BackgroundGlucocorticoids are frequently employed in systemic lupus erythematosus (SLE) patients and play a critical role in the induction therapy of lupus nephritis (LN), despite their many side effects, including steroid-induced diabetes (SID). Information regarding SID in SLE patients is quite scant.PurposeThe aim of this study was to determine risk factors associated with the development of SID in patients with LN.Research Design A nested case-control study was conducted.Study sampleWe included patients with biopsy-proven LN, who received induction treatment with steroids.Data Collection and/or AnalysisOut of the total of 358 patients, 35 (9.7%) developed SID.ResultsPatients with SID had more metabolic risk factors, including the metabolic score for insulin resistance (METS-IR); more factors related with lupus activity, with higher SLEDAI and SLICC-DI scores; and lower cumulative pre-induction steroid dose. A higher percentage of patients who developed SID received steroid pulses and a lower percentage received antimalarials. After logistic regression, the variables significantly associated with the development of SID were the SLEDAI index (OR 1.25 [95% CI 1.04-1.50], p 0.01), SLICC-DI (OR 4.93 [95% CI 2.14-11.3], p < 0.001), METS-IR (OR 1.17 [95% CI 1.04-1.32], p 0.009), delta METS-IR at 6 months (OR 1.20 [95% CI 1.03-1.39], p 0.01), and the use of antimalarials (OR 0.14, [95% CI 0.02-0.85], p 0.03). After propensity score matching, METS-IR remained a significant predictor of SID. Patients with METS-IR >36.8 were at higher risk (OR: 2.83, 95% CI: 1.09-7.36, p = 0.034).ConclusionsIn conclusion, SDI development in patients receiving induction therapy for LN is associated with both classic metabolic risk factors and SLE-specific factors, and antimalarial use could be associated with a protective effect. Rheumatologists should be aware of this potential complication, in order to implement appropriate management strategies.

In people living with chronic obstructive pulmonary disease (COPD), we aimed to estimate: (1) the prevalence of glucocorticoid-induced hyperglycaemia (GIH); (2) whether the prevalence of GIH varies by age, baseline diabetes status, treatment duration, ascertainment of glycaemia, definition of hyperglycaemia, study design and year of publication; and (3) the relative risk (RR) of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids.

We searched electronic databases until 9 November 2023 for randomised controlled trials and observational studies including adults diagnosed with COPD, with or without diabetes at baseline, using systemic glucocorticoids equivalent to prednisolone ≥5 mg/day for ≥3 days if exposed. Hyperglycaemia was defined as a blood glucose above a study-specific cut-off. We extracted data on study and participant characteristics, exposure and outcome. We performed random-effects meta-analysis to calculate pooled prevalence estimate of GIH. Prevalence was expressed as the proportion of people who developed hyperglycaemia among all exposed to systemic glucocorticoids during follow-up. We calculated RR of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids from eight studies.

Of 25,806 citations, we included 18 studies comprising 3642 people of whom 3125 received systemic glucocorticoids and 1189 developed hyperglycaemia. Pooled prevalence of GIH was 38.6% (95%CI 29.9%-47.9%) with significant heterogeneity, I2 = 96% (p < 0.010), which was partially explained by differences in study design. Pooled RR = 2.39 (95%CI 1.51-3.78). Publication bias was present.

The prevalence of GIH was 38.6%. Being treated with systemic glucocorticoids for COPD was associated with 2.4 times higher risk of new-onset hyperglycaemia versus no glucocorticoid treatment.

Bullous pemphigoid (BP) is an autoimmune bullous disease characterized by subepidermal tense blisters, accompanied by urticarial or eczema-like lesions. Circulating autoantibodies in BP patients target BP180 and BP230 at the dermal-epidermal junction. There has been a growing interest in unraveling the intricate relationship between BP and diabetes mellitus (DM), but a comprehensive review is lacking.

A thorough search of PubMed was conducted to identify studies concerning the association between BP and DM (1978-2023). Our findings comprehensively summarize the intricate association between BP and DM, focusing on the characteristics, potential pathomechanisms, and the influence of various antidiabetic medications on BP development.

DM emerges as a prevalent comorbidity and potential risk factor for BP. New-onset DM can manifest during BP treatment, primarily due to corticosteroid therapy. Among all antidiabetic medications, dipeptidyl peptidase-IV inhibitors (DPP-4i) have the most solid association with BP onset. Other antidiabetic medications have also been reportedly associated with BP, including meglitinides, glucagon-like peptide 1 (GLP-1)-receptor agonists, and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i). We suggest prescribing DPP-4i in caution for elderly DM patients with a history of autoimmune diseases.

Data on type 2 diabetes (T2D) risk after breast cancer (BC) could guide preventive strategies. Yet, studies had limitations regarding sample size, follow-up, and contemporary treatments. We evaluated the risk of T2D after BC overall, by cancer treatment, and compared with a matched cohort of cancer-free women.

We assembled a population-based cohort of early-stage BC patients aged 30 years or more diagnosed during 1996-2021 in Denmark. We created a comparison cohort of 5 cancer- and T2D-free women for each BC patient, matched 6 months after BC diagnosis date on age and region. We followed both cohorts until T2D diagnosis, emigration, death, or December 31, 2022. We computed 5-year cumulative incidences and used Cox models to calculate time-varying adjusted hazard ratios (aHR) of T2D.

