Symptoms of hypoglycemia — A comparison between porcine and human insulin

Summary For more than 2 years now it has been controversially debated whether awareness of hypoglycemia is reduced when type I diabetic patients are switched from porcine to human insulin. In order to address this question, we studied nine C-peptide negative diabetics (age 27.6 years, Broca index 106%, duration of diabetes 5.7 years, HbA₁, 8.8%) in comparison with eight healthy volunteers (age 22.4 years, Broca index 104%). Following euglycemic monitoring overnight, a controlled hypoglycemia was induced by altering the algorithms of the Biostator. This was done in a double-blind, cross-over fashion using porcine or human insulin on 2 nonconsecutive days. There were no differences between the results obtained with respect to the time course of the study, blood glucose, amount of insulin infused, and concentration of venous free insulin achieved. Of the nine diabetics, eight were aware of hypoglycemia at a higher blood glucose level under porcine insulin. The first symptom of hypoglycemia was percieved at a mean blood glucose level of 61.1±5.4 mg/dl under porcine insulin and of 44.4 ± 5.3 mg/dl under human insulin (P0.05). Thirty symptoms were noted under porcine insulin exclusively or preferentially as opposed to only eight which were observed exclusively or preferentially under human insulin. The healthy volunteers evidenced fewer symptoms at lower blood glucose concentrations than the diabetics. The clear difference between human and porcine insulin could not unequivocally be reproduced in this group. We conclude that type I diabetic patients, who are maintained on a treatment regimen with human insulin, perceive symptoms of hypoglycemia at higher blood glucose concentrations when hypoglycemia is induced by porcine insulin as compared with human insulin. As every single patient and healthy volunteer was aware of at least one symptom of hypoglycemia under both insulins, it is possible to react appropriately to counteract this situation. Nevertheless, diabetic patients should be informed about this phenomenon.Abbreviations P porcine insulin - H human insulin - IU international units Supported by Nordisk Deutschland     

Antihypertensive drug therapy and hypoglycemia in elderly diabetic patients treated with insulin and/or sulfonylureas

We performed this case–control study to evaluate the risk of hypoglycemia associated with the use of antihypertensive drugs in older hospitalized diabetic patients treated with sulfonylureas and/or insulin. All diabetic patients admitted during 4 months in 1988, 1 month in 1991, 4 months in 1993 and 4 months in 1995 (n = 3477, mean age 71.4 ± 0.2 years, 1542 males and 1935 females) were enrolled in the study. During the four annual surveys 86 patients (mean age 71.1 ± 1.4 years, 33 males and 53 females) presented hypoglycemia during hospital stay. The patients who presented hypoglycemia were less frequently users of sulfonylureas and more frequently users of a combination of insulin and sulfonylureas. Use of antihypertensive drugs was similar in the two groups studied, and among potentially interacting drugs considered in the analysis, sulfonamides were more frequently used in patients who experienced hypoglycemia. Moreover, patients with hypoglycemia used a higher number of drugs, had a longer length of stay and had a greater prevalence of hypoglycemia as admission problem. Finally, although not significant, liver and renal diseases were more frequent among patients with hypoglycemia. In the multivariate analysis, contemporary use of insulin and sulfonylureas, liver disease and length of stay were significantly associated with hypoglycemia, while none of the antihypertensive drugs showed a significant association with the occurrence of hypoglycemia during hospital stay. Our results indicate that antihypertensive drugs do not increase the risk of hypoglycemia in elderly diabetic patients.     

Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia

Summary Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg^-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h), with dizocilpine 0.33 mg · kg^-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg^-1 given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.     

先天性高胰岛素血症5例临床分析

目的　分析 5例先天性高胰岛素血症患儿的临床资料 ,探讨其早期诊断和治疗问题。方法　回顾性分析 5例先天性高胰岛素血症患儿的临床资料。结果　 5例临床表现除抽搐外 ,尚有发绀、呼吸暂停、饥饿感和多汗等 ,实验室检查有持续性低血糖和高胰岛素血症 ,胰腺病理均为胰岛细胞增殖。 5例经胰腺 95 %次全切除术后 ,血胰岛素和血糖逐渐恢复正常 ,4例治愈 ,随访 3例有继发性癫疒间 后遗症 ,1例失访 ;另 1例术后 1个月死于败血症。结论　先天性高胰岛素血症可通过血糖监测、血胰岛素和尿酮检查作出早期诊断 ,胰腺 95 %次全切除术治疗有效。     

