糖皮质激素与高血糖

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,糖皮质激素与高血糖,糖皮质激素与高血糖糖皮质激素与高血糖,概述,流行病学,机制,诊断,治疗,History,1855 ,Addisons disease,1856 Adrenal glands essential for life,1930 Cortex medulla,1932 Cushings syndrome,1949 Hench et al,(Steroids in rheumatoid arthritis),1952 Aldosterone,Promote normal intermediary metabolism:,Gluconeogenesis,Stimulate protein catabolism,Stimulate lipolysis,Increase resistance to stress by:,Raising blood glucose level,Modest rise in BP,Alter blood cell levels in plasma:,Decrease in eosinophils, basophils, monocytes and lymphocytes by redistribution from circulation to lymphoid tissue,Increase in the number of RBC, platelets, neutrophils,Actions of Glucocorticoids,Anti inflammatory action: (Complex mechanism),Suppression of immunity,Indirect inhibition of phospholipase A2,Alter other endocrine systems:,Decrease in ACTH and TSH,Increase in GH,Effects on other systems:,Increased production of gastric acid, pepsin,Effects on CNS,Bone loss,Myopathy,ActionsCont.,常用糖皮质激素剂量换算、作用、半衰期及效能,药 物 等效剂量 糖皮质激素作用 抗炎效价 钠潴留作用 生物学半衰 期（小时）,低效,可的松,25mg 0.8 2 8,12 8,36,氢化可的松,20mg 1 1.0 2 8,12,中效,强的松,5mg 4 3.5 1 12,26,强的松龙,5mg 4 4.0 1 12,36,甲基强的松龙,4mg 5 5.0 0 12,36,去炎松,4mg 5 5.0 0 12,36,高效,倍他米松,0.6mg 25 30.0 0 36,54,地塞米松,0.75mg 25 30.0 0 36,54,Adverse effects,Psychiatric,Sleep disturbance/activation,Mood disturbance,Psychosis,Skin/soft tissue,Cushingoid appearance,Abdominal striae,Acne,Hirsutism,Oedema,Neurologic,Neuropathy,Pseudomotor cerebri,Cardiovascular,Hypertension,Occur with prolonged use of high doses,Cushings disease,MSK,Osteoporosis,Asceptic necrosis of bone,Myopathy,Endocrine,Diabetes mellitus,Adrenal cortex suppression,Immunologic,Lymphocytopenia,Immunosuppression,False-negative skin test,Opthalmic,Cataract,Narrow-angle glaucoma,Developmental,Growth retardation,糖皮质激素因其多种生物学作用被广泛用于临床多种疾病的短期或长期治疗,“双刃剑”：发挥治疗作用的同时，也不可避免的引起一些副作用，血糖异常便是其中常见的情况之一,了解其发病规律、临床特性及治疗策略对于在临床上合理、安全运用皮质激素，避免或者有效控制高血糖具有重要意义,类固醇性糖尿病,(Steroid diabetes),内源性肾上腺皮质类固醇分泌增多，或外源应用糖皮质激素所导致的继发性糖尿病,一种特殊类型的糖代谢紊乱综合征,概述,流行病学,机制,诊断,治疗,类固醇性糖尿病的流行病学,患病率因原因不同而有差异,Cushing,综合征：,60,90,可出现糖耐量减退,30,40,可出现类固醇糖尿病,糖皮使用质激素人群，尚缺乏大样本研究结果，一些小样本统计约,8.8,40,。差异与样本大小、原发病不同等因素有关,Hoogwerf,等汇总的器官移植后糖皮质激素治疗的病人的资料，原无糖耐量异常，服用糖皮质激素约,10,20,的患者发生糖尿病,Prevalence of Steroid Diabetes in Hospitalized Patients,50% or more of patients,Less than half of these patients will have had a history of diabetes,Endocr Pract. 