The Impact of Measurement Frequency on the Domains of Glycemic Control in the Critically Ill-A Monte Carlo Simulation

Background:

The role of blood glucose (BG) measurement frequency on the domains of glycemic control is not well defined.

Methods:

This Monte Carlo mathematical simulation of glycemic control in a cohort of critically ill patients modeled sets of 100 patients with simulated BG-measuring devices having 5 levels of measurement imprecision, using 2 published insulin infusion protocols, for 200 hours, with 3 different BG-measurement intervals—15 minutes (Q15’), 1 hour (Q1h), and 2 hours (Q2h)—resulting in 1 100 000 BG measurements for 3000 simulated patients. The model varied insulin sensitivity, initial BG value and rate of gluconeogenesis. The primary outcomes included rates of hyperglycemia (BG > 180 mg/dL), hypoglycemia (BG < 70 and 40 mg/dL), proportion of patients with elevated glucose variability (within-patient coefficient of variation [CV] > 20%), and time in range (BG ranges 80-150 mg/dL and 80-180 mg/dL).

Results:

Percentages of hyperglycemia, hypoglycemia at both thresholds, and patients with elevated glucose variability as well as time outside glycemic targets were substantially higher in simulations with measurement interval Q2h compared to those with measurement interval Q1h and moderately higher in simulations with Q1h than in those with Q15’. Higher measurement frequency mitigated the deleterious effect of high measurement imprecision, defined as CV ≥ 15%.

Conclusions:

This Monte Carlo simulation suggests that glycemic control in critically ill patients is more optimal with a BG measurement interval no longer than 1h, with further benefit obtained with use of measurement interval of 15’. These findings have important implications for the development of glycemic control standards.     

外源性胰岛素致自身免疫性低血糖一例报告

报告一例使用人胰岛素后出现自身免疫性低血糖患者,测定IAA(+),停胰岛素改为阿卡波糖口服后,低血糖发作减轻.     

The relation between HbA1c and hypoglycemia revisited; a secondary analysis from an intervention trial in patients with type 1 diabetes and impaired awareness of hypoglycemia

Aims

We aimed to re-assess the previously shown but recently disputed association between HbA1c and severe hypoglycemia.

糖尿病患者动态血糖监测低血糖及危险因素评估

目的探讨糖尿病患者实施动态血糖监测低血糖的意义,同时评估发生低血糖的危险因素。方法选择1型糖尿病或胰岛功能较差的2型糖尿病患者41例。采用动态血糖监测系统连续72h血糖监测,同期每天测毛细血管血糖,采集患者的身高、体重、血压、糖尿病病程、HbA1c等资料。分析低血糖发生次数及持续时间,总结低血糖发生特点及与患者临床特征的相关性。结果 41例糖尿病患者中,72h内指测毛细血管血糖发现低血糖患者13例(17例次),动态血糖监测发现低血糖29例(43例次),其中无症状低血糖22例(占75.9%)、有症状低血糖7例(占24.1%)。低血糖好发于后半夜,危险因素包括性别、年龄、时段、HbA1c和指测最低血糖值。当HbA1c/(指测最低血糖值·BMI)≥0.04时,78%患者动态血糖监测可见低血糖反应;当该指数0.04时,未见低血糖患者。结论对于胰岛功能较差的糖尿病患者,常规每天6次指测毛细血管血糖易漏诊后半夜低血糖的发现。HbA1c/(指测最低血糖值·BMI)可作为低血糖的预测指数,该指数≥0.04提示低血糖风险较高,宜行动态血糖监测。     

Monitoring the Impact of Aggressive Glycemic Intervention during Critical Care after Cardiac Surgery with a Glycemic Expert System for Nurse-Implemented Euglycemia: The MAGIC GENIE Project

A novel, multi-dimensional protocol named GENIE has been in use for intensive insulin therapy (IIT, target glucose <140 mg/dL) in the surgical intensive care unit (SICU) after open heart surgery (OHS) at VA Pittsburgh since 2005. Despite concerns over increased mortality from IIT after the publication of the NICE-SUGAR Trial, it remains in use, with ongoing monitoring under the MAGIC GENIE Project showing that GENIE performance over 12 years (2005-2016) aligns with the current consensus that IIT with target blood glucose (BG) <140 mg/dL is advisable only if it does not provoke severe hypoglycemia (SH). Two studies have been conducted to monitor glucometrics and outcomes during GENIE use in the SICU. One compares GENIE (n = 382) with a traditional IIT protocol (FORMULA, n = 289) during four years of contemporaneous use (2005-2008). The other compares GENIE’s impact overall (n = 1404) with a cohort of patients who maintained euglycemia after OHS (euglycemic no-insulin [ENo-I], n = 111) extending across 12 years (2005-2016). GENIE performed significantly better than FORMULA during contemporaneous use, maintaining lower time-averaged glucose, provoking less frequent, severe, prolonged, or repetitive hypoglycemia, and achieving 50% lower one-year mortality, with no deaths from mediastinitis (0 of 8 cases vs 4 of 9 on FORMULA). Those benefits were sustained over the subsequent eight years of exclusive use in OHS patients, with an overall one-year mortality rate (4.2%) equivalent to the ENo-I cohort (4.5%). The results of the MAGIC GENIE Project show that GENIE can maintain tight glycemic control without provoking SH in patients undergoing OHS, and may be associated with a durable survival benefit. The results, however, await confirmation in a randomized control trial.     

