Steroid‐induced diabetes: a clinical and molecular approach to understanding and treatment

Since the advent of glucocorticoid therapy for autoimmune disease in the 1940s, their widespread application has led to the concurrent therapy‐limiting discovery of many adverse metabolic side effects. Unanticipated hyperglycemia associated with the initiation of glucocorticoids often leads to preventable hospital admissions, prolonged hospital stays, increased risks for infection and reduced graft function in solid organ transplant recipients. Challenges in managing steroid‐induced diabetes stem from wide fluctuations in post‐prandial hyperglycemia and the lack of clearly defined treatment protocols. The mainstay of treatment is insulin therapy coincident with meals. This article aims to review the pathogenesis, risk factors, diagnosis and treatment principles unique to steroid‐induced diabetes. Copyright © 2013 John Wiley & Sons, Ltd.     

Identification of the designer steroid Androsta‐3,5‐diene‐7,17‐dione in a dietary supplement

A liquid chromatography‐mass spectrometry (LC–MS) screen for known anabolic‐androgenic steroids in a dietary supplement product marketed for “performance enhancement” detected an unknown compound having steroid‐like spectral characteristics. The compound was isolated using high performance liquid chromatography with ultraviolet detection (HPLC–UV) coupled with an analytical scale fraction collector. After the compound was isolated, it was then characterized using gas chromatography with simultaneous Fourier Transform infrared detection and mass spectrometry (GC–FT–IR–MS), liquid chromatography–high resolution accurate mass–mass spectrometry (LC–HRAM–MS) and nuclear magnetic resonance (NMR). The steroid had an accurate mass of m/z 285.1847 (error?0.57 ppm) for the protonated species [M + H]⁺, corresponding to a molecular formula of C₁₉H₂₄O₂. Based on the GC–FT–IR–MS data, NMR data, and accurate mass, the compound was identified as androsta‐3,5‐diene‐7,17‐dione. Although this is not the first reported identification of this designer steroid in a dietary supplement, the data provided adds information for identification of this compound not previously reported. This compound was subsequently detected in another dietary supplement product, which contained three additional active ingredients.     

Y1细胞生物学特性及其在肾上腺皮质功能研究中的应用

肾上腺皮质功能减退、肾上腺糖皮质激素分泌减少是肾虚证发生的主要物质基础,因此肾上腺皮质细胞在探索肾虚及补肾机制研究方面具有重要价值。Y1小鼠肾上腺皮质瘤细胞(Y1细胞)已广泛用于肾上腺皮质功能的体外研究。综述Y1细胞的来源、不同细胞系的衍变、类固醇激素的合成途径以及Y1细胞增殖与功能相关的信号通路,以期为肾虚证发病机制、补肾中药的有效成分筛选及作用机制研究提供参考。     

Infliximab or cyclosporine for acute severe ulcerative colitis: a retrospective analysis

Background and Aim: Medical treatment of steroid‐refractory ulcerative colitis (UC) is limited to either cyclosporine or infliximab. Studies comparing cyclosporine with either placebo or intravenous methylprednisone showed promise for cyclosporine, but associated it with significant toxicity. There is conflicting, but increasingly positive evidence for using infliximab. There are no studies directly comparing these two treatments. Our aim was to compare the outcomes of patients with steroid‐refractory UC treated with either intravenous cyclosporine or infliximab. Methods: We carried out a retrospective review of inpatients with steroid‐refractory UC, treated with either intravenous cyclosporine or infliximab, at Waitemata District Health Board, between January 2001 and February 2010. The primary end‐points were time to colectomy, and colectomy rates at 3 and 12 months. Secondary end‐points were time to discharge from initiation of treatment, steroid dependence at 12 months, and reported adverse events. Results: The total study population was 38, with 19 in the infliximab group. Follow up to 12 months was complete in all patients. At 3 months, the colectomy rate was 63% for cyclosporine, compared to 21% (P = 0.0094). By 12 months the rate was 68% and 37% for cyclosporine and infliximab, respectively (P = 0.06). Patients in the cyclosporine group required an additional 5 days in hospital (P = 0.0086). Steroid dependence at 12 months was 50% for cyclosporine versus 25% for infliximab (P = 0.36). Cyclosporine caused more adverse events (P = 0.17). Conclusions: Infliximab improved clinical outcomes compared to the previous use of intravenous cyclosporine in patients admitted with steroid‐refractory acute severe UC.     

Steroid Responsiveness of Children with Idiopathic Nephrotic Syndrome in Southeastern Region of Turkey

Background. Our aim was to determine the prognostic factors effective in the response to steroid treatment and relapse frequency. Patients and Methods. In this study, we evaluated 84 children with idiopathic nephrotic syndrome followed-up from 1997–2002. The variables were analyzed with respect to medical history, physical examination, laboratory findings, response to treatment, and factors associated with remissions and relapses. Our study group consisted of 62 children with minimal change nephrotic syndrome (MCNS), 11 children with focal segmental glomerulosclerosis (FSGS), and 11 children with diffuse mesangial proliferation (DMP). Results. According to response to steroids; 57.1% were steroid-sensitive with infrequent relapses, 22.6% were steroid-dependent with frequent relapses, and 20.2% were steroid-non-responders. Significantly high non-responder ratios to steroids were found in children with initial hypertension and hematuria (p < 0.05). Although patients older than six years were found to be associated with steroid non-response (p < 0.05), the number of relapses were found to be increased with an increasing number of infections (p < 0.05). The time period for the first relapse was found to be statistically correlated with relapse numbers of the first 6 (p = 0.001) and 12 (p = 0.01) months. Conclusion. The time span between initial presentation and remission and the number of infections were significant for relapse frequency. The existence of hematuria and hypertension and age greater than 6 years at initial presentation were associated with steroid non-responsiveness. The likelihood of developing resistance to the treatment should be emphasized early to the parents of patients bearing these risk factors, and hence the possible disappointment in the family should be prevented.     

Prospective Randomized Trial of Maintenance Immunosuppression With Rapid Discontinuation of Prednisone in Adult Kidney Transplantation

Rapid discontinuation of prednisone (RDP) has minimized steroid‐related complications following kidney transplant (KT). This trial compares long‐term (10‐year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n = 440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n = 151); high‐level tacrolimus (TAC, 8–12 μg/L) and low‐level sirolimus (SIR, 3–7 μg/L) (TAC^H/SIR^L, n = 149) or low‐level TAC (3–7 μg/L) and high‐level SIR (8–12 μg/L) (TAC^L/SIR^H, n = 140). Median follow‐up was ～7 years. There were no differences between arms in 10‐year actuarial patient, graft and death‐censored graft survival or in allograft function. There were no differences in the 10‐year actuarial rates of biopsy‐proven acute rejection (30%, 26% and 20% in CSA/MMF, TAC^H/SIR^L and TAC^L/SIR^H) and chronic rejection (38%, 35% and 31% in CSA/MMF, TAC^H/SIR^L and TAC^L/SIR^H). Rates of new‐onset diabetes mellitus were higher with TAC^H/SIR^L (p = 0.04), and rates of anemia were higher with TAC^H/SIR^L and TAC^L/SIR^H (p = 0.04). No differences were found in the overall rates of 16 other post‐KT complications. These data indicate that RDP‐based protocol yield acceptable 10‐year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.