胰岛素的不良反应

胰岛素是人体内的固有成份,对有肝肾功能障碍、口服降糖药不耐受的糖尿病患者,也无治疗禁忌。所以,很多糖尿病患者,在治疗糖尿病中,都会使用胰岛素。胰岛素可单用或与口服降糖药联合应用,根据患者具体情况设定不同治疗模式。值得注意的是,过量胰岛素可能导致低血糖反应,严重低血糖反应对合并心脑血管病变的糖     

低血糖脑损害及后续效应

正低血糖即血浆葡萄糖水平低于生理范围的状态,也是内科急症之一。原因包括药物、肝肾功能衰竭、升糖激素缺乏,葡萄糖摄入不足、内源性高胰岛素、重症感染等~([1])。临床上大部分低血糖发生在糖尿病人群中,尤其是使用胰岛素的糖尿病患者~([2])。对于非糖尿病患者,低血糖的诊断标准为血糖2.8 mmol/L,正在接受药物治疗的糖尿病患者血糖≤3.9 mmol/L即属于低血糖范畴~([3])。低血糖可导     

郊区糖尿病患者发生低血糖情况分析

随着口服降糖药及胰岛素的应用,糖尿病患者低血糖事件时有发生。严重低血糖可诱发心脑血管事件,甚至引起死亡。本文通过对郊区糖尿病患者发生低血糖情况进行分析,旨在找出其原因和特点、寻求预防和减少其发生的对策。     

胰岛素自身免疫综合征—胰岛素自身抗体所致低血糖症

本文报道1例胰岛素自身免疫综合征及有关的文献。患者为49岁男性病人,曾因弥漫性甲状腺肿接受1个月的他巴唑治疗,无糖尿病及低血糖发作史,以往从未注射过胰岛素。于1984年8月12日晨10时出现严重低血糖昏迷、癫痫样发作,血糖16mg/dl,静脉注射葡萄糖后好转,实验室检查示空腹低血糖、糖耐量减退和餐后尿糖、血清中检得大量胰岛素抗体,应用PEG处理后的血浆胰岛素测定示有空腹高胰岛素血症,于葡萄糖负荷后无胰岛素高峰,免疫学检查发现有抗胰岛素抗体、抗TSH受体抗体、抗甲状腺微粒体抗体和抗垂体细胞抗体。1个月后空腹低血糖消失,糖耐量恢复正常、胰岛素抗体值明显降低。     

胰岛β细胞替代治疗研究进展北大核心CSCD

糖尿病可导致包括糖尿病肾病、视网膜病以及心脑血管疾病在内的多种并发症,严重损害患者的生活质量。尽管胰岛素注射能够挽救患者的生命,但这种外源性胰岛素替代手段无法复制胰腺β细胞感应血糖变化而产生的胰岛素动态变化,因此无法降低糖尿病晚期并发症的发生[1],并且由于注射剂量控制不准确,低血糖发作并不少见,甚至会发生危险的医源性低血糖。     

胰岛素及C肽监测在低血糖昏迷病因诊断及治疗中的价值

目的探讨胰岛素及C肽水平监测在低血糖昏迷诊断治疗中的价值。方法对16例低血糖昏迷患者,除按低血糖昏迷诊疗常规处理外,同时进行血清胰岛素和C肽检测,在治疗过程中监测血糖和血清胰岛素水平变化以指导治疗。结果10例糖尿病服用磺脲类降糖药的低血糖昏迷患者中8例血清胰岛素及C肽水平均增高。3例酒精中毒患者血清胰岛素及C肽水平亦增高。1例非糖尿病患者血清胰岛素和C肽水平严重增高,经B超及CT检查诊断为胰岛素瘤。全部患者经吸氧、50％葡萄糖注射后续10％葡萄糖液静脉滴注0．5-4h后逐渐清醒,血糖逐渐恢复正常水平。前述磺脲类降糖药过量患者,其血清胰岛素水平分别在3～5d后降至正常范围,之后根据血糖逐步恢复降糖药物治疗,并根据血清胰岛素水平调整降糖药物剂量,随访观察患者未再发生低血糖发作。结论对低血糖患者进行血胰岛索和C肽水平检测,有助于病因诊断和提高抢救治疗效果和防止再次和反复发生低血糖昏迷。     

