Colunga-Lozano Luis Enrique, Gonzalez Torres Franscisco Javier, Delgado-Figueroa Netzahualpilli, Gonzalez-Padilla Daniel A, Hernandez Adrian V, Roman Yuani, Cuello-García Carlos A
Departments of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada, L8S 4L8.
Cochrane Database Syst Rev. 2018 Nov 29;11(11):CD011296. doi: 10.1002/14651858.CD011296.pub2.
Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, function, or both. Hyperglycaemia in non-critically ill hospitalised people is associated with poor clinical outcomes (infections, prolonged hospital stay, poor wound healing, higher morbidity and mortality). In the hospital setting people diagnosed with diabetes receive insulin therapy as part of their treatment in order to achieve metabolic control. However, insulin therapy can be provided by different strategies (sliding scale insulin (SSI), basal-bolus insulin, and other modalities). Sliding scale insulin is currently the most commonly used method, however there is uncertainty about which strategy provides the best patient outcomes.
To assess the effects of SSI for non-critically ill hospitalised adults with diabetes mellitus.
We identified eligible trials by searching MEDLINE, Embase, LILACS, and the Cochrane Library. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov trial registers. The date of the last search for all databases was December 2017. We also examined reference lists of identified randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors.
We included RCTs comparing SSI with other strategies for glycaemic control in non-critically ill hospitalised adult participants of any sex with diabetes mellitus.
Two review authors independently extracted data, assessed trials for risk of bias, and evaluated the overall certainty of evidence utilising the GRADE instrument. We synthesised data using a random-effects model meta-analysis with 95% prediction intervals, if possible, or descriptive analysis, as appropriate.
Of 720 records screened, we included eight trials that randomised 1048 participants with type 2 diabetes (387 SSI participants and 615 participants in comparator groups were available for final analysis). We included non-critically ill medical and surgical adults with the diagnosis of diabetes mellitus. The mean follow-up time was measured by the mean length of hospital stay and ranged between five and 24 days. The mean age of participants was 44.5 years to 71 years.Overall, we judged the risk of bias on the trial level as unclear for selection bias, high for outcome-related performance and detection bias with regard to hypoglycaemic episodes, other adverse events, and mean glucose levels, and low for all-cause mortality and length of hospital stay. Attrition bias was low for all outcome measures.Six trials compared SSI with a basal-bolus insulin scheme, three of which investigating 64% of all participants in this category also applying an SSI approach in the bolus comparator part. One trial had a basal insulin-only comparator arm, and the remaining trial used continuous insulin infusion as the comparator. For our main comparison of SSI versus basal-bolus insulin, the results were as follows. Four trials reported mortality data. One out of 268 participants in the SSI group (0.3%) compared with two out of 334 participants in the basal-bolus group (0.6%) died (low-certainty evidence). Severe hypoglycaemic episodes, defined as blood glucose levels below 40 mg/dL (2.2 mmol/L), showed a risk ratio (RR) of 0.22, 95% confidence interval (CI) 0.05 to 1.00; P = 0.05; 5 trials; 667 participants; very low-certainty evidence. The 95% prediction interval ranged between 0.02 and 2.57. All nine severe hypoglycaemic episodes were observed among the 369 participants on basal-bolus insulin (2.4%). The mean length of hospital stay was 0.5 days longer for the SSI group, 95% CI -0.5 to 1.4; P = 0.32; 6 trials; 717 participants; very low-certainty evidence. The 95% prediction interval ranged between -1.7 days and 2.7 days. Adverse events other than hypoglycaemic episodes, such as postoperative infections, showed a RR of 1.16, 95% CI 0.25 to 5.37; P = 0.85; 3 trials; 481 participants; very low-certainty evidence. The mean blood glucose levels ranged across basal-bolus groups from 156 mg/dL (8.7 mmol/L) to 221 mg/dL (12.3 mmol/L). The mean blood glucose level in the SSI groups was 14.8 mg/dL (0.8 mmol/L) higher (95% CI 7.8 (0.4) to 21.8 (1.2); P < 0.001; 6 trials; 717 participants; low-certainty evidence). The 95% prediction interval ranged between -3.6 mg/dL (-0.2 mmol/L) and 33.2 mg/dL (1.8 mmol/L). No trial reported on diabetes-related mortality or socioeconomic effects.
AUTHORS' CONCLUSIONS: We are uncertain which insulin strategy (SSI or basal-bolus insulin) is best for non-critically hospitalised adults with diabetes mellitus. A basal-bolus insulin strategy in these patients might result in better short-term glycaemic control but could increase the risk for severe hypoglycaemic episodes. The certainty of the body of evidence comparing SSI with basal-bolus insulin was low to very low and needs to be improved by adequately performed, well-powered RCTs in different hospital environments with well-educated medical staff using identical short-acting insulins in both intervention and comparator arms to compare the rigid SSI approach with flexible insulin application strategies.