党参皂苷L1抗缺氧缺糖再给氧诱导大鼠皮质神经细胞凋亡的作用

目的:以原代培养的胚胎大鼠大脑皮质神经细胞进行缺氧缺糖再给氧处理,观察党参皂苷L1对神经细胞凋亡的抑制作用.方法:胚胎大鼠大脑皮质神经细胞原代培养,含连二亚硫酸钠的无糖Earles液进行缺氧/缺糖处理造模,MTT法测定细胞存活率,Hoechst 33342和PI原位双染法荧光显微镜观察细胞形态学变化和坏死、凋亡细胞百分率,APO-BRDU法流式细胞术检测凋亡细胞百分率,Fluo-3法流式细胞术检测细胞内Ca2 浓度,评价药效.结果:(1)细胞存活率(%):与模型组(29.89±6.28)比较党参皂苷L1 1.0mg/L组(46.05±8.92)、0.1mg/L组(46.83±6.76)、0.01mg/L组(41.05±9.18)均能显著提高细胞存活率(P<0.01和P<0.05);(2)细胞坏死率(%):与模型组(44.99±12.81)比较,党参皂苷L1 1.0mg/L组(19.45±2.31)、0.1mg/L组(18.78±4.95)和0.01mg/L组(22.37±4.44)能显著降低细胞坏死率(P<0.001);(3)原位双染法细胞凋亡率(%):与模型组(17.44±4.82)比较,党参皂苷L1 1.0mg/L组(8.75±1.88)、0.1mg/L组(9.73±1.76)能显著降低细胞凋亡率(P<0.01和P<0.05);(4)流式细胞术检测细胞凋亡率(%):与模型组(8.55±3.84)比较,党参皂苷L1 1.0mg/L组(4.21±2.31)、0.1mg/L组(3.83±2.95)能显著降低细胞凋亡率(P<0.05);(5)细胞内Ca2 平均荧光值,与模型组(47.37±9.68)比较,党参皂苷L1 1.0mg/L组(28.67±11.12)、0.1mg/L组(27.34±8.57)能显著降低细胞内Ca2 平均荧光值(P<0.05),表明党参皂苷L1能明显降低细胞内Ca2 浓度.结论:党参皂苷L1对缺血再灌注损伤后神经细胞的坏死和凋亡过程均具有抑制作用,这种作用可能与其能降低细胞内Ca2 浓度有关,提示党参皂苷L1是党参治疗脑卒中急性期的主要效应成分.     

动态血糖监测胰岛素瘤一例并文献复习

目的探讨动态血糖监测对胰岛素瘤术前诊断及术后疗效判断的价值。方法应用动态血糖监测系统(CGMS)对1例胰岛素瘤患者术前及术后分别进行连续3 d的血糖监测。结果①术前CGMS共累计监测血糖值871个,平均绝对差为12．9％,血糖的平均值、最高值、最低值分别为4．8、10．8和2．2 mmol/L;患者监测期间表现为夜间及餐前的反复低血糖,血糖<2．8 mmol/L及>7．8 mmol/L所占的时间百分比分别为 14％(595 min)和5％(215 min)。②术后CGMS监测显示患者血糖波动于3．5-7．7 mmol/L,平均血糖值为 5．1 mmol/L。结论动态血糖监测有助于胰岛素瘤的术前诊断及术后疗效判断。     

再发性低血糖对幼鼠脑内GLUT1及GLUT3表达的影响

目的观察再发性低血糖后脑内葡萄糖转运蛋白1(glucose transporter 1,GLUT1)及葡萄糖转运蛋白3(GLUT3)表达的变化,从而探讨无症状低血糖的发生机制。方法将80只15日龄野生型小鼠随机分为正常对照组及低血糖组,每组40只。低血糖组给予正规胰岛素腹腔注射3次,每次剂量为5U/kg,对照组注射等体积生理盐水。两组分别在最后1次注射后12、24、48及72 h处死小鼠取脑组织(每组每时间点10只),应用免疫组化方法观察小鼠脑内GLUT1及GLUT3表达的变化。结果低血糖后脑内微血管上GLUT1表达有增加趋势,皮质增加高于海马,72 h皮质GLUT1表达显著高于对照组;低血糖后48、72 h皮质及海马GLUT3表达均显著高于相应对照组。结论再发性低血糖后脑内GLUT1及GLUT3适应性增高,这种适应既能节省神经元的能量代谢,但也能削减神经元对低血糖的反应。     

