Postmarketing study of nateglinide in Japan: treatment of medication-naïve patients with type 2 diabetes

Nateglinide is an oral antidiabetic medication (OAD) that acts through rapid, short-term stimulation of insulin production. This study was conducted to identify the nature of any adverse effects associated with nateglinide and to evaluate its clinical efficacy in patients with type 2 diabetes, with particular attention to hypoglycemia. Patients with type 2 diabetes who were OAD naïve (n=547), whose fasting blood glucose levels were 150 mg/dL or lower, and who had started to take nateglinide alone were recruited from 139 centers in Japan with a 12-week observation period. The incidence of adverse reactions was 7.62%. Hypoglycemia accompanied by hypoglycemic symptoms was the most prevalent adverse event (2.10%; 11/525). Nine of 11 episodes required no therapeutic intervention. Severe hypoglycemia was recognized in only 1 case of diabetes complicated by serious renal dysfunction, for which nateglinide has been contraindicated in Japan. No subject experienced symptoms of nocturnal or prolonged hypoglycemia. After 12 weeks of nateglinide treatment, decreases were noted in hemoglobin A_1c (0.82%), postprandial glucose (reduced by 59.4 mg/dL to 158.0 mg/dL), and fasting glucose (reduced by 11.7 mg/dL to 122.4 mg/dL). Nateglinide, which demonstrates limited risk of hypoglycemia and effectively controls blood glucose level, is regarded as a useful drug for the treatment of patients with type 2 diabetes.     

Time-dependent effect of an oral hypoglycemic agent upon serum glucose levels

Summary A constant dosage of glibenclamide (50 μg/kg i.p.) was administered to normal mice at 4-h intervals during the day. Blood samples were collected up to 360 min after the injection, for glucose determination. It was found that neither the depth nor the duration of the glibenclamide-induced hypoglycemia was constant throughout the day. These results demonstrate the existence of a circadian rhythm of the glibenclamide effect on serum glucose levels. They also suggest that a day-time schedule of therapy with this drug should result in improved control of serum glucose. Traduzione a cura di G.U.     

老年低血糖脑病误诊分析

目的探讨老年低血糖脑病误诊原因。方法回顾性分析16例老年低血糖脑病患者的临床资料。结果16例老年低血糖脑病患者被误诊为急性脑血管病、癫痫或脑炎。结论老年低血糖脑病易被误诊,临床上对老年突发的意识障碍、癫痫发作及精神异常者应常规行血糖检查,及时确诊并尽早治疗,以免影响预后。     

血清心型脂肪酸结合蛋白联合心肌肌钙蛋白I在低血糖后心肌损害中的诊断价值

目的研究血清心型脂肪酸结合蛋白(H-FABP)联合心肌肌钙蛋白I(cTnI)在低血糖心肌损害中的诊断价值。方法将2013年5月至2015年5月在该院治疗并出现低血糖的糖尿病患者80例纳入本研究;同期体检且一般资料与研究组匹配的80例健康志愿者为对照组。采集两组受试者的血清并测定H-FABP和cTnI水平。结果心肌损伤组患者0~2h H-FABP出现明显升高,以0~2h各指标水平为标准对心肌损伤进行诊断发现H-FABP+cTnI的诊断效能较高,诊断的灵敏度、特异度、阳性预测值、阴性预测值均明显高于单用H-FABP和cTnI进行诊断的患者。H-FABP+cTnI阳性作为诊断标准的阳性患者48h心肌酶谱水平明显高于单cTnI阳性和H-FABP单阳性作为诊断标准的患者,差异有统计学意义(P0.05)。结论联合HFABP和cTnI诊断心肌损伤,有助于减少心肌损伤的漏诊。     

以急性脑血管病表现的低血糖反应40例分析

目的提高对以急性脑血管病表现的低血糖反应的认识。方法回顾分析本科40例有神经系统症状及体征,以急性脑血管病表现的低血糖反应患者的头部CT及临床资料。结果 40例患者头部CT检查阴性,血糖〈2.8mmol/L,给予高渗糖治疗,症状、体征均消失。结论对有神经系统症状、体征,头部CT检查阴性的患者应注意监测血糖,提高低血糖的早期诊断,为治疗争取时机。     

格列苯脲低血糖反应致死亡37例文献分析

目的 调查格列苯脲低血糖反应致死亡病例的情况并分析相关因素,为临床合理用药提供参考.方法 对37例格列苯脲低血糖反应致死亡病例进行分类统计与分析.结果 男女比例为1.6∶1,87.8％的病例为老年人(＞60岁),86.5％的病例不规范用药,8.1％单独用药,75.7％联合用药,100％的病例临床表现均为不同程度的低血糖昏迷,54.1％的病例因发现不及时、误诊、漏诊等原因而延误治疗、抢救时机.死亡的原因是多方面的,56.8％的病例因长时间低血糖昏迷造成多器官衰竭或呼吸、循环衰竭而死亡.结论 格列苯脲低血糖昏迷危害极大,要重视降糖药物安全性.使用时须慎重考虑年龄、用法用量等相关因素,做到合理用药,做到早诊断,早治疗,以减少格列苯脲低血糖反应及其严重后果的发生.     

