酮症酸中毒与月经

西苑医院内分泌科 邹本良,病例分享 DKA与月经,1,内容简介,2,主诉：发现血糖升高12年，恶心呕吐3天现病史：2000年患者在我院查出患有1型糖尿病，予每天四次胰岛素皮下注射，血糖波动较大。曾多次于我院住院治疗。慢性并发症诊断：糖尿病视网膜病变期。最近2个月来两次发生恶心呕吐以“糖尿病酮症酸中毒”住院治疗，分别为2012.9.3、2012.10.10。末次出院时调整胰岛素方案为诺和锐7u-6u-6u，甘精胰岛素8u，阿卡波糖片 25mg tid，血糖相对稳定。,吴 ，女，49岁，入院时间：12.11.11,3,出院后未检测血糖，饮食规律。入院前3天无明显诱因出现恶心、呕吐症状，呕吐为胃内容物，乏力，心慌，轻度腹痛，无腹泻，于我院急诊就诊，查尿常规(10/11):GLU 1000mg/dl(+),KET 150mg/dl,ERY 50/ul(+);急查血生化十项：TCO2 9.90mmol/l K 4.93mmol/l Na 130.40mmol/l Cl 91.70mmol/l GLU 35.90mmol/l 肝肾功能正常；血常规：WBC 11.29*1O9/L N 82.00% L 15.50% Hb 127g/l PLT 318*109/L,病例简介,4,血气三项：PH 7.013 PCO2 14.6mmHg PO2 149mmHg SBE -23.8mmol/l ABE -24.6mmol/l入院症见：恶心，呕吐胃内容物，乏力，轻度腹痛，无发热，无腹泻，小便少。既往史：1987行剖腹产手术，否认高血压病史、心脏病史。个人史：月经规律，每月1315日月经来潮。,病例简介,5,查体: T:37.0C ,P 118次/分，R 20次/分,Bp 124/53mmHg, BMI:20.84Kg/m2 患者神清，精神差，胸廓对称，双肺呼吸音清，未闻及干湿啰音。心律118次/分，心音可，心律齐，各瓣膜听诊区未闻及病理性杂音。腹部膨隆，无压痛、反跳痛及肌紧张。肝脾肋下未触及，肝肾区无叩击痛。,病例简介,6,入院辅助检查： 快速查血糖 31.6mmol/l。 心电图：窦性心动过速伴偶发室性早搏。 血气三项：PH 7.178 PCO2 14.10mmHg PO2 142mmHg SBE -22.2mmol/l,ABE -22.3mmol/l。,病例简介,7,入院诊断：1型糖尿病 糖尿病酮症酸中毒 糖尿病性视网膜病变期,病例简介,8,治疗： 补液：日补液量3000ml4000ml，盐水与葡萄糖盐水结合。 降糖：胰岛素泵人2 4ml/h 补钾：4.56g，根据饮食及尿量情况。 保护胃黏膜及止吐：奥美拉唑。 进食：鼓励饮水进食,病情简介,9,治疗经过辅助检查,10,治疗经过辅助检查,11,饮食正常后餐前+基础胰岛素治疗；保肝降酶：多烯磷脂酰胆碱、水飞蓟素胶囊；病情好转出院。,治疗经过,12,治疗经过辅助检查,13,患者2012.9、2012.10、2012.11连续3次因糖尿病酮症酸中毒发病住院，现对其近3月来住院情况进行回顾。,病例回顾,14,2012.9.32012.9.21 入院前一周频繁出现低血糖症状自行停用胰岛素，急诊以“糖尿病酮症酸中毒”收入院。2012.10.102012.10.23 出院后未检测血糖，入院前3天曾无明显诱因出现腹泻症状，不伴发热、腹痛，对症治疗后缓解。入院当日，患者晨起后自觉恶心不适，后呕吐3次，呕吐物为胃内容物，无呕吐咖啡色液体，无腹痛、腹泻。,病例回顾,15,病例回顾辅助检查,16,病例回顾辅助检查,17,病例回顾辅助检查,18,月经周期的激素变化：月经周期的开始阶段，雌激素和黄体酮都处于最低水平，月经第7日雌激素水平明显增加，于排卵前形成高峰，排卵后稍减少，约在排卵后12日，黄体开始分泌大量黄体酮与雌激素，使子宫内膜增厚，为孕育胚胎做好准备，如果没有受孕，体内雌激素和黄体酮水平迅速下降，子宫内膜开始脱落，形成月经。,DKA与月经期的关系,19,研究显示，月经期胰岛素敏感性会下降，胰岛素敏感性的降低与月经周期里激素水平的变化炎症及经前综合征有关。雌激素和黄体酮都能影响女性血糖水平，雌激素能增强胰岛素的敏感性。在月经期，体内雌激素和黄体酮水平下降，雌激素水平的降低使得胰岛素敏感性下降而子宫内膜剥脱出血过程中，会对胰岛素产生拮抗作用，使血糖升高。,DKA与月经期的关系,20,雌激素通过雌激素受体防止胰岛细胞的凋亡；雌激素通过基因组效应机制保护细胞；雌激素和雌激素类似物能通过作用于细胞的雌激素膜受体，产生一种快速的促胰岛素分泌功能；雌激素对细胞分泌有间接作用；,雌激素与胰岛细胞功能,21,The clinic and hospital medical records of 2 subjects with type 1 diabetes mellitus (T1DM) and unexplained DKA are reviewed. An electronic MEDLINE search of relevant medical literature published from 1965 to 2007 was performed.,Review,Catamenial diabetic ketoacidosis and catamenial hyperglycemia:case report and review of the literature,22,To date there have been 7 reported cases between menstruation and DKA. The 2 new cases highlight the potentially significant changes in glucose metabolism during the late luteal and decidual phases of the menstrual cycle.,Review,23,Through unclear mechanisms, some women with diabetes mellitus demonstrate significant changes in glucose control around the time of their menses, including DKA. Accordingly, we propose that the terms catamenial DKA and catamenial hyperglycemia be used to refer to these disorders and that catamenial