Insulin-meal interval and short-term glucose fluctuation in tightly controlled gestational diabetes mellitus

Objective: To study the effect of two insulin-meal intervals on short-term glucose fluctuations in tightly controlled gestational diabetes mellitus (GDM). Methods: We performed a prospective and paired study in 11 Japanese GDM women requiring insulin for good glycemic control during the third trimester. The women were subjected to test two insulin-meal intervals: 15 min and 30 min. Both regimens were examined in each patient in random order, 2 days apart. Blood glucose was measured by an automated glucose monitor every 2 min. Short-term glucose fluctuations of the two observations were analyzed by two-way ANOVA for repeated measurements with a post hoc t test ( p < 0.05). Data were expressed as mean &#45 SD. Results: Daily glucose profiles of the two groups showed that their glycemic controls on the days of observation were good and that the two glucose profile curves were superimposable. A transient decrease in glucose (nadir 62 &#45 6 mg/dl) was observed at 6-10 min of meal ingestion in the 30-min regimen, which was significantly different from the glucose fluctuations during the 15-min regimen. The 2-h postprandial glucose levels were similar in both experiments. Conclusions: In women with tightly controlled GDM during the third trimester, insulin-meal intervals of 15 min are beneficial when compared with 30-min intervals, in that they avoid preprandial hypoglycemia without increasing 2-h postprandial hyperglycemia.     

基于信息化血糖监测系统建立血糖基准报告研究

背景　随着糖尿病患病率的增高，住院患者血糖管理已成为医院关注的焦点，但目前尚缺乏公认的绩效指标定义、指标测算和标准化血糖基准报告，影响了医院血糖管理持续质量改进。目的　基于信息化血糖监测系统（IGMS）构建血糖基准报告，一为同行建立标准化血糖报告提供方法学指导，二为同行提供血糖基准参考。方法　纳入2019年10月至2020年3月遂宁市中心医院安装了IGMS（该系统能自动上传血糖数据和按需求查阅血糖数据）的非重症监护病区（10个内科和7个外科）的糖尿病患者或高血糖患者（无糖尿病病史但随机末梢血糖超过11.1 mmol/L），排除住院第1天的血糖数据。采用群体（population）、患者（patient）和患者日（patient-day）三种模型报告理想血糖、高血糖和低血糖发生率，低血糖报告增加患者低血糖发生天数比、发生频次比和管理及时性比，采用四分位数分析不同病区的血糖数据，并与美国、澳大利亚、重庆和广东医疗机构的血糖数据进行比较。结果　三种模型平均血糖、理想血糖、平均高血糖和任意高血糖（>10.0 mmol/L、≥15.0 mmol/L、≥16.7 mmol/L）、任意低血糖（≤3.9 mmol/L、<3.0 mmol/L、<2.8 mmol/L、<2.2 mmol/L）比较，差异均有统计学意义（P<0.001）。17个病区任意低血糖≤3.9 mmol/L发生>3次者312例（3.9%），发生>3 d者202例（2.5%），复测血糖时间≤15 min者446例（5.6%），>30 min者2 187例（27.5%）。患者日任意高血糖≥15.0 mmol/L、任意低血糖≤3.9 mmol/L、理想血糖下四分位数分别为38.6%、5.5%和38.0%，上四分位数分别为21.5%、2.1%和58.1%。17个病区与美国、澳大利亚、重庆医疗机构的平均高血糖和任意高血糖（>10.0 mmol/L、≥15.0 mmol/L、≥16.7 mmol/L）、任意低血糖（≤3.9 mmol/L、<3.0 mmol/L、<2.8 mmol/L、<2.2 mmol/L）比较，差异均有统计学意义（P<0.05）。本研究内分泌病区和广东省某内分泌病区血糖、理想血糖、任意高血糖≥16.7 mmol/L、任意低血糖≤3.9 mmol/L比较，差异均有统计学意义（P<0.05）。结论　IGMS允许医疗机构建立全方位、标准化血糖报告。因目的不同，其选择模型也不同。群体模型更适用药物管理和风险管理人员，患者模型更适用个体化护理评估，患者日模型适用于某单元或单位进行质量改进方向和目标的制定。