Supplementary Material for: Insulin Regimens to Treat Hyperglycemia in Hospitalized Patients on Nutritional Support: Systematic Review and Meta-Analyses

Background: The best insulin regimen to treat hyperglycemia in hospitalized patients on nutritional support (NS) is unclear. Methods: We searched electronic databases to identify cohort studies or randomized clinical trials in order to evaluate the efficacy of different insulin regimens used to treat hyperglycemia in hospitalized patients on NS on diverse outcomes: mean blood glucose (MBG), hypoglycemia, length of stay in hospital, and mortality. Results: Seventeen studies from a total of 5,030 were included. Enteral Group included 8 studies; 1,203 patients using rapid, glargine, NPH, or Premix insulin; MBG 108-225 mg/dL; hypoglycemia 0-13%. In indirect meta-analyses, NPH insulin ranked best for glucose control (MD 95% CI -2.50 mg/dL [2.65 to -2.35]). Parenteral Group included 4 studies; 228 patients using regular and glargine or NPH insulin; MBG 137-202 mg/dL; hypoglycemia 0-40%. In meta-analyses comparing regular insulin added to parenteral nutrition bag with glargine, MBG (MD 95% CI -3.78 mg/dL [-11.93 to 4.37]; I2 = 0%) or hypoglycemia frequency (RR 95% CI 1.37 [0.43-4.32]; I2 = 70.7%) did not differ. The description related to hospital length of stay and mortality was inconsistent between groups. Conclusions: The best insulin regimen to treat hyperglycemia in hospitalized patients on NS has not been established; best results using insulin regimens with NPH in enteral nutrition do not seem to be clinically relevant.

背景：针对接受营养支持（Nutritional Support，NS）的住院患者，治疗高血糖的最佳胰岛素治疗方案尚不明确。
方法：我们检索电子数据库以纳入队列研究或随机对照临床试验，旨在评估不同胰岛素治疗方案用于治疗接受营养支持的住院患者高血糖的疗效，评估结局指标包括平均血糖（Mean Blood Glucose，MBG）、低血糖事件、住院时长及死亡率。
结果：最终纳入5030项研究中的17项。肠内营养组纳入8项研究，共1203例患者，使用的胰岛素包括速效胰岛素、甘精胰岛素、中性鱼精蛋白锌胰岛素（Neutral Protamine Hagedorn，NPH）或预混胰岛素；患者平均血糖水平为108~225 mg/dL，低血糖事件发生率为0~13%。间接Meta分析显示，NPH胰岛素在血糖控制方面表现最优（均数差95%置信区间：-2.50 mg/dL [2.65~-2.35]）。肠外营养组纳入4项研究，共228例患者，使用的胰岛素包括普通胰岛素、甘精胰岛素或NPH胰岛素；患者平均血糖水平为137~202 mg/dL，低血糖事件发生率为0~40%。对比肠外营养袋中添加普通胰岛素与甘精胰岛素的Meta分析结果显示，两组平均血糖水平（均数差95%置信区间：-3.78 mg/dL [-11.93~4.37]；I²=0%）及低血糖事件发生率（相对危险度95%置信区间：1.37 [0.43~4.32]；I²=70.7%）均无显著差异。两组关于住院时长及死亡率的相关研究结果不一致。
结论：针对接受营养支持的住院患者，治疗高血糖的最佳胰岛素治疗方案仍未明确；肠内营养中使用含NPH胰岛素的治疗方案所获得的最优血糖控制效果，似乎并无临床意义。