Glucose-dependent Insulinotropic Polypeptide as a Safeguard Against Hypoglycemia in Patients With Type 1 Diabetes

Not Applicable

Completed

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

• Registration Number: NCT03556098
• Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-04-16
• Study First Submitted QC: 2018-06-01
• Study First Posted: 2018-06-14
• Study Start: 2019-02-22
• Primary Completion: 2020-02-11
• Study Completion: 2020-02-11
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-05
• Last Update Posted: 2021-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
GIP	glucose-dependent insulinotropic peptide	Infusion of Glucose-dependent insulinotropic peptide
GIP[3-30]	Glucose-Dependent Insulin-Releasing Hormone[3-30]	Infusion of GIP\[3-30\]
Saline	Saline Solution	Infusion of saline

Primary Outcome Measures

Name	Time	Method
plasma glucose concentration	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	plasma glucose excursions and plasma glucose nadir

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Steno Diabetes Center Copenhagen, Clinical Metabolic Physiology; 🇩🇰 Hellerup, Denmark