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

Investigate GIP effects on biomarkers involved in bone homeostasis

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Other: Saline; Other: GIP; Other: GLP-1

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Hypoglycemia-saline	Other: Saline; 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.; Other Names: placebo
Experimental: Hypoglycemia-GIP	Other: GIP; 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.; Other Names: Glucose-Dependent Insulinotropic Polypeptide
Active Comparator: Hypoglycemia-GLP-1	Other: GLP-1; 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.; Other Names: glucagon-like-peptide-1
Experimental: Hyperglycemia-GIP	Other: GIP; 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.; Other Names: Glucose-Dependent Insulinotropic Polypeptide
Placebo Comparator: Hyperglycemia-Saline	Other: Saline; 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.; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mikkel Christensen

Publications and helpful links

General Publications

• Christensen MB, Lund A, Calanna S, Jorgensen NR, Holst JJ, Vilsboll T, Knop FK. Glucose-Dependent Insulinotropic Polypeptide (GIP) Inhibits Bone Resorption Independently of Insulin and Glycemia. J Clin Endocrinol Metab. 2018 Jan 1;103(1):288-294. doi: 10.1210/jc.2017-01949.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2012
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (Actual): June 22, 2017

Study Record Updates

• Last Update Posted (Actual): June 23, 2017
• Last Update Submitted That Met QC Criteria: June 21, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1
• Other Study ID Numbers: GIP-T1DM-BTM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No