SGLT2抑制剂引起酮症酸中毒的机制及处理

钠-葡萄糖协同转运蛋白-2（SGLT2）抑制剂是一类新型的降糖药物,通过抑制肾小管对葡萄糖的重吸收降低血糖。但临床中发现SGLT2抑制剂可导致血糖不明显升高的酮症酸中毒。本文就SGLT-2抑制剂引起酮症酸中毒的发生机制及处理措施进行了综述。     

2015年5月美国FDA公布的药品安全信息

1 FDA警告SGLT2抑制剂可能导致酮症酸中毒
　　5月15日,FDA 公告称,钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可能导致患者酮症酸中毒。FDA表示将“继续调查这个安全问题,并最终明确改变此类降糖药物说明书的必要性”。     

钠-葡萄糖共转运蛋白2抑制剂致酮症酸中毒的风险分析

目的 基于美国食品药品管理局不良事件报告系统(FAERS)挖掘与分析钠-葡萄糖共转运蛋白2受体抑制剂(SGLT-2i)致酮症酸中毒的风险.方法 下载FAERS系统2013年1月至2021年6月收到的SGLT-2i与非SGLT-2i致酮症酸中毒报告,采用报告比值比法(ROR)分析SGLT-2i抑制剂与酮症酸中毒的相关性,...     

SGLT抑制剂联合胰岛素在1型糖尿病中的应用

钠-葡萄糖共转运蛋白抑制剂(SGLTi)通过抑制肾脏葡萄糖重吸收/延缓肠道葡萄糖吸收发挥降糖作用。SGLTi辅助胰岛素治疗1型糖尿病,不仅可降低糖化血红蛋白、改善血糖变异性和增加葡萄糖目标范围内时间,而且不增加低血糖、心肾事件和骨折的风险,还具有减少胰岛素用量和改善代谢的作用。SGLTi的不良反应主要有酮症酸中毒和生殖系统感染,其作为1型糖尿病患者胰岛素的补充治疗显示出一定的应用前景,但要根据患者的个体情况,平衡获益与风险,为患者选择最佳的治疗决策。     

治疗糖尿病新药:钠-葡萄糖协同转运蛋白抑制剂dapagliflozin

钠-葡萄糖协同转运蛋白2(SGLT-2)是一种跨膜蛋白,主要分布在肾脏近曲小管,将葡萄糖从肾小管液转运入肾小管细胞内,约占肾脏重吸收葡萄糖的90%。SGLT-2抑制剂是治疗糖尿病的新药,可降低SGLT-2活性,减少肾脏对葡萄糖的重吸收量,增加尿糖排出,从而降低血糖。已有的临床试验表明SGLT-2抑制剂dapagliflozin治疗糖尿病有效且安全,患者耐受性良好。SGLT-2抑制剂很可能是未来糖尿病治疗的一个新的突破口。     

SGLT-2选择性抑制剂的代谢调节作用与不良反应

钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂是一种非胰岛素依赖型的降糖药物,其作用的靶点是肾脏,可以通过抑制肾脏对葡萄糖的重吸收,使过量的葡萄糖从尿液中排出,从而发挥降低血糖的疗效。此类药物对改善血糖和血脂水平,保护胰岛细胞均有确切疗效,且不增加体重,主要的不良反应为生殖器感染、尿路感染和酮症酸中毒。本文通过检索中国知网、万方数据库、维普数据库和PubMed数据库,综述了SGLT-2选择性抑制剂的开发过程、作用机制以及治疗糖尿病的疗效与不良反应,为临床合理用药提供参考。     

钠-葡萄糖共转运蛋白2抑制剂致非高血糖性酮症酸中毒研究进展

钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)通过抑制近端小管的葡萄糖重吸收,增加尿糖排泄来降低血糖水平,并且具有心血管、肾脏保护作用,已经逐渐成为二线降糖药物。随着应用人群的不断扩大,其非高血糖性酮症酸中毒(euDKA)的副作用报道逐渐增加,因患者血糖通常正常或稍高于正常值,不易引起医生及患者注意,易误诊。因此,本文主要就SGLT2i导致euDKA的相关机制及诱因、预防措施进行综述,为降低此类药物在临床上的不良风险提供依据。     

美国FDA近期公布的药品安全信息（之一）

1钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂：药品安全通讯--增加标签的警示信息,血液酸性增强和严重尿路感染经 FDA 安全性审查,在钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂的标签中增加导致血液酸性增强和严重尿路感染的风险警示,SGLT2抑制剂是一类Ⅱ型糖尿病药物。上述两种情况都有可能导致患者住院。     