Among 74 526 BC survivors and 372 630 matched cancer-free women, 5-year cumulative incidences of T2D were 3.8% (95% confidence interval [CI] = 3.7 to 3.9) and 3.3% (95% CI = 3.3 to 3.4), respectively. The aHR of T2D was elevated but attenuated over follow-up (aHR5-years = 1.20, 95% CI = 1.15 to 1.25, and aHR15-years = 1.09, 95% CI = 1.05 to 1.12). Adjuvant endocrine therapy (aHR = 1.14; 95% CI = 1.10 to 1.19), aromatase inhibitors (aHR = 1.25; 95% CI = 1.18 to 1.32), and less so tamoxifen (aHR = 1.05; 95% CI = 0.99 to 1.11), were associated with elevated risk of T2D in women with BC vs cancer-free women. Among BC patients, chemotherapy (aHR = 1.10, 95% CI = 1.03 to 1.17) and radiation therapy (right-sided aHR = 1.18, 95% CI = 1.09 to 1.27 and left-sided aHR = 1.24, 95CI = 1.15 to 1.33) were associated with increased T2D risk.

BC was associated with excess risk of T2D, although of lower magnitude than previously reported. The excess risk was temporary and related to BC treatment but could also be influenced by obesity and heightened T2D diagnostic activity.

Posttransplantation diabetes mellitus (PTDM) is a form of diabetes developed after solid organ or stem cell transplantation. This condition shares physiopathological traits with type 2 diabetes, including insulin resistance and β-cells dysfunction and its prevalence varies significantly based on the diagnostic criteria used. Immunosuppressive drugs directly contribute to PTDM risk through intricate impacts on glucose regulation, insulin secretion, and inflammation. In addition, modifiable and non-modifiable environmental risk factors are associated with the onset of this condition. This review aims to provide a comprehensive overview of the multifactorial nature of PTDM in order to highlight candidate genes and variants for pharmacogenetic research. An extensive literature search was conducted to identify studies on pharmacological and genetic factors influencing PTDM development. This review stresses the importance of understanding these interactions for improving PTDM management and underscores the need for further research to refine preventive approaches, ultimately enhancing patient outcomes post-transplantation.

Kidney transplantation is the best treatment for patients with chronic renal failure, capable of improving life expectancy and the risk of death from all causes, which, however, remains higher than in the general population. The leading cause of death in transplant patients is cardiovascular events, burdened by a significant impact brought about by anti-rejection therapy. Experimental and clinical studies to date show that in kidney transplant recipients, traditional cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, tobacco, etc.) may be exacerbated or worsened by the dysmetabolic effects of immunosuppressive drugs, which may also result in additional risk factors such as proteinuria, anemia, and arterial stiffness. The aim of this review was to provide an in-depth evaluation of the effect of immunosuppressive treatments on cardiovascular risk factors.

We have investigated and described the main cardiovascular risk factors related to immunosuppressive drugs. We searched for relevant scientific articles in medicine, transplant, cardiologic, and nephrological journals in major medical science libraries.

Immunosuppressive drugs allow graft survival and successful bunking of the transplant; however, they are not without significant side effects and should always be prescribed weighing the risk/benefit ratio and the individual patient's therapeutic needs.

Hospital Hyperglycemia (HH) is linked to poorer outcomes, including higher mortality rates, increased ICU admissions, and extended hospital stays, and occurs in both people living with diabetes or not. The prevalence of HH in non-critical patients ranges from 22 to 46%. This panel reviewed the evidence and made recommendations for the best care for hospitalized hyperglycemic patients, with or without diabetes mellitus.

The methodology was published previously and was defined by the internal institutional steering committee. The SBD Acute and Hospital Complications Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to Hospital Hyperglycemia.

The department members and external experts developed 23 recommendations for the management of patients with HH, including screening, initial interventions, treatment adjustments, and care for potential complications. Based on the best available evidence, our article provides safe and effective management strategies for both public and private healthcare settings.

The widespread use of glucocorticoids in clinical practice may occasionally be complicated by hypokalemic paralysis. Previously, only a few cases of glucocorticoid-induced hypokalemic paralysis in healthy adults had been reported. Intriguingly, cases of B12-induced hypokalemia have previously been reported in patients with pernicious anemia. Recently, we experienced a case of hypokalemic paralysis in an adolescent following intramuscular injections of dexamethasone and vitamin B12. Upon exclusion of other causes, a presumptive diagnosis of glucocorticoid-induced hypokalemic paralysis, with a possible but uncertain contribution from B12 supplementation, was made for the patient. After potassium replacement therapy, the patient fully recovered and was discharged after five days. Although glucocorticoids are known to cause hypokalemia through mechanisms such as enhanced transcellular shift or renal excretion, the potential role of vitamin B12 in worsening this effect remains unclear. It is hypothesized that B12 supplementation under certain conditions could influence electrolyte balance and potentially amplify the hypokalemic effects of glucocorticoids. However, this hypothesis is based on a few cases, and further pathophysiological and clinical studies are needed to clarify whether B12 supplementation exacerbates hypokalemia induced by glucocorticoids or if the observation is coincidental or context-specific. Meanwhile, clinicians should be cautious when prescribing glucocorticoids, particularly in combination with B12 supplements. This includes ensuring that both are administered only when clinically indicated, monitoring vital signs and serum potassium levels in at-risk patients, and considering alternatives when appropriate.

Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. However, limited data about DKA and HHS are available in patients with cancer. The current study aimed to determine characteristics and outcomes of patients with cancer who were admitted with DKA/HHS in a mid-size Canadian city.

Consecutive adult patients with an active cancer who were admitted with DKA or HHS from January 2008 to December 2020 in the city of Saskatoon, Saskatchewan, Canada were retrospectively evaluated. A univariate logistic regression analysis was performed to examine the correlation of various clinical variables with hospital mortality.

During the study period 6,555 patients with diabetes and cancer were admitted in one of the three tertiary care hospitals. Among them 33 (0.5 %) eligible patients with DKA or HHS with a median age of 60 years (range 36-94 years) were identified. In 36 % of patients, DKA or HHS was the presenting manifestation of newly diagnosed diabetes. Of all patients, 66 % developed DKA and 73 % had an advanced cancer. Overall, 52 % patients received a systemic cancer therapy prior to the admission, and 41 % received steroids. Ten (42 %) of 24 patients with an advanced cancer died, compared to none of the nine patients with an early-stage cancer (p = 0.032). No clinical factors significantly correlated with hospital mortality.

