often leads to metabolic complications, such as diabetes mellitus. This case report describes steroid-induced diabetes mellitus in PV, where the side effect of long-term high dosages steroid used and the method to manage it can be used as a study case.Case report: A 31-year-old man complained of new blisters from almost the entire body. He had a history of PV 1 year ago and no history of diabetes mellitus in the patient or family. He had a medication history of methylprednisolone 8 mg every 8 hours. Dermatological status showed erythema macules, extensive erosion almost on the entire body, the Nikolsky sign (+), and the Asboe-Hansen sign (+). Blood laboratory result: random blood glucose 451 mg/dl, HbA1c 12.3%. Histopathological examination: suprabasal blister, in which the basal cells still attached to the basement membrane show a “tombstone” appearance. The diagnosis was steroid-induced diabetes in pemphigus vulgaris. He was treated with steroids and insulin.Conclusion: Steroid use in PV treatment can lead to metabolic complications, such as diabetes mellitus. Regularly monitoring is needed to prevent complications due to steroid use.

New Onset Persistent Hyperglycemia with Initiation of Brentuximab Treatment

Brentuximab is a CD-30-directed antibody-drug conjugate. The addition of brentuximab vedotin (BV) to adriamycin, vinblastine, and dacarbazine (AVD) has become a standard-of-care approach for advanced stage Hodgkin Lymphoma. BV has well known toxicities including peripheral neuropathy and infusion reactions. One emerging toxicity that is beginning to be recognized is new-onset hyperglycemia and diabetes mellitus. This case describes a rare presentation of new-onset diabetes mellitus one month after initiation of BV+AVD therapy in a patient with Hodgkin Lymphoma.A 41 year old previously healthy woman presented initially with complaints of chest and back pain. Cardiac etiology was ruled out, and lymphadenopathy was noted on chest imaging. Subsequent pathologic report from a robotic-assisted excision of a mediastinal mass and level five lymph node revealed Classical Hodgkin Lymphoma, nodular sclerosis type. Her baseline Hba1c was 5.8% at time of diagnosis. BV+AVD therapy was initiated about five weeks later.Six weeks after initiating treatment, she was admitted for abdominal pain secondary to constipation, at which time her blood glucose was noted to be 357 mg/dL. A repeated Hba1c was 8.1%. She required rapid acting insulin, and her glucoses ranged from 132-263 mg/dL. After discharge, a fasting glucose of over 250 mg/dL deemed her ineligible to have a PET/CT performed to assess disease status after completing cycle 2. She was referred urgently to the endocrinology clinic. She had been receiving dexamethasone 12mg every two weeks in conjunction with her chemotherapy, as well as additional lower doses for chemotherapy induced nausea. Thus, there was some thought she could have steroid-induced diabetes mellitus. However, her last dose of dexamethasone was given more than ten days prior to her most recent FSBG reading of 220 mg/dL, so steroid-induced diabetes was deemed less likely. The more likely etiology considered was BV-induced hyperglycemia. The patient was started on basal insulin, a DPP4i, and a meglitinide analog. Since initiation of this therapy, her glucose levels are now better controlled with readings consistently under 200 mg/dL. Furthermore, her lymphoma is in remission after three cycles of BV+AVD therapy, with a plan to complete six cycles.For many years, the standard of Hodgkin Lymphoma treatment consisted of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). In 2017, the results of the ECHELON-1 phase 3 clinical trial demonstrated that a regimen with BV in conjunction with adriamycin, vinblastine, and dacarbazine (BV+AVD) has superior modified progression-free survival for patients with stage III/IV classical Hodgkin Lymphoma when compared to ABVD (Connors, NEJM, Jan, 2018). In a subsequent 3-year follow up study published in Blood, the authors demonstrated superior 3-year PFS for BV+AVD relative to ABVD.While BV has been a preferred treatment option to bleomycin, and one that avoids the dreaded complication of pulmonary fibrosis, we are learning more about other emerging toxicities related to its use. When the drug was first approved in 2011 for use in relapsed/refractory Hodgkin Lymphoma, the toxicity of hyperglycemia was not noted in the side effect profile. As the drug has now been in use for ten years, emerging data on other toxicities have been noted in trials and reported to the manufacturer. Hyperglycemia is a listed adverse effect in the prescribing label with an incidence of up to 8% of patients experiencing any grade hyperglycemia, and 6% experiencing Grade 3 or 4 hyperglycemia.The pathophysiology of hyperglycemia with BV administration is currently unclear. Interestingly, there is a paucity of literature describing this toxicity of the drug, and most incidence reports may be related to clinical trial data or post-approval reporting. An extensive literature search revealed only one other case report of new onset diabetes mellitus in patients receiving BV (Chiang, AACE, 2020). The authors suggest a general decrease in immune surveillance while on the drug leading to autoimmune conditions. Regardless of the mechanism of action, the above case report demonstrates a need to monitor blood glucose levels carefully during the initiation of BV therapy, especially in those individuals who have risk factors such as obesity or pre-diabetes mellitus. Future studies may further address the mechanism of hyperglycemia from BV and if the resultant diabetes is reversible. DisclosuresNo relevant conflicts of interest to declare.

