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

NCT03195257 — Not applicable, Completed, 10 participants, Mikkel Christensen

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Registry	NCT03195257
Status	Completed
Phase	Not applicable
Study type	Interventional; randomized, crossover, masking: triple, basic science
Enrollment	10 (Actual)
Sponsor	Mikkel Christensen (Other)
Conditions	Type 1 Diabetes Mellitus
Interventions	GIP, GLP-1, Saline (Other)
Dates	start 2012-11-17, primary completion 2016-12-01, completion 2016-12-01, first posted 2017-06-22, last updated 2017-06-23

-Summary

Investigate GIP effects on biomarkers involved in bone homeostasis

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+Arms and interventions

Arm	Type	Interventions
Hypoglycemia-saline	Placebo comparator	Other: Saline
Hypoglycemia-GIP	Experimental	Other: GIP
Hypoglycemia-GLP-1	Active comparator	Other: GLP-1
Hyperglycemia-GIP	Experimental	Other: GIP
Hyperglycemia-Saline	Placebo comparator	Other: Saline

GIP (Other), also known as Glucose-Dependent Insulinotropic Polypeptide: 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.
GLP-1 (Other), also known as glucagon-like-peptide-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.
Saline (Other), also known as placebo: 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.

+Outcome measures

Primary outcomes

C-terminal telopeptide of type I collagen (CTX). [30 minutes intervals, time 0 up to 120 min]

Secondary outcomes

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]

+Eligibility

Sex: Male, ages: 18 Years to 50 Years, accepts healthy volunteers

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.

+Publications

Results publication: 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. PMID 29099978