2006:12:358-362,概述,流行病学,机制,诊断,治疗,类固醇糖尿病的发生机制,促进肝糖异生，增加肝糖合成,促进,AA,、,FA,和,TG,的释放，糖异生底物增多,增强糖异生限速酶,-,烯醇化酶的表达，加速糖异生,拮抗胰岛素,(INS),的作用,增加胰高血糖素分泌,减少周围组织对葡萄糖的摄取和利用,抑制,INS,与受体结合，抑制,Glut-4,向细胞膜的移位与锚着,地塞米松明显抑制体外培养的内脏脂肪细胞的基础以及,INS,刺激下葡萄糖的利用,; INS,信号传导的重要物质，如,INS,受体底物、蛋白激酶,B,等表达也相应降低,对胰高血糖素、肾上腺素及生长激素的升糖效应的“允许”和“协同”作用,对胰岛功能可能有损害作用,糖皮质激素诱发糖尿病的因素,年龄,随年龄胰岛功能减退、,INS,抵抗加重,性别,男性较女性稍高,糖尿病家族史,肥胖,糖皮质激素,剂量：强的松,20mg,较,20mg,多，总量,5000mg,是,1000mg,的,3,倍,疗程,种类：强的松和强的松龙比氢考强,4,倍,原发疾病的种类,肝病易发，另外血液病如再障、白血病、网状内皮细胞增生症、溶血性黄疸等,肉瘤、结节病、血管病、溃结不易发,Short Term Uses of Steroids,Burst and Taper or short course,Allergy,Joint Injections,Asthma Exacerbation,Herniated Disc,Chemo pretreatment,Long Term Uses of Steroids and Immunosupressant Drugs,COPD,Pulmonary Interstitial Fibrosis,Renal, Heart, Liver Transplantation,Rheumatoid Arthritis,Myasthenia Gravis(MG),Lupus,概述,流行病学,机制,诊断,治疗,临床特点,病程长短和病情轻重不同，临床表现各异,典型可有 “三多一少”以及其它相关表现，与,2,型糖尿病相类似,临床特点,类固醇性糖尿病临床特点,起病较快，无糖尿病史者在糖皮质激素治疗后平均,2,3,周内可出现糖耐量异常,病情相对较轻，多数没有明显症状，或症状不典型，而是经血糖筛查发现，并发酮症酸中毒的比例低,肾糖阈降低，血糖和尿糖不成比例,对胰岛素反应不一，部分患者有拮抗现象，需要较大剂量的胰岛素方可有效控制血糖,停用激素后，许多患者的高血糖能够逐渐缓解，部分患者无法恢复正常，提示病情不可逆转,诊断,无糖尿病史，糖皮质激素治疗过程中出现血糖升高，同时达到糖尿病标准者即可诊断为类固醇性糖尿病,不同的剂型、给药时间和间隔，药物在体内的峰浓度出现的时间不同，故糖皮质激素升血糖作用出现的时间也不同，例如许多患者以下午至睡前血糖升高为主,为避免漏诊，应同时注重餐前、餐后血糖，并进行多点血糖的检测,TYPICAL PATTERN OF SDM,Elevated glucose after meals,Decrease to normal glucose overnight,上午,7,时服用强的松,10mg,Diagnosing Steroid Diabetes,25 patients with neurological disease treated with 30-60mg of prednisolone orally after breakfast for 2 weeks,No prior history of DM, family history of DM, or medications that might affect blood sugar (thiazides, B-blockers, etc.),Pharmacotherapy 2004;24(4):508-514,NORMAL IMPAIRED SDM* SENSITIVITY,AC BREAKFAST 24 1 0 0%,PC BREAKFAST 17 4 4 30.8%,PC LUNCH 2 10 13 100.0%,PC DINNER 7 7 10 76.9%,*Fasting or = 126 mg/dl; Random or = 200 mg/dl,诊断,2,型糖尿病或者糖耐量异常者，使用激素后诱发糖代谢紊乱进一步加重，停用激素后血糖往往无法恢复正常,未诊断的糖尿病，使用激素过程中出现典型表现或发现血糖升高，糖尿病类型的确认就比较困难。可参考患者家族史，依据其它代谢综合征组分加已判断，,HbA1c,有助于鉴别,概述,流行病学,机制,诊断,治疗,Hyperglycemia ManagementDecision Making,Short term drug use?,Long term,drug use?,Is this new hyperglycemia/diabetes?,Do they have pre existing diabetes?,What is their current control?,What is their current therapy?,Orals- non sulfonylurea vs. sulfonylurea,Insulin- premix vs. basal/bolus