Risk of Incident Diabetes and Dysregulated Pre-Existing Diabetes Mellitus in Newly Diagnosed Lymphoma Patients Treated with Steroid-Containing Immunochemotherapy: A Danish Population-Based Study

IntroductionPrednisolone has important potential side-effects, one of which is steroid-induced diabetes mellitus (DM). Due to the exposure to a high cumulative dosage of steroids during first-line treatment, patients with non-Hodgkin lymphoma (NHL) could face increased risk of new onset steroid-induced DM or dysregulation of a pre-existing DM. This nationwide observational cohort study evaluated the risk of new onset DM in lymphoma patients and the impact on pre-existing DM in lymphoma survivors following treatment with steroid-containing regimens.MethodsAdult NHL patients (≥18 years) treated with ≥3 cycles of steroid-containing immunochemotherapy, such as R-CHOP(-like) and R-CVP, between 2002 and 2015 were identified in the Danish Lymphoma Register and matched to five random individuals from the general population on birth year, sex, Charlson Comorbidity Index score, baseline DM status (DM or not), and DM duration. NHL patients and matched comparators were followed from start of treatment for the patients until the event of interest (DM, insulin prescription), death, relapse, NHL diagnosis (for matched comparators), or censoring (emigration, missing, or end of study on 31 December 2018), whichever came first.DM was captured by either a diagnosis of any DM (ICD-10 codes: E10-E14) in the Danish National Patient Register or any redeemed anti-diabetic prescription registered in the National Prescription Register (insulin or oral anti-diabetic medicine; ATC A10A or A10B). In the analysis of insulin prescriptions following lymphoma treatment initiation, patients with any redeemed prescription of insulin prior to start of lymphoma treatment were excluded.Time-varying incidence rates (IRs) per 1,000 person years and incidence rate ratios (IRRs) with 95% confidence intervals were estimated using a spline-based Poisson regression approach with two-month time splits and five knots. The Aalen-Johansen estimator was used to compute the cumulative risk of an event treating death, relapse, and NHL diagnosis (in comparators) as competing events. Risk differences at specific time points were calculated using pseudo-observations. Crude and adjusted cause-specific hazard ratios (HR) were obtained using Cox regression.ResultsA total of 4,703 NHL patients were included in the present study. Median age was 66 years and median follow-up was 8.5 years.Among the NHL patients, 4,325 patients did not have pre-existing DM and were matched to 21,625 comparators without DM. The time-varying IR of DM among comparators was 8-10 cases/1000 person years. The IRR of DM for patients vs comparators was higher for patients in the first year following treatment initiation (maximum IRR: 2.40), lower from 1 to 5 years (minimum IRR: 0.52), and higher from 5 to 10 years (maximum IRR: 1.18) (Fig. 1).The cumulative incidence of DM was higher for NHL patients at six months (0.58 percentage units (%U), p <0.01), but lower at 5 years (-1.17%U, p <0.01) and 10 years (-2.09%U, p <0.01) compared to the matched comparators (p <0.01 for the whole period, Fig. 2).Among the NHL patients, 378 had pre-existing non-insulin dependent DM and were matched to 1,890 comparators. The cumulative incidence difference of any insulin use was higher for patients at 6 months (14.29%U, p <0.01), 5 years (9.95%U, p <0.01), and 10 years (4.61%U, p =0.15) (p <0.01 for the whole period, Fig. 3). However, when events were limited ≥5 prescriptions of insulin, no difference was found (p =0.84 for the whole period). The crude HR for ≥5 prescriptions of insulin was 1.42 [1.10;183] for patients compared to the matched comparators and the HR adjusted for sex, age, and comorbidities was 1.39 [1.08;1.79].ConclusionIn conclusion, patients treated with steroid-containing immunochemotherapy did not experience a higher risk of diabetes mellitus compared to matched comparators beyond the first year. Matched comparators had a higher cumulative incidence of diabetes mellitus after 2 years, which was partly explained by the high competing risk of death in the patient group.NHL patients with pre-existing non-insulin dependent diabetes mellitus had an increased cumulative incidence of any insulin prescriptions; however, the difference was diminished when assessing the risk of at least five insulin prescriptions, suggesting that the impact of steroids on diabetes regulation is limited in time when taking competing risks into account. [Display omitted] DisclosuresØvlisen: Abbvie: Other: Travel expenses. Frederiksen: Abbvie: Research Funding; Gilead: Research Funding; Alexion: Research Funding; Novartis: Research Funding; Janssen Pharmaceuticals: Research Funding. Vestergaard: Novo Nordisk Foundation: Other: Head of Research at Steno Diabetes Center North Jutland funded by the Novo Nordisk Foundation, Research Funding. Jørgensen: Gilead: Consultancy; Novartis: Consultancy; Roche: Consultancy; Celgene: Consultancy. Clausen: Gilead: Consultancy, Other: Travel expences 15th ICML ; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expences ASH 2019; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Poulsen: Janssen: Consultancy; Abbvie: Consultancy. Ekstroem Smedby: Janssen Cilag: Research Funding; Takeda: Consultancy. Eloranta: Janssen Pharmaceutical NV: Other: NV. El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee.

