The Separate and Combined Effects of GIP, GLP-1, and GLP-2 on Markers of Bone Turnover in Type 2 Diabetes

Abstract

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.