DKA be included in the differential diagnosis list of causes or precipitating events that can lead to DKA.,Review,24,A 32-year-old lady with type 1 diabetes mellitus in whom DKA precipitated 1 to 2 days before her menstrual periods resulting in repeated admissions to hospital.she had similar symptoms starting before each menstrual cycle for the past 5 months.Her urine culture was sterile; electrocardiogram was normal except for sinus tachycardia; and her chest x-ray, ultrasound abdomen, and 2-dimensional echocardiography were also normal. Her complete hormonal profile was done just before her next menstruation (late luteal phase).,Case Report,25,she was advised to increase the dose of insulin from 16 U subcutaneous twice a day to 30 U subcutaneous before breakfast and 20 U before dinner 2 days before the start of her menstrual period. Over the next months, she has not had any episode of DKA prior or during her menstru cycle.The mechanisms by which the menstrual cycle provokes DKA largely remain elusive.,Case Report,26,Goldner with the help of continuous glucose monitoring system demonstrated that increased progesterone level was the main reason for DKA and hyperglycemia during the luteal phase. Javanovic also supported this by demonstrating anti-insulin action of progesterone.,Case Report,27,Trout found a correlation between decreased insulin sensitivity and increased plasma progesterone levels. An average 24% decline in insulin sensitivity was recorded. However, no trends were recorded between insulin sensitivity and plasma estradiol or cortisol level.Several animal studies indicate that progesterone impairs glucose uptake in skeletal and adipose tissues and also augments pancreatic insulin release in animals presumably in response to concurrent insulin resistance.,Case Report,28,Another possible mechanism could be low-grade inflammation. Puder found that C-reactive protein level increased mainly during premenstrual and menstrual period.Alteration in appetite, food habits, and endometriosis have also been implicated in the occurrence of DKA.,Case Report,29,Increasing the dose of insulin in patients with type 1 diabetes mellitus 1 to 2 days before the menstrual period may abort the occurrence of DKA.,Case Report,30,60 例D K A 病人中有肝损害者28 例，男、女各14 例。DKA 伴肝损害的发生率为46 .7%。死亡6 例, 死亡率21.43 % 。统计分析肝功能损害与糖尿病类型、病程、性别、年龄及死亡率无统计学意义一周后复查肝功能, 18 例恢复正常, 6例因于一周内死亡而未能复查, 4 例未恢复( 18 . 18 % ) 。积极保肝治疗。半月后复查, 肝功能全部恢复正常。,DKA导致肝功能异常,刘菊芳.糖尿病酮症酸中毒伴肝脏损害28 例临床分析.重庆医学，1999,28（5）:365-366.,31,DKA 患者98 例,血清转氨酶异常升高者占27. 55%，其中单项丙氨酸氨基转移酶升高者占11. 22%；丙氨酸氨基转移酶和天冬氨酸氨基转移酶均升高者占16. 33%。,DKA导致肝功能异常,张永红.糖尿病酮症酸中毒并肝脏损害临床分析.中国综合临床,2005 ,21 (1 ):26-27.,32,缺氧使肝细胞磷酸化能力降低；由于严重失水、休克、脑血管意外以及手术创伤等, 肝血流量减少, 肝细胞钙膜稳态失调, 肿瘤坏死因子的增加以及氧自由基的产生等一系列神经、体液因子的作用, 引起肝脏内微循环障碍, 肝细胞缺血、缺氧,线粒体肿胀坏死、网状内皮系统功能减退, 导致胆红素及各种肝酶异常。有资料显示, 肝血容量减少6% 10