Co-Relation of Steriods in Diabetic and COVID-19 Patients

An unusual rise in blood glucose linked with the use of glucocorticoids in a patient with or without a prior history of diabetes mellitus is referred to as steroid-induced diabetes mellitus. The term steroid refers to a group of chemicals that have varied physiological effects. Hydrocortisone are a class of hormones that comprises both lab-made and naturally occurring hormones. Steroids are naturally occurring hormones in the human body. Corticosteroids have a wide spectrum of effects, from solely glucocorticoid to solely mineralocorticoid, and steroid compounds are chosen based on their suitability for a particular therapy. A drug may have anti-inflammatory resources, it could also have mineralocorticoid action, which lowers blood pressure. Steroids are drugs that have been used extensively in a variety of conditions. Glucocorticoids, despite being frequently recommended for their anti-inflammatory and immunosuppressive characteristics, have a number of side effects, with hyperglycemia being one of the most common and representative. In diabetic individuals, corticosteroids are generally contraindicated due to the danger of altering glucose control and resulting in severe decompensation. However, if given early and in a well-controlled regimen, corticosteroid medication can be useful in some patients. With good knowledge of the pharmacokinetics of the glucocorticoid utilized, glucose disequilibrium after withdrawal can be predicted.

Цукровий діабет, індукований екзогенним введенням глюкокортикостероїдів

В лекції розглядаються питання діагностики та лікування стероїдіндукованого цукрового діабету.

Analysis of a case of steroid-induced diabetes mellitus and pharmaceutical care

Analysis of a case of steroid-induced diabetes mellitus and pharmaceutical care