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

Study Overview
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Brief Summary
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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

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

Conditions
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Diabetes Mellitus, Type 1, Hypoglycemia

Intervention / Treatment
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* Drug: GIP


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: placebo-controlled, double-blinded, cross-over study
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Inhibitory Polypeptide, Diabetes Mellitus, Type 1, Hypoglycemia, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Glucagon, Incretin