Alpha 2.0
Login Register
» Articles » PMID: 34405256

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

Overview
Journal Diabetologia
Specialty Endocrinology
Date 2021 Aug 18
PMID 34405256
Authors
Sebastian M N Heimburger
Bjorn Hoe
Chris N Nielsen
Natasha C Bergmann
Bolette Hartmann
Jens J Holst
Tina Vilsboll
Thomas F Dejgaard
Mikkel B Christensen
Filip K Knop
Affiliations
Soon will be listed here.
Abstract

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.

References
1.
Nathan D, Genuth S, Lachin J, Cleary P, Crofford O, Davis M . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329(14):977-86. DOI: 10.1056/NEJM199309303291401. View
2.
Frier B . How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev. 2007; 24(2):87-92. DOI: 10.1002/dmrr.796. View
3.
Christensen M, Vedtofte L, Holst J, Vilsboll T, Knop F . Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes. 2011; 60(12):3103-9. PMC: 3219957. DOI: 10.2337/db11-0979. View
4.
Christensen M, Calanna S, Sparre-Ulrich A, Kristensen P, Rosenkilde M, Faber J . Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. Diabetes. 2014; 64(1):72-8. DOI: 10.2337/db14-0440. View
5.
Danne T, Nimri R, Battelino T, Bergenstal R, Close K, DeVries J . International Consensus on Use of Continuous Glucose Monitoring. Diabetes Care. 2017; 40(12):1631-1640. PMC: 6467165. DOI: 10.2337/dc17-1600. View