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,Diabetologia

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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
Diabetologia ( IF 8.4 ) Pub Date : 2021-08-17 , DOI: 10.1007/s00125-021-05547-8
Sebastian M N Heimbürger _{1,

2,

3} , Bjørn Hoe _{1,

4} , Chris N Nielsen ₁ , Natasha C Bergmann ₁ , Bolette Hartmann _{3,

5} , Jens J Holst _{3,

5} , Tina Vilsbøll _{1,

2,

4} , Thomas F Dejgaard _{1,

2} , Mikkel B Christensen _{1,

4,

6,

7} , Filip K Knop _{1,

2,

3,

4}

Affiliation

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/m², HbA_1c <69 mmol/mol [8.5%]) during two × 6 days of continuous s.c. GIP (6 pmol kg⁻¹ min⁻¹) 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.

Graphical abstract

中文翻译：

6天皮下输注葡萄糖依赖性促胰岛素多肽对1型糖尿病患者血糖范围内时间的影响：一项随机、双盲、安慰剂对照的交叉试验

目标/假设

1 型糖尿病的特征是胰高血糖素对低血糖的反应降低，从而增加了已知会妨碍血糖控制的胰岛素治疗相关低血糖的风险。我们之前报道了 1 型糖尿病患者胰岛素诱导的低血糖期间外源性葡萄糖依赖性促胰岛素多肽 (GIP) 的促胰高血糖素作用。在这里，我们通过连续血糖监测 (CGM) 对 1 型糖尿病患者进行评估，研究 6 天 sc GIP 输注对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，评估了 20 名 1 型糖尿病患者（18-75 岁，稳定胰岛素治疗≥3 个月，糖尿病病程）在血糖范围内的时间（通过双盲 CGM 评估） 2-15 年，在^{2 × 6 天的连续皮下}_GIP （6 pmol /kg ^-1 分钟^-1 ) 和安慰剂（生理盐水 [154 mmol/l NaCl]) 输注，分别有 7 天的清除期。主要结果是血糖低于范围的时间、范围内的时间和高于范围的时间。

结果

在夜间或白天，平均血糖或低血糖事件的时间低于范围（<3.9 mmol/l， p = 0.53）或高于范围（>10 mmol/l，p = 0.32）没有显着差异由 CGM 评估。GIP 既没有改变自我报告的低血糖症，也没有改变安全措施。与安慰剂相比，GIP 在白天（06:00-23:59 小时）显着增加了狭窄范围内的时间（3.9-7.8 mmol/l）[平均值 ± SEM] 11.2 ± 5.1% [95% CI 0.41, 21.9]（p = 0.02)。