Signs of a Glucose- and Insulin-Independent Gut-Bone Axis and Aberrant Bone Homeostasis in Type 1 Diabetes
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Signs of a Glucose- and Insulin-Independent Gut-Bone Axis and Aberrant Bone Homeostasis in Type 1 Diabetes. / 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.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 109, No. 1, 2024, p. e259-e265.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Signs of a Glucose- and Insulin-Independent Gut-Bone Axis and Aberrant Bone Homeostasis in Type 1 Diabetes
AU - Hartmann, Bolette
AU - Longo, Miriam
AU - Mathiesen, David S
AU - Hare, Kristine J
AU - Jørgensen, Niklas R
AU - Esposito, Katherine
AU - Deacon, Carolyn F
AU - Vilsbøll, Tina
AU - Holst, Jens J
AU - Knop, Filip K
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Humans
KW - Glucose
KW - Insulin
KW - Blood Glucose/metabolism
KW - Diabetes Mellitus, Type 1
KW - Case-Control Studies
KW - Peptide Fragments
KW - Bone Remodeling
KW - Bone Resorption
KW - Procollagen
KW - Homeostasis
KW - Collagen Type I
KW - Biomarkers
U2 - 10.1210/clinem/dgad431
DO - 10.1210/clinem/dgad431
M3 - Journal article
C2 - 37466204
VL - 109
SP - e259-e265
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 1
ER -
ID: 378956333