老年2型糖尿病住院患者发生严重低血糖的相关危险因素

目的探讨老年2型糖尿病(T2DM)住院患者严重低血糖的相关危险因素。方法选择2012年1月至2014年1月该院收治的老年T2DM住院患者310例,根据严重低血糖的发生情况将其分为严重低血糖组(n=80例)与对照组(未发生低血糖,n=230例)。收集整理两组患者的基础疾病情况、心脑血管用药情况、糖尿病治疗情况以及生化、血液检查结果进行单因素和多因素Logistic回归分析。结果严重低血糖组发病时血糖水平、经静脉葡萄糖治疗后血糖水平、葡萄糖应用的平均量显著高于对照组(P0.05);二甲双胍的应用情况低于对照组(P0.05);胰岛素、胰岛素与口服降糖药物(OAD)联用显著高于对照组(P0.05)。严重低血糖组糖化血红蛋白、果糖胺显著低于对照组(P0.05);白细胞总数、中性粒细胞高于对照组(P0.05);血红蛋白低于对照组(P0.05);肾功能相关指标高于对照组(P0.05);血脂总胆固醇低于对照组(P0.05)。多因素Logistic回归分析发现,严重低血糖的发生与病程(10年)、果糖胺水平(≤25 mmol/L)、胰岛素与OAD联用、肾功能受损、血白细胞计数升高是老年T2DM住院患者严重低血糖的危险因素(OR=0.987,1.932,10.381,5.228,2.226;P均0.05)。结论严重低血糖的发生与病程(10年)、果糖胺水平(≤25 mmol/L)、胰岛素与OAD联用、肾功能受损、血白细胞计数升高有关,医务人员应给予高度的重视,早期采取预防及干预措施,以此降低严重低血糖的发生率。     

老年2型糖尿病患者发生严重低血糖的危险因素分析

选择2014年1月~2015年9月老年2型糖尿病患者136例为研究对象进行回顾性资料分析,按照是否发生严重低血糖将其分为非低血糖组(102例)和低血糖组(34例),采用logistic多因素分析危险因素。结果低血糖组和非低血糖组住院时间、体重指数及病程比较差异均有统计学意义(P<0.05);低血糖组二甲双胍使用比例明显低于非低血糖组(P<0.05),心脑血管疾病药物联用比例、胰岛素及口服降糖药与胰岛素的联合使用比例明显高于非低血糖组(P<0.05);低血糖组低血钾症发生率和肾功能相关指标明显高于非低血糖组(P<0.05),低血糖组中性粒细胞和白细胞明显高于非低血糖组(P<0.05)。logistic多因素分析表明病程>10年、果糖胺<2.5mmol/L、使用胰岛素及胰岛素与口服降糖药联用、肾功能受损、白细胞升高均与严重低血糖相关。结论治疗老年2型糖尿病行降糖治疗时应认真评估上述各危险因素,以避免老年2型糖尿病患者发生严重低血糖。     

慢性胰岛素过量综合征

慢性胰岛素过量综合征,是指依赖胰岛素的糖尿病患者长期过量应用胰岛素所致低血糖后高血糖状态,其临床表现错综复杂,常导致酮症和糖尿病加重,也常造成医生判断错误,不适当地增加胰岛素剂量。当胰岛素减量后,糖尿病好转。这个现象1959年被Somog-yi提出,故又称Somogyi效应或Somogyi综合征。一,历史及临床证据反跳性高血糖或低血糖后高血糖早在1922年由Joslin首先发现,但对这一现象未找到满意的解释。     

持续皮下胰岛素注射治疗糖尿病合并与伴发心力衰竭患者37例疗效的观察

目的比较不同给药方法对糖尿病合并与伴发心力衰竭疗效的影响。方法将74例糖尿病患者分为胰岛素泵持续皮下输注门冬胰岛素(CSII)组(静脉输注5%葡萄糖者,每4g葡萄糖增加基础量胰岛素1U)及多次皮下注射胰岛素(MSII)组4次/d。结果两组治疗24h平均血糖值、疗效、治疗后B型尿钠肽(BNP)及LVEF、低血糖事件发生率比较差异有统计学意义(P≤0.01)。结论 CSII治疗糖尿病合并与伴发心力衰竭疗效优于MSII。     

