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 intravenous 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 six experimental days, participants underwent an OGTT and subsequently five 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.