2型糖尿病治疗药物——SGLT-2抑制剂研究进展

钠-葡萄糖协同转运蛋白-2抑制剂通过减少人体肾脏对葡萄糖的重吸收,增加尿糖的排泄,达到降低血液中葡萄糖水平的目的,从而成为治疗2型糖尿病的新途径。近年来,SGLT-2抑制剂类药物也不断的问世,给2型糖尿病患者的治疗带来了新的希望。     

糖尿病药物-SGLT-2抑制剂专利技术分析

钠-葡萄糖协同转运蛋白2(SGLT-2)抑制剂是治疗2型糖尿病的新型药物,简介钠-葡萄糖协同转运蛋白2抑制剂的研究现状,重点分析钠-葡萄糖协同转运蛋白2抑制剂的专利申请量、申请人、重点专利等,梳理出钠-葡萄糖协同转运蛋白2抑制剂的技术发展过程。     

Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium–Glucose Cotransporter 2 Inhibitor Treatment

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have been suggested to predispose to ketoacidosis. Here, we present a case of diabetic ketoacidosis (DKA) developed in an obese, poorly controlled male patient with T2D treated with the SGLT2i dapagliflozin. He was admitted with DKA 5 days after the initiation of treatment with the SGLT2i dapagliflozin. On admission, the primary symptoms were nausea and dizziness, and he was hypertensive (170/103) and tachycardic (119 bpm) and had mild hyperglycaemia (15.3 mmol/l), severe ketonuria and severe metabolic acidosis (pH 7.08). He responded well to infusions of insulin, glucose and saline and was discharged after 72 hr with insulin as the only glucose‐lowering therapy. After 1 month, dapagliflozin was reintroduced as add‐on to insulin with no recurrent signs of ketoacidosis. During acute illness or other conditions with increased insulin demands in diabetes, SGLT2i may predispose to the formation of ketone bodies and ensuing acidosis.     

糖尿病酮症酸中毒30例临床分析

目的探讨糖尿病急性并发症糖尿病酮症酸中毒(Diabetic ketoacidosis,DKA)的诊治方案。方法对30例DKA患者的性别、年龄、病程、诱因、临床表现、误诊及治疗方案等进行回顾性分析。结果 28例患者临床治愈出院,血糖、血钾等恢复正常,尿酮、血酮消失,2例死亡,治愈率达93.3%。结论早期诊断、治疗及时是降低糖尿病急性并发症DKA致死率的重要因素。     

Effects of sodium-glucose co-transporter 2 inhibitors on metabolism: unanswered questions and controversies

Introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. These drugs also affect many anthropometric and metabolic parameters with various mechanisms of action.

Areas covered: We present the available evidence regarding these effects. SGLT2 inhibitors can decrease body weight mainly due to a reduction of total fat mass. SGLT2 inhibitors can decrease blood pressure levels and serum uric acid levels and may also reduce the degree of diabetes-related albuminuria. These effects may have contributed in the beneficial cardiovascular effects seen in the EMPA-REG OUTCOME trial. On the other hand, the SGLT2 inhibition-induced natriuresis and osmotic diuresis could lead to a decrease of extracellular volume. A small increase in serum low-density lipoprotein cholesterol has been observed with SGLT2 inhibitors. A small increase in serum phosphate concentration has been reported with these drugs due to increased phosphate reabsorption, which combined with an increase in serum parathormone may adversely affect bone homeostasis. In rare cases, SGLT2 inhibitors administration may be followed by euglycemic diabetic ketoacidosis.

Expert opinion: SGLT2 inhibitors improve many aspects of human metabolism and may be beneficial in diabetic patients if certain precautions are followed by clinicians during the administration of these drugs.     

Diabetic emergencies

Diabetic emergencies continue to be a significant cause of premature death in patients with diabetes. They include the diabetic comas (hypoglycaemia, severe diabetic ketoacidosis, hyperosmolar hyperglycaemic non-ketotic coma, lactic acidosis), emergency surgery and myocardial infarction. There is still considerable avoidable morbidity and mortality during treatment, and as a result of misdiagnosis. Simple guidelines are thus needed for the general practitioner and admitting physician to improve management. Hypoglycaemia is far the commonest diabetic emergency, and is relatively easy to diagnose and treat. Delays in treatment are potentially damaging and largely unnecessary. Diabetic ketoacidosis is still relatively common but is often preventable. Initial treatment for this and hyperosmolar nonketotic coma is rehydration. This is followed by IM or IV infusion of moderate amounts of insulin, early potassium replacement, and alkali only if the acidaemia is severe. Lactic acidosis requires mainly rigorous alkalinisation but is very rare. The metabolic derangements in emergency surgery and myocardial infarction are best treated by combined glucose, potassium and insulin infusions. In all cases treatment is easiest and probably more successful if consistent simple guidelines are provided.     

