The Role of Glucose-Dependent Insulinotropic Polypeptide in the Pathological Glucose Homeostasis Of Type 1 Diabetes

The Role of Glucose-dependent Insulinotropic Polypeptide in the Pathological Glucose Homeostasis of Type 1 Diabetes

In the present project the investigators will evaluate whether glucagonotropic properties of the gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may be utilized as a safeguard against hypoglycemia in the daily life of participants with type 1 Diabetes

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: GIP

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2800
    • Steno Diabetes Center CopenhagenSteno Diabetes Center Copenhagen, Clinical Metabolic Physiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body mass index between 20 and 27 kg/m2
• T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c <69 mmol/mol (<8.5%)
• Treatment with a stable insulin regimen ≥3 months
• T1D duration between 2 and 15years
• C-peptide negative (C-peptide ≤ 16 ng/ml)
• Informed consent

Exclusion Criteria:

• Anemia (hemoglobin outside normal range)
• Known liver disease and/or ALAT and/or ASAT > 2 times normal values
• Estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73 m2 or albuminuria
• Prior Cardiovascular events and/or abnormal heart rate/blood pressure
• Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period or within 30 days prior to randomization
• Any physical or psychological condition that the investigator feels would interfere with trial participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Saline	Drug: GIP; Infusion of Glucose-dependent insulinotropic peptide
Active Comparator: Glucose-Dependent Insulinotropic Polypeptide; 6-day continuous infusion of Glucose-Dependent Insulinotropic Polypeptide	Drug: GIP; Infusion of Glucose-dependent insulinotropic peptide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose	Time spent in hypoglycemia, near-normoglycemia and hyperglycemia	an average of 6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incretin hormones	Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve	Evaluated at experimental day 0,1 and 6 of each intervention
Free fatty acids (FFA)	Incremental and total area under the Concentration-Time Curve	Evaluated at experimental day 0,1 and 6 of each intervention
Fat mRNA	mRNA analysis of fat biopsies	At day 6, and 10 of the study
Fat Protein content	Protein analysis of fat biopsies	Evaluated at experimental day 0,1 and 6 of each intervention
Blood pressure	Changes in blood pressure, mm Hg	The first 24 hours of intervention and at experimental day 6
Pulse	Changes in pulse, beats per minute	The first 24 hours of intervention and at experimental day 6
Glucose regulatory hormones	Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve	Evaluated at experimental day 0,1 and 6 of each intervention
Number of symptomatic hypoglycemic events	Self-reported events	An average of 1 week

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen

Publications and helpful links

General Publications

• Heimburger SMN, Hoe B, Nielsen CN, Bergmann NC, Hartmann B, Holst JJ, Vilsboll T, Dejgaard TF, Christensen MB, Knop FK. 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. 2021 Nov;64(11):2425-2431. doi: 10.1007/s00125-021-05547-8. Epub 2021 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 8, 2018

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 23, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Hypoglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Gastric Inhibitory Polypeptide; Glucagon; Diabetes Mellitus, Type 1; Incretin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: GIPHOT; H-18015379 (Other Identifier: Research Ethics in the Capital of Denmark)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No