Although DKA or HHS is uncommon in patients with diabetes and cancer, it is the manifestation of undiagnosed diabetes in about one-third of patients with cancer. It has been associated with high hospital mortality in patients with advanced cancer.

Adrenal insufficiency (AI) is a serious disorder characterized by the adrenal glucocorticoid deficiency. Regardless of the etiology, AI patients need long-term replacement therapy for glucocorticoids and, in some cases, for mineralocorticoids. The replacement therapy cannot completely mirror the physiological secretion patterns, and therefore, glucocorticoid excess is a common sequela in AI patients. Moreover, due to the absence of the reliable clinical markers to monitor the adequacy of the replacement therapy, clinicians often over-treat the AI patients to avoid adrenal crisis. Long-term glucocorticoid use is associated with the loss of bone density and osteoporosis, increasing the risk of fractures. Moreover, glucocorticoid-induced hyperglycemia and type 2 diabetes mellitus further aggravates the bone disorders. In the recent years, ameliorating effects of metformin on glucocorticoid-induced bone disorders, as well as hyperglycemia, have been reported by a multitude of studies; and here, we reviewed and discussed the most recent findings regarding the positive effects of metformin on alleviating the bone disorders, and their implications in the AI patients.

As corticosteroids can cause diabetes, it is important to assess the benefit-risk balance for patients before introducing them, and to monitor the development of hyperglycemia in people treated with this therapeutic class. As soon as cortico-induced diabetes is discovered, multidisciplinary, cross-disciplinary management improves follow-up conditions.

Growing epidemiological evidence indicates an association between obesity, type 2 diabetes, and certain cancers, suggesting the existence of common underlying mechanisms in these diseases. Frequent hyperglycemias in type 2 diabetes promote pro-inflammatory responses and stimulate intracellular metabolic flux which rewires signaling pathways and influences the onset and advancement of different types of cancers. Here, we review the provocative impact of hyperglycemia on a subset of interconnected signalling pathways that regulate (i) cell growth and survival, (ii) metabolism adjustments, (iii) protein function modulation in response to nutrient availability (iv) and cell fate and proliferation and which are driven respectively by PI3K (Phosphoinositide 3-kinase), AMPK (AMP-activated protein kinase), O-GlcNAc (O-linked N-acetylglucosamine) and Wnt/β-catenin. Specifically, we will elaborate on their involvement in glucose metabolism, inflammation, and cell proliferation, highlighting their interplay in the pathogenesis of diabetes and cancer. Furthermore, the influence of antineoplastic and antidiabetic drugs on the unbridled cellular pathways will be examined. This review aims to inspire the next molecular studies to understand how type 2 diabetes may lead to certain cancers. This will contribute to personalized medicine and direct better prevention strategies.

Glucocorticoid (GC) treatments are often used. There is limited information on the prediction of hyperglycaemia after GC administration.

This study aimed to identify the risk factors for hyperglycaemia after glucocorticoid (GC) administration and the need for hypoglycaemic agents to correct it and to develop and validate a novel scoring system for predicting GC-induced hyperglycaemia.

In a development set, 508 adults receiving prednisolone (PSL) for the first time were divided into two groups based on treatment with or without hypoglycaemic agents. Clinical and laboratory parameters were compared, and risk factors were identified using logistic regression analysis after performing univariate analyses between the two groups. A point-addition scoring system with several categories and coefficients for each risk factor was constructed to predict the need for hypoglycaemic agents. The scoring system was then applied and validated on two validation sets: A and B.

Older age, higher glycated haemoglobin percentage, body mass index and initial PSL dosage were identified as risk factors. The sensitivity, specificity and accuracy of the scoring system were 70.6%, 81.9% and 77.1% in the development set; 75.8%, 78.4% and 77.4% in validation set A; and 79.4%, 73.9% and 75.3% in validation set B respectively. By fitting the total score in the development set and the probability of hyperglycaemia to a logistic curve, a figure was created to show the probability of GC-induced hyperglycaemia in patients scheduled to receive GC.

This scoring system is a novel, valid and reliable tool for predicting GC-induced hyperglycaemia and the need for hypoglycaemic agents to correct it.

Corticosteroids are used frequently in oncology and many patients require short- or long-term corticosteroid therapy. General clinical guidelines and recommendations exist on the use of corticosteroids; however, evidence is lacking for recommendations on their appropriate use in older adult with cancer. Treatment of chemotherapy-induced nausea and vomiting (CINV) has dramatically improved over the last decade with 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists and neurokinin-1 (NK-1) receptor antagonists or a combination of both. However, corticosteroids continue to play an important role in the management of acute and delayed CINV prevention. While highly efficacious, the toxicity profile of corticosteroids must be considered, particularly in heterogeneous older patients with multiple comorbidities and polypharmacy. Guidance on corticosteroid-reducing/sparing strategies in this specific population is needed. This consensus, supported by the International Society of Geriatric Oncology, aims to provide evidence-based recommendations for the use of corticosteroid therapy in older adults with cancer.

