Signs of a Glucose and Insulin-Independent Gut-Bone Axis and Aberrant Bone Homeostasis in Type 1 Diabetes

Context: Gut hormones seem to play an important role in postprandial bone turnover, which also may be affected by postprandial plasma glucose excursions and insulin secretion. Objective: To investigate the effect of an oral glucose tolerance test (OGTT) and an isoglycemic IV glucose infusion (IIGI) on the bone resorption and formation markers in individuals with type 1 diabetes and healthy controls. Design: Observational case-control study. Setting: Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Denmark. Participants: Nine individuals with C-peptide negative type 1 diabetes and 8 healthy controls matched for gender, age and body mass index were included. Intervention: Subjects underwent an OGTT and a subsequent IIGI. Main outcome measure: Exploratory analysis on changes in bone resorption assessed by measurements of carboxy-terminal type I collagen crosslinks (CTX) and in bone formation as assessed by procollagen type I N-terminal propeptide (PINP) concentrations. Results: Baseline CTX and PINP levels were similar in the two groups. Both groups exhibited significantly greater suppression of CTX during OGTT than IIGI. PINP levels were unaffected by OGTT and IIGI, respectively, in healthy controls. Participants with type 1 diabetes displayed impaired suppression of CTX-assessed bone resorption and inappropriate suppression of PINP-assessed bone formation during OGTT. Conclusions: Our data suggest the existence of a gut-bone axis reducing bone resorption in response to oral glucose independently of plasma glucose excursions and insulin secretion. Subjects with type 1 diabetes showed impaired suppression of bone resorption and reduced bone formation during OGTT, which may allude to the reduced bone mineral density and the increased fracture risk characterizing these individuals.