Severe Hypoglycemia in Adults

Reviews in Endocrine and Metabolic Disorders -     

胰岛素泵与多次胰岛素皮下注射治疗2型糖尿病疗效对比分析

目的比较短期胰岛素泵(CSII)与多次皮下胰岛素(MSII)注射强化控制2型糖尿病(T2DM)的有效性和安全性。方法对解放军总院内分泌科2006年6月至2007年5月收治住院的96例糖化血红蛋白(HbA1c)>7.5%的T2DM患者随机分为2组,分别给予CSII和MSII进行短期强化达标治疗,比较两组治疗前后的多时点血糖、糖化血清蛋白(GSP)、血糖达标天数、达标时胰岛素总剂量及低血糖事件发生的差异。结果治疗后CSII组与MSII组静脉血空腹血糖(FBG)分别由(13.53±5.01)mmol/L和(12.25±3.49)mmol/L下降到(5.56±0.76)mmol/L和(6.07±0.97)mmol/L,CSII组FBG下降程度更大(P=0.005)。静脉血餐后2h血糖(2hPG)分别由(19.56±5.82)mmol/L和(18.69±3.98)mmol/L下降到(6.93±1.07)mmol/L和(7.28±1.54)mmol/L,两组间比较差异无统计学意义(P>0.05)。两组的7个时点指血血糖均显著降低,两组间差异无统计学意义(P>0.05)。但达标时最高与最低血糖差值CSII组明显小于MSII组(P=0.029),血糖曲线下面积CSII组明显小于MSII组(P=0.017)。CSII组与MSII组GSP分别由(407±79)μmol/L和(410±100)μmol/L下降到(266±74)μmol/L和(297±83)μmol/L,均有显著改善(P均<0.01),两组治疗后绝对下降值CSII组更显著(P<0.05)。CSII组血糖达标时间平均为(3.66±1.41)d,显著短于MSII组的(5.83±1.77)d(P<0.05)。CSII组在达标时和治疗第7天的胰岛素剂量分别是(40.23±7.47)U/d和(36.06±9.71)U/d,均显著少于MSII组的(47.71±17.74)U/d和(45.63±11.91)U/d(P均<0.05)。两组有症状性低血糖事件共35例次,CSII组与MSII组分别有15例次和20例次,其中CSII组血糖≤3.9mmol/L和≤2.8mmol/L的分别为7和0例次,MSII组分别为19和8例次,前者均少于后者。结论两种胰岛素强化治疗均能有效控制尚未胰岛素治疗的T2DM患者的血糖,促进短期血糖达标。但与MSII相比,CSII治疗在降低FBG、缩小血糖波动和整体血糖控制方面更显著,并能够缩短血糖达标时间,减少胰岛素用量和降低低血糖的发生率。     

Quantitative measurement of islet glucagon response to hypoglycemia by confocal fluorescence imaging in diabetic rats

We have shown that the glucagon irresponsiveness to hypoglycemia in diabetic rats is markedly improved by correction of hyperglycemia independent of insulin. In contrast, normalization of glycemia by insulin did not improve this response. To find out whether these glucagon responses reflect changes in islet glucagon, we directly quantified glucagon area and content in each pancreatic islet by using fluorescent immunostaining and computerized image analysis with confocal laser scanning microscopy (CLSM). The pancreases were analyzed in four groups of rats.

Real-Time Continuous Glucose Monitoring in the Clinical Setting: The Good, the Bad, and the Practical

Real-time continuous glucose monitoring (RT-CGM) is the latest technological breakthrough in diabetes care. Despite its limitations of lag time between sensor and blood glucose, the need for calibration, false detection of and failure to detect hypoglycemia, and mild discomfort or skin irritation reported in some users, RT-CGM is a highly beneficial tool that can be used to detect nocturnal or unrecognized hypoglycemia and glycemic variability. This, in turn, can lead to better treatment decisions, which may improve metabolic control and decrease the incidence and progression of diabetes complications. The RT-CGM devices are fairly accurate and easy to use. It is not difficult to establish a clinical RT-CGM program in the office. However, it requires persistence and an understanding of the patient''s perspective of using RT-CGM so it can be presented and taught appropriately. This article discusses the benefits and limitations of RT-CGM and establishment of a RT-CGM program in the clinical setting.