Insulin Analogues and Hypoglycemia in Patients With Type 1 Diabetes To the Editor The SWITCH 1 randomized clinical trial compared the effect of 2 insulin analogues, insulin degludec vs insulin glargine, on the frequency of hypoglycemic events in patients with type 1 diabetes and risk factors for hypoglycemia.1 According to the study protocol, the insulin dose was titrated to reach fasting glucose values between 71 mg/dL and 90 mg/dL (3.9-5.0 mmol/L). Such low target values increase the risk of severe hypoglycemia. The American Diabetes Association2 and National Institute for Health and Care Excellence3 in the United Kingdom recommend fasting glucose values that range from 90 mg/dL to 130 mg/dL. Also, professional diabetes organizations suggest less-stringent hemoglobin A1c (HbA1c) targets and, thus, higher target glucose values for patients at risk of severe hypoglycemia to prevent this complication. In the SWITCH 1 study, the authors did just the opposite. They increased the basal insulin dose in these vulnerable patients to 0.5 U/kg body weight (calculated from the data on body weight in Table 1 and basal insulin in eTable 5 in Supplement 2 of the article) and provoked a high frequency of severe hypoglycemic events throughout the study period, reaching 86 events per 100 patient-years in the insulin degludec group and 105 events per 100 patient-years in the insulin glargine group. We are concerned that the study design exposed patients at increased risk of severe hypoglycemia. It remains unclear whether the small pharmacokinetic difference between insulin degludec and insulin glargine (which increases with higher insulin doses)4 would still translate into a clinically meaningful difference in the frequency of hypoglycemic episodes if a more appropriate basal insulin dose was given. When the quality of care of all patients with type 1 diabetes followed up at our institution in 2011 was analyzed, a median HbA1c of 7.1% was found, with a mean basal insulin dose of only 0.26 U/kg of body weight and a frequency of 15 severe hypoglycemic events per 100 patient-years, whereas 72% of patients did not experience any severe hypoglycemic event in the last 5 years.5

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胰岛素类似物和 1 型糖尿病患者的低血糖症——答复

胰岛素类似物和 1 型糖尿病患者的低血糖症 致编辑 SWITCH 1 随机临床试验比较了 2 种胰岛素类似物德谷胰岛素与甘精胰岛素对 1 型糖尿病患者低血糖事件频率和低血糖危险因素的影响.1 根据研究方案，胰岛素剂量被滴定以达到 71 mg/dL 和 90 mg/dL (3.9-5.0 mmol/L) 之间的空腹血糖值。如此低的目标值会增加严重低血糖的风险。美国糖尿病协会 2 和英国国家健康与护理卓越研究所 3 建议空腹血糖值范围为 90 毫克/分升至 130 毫克/分升。此外，专业糖尿病组织建议降低血红蛋白 A1c (HbA1c) 目标，因此，为有严重低血糖风险的患者提供更高的目标葡萄糖值，以预防这种并发症。在 SWITCH 1 研究中，作者的做法正好相反。他们将这些易感患者的基础胰岛素剂量增加至 0.5 U/kg 体重（根据表 1 中的体重数据和文章补充 2 中 eTable 5 中的基础胰岛素数据计算），并引发了高频率的严重低血糖事件在整个研究期间，德谷胰岛素组每 100 患者年发生 86 次事件，甘精胰岛素组每 100 患者年发生 105 次事件。我们担心研究设计使患者面临更高的严重低血糖风险。如果给予更合适的基础胰岛素剂量，德谷胰岛素和甘精胰岛素之间的微小药代动力学差异（随着胰岛素剂量的增加而增加）4 之间的微小药代动力学差异是否仍会转化为具有临床意义的低血糖发作频率差异，目前尚不清楚。对 2011 年在我们机构随访的所有 1 型糖尿病患者的护理质量进行分析时，发现 HbA1c 中位数为 7.1%，平均基础胰岛素剂量仅为 0.26 U/kg 体重，频率为每 100 患者年发生 15 次严重低血糖事件，而 72% 的患者在过去 5 年内未发生任何严重低血糖事件。 5