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

• Published in: The journal of clinical endocrinology and metabolism 2023-12, Vol.109 (1), p.e259-e265
• Main Authors: Hartmann, Bolette, Longo, Miriam, Mathiesen, David S, Hare, Kristine J, Jørgensen, Niklas R, Esposito, Katherine, Deacon, Carolyn F, Vilsbøll, Tina, Holst, Jens J, Knop, Filip K
• Format: Article
• Language: English
• Subjects: Biomarkers; Blood Glucose - metabolism; Body mass index; Bone Remodeling; Bone Resorption; Bones; Case-Control Studies; Collagen; Collagen Type I; Density; Dextrose; Diabetes Mellitus, Type 1; Diabetes therapy; Glucagon; Glucose; Glucose tolerance tests; Glycosylated hemoglobin; Homeostasis; Humans; Hypoglycemic agents; Insulin; Peptide Fragments; Procollagen; Type 1 diabetes; Type 2 diabetes
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgad431

Abstract 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 intravenous glucose infusion (IIGI) on bone resorption and formation markers in individuals with type 1 diabetes and healthy controls. Methods This observational case-control study, conducted at the Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, Denmark, included 9 individuals with C-peptide negative type 1 diabetes and 8 healthy controls matched for gender, age, and body mass index. Subjects underwent an OGTT and a subsequent IIGI. We analyzed 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 2 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. Conclusion 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 increased fracture risk characterizing these individuals.