The Separate and Combined Effects of GIP, GLP-1, and GLP-2 on Markers of Bone Turnover in Type 2 Diabetes
Josefine V Hansen1, David S Mathiesen1, Mikkel B Christensen1,2,3
1Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup DK-2900, Denmark.
Context:
Oral glucose tolerance test (OGTT) induces greater acute suppression of bone resorption than isoglycaemic IV glucose infusions (IIGI).
Objective:
To study the separate and combined effects of the gut-derived hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon-like peptide 2 (GLP-2) on postprandial bone turnover.
Design:
A randomized, crossover study with 6 experimental days.
Participants:
Ten individuals with type 2 diabetes (T2D).
Interventions:
Over 6 experimental days, participants underwent an OGTT and subsequently 5 IIGIs with infusions of saline, GIP, GLP-1, GLP-2, and GIP + GLP-1 + GLP-2, respectively.
Main Outcome Measures:
Changes in plasma concentrations of carboxy-terminal telopeptide of type I collagen (β-CTX-I) and procollagen type I N-terminal propeptide (PINP).
Results:
β-CTX-I levels were significantly suppressed during OGTT compared to IIGI. Concomitant infusion of GIP + GLP-1 + GLP-2 during IIGI led to a suppression of β-CTX-I comparable to the suppression during the OGTT. During IIGI with infusions of GIP, GLP-1, and GIP + GLP-1 + GLP-2 we observed no reduction in PINP. By contrast, PINP levels were significantly reduced during both OGTT and IIGIs with saline and GLP-2, respectively.
Conclusion:
Our findings suggest that postprandial suppression of bone resorption in individuals with T2D is mediated by the additive effects of GIP, GLP-1, and GLP-2.
Related Concept Videos
Dipeptidyl Peptidase 4 Inhibitors
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Oral Hypoglycemic Agents: Glinides
Oral Hypoglycemic Agents: Biguanides and Glitazones
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
Diabetes Mellitus: Type 2 and Gestational


