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
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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, HbA1c <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: [Figure not available: see fulltext.]
|Publication status||E-pub ahead of print - 2021|
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
- Adipose tissue, Continuous glucose monitoring, GIP, Glucose-dependent insulinotropic polypeptide, Glycaemic control, Glycaemic time in range, Hypoglycaemia, Hypoglycaemic events, Insulin resistance, Insulin sensitivity