糖尿病是一种由于胰岛素分泌缺陷、功能缺陷或两者兼而有之导致的代谢紊乱。非危重症住院患者的高血糖与不良临床结局（感染、住院时间延长、伤口愈合不良、更高的发病率和死亡率）相关。在医院环境中，被诊断为糖尿病的患者接受胰岛素治疗作为其治疗的一部分，以实现代谢控制。然而，胰岛素治疗可以通过不同的策略（滑动血糖胰岛素（SSI）、基础 - 餐时胰岛素和其他方式）来提供。滑动血糖胰岛素是目前最常用的方法，然而，哪种策略能为患者带来最佳结局尚不确定。
评估滑动血糖胰岛素对非危重症住院成年糖尿病患者的影响。
我们通过检索MEDLINE、Embase、LILACS和Cochrane图书馆来识别符合条件的试验。我们检索了世界卫生组织国际临床试验注册平台（WHO ICTRP）和ClinicalTrials.gov试验注册库。所有数据库的最后检索日期为2017年12月。我们还检查了已识别的随机对照试验（RCT）和系统评价的参考文献列表，并联系了试验作者。
我们纳入了比较滑动血糖胰岛素与其他血糖控制策略的随机对照试验，试验对象为非危重症住院的成年糖尿病患者，性别不限。
两位综述作者独立提取数据，评估试验的偏倚风险，并使用GRADE工具评估证据的总体确定性。如果可能，我们使用随机效应模型荟萃分析并结合95%预测区间来综合数据，或在适当情况下进行描述性分析。
在筛选的720条记录中，我们纳入了八项试验，这些试验将1048名2型糖尿病患者随机分组（最终分析中，387名接受滑动血糖胰岛素治疗的患者和615名对照组患者可用）。我们纳入了诊断为糖尿病的非危重症内科和外科成年患者。平均随访时间通过平均住院天数来衡量，范围在5至24天之间。参与者的平均年龄在44.5岁至71岁之间。总体而言，我们判断试验水平上的偏倚风险在选择偏倚方面不明确，在低血糖事件、其他不良事件和平均血糖水平方面与结局相关的表现和检测偏倚较高，在全因死亡率和住院时间方面较低。所有结局指标的失访偏倚均较低。六项试验将滑动血糖胰岛素与基础 - 餐时胰岛素方案进行了比较，其中三项试验（调查了该类别中64%的所有参与者）在餐时对照组部分也采用了滑动血糖胰岛素方法。一项试验有仅使用基础胰岛素的对照组，其余试验使用持续胰岛素输注作为对照。对于我们滑动血糖胰岛素与基础 - 餐时胰岛素的主要比较，结果如下。四项试验报告了死亡率数据。滑动血糖胰岛素组268名参与者中有1名（0.3%）死亡，而基础 - 餐时组334名参与者中有2名（0.6%）死亡（低确定性证据）。定义为血糖水平低于40 mg/dL（2.2 mmol/L）的严重低血糖事件，风险比（RR）为0.22，95%置信区间（CI）为0.05至1.00；P = 0.05；5项试验；667名参与者；极低确定性证据。95%预测区间在0.02至2.57之间。在接受基础 - 餐时胰岛素治疗的369名参与者（2.4%）中观察到了所有九例严重低血糖事件。滑动血糖胰岛素组的平均住院时间长0.5天，95% CI为 -0.5至1.4；P = 0.32；6项试验；717名参与者；极低确定性证据。95%预测区间在 -1.7天至2.7天之间。除低血糖事件外的不良事件，如术后感染，风险比为1.16，95% CI为0.25至5.37；P = 0.85；3项试验；481名参与者；极低确定性证据。基础 - 餐时组的平均血糖水平在156 mg/dL（8.7 mmol/L）至221 mg/dL（12.3 mmol/L）之间。滑动血糖胰岛素组的平均血糖水平高14.8 mg/dL（0.8 mmol/L）（95% CI为7.8（0.4）至21.8（1.2）；P < 0.001；6项试验；717名参与者；低确定性证据）。95%预测区间在 -3.6 mg/dL（-0.2 mmol/L）至33.2 mg/dL（1.8 mmol/L）之间。没有试验报告糖尿病相关死亡率或社会经济影响。
我们不确定哪种胰岛素策略（滑动血糖胰岛素或基础 - 餐时胰岛素）对非危重症住院成年糖尿病患者是最佳的。这些患者采用基础 - 餐时胰岛素策略可能会导致更好的短期血糖控制，但可能会增加严重低血糖事件的风险。比较滑动血糖胰岛素与基础 - 餐时胰岛素的证据质量低至极低，需要通过在不同医院环境中进行充分实施、样本量充足的随机对照试验来改善，试验中要有受过良好教育的医务人员，在干预组和对照组中使用相同的短效胰岛素，以比较严格的滑动血糖胰岛素方法与灵活的胰岛素应用策略。