insulin,根据原发病的需要，考虑激素能否停用或者减量，随着糖皮质激素的减量或停药，胰岛素敏感性可升高，高血糖可以渐渐减轻或消失,原发疾病需要足够量的激素治疗时，则应该在适当的时机合理地综合运用饮食、运动、药物等多种治疗方法以有效控制血糖、缓解症状、预防并发症,饮食和运动,是类固醇性糖尿病降糖治疗的基石,注意评价患者的原发疾病是否能够接受运动疗法,口服降糖药,饮食、运动治疗效果不理想，空腹血糖超过,10mmol/L,时，应考虑开始口服降糖药，应用原则与,2,型糖尿病相同,单用或者联合使用磺脲类、双胍类、阿卡波糖、格列奈类以及噻唑烷二酮类降糖药,综合考虑患者肝肾功能、年龄、体重、原发病及合并症等多重因素选择,Oral Diabetes Medications,In general minimal benefits,Long acting agents like glyburide and glimiperide will have minimal effect on post prandial hyperglycemia and increase risk of fasting hypoglycemia.,The use of repaglinide, nateglimide, acarbose, TZDs, and metformin all make physiological sense but in clinical practice often are ineffective.,Incretins (?),胰岛素,仍是血糖较高、急需平稳控制血糖、不适合用口服降糖药以及重症患者的首选治疗方式,根据不同时点的血糖水平灵活将不同制剂的胰岛素或胰岛素类似物配合使用，具体方案与常见,2,型糖尿病治疗基本相同,需要静脉使用激素者，比如血液病化疗时，高血糖常常会随着激素的减量而改善，需要注意及时监测血糖并及时调整治疗，预防低血糖发生,INSULIN,Most effective,Peak action of the insulin needs to correspond to the post absorptive state - the primary affect of steroids is on glucose disposal following the meal.,Rapid acting analog insulin before the meals,AM: R/NPH Supper: R,Cautious use of long acting insulin,Ratio prandial:basal 70:30,糖皮质激素与高血糖,中效制剂强的松在每日上午,1,次口服时血糖特点,午后（午餐至睡前）严重高血糖，空腹多轻微升高甚至正常，严重者空腹午后均明显升高,大剂量、长疗程时应注意清晨和上午低血糖（内源皮质醇分泌抑制）,治疗同,2,型糖尿病，往往需要胰岛素治疗。胰岛素以午餐、晚餐需用量多，午晚早，睡前少用或不用,糖皮质激素与高血糖,糖皮质激素制剂不同、应用时间不同血糖变化不同，和激素作用高峰不同有关,治疗上应充分考虑血糖变化特点，灵活调整方案,激素减量过程中，应提前调整胰岛素剂量，避免低血糖发生,监测血糖谱，必要时动态监测，,及时调整剂量,血糖控制目标,长期需要激素治疗，则血糖控制目标应等同于普通糖尿病患者,糖尿病的全方位管理，如加强教育与自我血糖监测，重视血压、血脂达标等,短期使用时，目标可适当放宽,口服药物的升糖作用一般持续到停用后,48,小时，肌肉或关节内注射时，作用会持续,3,10,天,为了避免高血糖引起一些急性并发症，在激素升糖作用期间，应综合运用多种手段，血糖控制在,11.1mmol/L,以下,选择激素时要考虑风险,/,利益比，严格掌握适应症和禁忌症，合理选择种类和给药方式,激素应用前，详尽了解既往糖尿病史、家族史，并检测空腹和餐后血糖，必要时进行,OGTT,激素应用后定期监测血糖，特别是,40,岁以上、肥胖、有糖尿病家族史、基础血糖水平较高以及激素用量较大者更需要密切关注,曾有过糖皮质激素诱导的高血糖而在停用激素后血糖恢复正常的患者是糖尿病的高危人群，需要每年接受一次血糖筛查,CHALLENGES,Steroid dosing,AM,Multiple daily doses,Potency (prednisone, dexamethasone),Alternate day dosing,Tapering,Meal schedule,Variable time,Variable amounts,Omitting meals,Hepatic and renal impairment, use with caution,Pregnancy and breast-feeding, safe,Children and adolescents growth restriction,Elderly because theyre old,History of TB CXR,HTN/MI rupture reported,Congestive Cardiac Failure,DM (inc. FHx),Osteoporosis,Ocular Herpes Simplex corneal perforation,Severe affective disorders psychosis,Steroid myopathy,UC,Diverticulitis,Thromboembolic disorders,Cautions,谢谢!,谢谢！,