Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18–45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6–11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5–7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14–17 weeks, 20–23 weeks, 26–29 weeks, and 33–36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with (). Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI –0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference –1·34 percentage points [95% CI, –2·19 to –0·49], p=0·0020) and overnight (adjusted mean difference –1·86 percentage points [95% CI –2·90 to –0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. Diabetes Liga Research Fund and Medtronic.

中文翻译：

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比较先进混合闭环疗法和标准胰岛素疗法对 1 型糖尿病孕妇的治疗效果 (CRISTAL)：一项平行组、开放标签、随机对照试验


先进的混合闭环 (AHCL) 疗法可以改善 1 型糖尿病孕妇的血糖控制。然而，需要有关 AHCL 系统的有效性和安全性的数据，因为这些系统（例如 MiniMed 780G）目前尚未批准用于孕妇。我们的目的是研究 MiniMed 780G 是否可以改善 1 型糖尿病孕妇的血糖控制并减少低血糖发生。 CRISTAL 是一项双臂、平行组、开放标签、随机对照试验，在 12 家医院（11 家在比利时，1 家在荷兰）的二级和三级护理专科内分泌中心进行。患有 1 型糖尿病的 18-45 岁孕妇被随机分配 (1:1) 接受 AHCL 治疗 (MiniMed 780G) 或标准胰岛素治疗（护理标准），中位数为 10·1 (IQR 8·6–11·) 6) 妊娠周数。随机化是集中进行的，最小化取决于基线 HbA1c、胰岛素给药方法和中心。参与者和研究团队不会被分组分配所蒙蔽。主要结局是在妊娠特定目标血糖范围 (3·5–7·8 mmol/L) 内花费的时间比例，通过连续血糖监测 (CGM) 在 14–17 周、20–23 周、26–26 周进行测量。 29 周和 33-36 周。关键的次要结局是过夜时间处于目标范围内，以及总体和过夜低于血糖范围 (<3·5 mmol/L) 的时间。分析是在意向治疗的基础上进行的。该试验已注册为（）。 2021年1月15日至2022年9月30日期间，对101名参与者进行了筛选，其中95名参与者被随机分配接受AHCL治疗（n=46）或标准胰岛素治疗（n=49）。 43 名接受 AHCL 治疗的患者和 46 名接受标准胰岛素治疗的患者完成了研究。 基线时，91 名 (95·8%) 参与者使用胰岛素泵，平均 HbA1c 为 6·5% (SD 0·6)。 AHCL 治疗组中花费在目标范围内的时间的平均比例（四个时间段的平均值）为 66·5% (SD 10·0)，而标准胰岛素治疗组为 63·2% (12·4) （调整后的平均差异为 1·88 个百分点 [95% CI –0·82 至 4·58]，p=0·17）。目标范围内的过夜时间较高（调整后平均差 6·58 个百分点 [95% CI 2·31 至 10·85]，p=0·0026），且时间低于总体范围（调整后平均差 –1·34）个百分点 [95% CI，–2·19 至 –0·49]，p=0·0020）和隔夜（调整后的平均差 –1·86 个百分点 [95% CI –2·90 至 –0·81] ，p=0·0005），AHCL 治疗组的疗效低于标准胰岛素治疗组。接受 AHCL 治疗的参与者报告了更高的治疗满意度。 AHCL 治疗没有发生意外的安全事件。对于开始严格血糖控制的孕妇，AHCL 治疗并未改善目标范围内的总体时间，但改善了目标范围内的过夜时间，减少了低于范围的时间，并提高了治疗满意度。这些数据表明，MiniMed 780G 可以在怀孕期间安全使用，并且与标准胰岛素治疗相比可提供一些额外的益处；然而，完善算法以更好地满足怀孕要求非常重要。糖尿病联盟研究基金和美敦力。