Exercise-related hypoglycemia in diabetes mellitus

Current recommendations are that people with Type 1 and Type 2 diabetes mellitus exercise regularly. However, in cases in which insulin or insulin secretagogues are used to manage diabetes, patients have an increased risk of developing hypoglycemia, which is amplified during and after exercise. Repeated episodes of hypoglycemia blunt autonomic nervous system, neuroendocrine and metabolic defenses (counter-regulatory responses) against subsequent episodes of falling blood glucose levels during exercise. Likewise, antecedent exercise blunts counter-regulatory responses to subsequent hypoglycemia. This can lead to a vicious cycle, by which each episode of either exercise or hypoglycemia further blunts counter-regulatory responses. Although contemporary insulin therapies cannot fully mimic physiologic changes in insulin secretion, people with diabetes have several management options to avoid hypoglycemia during and after exercise, including regularly monitoring blood glucose, reducing basal and/or bolus insulin, and consuming supplemental carbohydrates.     

强化胰岛素治疗在重型颅脑损伤中的临床应用价值探讨

目的：探讨强化胰岛素治疗（intensive insulin therapy,IIT）在重型颅脑损伤（severe traumatic brain injury,sTBI）中的临床应用价值。方法对200例sTBI患者（GCS评分3～8分）,入院后随机分为IIT组100例及常规胰岛素治疗（conventional insulin treatment ,CIT）组100例。 IIT组血糖（blood glucose,BG）控制在3.9～6.1 mmol／L,CIT组血糖控制在8.3～10.1 mmol／L。患者入院后即开始采用持续静脉泵入胰岛素对血糖进行控制,记录两组患者平均血糖水平、胰岛素用量、低血糖发生率,于伤后6个月时根据GOS评估法判断疗效（分为良好、中残、重残、植物生存和死亡）。结果治疗期IIT组BG低于CIT组（ P＜0.01）,低BG发生率、单位时间胰岛素用量均高于CIT组（ P＜0.05或P＜0.01）。伤后6个月,两组在良好、中残、重残、植物生存和死亡例数比较差异无统计学意义（ P＞0.05）。结论强化胰岛素治疗并不能改善sTBI的预后,且增加了低BG发生率,血糖控制在8.3～10.1 mmol／L是比较理想的水平。     

Insulin therapy and exercise

Medical nutrition therapy and physical exercise are the cornerstones of the diabetes management. Patients with type 1 DM always need exogenous insulin administration, recently available in the form of insulin analogs. In type 2 DM, characterized by increased insulin resistance and progressive decline of the beta-cell function, various antidiabetic medications are used. Most of the subjects with type 2 DM will finally need insulin. The main site of insulin action is the skeletal muscle, while the liver is the main site of glucose storage in the form of glycogen. With the modern diabetes therapies it is possible to rapidly reach and maintain normoglycemia in both types of DM but with the cost of higher incidence of hypoglycemia, especially related to exercise. Regular physical exercise causes a lot of beneficial effects in healthy as well as diabetic subjects of all age groups. In type 1 DM physical exercise is a fundamental element for both physical and mental development. In type 2 DM it has a main role in diabetes control. The increased hepatic glucose production and the increased muscular glucose uptake during exercise are closely interrelated in all exercise intensities. In diabetes mellitus there is a disturbed energy substrate use during exercise leading to either hypo- or hyperglycemia. The influence of low or moderate intensity aerobic exercise on diabetes control has been well studied. The inappropriately high insulinemia combined with the low glucose levels can lead to severe hypoglycemia if proper measures are not taken. Prolonged exercise can also predispose to decreased glucose counter regulation. It is better for the type 1 diabetic subject to postpone the exercise session in very high (>300 mg/dl) or very low (<70 mg/dl) BG levels. Every insulin treated subject is recommended to be checked for any existing diabetic complication before the start of every exercise program. Glucose measurement with glucose meters or sometimes with Continuous Glucose Monitoring System (CGMS) must be made before, during and most importantly after the end of the exercise session. It is recommended either to reduce or suspend the previous insulin dose depending on the insulin regime or to receive extra carbohydrates before, during or after the exercise session or both. Subjects with type 1 DM may participate at almost all the competitive sports if precautions are taken. These measures must be individualized and readjusted, even empirically. In very high intensity exercise (about 80% of VO(2 max)) or when high intensity exercise follows a low intensity one, there is a tendency of the BG to increase due to excessive circulating catecholamines necessitating postexercise short acting insulin. In anaerobic or resistance exercise lactic acid is produced. This exercise type is recommended for people in whom aerobic exercise is contraindicated. These two exercise types can be combined. The incidence of hypoglycemia or hyperglycemia in specific forms of resistance exercise as well as the appropriate insulin dose adjustment are not well studied. In conclusion all exercise types are beneficial for both types of diabetes.     