Glucocorticoids (GS) are widely used in multiple medical indications due to their anti-inflammatory, immunosuppressive, and antiproliferative effects. Despite their effectiveness in treating respiratory, skin, joint, renal, and neoplastic diseases, they dysregulate glucose metabolism, leading to steroid-induced diabetes (SID) or a significant increase of glycemia in people with previously diagnosed diabetes. The risk of adverse event development depends on the prior therapy, the duration of the treatment, the form of the drug, and individual factors, i.e., BMI, genetics, and age. Unfortunately, SID and steroid-induced hyperglycemia (SIH) are often overlooked, because the fasting blood glucose level, which is the most commonly used diagnostic test, is insufficient for excluding both conditions. The appropriate control of post-steroid hyperglycemia remains a major challenge in everyday clinical practice. Recently, the most frequently used antidiabetic strategies have been insulin therapy with isophane insulin or multiple injections in the basal-bolus regimen. Alternatively, in patients with lower glycemia, sulphonylureas or glinides were used. Taking into account the pathogenesis of post-steroid-induced hyperglycemia, the initiation of therapy with glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors should be considered. In this article, we present a universal practical diagnostic algorithm of SID/SIH in patients requiring steroids, in both acute and chronic conditions, and we present a new pharmacotherapy algorithm taking into account the use of all currently available antidiabetic drugs.

The spectrum of pediatric rheumatological disorders is diverse and they are important differential diagnoses in a variety of clinical scenarios. Basic investigations not only provide supporting evidence for the diagnosis of a rheumatological illness but also help in exclusion of other diseases as well as for monitoring the activity of disease. Among these, complete blood count, biochemical assays including tests for inflammatory response, urine analysis, and various autoantibodies are often used. In addition, depending on the clinical features, imaging and tissue biopsies are used to confirm the diagnosis.

Major depressive disorder (MDD) increases the risk of type 2 diabetes (T2D) by 60% in untreated patients, and hypercortisolism is common in MDD as well as in some patients with T2D. Patients with MDD, despite hypercortisolism, show inappropriately normal levels of corticotropin-releasing hormone (CRH) and plasma adrenocorticotropin (ACTH) in the cerebrospinal fluid, which might implicate impaired negative feedback. Also, a positive feedback loop of the CRH-norepinephrine (NE)-CRH system may be involved in the hypercortisolism of MDD and T2D. Dysfunctional CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2), both of which are involved in glucose regulation, may explain hypercortisolism in MDD and T2D, at least in a subgroup of patients. CRHR1 increases glucose-stimulated insulin secretion. Dysfunctional CRHR1 variants can cause hypercortisolism, leading to serotonin dysfunction and depression, which can contribute to hyperglycemia, insulin resistance, and increased visceral fat, all of which are characteristics of T2D. CRHR2 is implicated in glucose homeostasis through the regulation of insulin secretion and gastrointestinal functions, and it stimulates insulin sensitivity at the muscular level. A few studies show a correlation of the CRHR2 gene with depressive disorders. Based on our own research, we have found a linkage and association (i.e., linkage disequilibrium [LD]) of the genes CRHR1 and CRHR2 with MDD and T2D in families with T2D. The correlation of CRHR1 and CRHR2 with MDD appears stronger than that with T2D, and per our hypothesis, MDD may precede the onset of T2D. According to the findings of our analysis, CRHR1 and CRHR2 variants could modify the response to prolonged chronic stress and contribute to high levels of cortisol, increasing the risk of developing MDD, T2D, and the comorbidity MDD-T2D. We report here the potential links of the CRH system, NE, and their roles in MDD and T2D.

To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA).

We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia.

31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes.

In non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.

Studies have shown that cardiovascular health (CVH) is related to depression. We aimed to identify gene networks jointly associated with depressive symptoms and cardiovascular health metrics using the whole blood transcriptome.

We analyzed human blood transcriptomic data to identify gene co-expression networks, termed gene modules, shared by Beck's depression inventory (BDI-II) scores and cardiovascular health (CVH) metrics as markers of depression and cardiovascular health, respectively. The BDI-II scores were derived from Beck's Depression Inventory, a 21-item self-report inventory that measures the characteristics and symptoms of depression. CVH metrics were defined according to the American Heart Association criteria using seven indices: smoking, diet, physical activity, body mass index (BMI), blood pressure, total cholesterol, and fasting glucose. Joint association of the modules, identified with weighted co-expression analysis, as well as the member genes of the modules with the markers of depression and CVH were tested with multivariate analysis of variance (MANOVA).

We identified a gene module with 256 genes that were significantly correlated with both the BDI-II score and CVH metrics. Based on the MANOVA test results adjusted for age and sex, the module was associated with both depression and CVH markers. The three most significant member genes in the module were YOD1, RBX1, and LEPR. Genes in the module were enriched with biological pathways involved in brain diseases such as Alzheimer's, Parkinson's, and Huntington's.

The identified gene module and its members can provide new joint biomarkers for depression and CVH.

Physical activity has the potential to reduce the risk of diabetes after cancer diagnosis. However, current evidence supporting its effects is limited. This study aims to examine the associations between changes in physical activity and subsequent risk of diabetes among cancer survivors.

A total of 264,250 cancer survivors (mean age 56.7 (12.5) years, 44.2% males) without a prior history of diabetes were assessed for adherence to physical activity both before and after their diagnosis. The primary outcome was incident diabetes. The Fine-Gray proportional sub-distribution hazards model was used to calculate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for diabetes risk, considering death as a competing risk.

Over a follow-up of 1,065,802 person-years, maintaining regular physical activity from pre-diagnosis was associated with a 10% reduced risk of diabetes after cancer diagnosis (sHR 0.90, 95% CI 0.85-0.96), considering traditional diabetes risk factors, sociodemographics, and primary cancer sites. Cancer survivors who became active and inactive after their cancer diagnosis exhibited a marginally decreased risk of diabetes (sHR 0.98, 95% CI 0.93-1.03; sHR 0.97, 95% CI 0.92-1.03). The strength and direction of the association varied depending on the primary site of cancer.

Regular physical activity starting before a cancer diagnosis is associated with a lower risk of diabetes following the diagnosis, independent of established diabetes risk factors.