Recurrent hypoglycemia increases oxygen glucose deprivation-induced damage in hippocampal organotypic slices

More than 65% of mortality among diabetics is due to stroke and heart disease. The major side effect of intensive therapy in both type 1 and type 2 diabetics is recurrent hypoglycemic episodes (RH). Our previous study in a rat model of insulin-requiring diabetes indicated that RH exacerbates cerebral ischemic damage. Studies related to RH in hypoglycemia unawareness suggest that RH may be deleterious to outcome following cerebral ischemia owing to systemic effects, since hormonal response to hypoglycemia is impaired following RH. The goal of the present study was to determine if RH increases oxygen-glucose deprivation (OGD)-induced damage in hippocampal organotypic slices, which are devoid of systemic influence. Hippocampal slices cultured in ex vivo conditions for 9–10 days were exposed to ten 30-min episodes of “hypoglucose” (to mimic the hypoglycemic condition) medium (1.06 mM) twice a day. Slices were exposed to OGD 12 h after the last hypo/normo-glucose exposure. OGD in control slices resulted in 60% neuronal death. The percentage of cell death in RH-treated slices was significantly higher by 24% than in control slices. The results demonstrate that RH can affect brain cells in the absence of humoral influence. In conclusion, the previous exposure of hippocampal slices to RH exacerbates OGD-induced damage. Understanding the mechanism by which RH increases ischemic damage in diabetics will help improve outcome following stroke.     

Stephen C. Woods: a precocious scientist

To investigate the early scientific development of Steve Woods, I reviewed his research during the first decade after he received his doctoral degree in 1970. The main parts of his research program were conditioned insulin secretion and hypoglycemia, Pavlovian conditioning of insulin secretion before a scheduled access to food, and basal insulin as a negative-feedback signal from fat mass to the brain. These topics were pursued with experimental ingenuity; the resulting publications were interesting, clear, and rhetorically effective. Although the theoretical framework for his experiments with insulin was homeostatic, by the end of the decade he suggested that classic negative-feedback homeostasis needed to be revised to include learning acquired by lifestyle. Thus, Woods functioned as a mature scientist from the beginning of his research—he was very precocious. This precocity also characterized his teaching and mentoring as recalled by two of his students during that time, Joseph Vasselli and Paul Kulkosky. The most unusual and exemplary aspect of his precocity is that the outstanding performance of his first decade was maintained during the subsequent 30 years.     

Sensors & Algorithms for Continuous Glucose Monitoring: Hypoglycemia Detection and Prediction Using Continuous Glucose Monitoring��A Study on Hypoglycemic Clamp Data

Motivation

The fear of hypoglycemia remains an important limiting factor in the ability of an individual with type 1 diabetes to tightly regulate glycemia. Continuous glucose monitors provide important feedback to improve glycemic control, but there remains a need for these devices to better alarm of possible impending hypoglycemia, particularly overnight or other periods when the individual is engaged in activities that take their focus away from glucose monitoring.

Methods

We have previously proposed an algorithm, based on the use of real-time glucose sensor signals and optimal estimation theory (Kalman filtering), to predict hypoglycemia; the algorithm was validated in simulation-based studies. In this article we further refine and validate the prediction algorithm based on the analysis of clinical hypoglycemic clamp data from 13 subjects. The sensitivity and specificity of the predictions are calculated with respect to reference blood glucose values obtained at the same sampling rate of the sensor.

Results

For a 30-minute prediction horizon and alarm threshold of 70 mg/dl, the sensitivity and specificity were 90 and 79%, respectively, indicating that a 21% false alarm rate must be tolerated to predict 90% of the hypoglycemic events 30 minutes ahead of time. Shorter prediction horizons yield a significant improvement in sensitivity and specificity.

Discussion

Sensitivity and specificity data as a function of prediction horizon and alarm threshold enable an individual to adjust the alarm to best meet their needs. Such decisions can be made depending on the subject''s risk for hypoglycemia, for example.