Glucose-Dependent Insulinotropic Polypeptide - Effects on Markers of Bone Turnover in Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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Investigate GIP effects on biomarkers involved in bone homeostasis

Official Title
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Glucose-Dependent Insulinotropic Polypeptide - Effects on Markers of Bone Turnover in Patients With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Other: GIP
* Other: GLP-1
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 1 diabetes (positive islet cell/ glutamic acid decarboxylase-65 antibodies) Patients without measurable beta cell function (i.e. incremental C-peptide below detection limit (<0.16 nmol/l) following an 5 g-iv-arginine stimulation test, Exclusion Criteria: HbA1c >9% (75 mmol/mol), standard plasma biochemical measurements outside normal reference interval (alanine aminotransferase, bilirubin, thyroid-stimulating hormone, hemoglobin, creatinine, and spot urine albumin-creatinine ratio); an abnormal state of hypoglycemia awareness, significant diabetic complications (i.e. proliferative diabetic retinopathy, neuropathy, severe atherosclerosis, heart disease) and, treatment with medication (besides insulin) that could not be paused for 12 hours up to and during the days of the experiments.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Hypoglycemia-saline<br> | Other: Saline<br>* On 3 matched days with 'hypoglycemia' (i.e. plasma glucose clamped between 3-7 mol/L for 120 minutes) either GIP (4 pmol/kg/min), glucagon-like-peptide-1 (GLP-1) (1 pmol/kg/min) or placebo (saline) was administered; and on 2 separately matched days with 'hyperglycemia' (i.e. clamped at 12 mmol/L for 90 minutes) either GIP (4 pmol/kg/min) or saline was administered.<br>* Other names: placebo;|
| Experimental: Hypoglycemia-GIP<br> | Other: GIP<br>* On 3 matched days with 'hypoglycemia' (i.e. plasma glucose clamped between 3-7 mol/L for 120 minutes) either GIP (4 pmol/kg/min), glucagon-like-peptide-1 (GLP-1) (1 pmol/kg/min) or placebo (saline) was administered; and on 2 separately matched days with 'hyperglycemia' (i.e. clamped at 12 mmol/L for 90 minutes) either GIP (4 pmol/kg/min) or saline was administered.<br>* Other names: Glucose-Dependent Insulinotropic Polypeptide;|
| Active Comparator: Hypoglycemia-GLP-1<br> | Other: GLP-1<br>* On 3 matched days with 'hypoglycemia' (i.e. plasma glucose clamped between 3-7 mol/L for 120 minutes) either GIP (4 pmol/kg/min), glucagon-like-peptide-1 (GLP-1) (1 pmol/kg/min) or placebo (saline) was administered; and on 2 separately matched days with 'hyperglycemia' (i.e. clamped at 12 mmol/L for 90 minutes) either GIP (4 pmol/kg/min) or saline was administered.<br>* Other names: glucagon-like-peptide-1;|
| Experimental: Hyperglycemia-GIP<br> | Other: GIP<br>* On 3 matched days with 'hypoglycemia' (i.e. plasma glucose clamped between 3-7 mol/L for 120 minutes) either GIP (4 pmol/kg/min), glucagon-like-peptide-1 (GLP-1) (1 pmol/kg/min) or placebo (saline) was administered; and on 2 separately matched days with 'hyperglycemia' (i.e. clamped at 12 mmol/L for 90 minutes) either GIP (4 pmol/kg/min) or saline was administered.<br>* Other names: Glucose-Dependent Insulinotropic Polypeptide;|
| Placebo Comparator: Hyperglycemia-Saline<br> | Other: Saline<br>* On 3 matched days with 'hypoglycemia' (i.e. plasma glucose clamped between 3-7 mol/L for 120 minutes) either GIP (4 pmol/kg/min), glucagon-like-peptide-1 (GLP-1) (1 pmol/kg/min) or placebo (saline) was administered; and on 2 separately matched days with 'hyperglycemia' (i.e. clamped at 12 mmol/L for 90 minutes) either GIP (4 pmol/kg/min) or saline was administered.<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-terminal telopeptide of type I collagen (CTX). |  | 30 minutes intervals, time 0 up to 120 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parathyroid hormone (PTH) |  | 30 minutes intervals, time 0 up to 120 min | 
| N-terminal propeptide of type 1 procollagen (P1NP). |  | 30 minutes intervals, time 0 up to 120 min |