The study underscores the importance of engaging in sufficient physical activity to mitigate the risk of diabetes in cancer survivors.

Objective: Observational studies showed that Type 2 diabetes increased the risk of breast cancer, and vice versa. However, it is uncertain whether the link is causal or just due to confounding factors. Using bidirectional Mendelian randomization analysis, we assessed the bidirectional causal relationship from a genetic level. Methods: Large genome-wide association studies yielded summary-level data for Type 2 diabetes and breast cancer. Results: Genetically predicted Type 2 diabetes presented no statistically significant association with overall breast cancer or its subtypes. Similarly, genetically predicted overall breast cancer or its subtypes had no causal effect on Type 2 diabetes. Sensitivity analyses yielded similar results. Conclusion: Our bidirectional Mendelian randomization studies revealed no causal links between Type 2 diabetes and breast cancer.

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.

To determine the optimal initial insulin dosage for controlling hyperglycemia in COVID-19 patients receiving steroids, an area with limited data.

We retrospectively analyzed 156 COVID-19 patients with steroid-induced hyperglycemia treated with insulin. Patients were categorized by their total daily dose of subcutaneous insulin therapy when starting dexamethasone ⩾6 mg/day or equivalent dose of glucocorticoid: Group A (⩽0.29 units/kg), Group B (0.3-0.49 units/kg), Group C (0.5-0.69 units/kg), and Group B (⩾0.7 units/kg). Treatment failure was defined as mean blood glucose level > 280 mg/dL for two consecutive days after initiating insulin or any blood glucose ⩾ 400 mg/dL.

The mean age was 64 ± 14 years, with 50% male, and a mean body mass index of 26.9 ± 6.9 kg/m2. Most had preexisting type 2 diabetes (62%). Mean admission blood glucose and HbA1c were 233 ± 112 mg/dL and 7.8 ± 2.3%, respectively. Group A had the lowest HbA1c (6.7 ± 1.2%), while group D had the highest (9.8 ± 2.5%). Median daily dexamethasone dosage or equivalent was 36 (IQR 16.72) mg, with no significant differences in among groups. Group A had the lowest treatment failure rate. There were no significant differences in treatment failure rate between Groups B, C, and D. Additionally, there were no statistically significant differences in mean BG across the groups: Group A 232 ± 42 mg/dL, Group B 247 ± 57 mg/dL, Group C 247 ± 61 mg/dL, and Group D 227 ± 67 mg/dL (p = 0.2). Group D had a significantly higher rate of level 1 hypoglycemia (p = 0.008), while no differences in clinically significant hypoglycemia (level 2 or 3) were observed between groups.

Among patients requiring TDD ⩾ 0.3 units/kg/day, there was no significant difference in treatment failure rate between Groups B, C, and D. Group D had the highest rate of level 1 hypoglycemia. This initial insulin dosage for hospitalized COVID-19 patients on high-dose steroid therapy should be personalized.

The Outcome Measures in Rheumatology (OMERACT) Glucocorticoid (GC) Impact Working Group has been working to develop a core domain set to measure the impact of GCs on patients living with rheumatic and musculoskeletal diseases. The mandatory domains previously identified for inclusion in all clinical trials measuring the GC effects include infection, bone fragility, mood disturbance, hypertension, diabetes, weight, fatigue, and mortality. Before progressing to instrument selection, the Working Group sought to establish precise definitions of all mandatory domains within the core domain set.

OMERACT methodology was applied with the use of evidence and consensus-based decision making of all stakeholder groups (patient research partners, health care professionals, clinician researchers, industry members and methodologists) to develop detailed definitions for the broad domain, target domain and domain components, taking into consideration sources of variability that could affect measurement of the domain.  The working group synthesized prior qualitative studies, quantitative work, and results from Delphi rounds, to develop a rich definition of 'what' is to be measured.

Between 2021 and 2023, the OMERACT Working Group on GC Impact conducted virtual meetings to establish domain definitions. First, we mapped each domain onto an OMERACT Core Area. All domains were primarily represented within the Pathophysiological Manifestations Core Area, except from Fatigue which was primarily Life Impact and Weight which spanned both Core Areas. Sources of variability included cultural factors, age, gender, education level, socioeconomic status, personal experiences, emotional state, and language barriers. The domain definitions will form the foundation for instrument selection and the initial step of domain / concept match and content validity in the OMERACT pillar of 'truth' before moving on to feasibility and discrimination.

The OMERACT GC Impact Working Group has developed and agreed upon detailed domain definitions for core domains. Future steps of the working group are to select instruments and develop the core outcome measurement set for clinical trials measuring the impact of GC on patients with rheumatic and musculoskeletal diseases.

Patients with cancer and diabetes face unique challenges. Limited data are available on diabetes management in patients undergoing concurrent chemoradiotherapy (CCRT), a curative intent anticancer therapy commonly associated with glucocorticoid administration, weight fluctuations and enteral feeds. This retrospective case-control study examined the real-world incidence of acute diabetes-related complications in patients with head and neck cancer receiving CCRT, along with the impact of diabetes on CCRT tolerance and outcomes.

Consecutive patients with head and neck squamous cell or nasopharyngeal cancer who underwent definitive or adjuvant CCRT between 2010 and 2019 at two large cancer centers in Australia were included. Clinicopathological characteristics, treatment complications and outcomes were collected from medical records.

Of 282 patients who received CCRT, 29 (10.3%) had pre-existing type 2 diabetes. None had type 1 diabetes. The majority (74.5%) required enteral feeding. A higher proportion of patients with diabetes required admission to a high-dependency or intensive care unit (17.2 versus 4.0%, p = 0.003). This difference was driven by the group who required insulin at baseline (n = 5), of which four (80.0%) were admitted to a high-dependency unit with diabetes-related complications, and three (60.0%) required omission of at least one cycle of chemotherapy.

