Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With 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 patients with T1D.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: glucose-dependent insulinotropic peptide; Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30]; Drug: Saline Solution

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Steno Diabetes Center Copenhagen, Clinical metabolic physiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Caucasian men
• Body mass index between 20-27 kg/m^2
• T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c<69 mmol/l (<8,5%)
• T1D duration between 2-20 years
• Stimulated C-peptide ≤ 100 pmol/mL)
• Treatment with a stable basal bolus or insulin pump regimen ≥ 3 months
• Informed consent

Exclusion Criteria:

• Anemia (hemoglobin below normal range)
• Liver disease (ALAT and/or ASAT >2 times normal values) or history of hepatobiliary disorder
• Nephropathy (serum creatinine above normal range and/or albuminuria)
• Allergy or intolerance to ingredients included in the standardized meals
• Prior myocardial infarction or other cardiac events
• Any physical or psychological condition that the investigator fells would interfere with trial participation
• Treatment with any glucose-lowering drugs beside insulin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GIP; Infusion of Glucose-dependent insulinotropic peptide	Drug: glucose-dependent insulinotropic peptide; Infusion of GIP
Active Comparator: GIP[3-30]; Infusion of GIP[3-30]	Drug: Glucose-Dependent Insulin-Releasing Hormone[3-30]; Infusion of GIP antagonist GIP[3-30]
Placebo Comparator: Saline; Infusion of saline	Drug: Saline Solution; Infusion of Saline; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma glucose concentration	plasma glucose excursions and plasma glucose nadir	At times (minute): - 30, - 15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 225, 240 on study days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose regulatory hormones	Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Incretin hormones	Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
GIP[3-30]	GIP[3-30]. Incremental and total area under the Concentration-Time Curve	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Free fatty acids (FFA)	Free fatty acids(FFA). Incremental and total area under the Concentration-Time Curve	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Blood analysis of paracetamol as an assessment of gastric emptying	Assessment of gastric emptying	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Fat mRNA	Fat biopsy to evaluate changes in fat mRNA	At time 240 minute on study days
Fat Lipoprotein lipase (LPL)	Fat biopsy to evaluate LPL changes in fat	At time 240 minute on study days
Fat Perilipin 4	Fat biopsy to evaluate Perilipin 4 changes in fat	At time 240 minute on study days
Fat Fatty acid binding protein 4 (FABP4)	Fat biopsy to evaluate Fatty acid binding protein 4 (FABP4) changes in fat	At time 240 minute on study days
Fat Hormonse-sensitive lipase (HSL)	Fat biopsy to evaluate Hormonse-sensitive lipase (HSL) changes in fat	At time 240 minute on study days
Fat Vascular endothelial growth factor 4 (VEGF-A)	Fat biopsy to evaluate Vascular endothelial growth factor 4 (VEGF-A) changes in fat	At time 240 minute on study days
Fat GIP receptor (GIPR)	Fat biopsy to evaluate GIP receptor (GIPR) changes in fat	At time 240 minute on study days
Blood pressure	Changes in blood pressure, mm Hg	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days
Pulse	Changes in pulse, beats per minute	At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Investigators: Study Director: Filip K Knop, MD, PhD, Steno Diabetes Center Copenhagen, Clinical metabolic physiology

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2019
• Primary Completion (Actual): February 11, 2020
• Study Completion (Actual): February 11, 2020

Study Registration Dates

• First Submitted: April 16, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hypoglycemia; 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; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Gastric Inhibitory Polypeptide; Incretins
• Other Study ID Numbers: H-18002707

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