Background

The effect of closed-loop insulin delivery on the risk of acute diabetes complications in people with type 1 diabetes is unclear. We investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy in a large cohort of young people.

Methods

In this population-based cohort study, we evaluated young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg participating in the Diabetes Prospective Follow-up (DPV) initiative. Included participants were aged 2–20 years, with diabetes duration of more than 1 year, and were treated between Jan 1, 2021, and Dec 31, 2023. The primary outcomes were the rates of severe hypoglycaemia and ketoacidosis in people using closed-loop therapy versus open-loop therapy. Key secondary outcomes were differences in HbA_1c levels, percentage of time in glucose range of 3·9–10·0 mmol/L, and glycaemic variability. To account for relevant confounders, we applied propensity score inverse probability of treatment weighting considering several baseline characteristics.

Findings

13 922 young people (median age 13·2 years [IQR 10·0 to 16·0]; 51% male) in the DPV database met inclusion criteria and were included in the analysis. 7088 used closed-loop therapy and 6834 used open-loop therapy, with a median observation time of 1·6 years [IQR 1·1 to 2·4]. Individuals using closed-loop therapy had a higher rate of ketoacidosis (1·74 per 100 patient-years) than those using open-loop therapy (0·96 per 100 patient-years; incidence rate ratio 1·81 [1·37 to 2·40], p<0·0001) and there was no significant difference between groups in the rate of severe hypoglycaemia (5·59 per 100 patient-years vs 6·63 per 100 patient-years; incidence rate ratio 0·84 [95% CI 0·69 to 1·03], p=0·089). Individuals using closed-loop therapy had a lower rate of hypoglycaemic coma (0·62 per 100 patient-years) compared with individuals using open-loop therapy (0·91 per 100 patient-years; incidence rate ratio 0·68 [95% CI 0·48 to 0·97], p=0·034). Those in the closed-loop therapy group also had a lower HbA_1c level (7·34% vs 7·50%; difference –0·16% [95% CI –0·20 to –0·13], p=0·0007), higher percentage of time in target glucose range of 3·9–10·0 mmol/L (64% vs 52%, difference 12% [10 to 14], p<0·0001), and less glycaemic variability (coefficient of variation 35·4% vs 38·3%; difference –2·9% [–3·3 to –2·5], p<0·0001) than those in the open-loop therapy group. The rate of ketoacidosis was particularly high in young people with HbA_1c of 8·5% or higher in the closed-loop therapy group (5·25 per 100 patient-years) compared with the open-loop therapy group (1·53 per 100 patient-years; incidence rate ratio 3·43 [95% CI 1·69 to 6·97], p<0·0001).

Interpretation

Hybrid closed-loop insulin delivery has no significant effect on the rate of severe hypoglycaemia, and is associated with an increased risk of diabetic ketoacidosis, but is associated with a reduced risk of hypoglycaemic coma and improved glycaemia. These findings indicate the need for additional educational measures for the use of closed-loop insulin delivery.

Funding

German Center for Diabetes Research, German Diabetes Society, and Robert Koch Institute.

中文翻译：

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混合闭环胰岛素治疗与年轻 1 型糖尿病患者 （2-20 岁） 严重低血糖和糖尿病酮症酸中毒的风险：一项基于人群的研究

 背景

闭环胰岛素输送对 1 型糖尿病患者急性糖尿病并发症风险的影响尚不清楚。我们调查了在一大群年轻人中，与传感器增强（开环）胰岛素疗法相比，混合闭环胰岛素疗法的严重低血糖和糖尿病酮症酸中毒的发生率是否较低。

 方法

在这项基于人群的队列研究中，我们评估了来自德国、奥地利、瑞士和卢森堡 250 个参与糖尿病前瞻性随访 （DPV） 计划的糖尿病中心的 1 型糖尿病年轻人。纳入的参与者年龄在 2-20 岁之间，糖尿病病程超过 1 年，并在 2021 年 1 月 1 日至 2023 年 12 月 31 日期间接受治疗。主要结局是使用闭环疗法与开环疗法的人的严重低血糖和酮症酸中毒的发生率。关键的次要结局是 HbA _1c 水平的差异、血糖范围内 3·9-10·0 mmol/L 的时间百分比和血糖变异性。为了解释相关的混杂因素，我们考虑了几个基线特征，应用了倾向评分治疗加权的逆概率。

 发现

DPV 数据库中的 13 922 名年轻人 （中位年龄 13·2 岁 [IQR 10·0 至 16·0];51% 为男性）符合纳入标准并被纳入分析。7088 例使用闭环疗法，6834 例使用开环疗法，中位观察时间为 1·6 年 [IQR 1·1 至 2·4]。使用闭环治疗的个体酮症酸中毒发生率（1·74/100 患者年）高于使用开环治疗的个体（0·96/100 患者年;发病率比 1·81 [1·37 至 2·40]，p<0·0001），并且组间严重低血糖发生率无显著差异（5·59/100 患者年 vs 6·63/100 患者年;发病率比 0·84 [95% CI 0·69 - 1·03]， p=0·089）。与使用开环治疗的个体 （0·91/100 患者年;发生率比 0·68 [95% CI 0·48 至 0·97]，p = 0·034）相比，使用闭环治疗的个体的低血糖昏迷率较低 （0·62/100 患者年）。闭环治疗组的 HbA _1c 水平也较低（7·34% 对 7·50%;差异 -0·16% [95% CI -0·20 至 -0·13]，p=0·0007），在目标血糖范围为 3·9-10·0 mmol/L 的时间百分比较高（64% 对 52%，差异 12% [10 至 14]，p<0·0001），血糖变异性较低（变异系数 35·4% 对 38·3%;差异 -2·9% [-3·3 至 –2·5]，p<0·0001）的发病率高于开环治疗组。与开环治疗组（每 100 患者年 5·25 例）相比，闭环治疗组（1·53/100 患者年;发病率比 3·43 [95% CI 1·69 至 6·97]，p<0·0001）中 HbA _1c 为 8·5% 或更高的年轻人的酮症酸中毒发生率特别高。

 解释

混合闭环胰岛素输送对严重低血糖的发生率没有显著影响，并且与糖尿病酮症酸中毒风险增加有关，但与低血糖性昏迷风险降低和血糖改善有关。这些发现表明需要对使用闭环胰岛素输送采取额外的教育措施。

 资金

德国糖尿病研究中心、德国糖尿病学会和罗伯特科赫研究所。