Patients with diabetes requiring insulin have a high risk of acute life-threatening diabetes-related complications while receiving CCRT. We recommend multidisciplinary management involving a diabetes specialist, educator, dietitian, and pharmacist, in collaboration with the cancer care team, to better avoid these complications.

Background Hyperglycemia is a common side effect of high-dose steroid therapy in hospitalized patients. Objectives To assess the prevalence of hyperglycemia among hospitalized patients receiving steroid therapy. Methods A retrospective study was conducted among 245 patients. The inclusion criteria were patients undergoing steroid therapy and admitted to a single tertiary care hospital due to medical complications or exacerbation of the diseases they were suffering from. Data encompassing patient demographics, admission, discharge dates, comorbidities, medication histories, laboratory results (including blood glucose levels), and documented corticosteroid administrations were meticulously gathered from electronic health records (EHRs). A logistic regression model analysis was done to predict the risk factors of poor glycemic control among hospitalized patients. Results The prevalence of hyperglycemia among the patients who were on steroid therapy was 34.2%. About 70.7% of the patients who required insulin at the time of admission required >17 units, and the insulin requirement was significantly higher among patients who received dexamethasone compared to other steroids (p<0.05). Older age (>65 years) was found to be independently associated with poor glycemic control (p<0.05). Conclusion The study revealed that almost one-third of patients on steroid therapy had hyperglycemia. Monitoring of patients for hyperglycemia after beginning high-dose steroid therapy should be done.

Despite known risks of hyperglycemia on postoperative complications, the influence of intraoperative dexamethasone on blood glucose has yet to be evaluated within the diabetic limb salvage population. This study aimed to assess the effect of intraoperative dexamethasone on postoperative blood glucose in diabetic patients undergoing atraumatic major lower extremity amputations. A single-center retrospective review of diabetic patients undergoing below-knee amputation between January 2017 and December 2022 was performed. Blood glucose levels for the 5 days before and after amputation were recorded and compared with the primary endpoints of postoperative hyperglycemia (>200 mg/dL) and glucose variability (>200 mg/dL). Cohorts were divided by patients who did and did not receive intraoperative administration of dexamethasone. Three hundred eighty-one were screened for eligibility with 180 patients included. Of these, 50 patients received dexamethasone intraoperatively (38.5%). Average pre- and postoperative blood glucose, rate of pre- and postoperative hyperglycemia, perioperative glucose variability, and postoperative dehiscence and infection were comparable between cohorts. On multivariate analysis, intraoperative administration of dexamethasone was not associated with postoperative hyperglycemia (p = .104) or perioperative blood glucose variability > 200 mg/dL (p = .334). Perioperative blood glucose variability > 200 mg/dL was associated with higher odds of surgical site infection (SSI) (odds ratio 5.12, p = .003). Administration of intravenous dexamethasone to diabetic patients undergoing below-knee amputation is not associated with postoperative hyperglycemia or complications. This study confirms previous findings that high glucose is a predictor of SSI. Concerted effort by a multidisciplinary team to attain tight glycemic control is critical to optimizing healing.

The effects of intravenous glucocorticoids on postoperative delirium (POD) in adult patients undergoing major surgery remain controversial. Therefore, we conducted this meta-analysis to assess whether intravenous glucocorticoids can decrease POD incidence in the entire adult population undergoing major surgery and its association with patients age, type of surgery, and type of glucocorticoid.

We searched the relevant literature published before November 3, 2023, through Cochrane Library, PubMed, Embase, and Web of Science. The primary outcome was POD incidence. The risk ratio for the primary outcome was calculated using the Mantel-Haenszel method. The secondary outcomes included 30-day mortality, length of hospital stay, ICU duration, mechanical ventilation duration, and occurrence of glucocorticoid-related adverse effects (e.g., infection and hyperglycemia). This meta-analysis was registered in PROSPERO: CRD42022345997.

We included eight randomized controlled studies involving 8972 patients. For the entire adult population undergoing major surgery, intravenous glucocorticoids reduced the POD incidence (risk ratio = 0.704, 95% confidence interval, 0.519-0.955; P = 0.024). However, subgroups defined by type of surgery showed differential effects of glucocorticoids on POD. Intravenous glucocorticoids can not reduce POD incidence in adult patients undergoing cardiac surgery (risk ratio = 0.961, 95% confidence interval, 0.769-1.202; P = 0.728), with firm evidence from trial sequential analysis. However, in major non-cardiac surgery, perioperative intravenous glucocorticoid reduced the incidence of POD (risk ratio = 0.491, 95% confidence interval, 0.338-0.714; P < 0.001), which warrants further studies due to inconclusive evidence by trial sequence analysis. In addition, the use of glucocorticoids may reduce the mechanical ventilation time (weighted mean difference, -1.350; 95% confidence interval, -1.846 to -0.854; P < 0.001) and ICU duration (weighted mean difference = -7.866; 95% confidence interval, -15.620 to -0.112; P = 0.047).

For the entire adult population undergoing major surgery, glucocorticoids reduced the POD incidence. However, the effects of glucocorticoids on POD appear to vary according to the type of surgery. In patients receiving major non-cardiac surgery, glucocorticoid may be an attractive drug in the prevention of POD, and further studies are needed to draw a definitive conclusion. In cardiac surgery, intravenous glucocorticoids have no such effect.

Hyperglycaemia is a common side effect of prednisolone, although there are no widely accepted guidelines for the management of glucocorticoid-induced hyperglycaemia (GIH). Our institution uses mixed insulin in a pre-breakfast or pre-breakfast and pre-lunch regimen, with the rationale that this profile of insulin action matches the physiological effect of prednisolone on blood glucose levels (BGLs).

