Melo Karla F S, Bahia Luciana R, Pasinato Bruna, Porfirio Gustavo J M, Martimbianco Ana Luiza, Riera Rachel, Calliari Luis E P, Minicucci Walter J, Turatti Luiz A A, Pedrosa Hermelinda C, Schaan Beatriz D
1Diabetes Division, Hospital de Clínicas, School of Medicine, Universidade de São Paulo, São Paulo, Brazil.
2Sociedade Brasileira de Diabetes, Rua Afonso Brás, Rua Afonso Brás, 579, cjs 72/74, Vila Nova Conceição, 04511-011 São Paulo, SP Brazil.
Diabetol Metab Syndr. 2019 Jan 3;11:2. doi: 10.1186/s13098-018-0397-3. eCollection 2019.
Strict glucose control using multiple doses of insulin is the standard treatment for type 1 diabetes mellitus (T1DM), but increased risk of hypoglycemia is a frequent drawback. Regular insulin in multiple doses is important for achieving strict glycemic control for T1DM, but short-acting insulin analogues may be better in reducing hypoglycemia and postprandial glucose levels.
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of short-acting insulin analogues regular human insulin on hypoglycemia and postprandial glucose in patients with T1DM.
Searches were run on the electronic databases MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and DARE for RCTs published until August 2017. To be included in the study, the RCTs had to cover a minimum period of 4 weeks and had to assess the effects of short-acting insulin analogues regular human insulin on hypoglycemia and postprandial glucose levels in patients with T1DM. Two independent reviewers extracted the data and assessed the quality of the selected studies. The primary outcomes analyzed were hypoglycemia (total episodes, nocturnal hypoglycemia, and severe hypoglycemia) and postprandial glucose (at all times, after breakfast, after lunch, and after dinner). Glycated hemoglobin (HbA1c) levels and quality of life were considered secondary outcomes. The risk of bias of each RCT was assessed using the Cochrane Collaboration Risk of Bias table, while the quality of evidence for each outcome was assessed using the GRADEpro software. The pooled mean difference in the number of hypoglycemic episodes and postprandial glucose between short-acting insulin analogues vs. regular human insulin was calculated using the random-effects model.
Of the 2897 articles retrieved, 22 (6235 patients) were included. Short-acting insulin analogues were associated with a decrease in total hypoglycemic episodes (risk rate 0.93, 95% CI 0.87-0.99; 6235 patients; I = 81%), nocturnal hypoglycemia (risk rate 0.55, 95% CI 0.40-0.76, 1995 patients, I = 84%), and severe hypoglycemia (risk rate 0.68, 95% CI 0.60-0.77; 5945 patients, I = 0%); and with lower postprandial glucose levels (mean difference/MD - 19.44 mg/dL; 95% CI - 21.49 to - 17.39; 5031 patients, I = 69%) and lower HbA1c (MD - 0,13%; IC 95% - 0.16 to - 0.10; 5204 patients; I = 73%) levels.
Short-acting insulin analogues are superior to regular human insulin in T1DM patients for the following outcomes: total hypoglycemic episodes, nocturnal hypoglycemia, severe hypoglycemia, postprandial glucose, and HbA1c.
使用多次胰岛素注射进行严格的血糖控制是1型糖尿病（T1DM）的标准治疗方法，但低血糖风险增加是一个常见的缺点。多次注射常规胰岛素对于实现T1DM的严格血糖控制很重要，但短效胰岛素类似物在降低低血糖和餐后血糖水平方面可能更好。
我们对随机对照试验（RCT）进行了系统评价和荟萃分析，以评估短效胰岛素类似物与常规人胰岛素对T1DM患者低血糖和餐后血糖的影响。
在电子数据库MEDLINE、Cochrane - CENTRAL、EMBASE、ClinicalTrials.gov、LILACS和DARE中检索截至2017年8月发表的RCT。要纳入研究，RCT必须涵盖至少4周的时间，并且必须评估短效胰岛素类似物与常规人胰岛素对T1DM患者低血糖和餐后血糖水平的影响。两名独立的评审员提取数据并评估所选研究的质量。分析的主要结局是低血糖（总发作次数、夜间低血糖和严重低血糖）和餐后血糖（所有时间、早餐后、午餐后和晚餐后）。糖化血红蛋白（HbA1c）水平和生活质量被视为次要结局。使用Cochrane协作偏倚风险表评估每个RCT的偏倚风险，同时使用GRADEpro软件评估每个结局的证据质量。使用随机效应模型计算短效胰岛素类似物与常规人胰岛素之间低血糖发作次数和餐后血糖的合并平均差异。
在检索到的2897篇文章中，纳入了22篇（6235例患者）。短效胰岛素类似物与总低血糖发作次数减少相关（风险率0.93，95%CI 0.87 - 0.99；6235例患者；I² = 81%）、夜间低血糖（风险率0.55，95%CI 0.40 - 0.76，1995例患者，I² = 84%）和严重低血糖（风险率0.68，95%CI 0.60 - 0.77；5945例患者，I² = 0%）；并且与较低的餐后血糖水平（平均差异/MD -19.44mg/dL；95%CI -21.49至-17.39；5031例患者，I² = 69%）和较低的HbA1c（MD -0.13%；95%CI -0.16至-0.10；5204例患者；I² = 73%）水平相关。
对于以下结局，短效胰岛素类似物在T1DM患者中优于常规人胰岛素：总低血糖发作次数、夜间低血糖、严重低血糖、餐后血糖和HbA1c。