Severe Lactic Acidosis in a Diabetic Patient after Ethanol Abuse and Floor Cleaner Intake

An intoxication with drugs, ethanol or cleaning solvents may cause a complex clinical scenario if multiple agents have been ingested simultaneously. The situation can become even more complex in patients with (multiple) co‐morbidities. A 59‐year‐old man with type 2 diabetes mellitus (without treatment two weeks before the intoxication) intentionally ingested a substantial amount of ethanol along with ~750 mL of laminate floor cleaner containing citric acid. The patient was admitted with severe metabolic acidosis (both ketoacidosis and lactic acidosis, with serum lactate levels of 22 mM). He was treated with sodium bicarbonate, insulin and thiamine after which he recovered within two days. Diabetic ketoacidosis and lactic acidosis aggravated due to ethanol intoxication, thiamine deficiency and citrate. The high lactate levels were explained by excessive lactate formation caused by the combination of untreated diabetes mellitus, thiamine deficiency and ethanol abuse. Metabolic acidosis in diabetes is multi‐factorial, and the clinical situation may be further complicated, when ingestion of ethanol and toxic agents are involved. Here, we reported a patient in whom diabetic ketoacidosis was accompanied by severe lactic acidosis as a result of citric acid and mainly ethanol ingestion and a possible thiamine deficiency. In the presence of lactic acidosis in diabetic ketoacidosis, physicians need to consider thiamine deficiency and ingestion of ethanol or other toxins.     

糖尿病合并促甲状腺激素、甲状腺激素异常28例临床分析

目的分析糖尿病合并甲状腺功能减退或低三碘甲状腺原氨酸（T3）综合征鉴别诊断与治疗。方法对照28例糖尿病合并甲状腺功能减退或低三碘甲状腺原氨酸（T3）综合征患者临床治疗前后血糖、血脂、甲状腺激素水平变化。结果糖尿病合并高胆固醇血症、甲状腺功能减退患者，仅用L型甲状腺素钠片替补治疗，胆固醇恢复正常者占60％，空腹及餐后2h血糖完全正常者20％，餐后2h血糖水平下降70％；糖尿病合并低T3综合征，同时分别合并高胆固醇血症、高三酰甘油血症、酮症酸中毒（DKA）、糖尿病肾病（DA），经控制血糖、血脂，积极治疗DKA及DA后，T3恢复正常。结论甲状腺功能减退可致高胆固醇血症，血脂代谢紊乱而产生胰岛素抵抗，引发2型糖尿病。甲状腺素激素替补治疗纠正甲减后，糖代谢紊乱也可纠正；糖尿病合并低T3综合征，经纠正血糖、血脂代谢紊乱、治疗各种并发症后，甲状腺激素水平也逐渐恢复正常。     

护理干预与恶性肿瘤合并糖尿病化疗患者血糖关系的回顾性研究

目的探讨护理模式对于恶性肿瘤合并糖尿病化疗患者血糖的影响。方法对于我院38例恶性肿瘤合并糖尿病化疗患者采用整体性的护理模式,尤其是对患者心理护理、治疗过程中密切监控血糖,尤其注意对低血糖反应的护理,加强营养以及饮食的指导。联合38例患者血糖控制情况分析护理模式的合理性。结果 38例患者均顺利完成化疗周期,所有患者化疗期间血糖控制在8.0-13.0mmoL·L^-1范围内。无酮症酸中毒以及高渗性非酮症酸中毒情况出现。结论采用有计划的护理干预对于保证化疗的顺利进行以及避免并发症的发生具有重要的意义,有助于患者提高生存质量。     

达格列净治疗早期糖尿病视网膜病变研究进展

糖尿病视网膜病变（diabetic retinopathy,DR）是糖尿病最常见的微血管并发症之一。因为该病初期症状不明显,患者对疾病认知不够,导致病情恶化,严重可导致失明。它是全球成年人获得性视力丧失的主要原因。因此延缓糖尿病视网膜并发症降糖药物的研发受到广大学者的关注。研究发现钠-葡萄糖协同转运蛋白2（sodium-glucose cotransporter 2,SGLT2）抑制剂（SGLT2 inhibitor,SGLT2i）在降低血糖的同时能延缓糖尿病视网膜并发症的进展。本文将主要对DR早期改变及SGLT-2i对DR保护作用的临床和实验证据进行综述。