6 天皮下葡萄糖依赖性胰岛素多肽输注对 1 型糖尿病患者血糖范围内时间的影响：一项随机、双盲、安慰剂对照交叉试验。
The effect of 6-day subcutaneous glucose-dependent insulinotropic polypeptide infusion on time in glycaemic range in patients with type 1 diabetes: a randomised, double-blind, placebo-controlled crossover trial.
机构信息
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
出版信息
Diabetologia. 2021 Nov;64(11):2425-2431. doi: 10.1007/s00125-021-05547-8. Epub 2021 Aug 17.
AIMS/HYPOTHESIS: Type 1 diabetes is characterised by reduced glucagon response to hypoglycaemia, increasing the risk of insulin treatment-associated hypoglycaemia known to hamper glycaemic control. We previously reported a glucagonotropic effect of exogenous glucose-dependent insulinotropic polypeptide (GIP) during insulin-induced hypoglycaemia in individuals with type 1 diabetes. Here we investigate the effect of a 6-day s.c. GIP infusion on time in glycaemic range as assessed by continuous glucose monitoring (CGM) in individuals with type 1 diabetes.
METHODS
In a randomised, placebo-controlled, double-blind crossover study, time in glycaemic range (assessed by double-blinded CGM) was evaluated in 20 men with type 1 diabetes (18-75 years, stable insulin treatment ≥3 months, diabetes duration 2-15 years, fasting plasma C-peptide below 200 pmol/l, BMI 20-27 kg/m, HbA <69 mmol/mol [8.5%]) during two × 6 days of continuous s.c. GIP (6 pmol kg min) and placebo (saline [154 mmol/l NaCl]) infusion, respectively, with an interposed 7-day washout period. The primary outcome was glycaemic time below range, time in range and time above range.
RESULTS
There were no significant differences in time below range (<3.9 mmol/l, p = 0.53) or above range (>10 mmol/l, p = 0.32) during night-time or daytime, in mean glucose, or in hypoglycaemic events as assessed by CGM. GIP altered neither self-reported hypoglycaemia nor safety measures. Compared with placebo, GIP significantly increased time in tight range (3.9-7.8 mmol/l) during daytime (06:00-23:59 hours) by [mean ± SEM] 11.2 ± 5.1% [95% CI 0.41, 21.9] (p = 0.02).
CONCLUSIONS/INTERPRETATION: Six-day s.c. GIP infusion in men with type 1 diabetes did not procure convincing effect on overall time in range, but increased time in tight glycaemic range during daytime by ~2 h per day.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03734718.
FUNDING
The study was funded by grants from The Leona M. and Harry B. Helmsley Charitable Trust and Aase og Ejnar Danielsens Fond.
目的/假设：1 型糖尿病的特征是胰高血糖素对低血糖的反应减弱，增加了与胰岛素治疗相关的低血糖风险，众所周知，这种低血糖会阻碍血糖控制。我们之前报道过在 1 型糖尿病患者中，外源性葡萄糖依赖性胰岛素多肽（GIP）在胰岛素诱导的低血糖期间具有胰高血糖素作用。在这里，我们研究了在 1 型糖尿病患者中，皮下注射 GIP 6 天对通过连续血糖监测（CGM）评估的血糖范围内时间的影响。
方法
在一项随机、安慰剂对照、双盲交叉研究中，20 名 1 型糖尿病男性（18-75 岁，稳定胰岛素治疗≥3 个月，糖尿病病程 2-15 年，空腹血浆 C 肽<200pmol/l，BMI 20-27kg/m，HbA <69mmol/mol[8.5%]）分别接受 2 次×6 天的连续皮下 GIP（6pmolkgmin）和安慰剂（生理盐水[154mmol/l NaCl]）输注，中间有 7 天的洗脱期。主要结局是血糖低于范围、在范围内的时间和血糖高于范围的时间。
结果
夜间或白天，CGM 评估的血糖低于范围（<3.9mmol/l，p=0.53）或高于范围（>10mmol/l，p=0.32）、平均血糖或低血糖事件的时间均无显著差异。GIP 既没有改变自我报告的低血糖，也没有改变安全性指标。与安慰剂相比，GIP 显著增加了白天（06:00-23:59 小时）的紧密范围（3.9-7.8mmol/l）时间[平均±SEM]11.2±5.1%[95%CI 0.41,21.9]（p=0.02）。
结论/解释：在 1 型糖尿病男性中，皮下注射 GIP 6 天并没有显著改善整体血糖范围内时间，但每天增加了约 2 小时的日间紧密血糖范围时间。
试验注册
ClinicalTrials.gov NCT03734718。
资金
该研究由利昂娜·M·和哈里·B·赫尔姆斯利慈善信托基金以及 Aase og Ejnar Danielsens 基金会资助。
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