Exercise and deficient carbohydrate storage and intake as causes of hypoglycemia

Exercise is associated with a marked increase in glucose uptake by muscle, which is initially supported by breakdown of hepatic glycogen and subsequently by increased gluconeogenesis. If hepatic glucose production is inadequate, hypoglycemia results. During exercise there is decreased plasma insulin and increased catecholamines, glucagon, cortisol, and growth hormone, which contribute to but are not essential for the increased hepatic output of glucose. Although insulin concentrations fall, insulin sensitivity is increased. However, the augmented glucose uptake by muscle is due to other factors. The symptoms of exhaustion during exercise are not due to hypoglycemia, and prevention of hypoglycemia may not prolong the time of exercise to exhaustion. During severe caloric restriction, hepatic glucose production decreases and free fatty acids and ketone bodies become important sources of calories. Although under these circumstances hepatic gluconeogenesis is usually sufficient to prevent hypoglycemia, with very severe caloric restriction hypoglycemia can result. With starvation, insulin concentrations fall while growth hormone and glucagon increase. Frequently the usual symptoms of hypoglycemia are absent in individuals with hypoglycemia from severe caloric restriction. Hypoglycemia from severe caloric restriction has not been totally restricted to underdeveloped areas of the world. In such patients no endocrine abnormalities have been found, and hypoglycemia has persisted despite administration of large amounts of carbohydrate. Pregnancy and lactation could predispose to hypoglycemia in the face of inadequate caloric intake.     

The Case for Combination Therapy as First-Line Treatment for the Type 2 Diabetic Patient

The glycosylated hemoglobin (HbA(1c)) goal in patients with type 2 diabetes mellitus should be to achieve as low a value as can be obtained without causing significant or frequent hypoglycemia. This is best achieved by utilizing agents that lower glucose levels without causing hypoglycemia (thiazolidinediones and metformin). To maintain these low HbA(1c) values and avoid the utilization of insulin secretagogues or insulin, which are associated with hypoglycemia and suboptimal dosing leading to higher HbA(1c) values, drugs that maintain or improve pancreatic beta-cell function (thiazolidinediones and possibly incretin-based therapies) should be utilized. Restoration of first-phase insulin release, as has been shown with thiazolidinediones, will not only improve postprandial hyperglycemia but will also improve postprandial hyperlipidemia, both of which will decrease cardiac risk. Utilizing small doses of two drugs will also result in a decreased incidence of adverse effects compared with a large dose of a single drug. The use of fixed-dose combination oral antihyperglycemics will not only improve compliance but will often decrease costs compared with individual component dual therapy.     

Challenges in Glycemic Control in Perioperative and Critically Ill Patients: An Overview of Hypoglycemia in the Critically Ill

Hypoglycemia is a common and serious problem among patients with diabetes mellitus. It is also perceived as the most important obstacle to tight glucose control using intensive insulin therapy in critically ill patients. Because glucose is an obligatory metabolic fuel for the brain, hypoglycemia always represents an emergency that signals the inability of the brain to meet its energy needs. When left untreated, hypoglycemia can result in permanent brain damage and ultimately, death. In the context of critical illness that limits endogenous glucose production and increases glucose utilization, inadequate nutrition, or insufficient provision of glucose, intensive insulin therapy is the most frequent cause of hypoglycemia. Neurogenic and neuroglycopenic symptoms of hypoglycemia can remain unknown because of the underlying critical illness and sedation. Thus, close and reliable monitoring of the glycemic level is crucial in detecting hypoglycemia. In prospective randomized controlled studies comparing the effects of two glucose regimens, intensive insulin therapy aimed to reach strict glucose control (<110 mg/dl) but increased the incidence of severe hypoglycemia (<40 mg/dl) by four- to sixfold. Severe hypoglycemia is statistically associated with adverse outcomes in intensive care unit patients, although a direct causal relationship has not been demonstrated.     