Evaluate the use of the mixed insulin (NovoMix30) in a pre-breakfast or pre-breakfast and pre-lunch regimen as management for GIH in a tertiary hospital setting.

We retrospectively evaluated all inpatients coprescribed prednisolone ≥7.5 mg and NovoMix30 for at least 48 hours over a 19-month period. BGLs were evaluated with repeated-measures analysis within four time periods across the day, beginning from the day prior to NovoMix30 administration.

A total of 53 patients were identified. NovoMix30 significantly reduced BGLs in the morning (mean 12.7 ± 4.5 vs. 9.2 ± 3.9 mmol/L, P < 0.001), afternoon (mean 13.6 ± 3.8 vs. 11.9 ± 3.8 mmol/L, P = 0.001) and evening (12.1 ± 3.8 vs. 10.8 ± 3.8 mmol/L, P = 0.01). With uptitration of insulin over 3 days, 43% of all BGLs were within the target range, compared with 23% on day 0 (P < 0.001). The final median dose of NovoMix30 was 0.15 (0.10-0.22) units/kg bodyweight, or 0.40 (0.23-0.69) units/mg of prednisolone, which is lower than our hospital guideline recommends. One overnight hypoglycaemic event was observed.

Mixed insulin as a pre-breakfast or pre-breakfast and pre-lunch regimen can target the hyperglycaemic pattern induced by prednisolone and minimise overnight hypoglycaemia. However, higher doses of insulin than those used in our study are likely required for optimal BGL control.

Cancer management has significantly evolved in recent years, focusing on a multidisciplinary team approach to provide the best possible patient care and address the various comorbidities, toxicities, and complications that may arise during the patient's treatment journey. The co-occurrence of diabetes and cancer presents a significant challenge for health care professionals worldwide. Management of these conditions requires a holistic approach to improve patients' overall health, treatment outcomes, and quality of life, preventing diabetes complications and cancer treatment side-effects. In this article, a multidisciplinary panel of experts from different Italian scientific societies provide a critical overview of the co-management of cancer and diabetes, with an increasing focus on identifying a novel specialty field, 'diabeto-oncology', and suggest new co-management models of cancer patients with diabetes to improve their care. To better support cancer patients with diabetes and ensure high levels of coordinated care between oncologists and diabetologists, 'diabeto-oncology' could represent a new specialized field that combines specific expertise, skills, and training.

Immune-related cutaneous adverse events (ircAEs) commonly occur in patients on treatment with immune checkpoint inhibitors and can significantly reduce patient quality of life. These are often treated with immunomodulatory agents, including glucocorticoids, immunosuppressants, and biologics. While often effective at managing symptoms, these therapies can cause several adverse events which may limit their use. In addition, immunomodulatory agents should be used with particular caution in patients receiving immunotherapy, as the efficacy of the oncologic regimen may potentially be undermined. In this review, we summarize the safety of systemic therapies that are used in the management of ircAEs, with a particular focus on the resultant risk of secondary tumor progression in patients with active cancer.

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.

Diabetes is a global concern. This article took a closer look at diabetes and precision medicine.

A literature search of studies related to the use of precision medicine in diabetes care was conducted in various databases (PubMed, Google Scholar, and Scopus).

Precision medicine encompasses the integration of a wide array of personal data, including clinical, lifestyle, genetic, and various biomarker information. Its goal is to facilitate tailored treatment approaches using contemporary diagnostic and therapeutic techniques that specifically target patients based on their genetic makeup, molecular markers, phenotypic traits, or psychosocial characteristics. This article not only highlights significant advancements but also addresses key challenges, particularly focusing on the technologies that contribute to the realization of personalized and precise diabetes care.

For the successful implementation of precision diabetes medicine, collaboration and coordination among multiple stakeholders are crucial.

Anti-glutamic acid decarboxylase (GAD) autoantibodies are a hallmark of stiff-person syndrome (SPS) and insulin-dependent diabetes mellitus (IDDM). However, patients with concurrent IDDM and SPS often manifest insulin resistance, and SPS-associated IDDM probably has heterogeneous causes. Some patients manifest IDDM associated only with high titers of anti-GAD65 caused by SPS. By contrast, other patients develop IDDM only after being treated with high-dose corticosteroids or they progress to insulin dependency following their treatment with high-dose corticosteroids. The profile of autoantibodies differs markedly between type 1 diabetes mellitus (T1DM), late-onset diabetes mellitus, and SPS-associated IDDM. Therefore, as with new-onset diabetes after transplantation (NODAT), SPS-associated IDDM should be classified as a specific diabetes entity, the pathophysiology of which requires increased attention.

In this study, we conducted a comprehensive assessment of the cytotoxicity of three glucocorticoids, namely Hydrocortisone, Dexamethasone, and Methylprednisolone, using three different human cell lines: MDA-MB-231, MCF-7 (both adenocarcinoma cell lines), and HEK293 (kidney epithelial cell line). At lower concentrations exceeding 50 µM, we did not observe any significant toxic effects of these glucocorticoids. However, when exposed to higher concentrations, Hydrocortisone exhibited dose-dependent cytotoxic effects on all three cell lines, with calculated IC50 values of 12 ± 0.6 mM for HEK293, 2.11 ± 0.05 mM for MDA-MB-231, and 2.73 ± 0.128 mM for MCF-7 cells after 48 h of exposure. Notably, Hydrocortisone, at its respective IC50 concentrations, demonstrated an inhibitory effect on the proliferation of the cancer cell lines, as evidenced by a substantial reduction in BrdU absorbance in a dose-dependent manner, coupled with a markedly reduced rate of colony formation in treated cells. Furthermore, Hydrocortisone exhibited remarkable anti-migratory properties in MDA-MB-231 and MCF-7 cells, and it induced cell cycle arrest in the SubG1 phase in MDA-MB-231 cells. In addition to these effects, Hydrocortisone triggered apoptosis in both cancer cell types, leading to observable morphological changes. This apoptotic response was characterized by a significant increase in the activity of caspase-3, which was time-dependent. Additionally, Hydrocortisone downregulated the expression of anti-apoptotic Bcl-2 proteins. In summary, our findings underscore the safety of clinical doses in terms of cell toxicity meanwhile increased concentration were showing an anti-proliferative potential of Hydrocortisone, particularly against adenocarcinoma breast cancer cell lines.

Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing's syndrome, Basedow-Graves' disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.

Primary and revision total joint arthroplasty (TJA) procedures have become increasingly popular worldwide. At the same time, a growing number of patients undergoing TJA are either known diabetics or exhibit evidence of hyperglycemia preoperatively. Based on extensive data, it is well-established that poor glycemic control in TJA patients is an independent risk factor for several complications, including periprosthetic joint infection and death. This article will serve as an overview of currently available evidence on how to prevent the impact of hyperglycemia and diabetes mellitus on patients undergoing TJA.

Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The β-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on β-cells.

Cancer and diabetes mellitus (DM) are diagnosed within the same individual more frequently and share common risk factors. Although diabetes among cancer patients may result in more aggressive clinical courses of cancer, there is limited evidence about its burden and associated factors. Hence, this study aimed to assess the burden of diabetes and prediabetes among cancer patients and its associated factors. Institution-based cross-sectional study was conducted at the University of Gondar comprehensive specialized hospital from 10 January to 10 March 2021. A systematic random sampling technique was used to select 423 cancer patients. The data was collected using a structured interviewer-administered questionnaire. Prediabetes and diabetes diagnosis was made based on World Health Organization (WHO) criteria. Bi-variable and multivariable binary logistic regression models were fitted to identify factors associated with the outcome. Adjusted Odds Ratio (AOR) with a 95% confidence interval was estimated to show the direction and strength of associations. Variables with a p-value less than 0.05 in the multivariable model were considered significantly associated with the outcome. The final analysis was based on 384 patients with cancer. The proportion of prediabetes and diabetes was 56.8% (95% CI 51.7, 61.7) and 16.7% (95% CI 13.3, 20.8), respectively. Alcohol consumption was found to increase the odds of elevated blood sugar among cancer patients (AOR: 1.96; 95%CI: 1.11, 3.46). The burden of prediabetes and diabetes is alarmingly high among cancer patients. Besides, alcohol consumption was found to increase the odds of having elevated blood sugar among cancer patients. Hence, it is essential to recognize cancer patients are at high risk of having elevated blood sugar and design strategies to integrate diabetes and cancer care.

High dose of corticosteroid has been found beneficial in complex regional pain syndrome type I (CRPS-I). We report the efficacy and safety of prednisolone 20 mg versus 40 mg in CRPS-I in an open label randomized controlled trial.

The patients with CRPS-I of the shoulder joint with a CRPS score of ≥8 were included. Their demographic details, comorbidities, and underlying etiology were noted. The severity of CRPS was assessed using a 0-14 CRPS scale, the pain using a 0-10 Visual Analogue Scale (VAS), and sleep quality using a 0-10. Daily Sleep Interference Scale (DSIS). Patients were randomized to prednisolone 40 mg/day (group I) or 20 mg/day (group II) for 14 days, then tapered to 10 mg in group I and to 5 mg in group II by 1 month. Thereafter both groups received prednisolone 5 mg/day for 2 months. The primary outcome was a >50% reduction in VAS score, and secondary outcomes were a reduction in CRPS score, DSIS score, and adverse events.

Fifty patients were included, and their baseline characteristics were comparable. At one month, all the patients had >50% reduction in the VAS score. The effect size was 0.38 (95% CI 0.93-0.20; p = 0.20). On the Kaplan-Mayer analysis, the improvement in the VAS score (Hazard ratio-1.43, 95 % CI-0.80-2.56, p = 0.22) and the CRPS score (HR-0.79,95 % CI-0.45-1.39; p = 0.41) was insignificant between the two groups. The DSIS score improved in group II (HR-1.85,95 % Cl-1.04-3.31,p = 0.04). Group I patients needed frequent adjustment of antidiabetic drugs (14 vs 6; p = 0.04).

The efficacy of prednisolone 20 mg is not inferior to 40 mg in CRPS-I, and is safe in diabetic patients.

This is an open label randomized controlled trial with small sample size without a placebo arm.

Clenbuterol is a potent beta-2 agonist widely misused by professional athletes and bodybuilders. Information on clenbuterol associated adverse events is present in case reports and case series, though it may not be readily available. This systematic review aimed to critically evaluate the evidence of adverse events associated with clenbuterol among athletes. The search strategy was in accordance with PRISMA guidelines. Databases such as PubMed, Science Direct, Scopus, and Google Scholar were searched from 1990 to October 2021 to find out the relevant case reports and case series. There were 23 included studies. Using a suitable scale, the included studies' methodological quality analysis was evaluated. In total, 24 athletes experienced adverse events. Oral ingestion of clenbuterol was the most preferred route among them. The daily administered dose of clenbuterol was ranging from 20 µg to 30 mg. Major adverse events experienced by athletes were supraventricular tachycardia, atrial fibrillation, hypotension, chest pain, myocardial injury, myocarditis, myocardial ischemia, myocardial infarction, cardiomyopathy, hepatomegaly, hyperglycemia, and death. The cardiac-related complications were the most commonly occurring adverse events. Clenbuterol is notorious to produce life-threatening adverse events including death. Lack of evidence regarding the performance-enhancing effects of clenbuterol combined with its serious toxicities questions the usefulness of this drug in athletes.