Hypoglycemia associated with the production of insulin-like growth factor II in a pancreatic islet cell tumor: a case report

An insulinoma is characterized by endogenous hyperinsulinemia and hypoglycemia. However, it has been reported that insulinomas with normal levels of plasma insulin and a normal insulin to glucose ratio occur in patients with hypoglycemia. Although overproduction of Insulin-like growth factor II (IGF-II) by non-islet cell tumors such as large mesenchymal tumors, can cause hypoglycemia, no cases of circulating plasma IGF-II from an islet cell tumor contributing to hypoglycemia have been reported. We report here a rare case of a pancreatic islet tumor in a patient with hypoglycemia that was associated with increased plasma IGF-II, which returned to normal after tumor resection.     

Enhanced 911/Global Position System Wizard: A Telemedicine Application for the Prevention of Severe Hypoglycemia—Monitor,Alert, and Locate

Intensive insulin therapy has an inherent risk of hypoglycemia that can lead to loss of consciousness, cardiac arrhythmia, seizure, and death (“dead-in-bed syndrome”). This risk of hypoglycemia is a major concern for patients, families, and physicians. The need for an automated system that can alert in the event of severe hypoglycemia is evident. In engineering systems, where there is a risk of malfunction of the primary control system, alert and safety mechanisms are implemented in layers of protection. This concept has been adopted in the proposed system that integrates a hypoglycemia prediction algorithm with a global position system (GPS) locator and short message service such that the current glucose value with the rate of change (ROC) and the location of the subject can be communicated to a predefined list. Furthermore, if the system is linked to the insulin pump, it can suspend the pump or decrease the basal insulin infusion rate to prevent the pending event. The system was evaluated on clinical datasets of glucose tracings from the DexCom Seven® system. Glucose tracings were analyzed for hypoglycemia events and then a text message was broadcast to a predefined list of people who were notified with the glucose value, ROC, GPS coordinates, and a Google map of the location. In addition to providing a safety layer to a future artificial pancreas, this system also can be easily implemented in current continuous glucose monitors to help provide information and alerts to people with diabetes.     

Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitus

Exercise is a cornerstone of diabetes management as it aids in glycemic control, weight management, reducing blood pressure, and improving the quality of life of patients. Unfortunately, owing to the complexity and difficulties of regulating exogenous insulin in a physiologic manner during exercise, physical activity often results in hypoglycemia in patients with type 1 diabetes mellitus (type 1 DM). When glucose levels fall below threshold glycemic levels, neuroendocrine, autonomic nervous system (ANS), and metabolic glucose counterregulatory mechanisms are activated. These hypoglycemic counterregulatory mechanisms in type 1 DM can be blunted irreversibly by disease duration or by acute episodes of prior stress. These reduced (or absent) counterregulatory responses result in a threefold increase in severe hypoglycemia when intensive glycemic control is implemented in type 1 DM. Much recent work has been focused on determining the in vivo mechanisms responsible for causing the increased incidence of severe hypoglycemia in type 1 DM. Studies from several laboratories have demonstrated the role played by episodes of antecedent hypoglycemia in producing blunted glucose counterregulatory responses during subsequent exposures of hypoglycemia. Until recently, the mechanisms responsible for exercise related hypoglycemia in type 1 DM have been attributed to relative or absolute increases of insulin levels or incomplete glycogen repletion after physical activity. Owing to the qualitative similarity of neuroendocrine, ANS, and metabolic responses to hypoglycemia and exercise, we have hypothesized that neuroendocrine and ANS counterregulatory dysfunction may also play an important role in the pathogenesis of exercise-related hypoglycemia in type 1 DM. Vicious cycles can be created in type 1 DM, where an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and ANS responses to a subsequent episode of either stress, thereby creating further hypoglycemia. This article will review the recent work that has studied the contribution of counterregulatory dysfunction to exercise-induced hypoglycemia in type 1 DM.     

Left Hemiplegia Possibly Due to Glucose Reperfusion Injury after Recovery of Severe Hypoglycemia in a Woman with Type 2 Diabetes Mellitus

A 79-year-old woman with type 2 diabetes receiving insulin was rushed to our hospital due to severe hypoglycemia. Glucose was administered, and the consciousness disturbance was promptly improved. A few hours later, conjugate deviation of the eyes to the right and left hemiplegia occurred at a normal glucose level. Cerebral magnetic resonance imaging (MRI) showed hyperintensities of the right posterior limb of the internal capsule and the medial thalamus on diffusion-weighted imaging sequences. However, the changes observed using MRI disappeared completely on the third day, and her symptoms subsequently improved. This may have been a case of glucose reperfusion injury.