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. 2022 Sep 3:30:100304.
doi: 10.1016/j.jcte.2022.100304. eCollection 2022 Dec.

Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis

Wang Shin Lei  1 , Marissa J Kilberg  2   3 , Babette S Zemel  3   4 , Ronald C Rubenstein  5 , Clea Harris  6 , Saba Sheikh  3   7 , Andrea Kelly  2   3 , Joseph M Kindler  1
Affiliations

Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis

Wang Shin Lei et al. J Clin Transl Endocrinol. .

Abstract

Background: Gut-derived incretin hormones, including glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), regulate post-prandial glucose metabolism by promoting insulin production. GIP, GLP-1, and insulin contribute to the acute bone anti-resorptive effect of macronutrient ingestion by modifying bone turnover. Cystic fibrosis (CF) is associated with exocrine pancreatic insufficiency (PI), which perturbs the incretin response. Cross-talk between the gut and bone ("gut-bone axis") has not yet been studied in PI-CF. The objectives of this study were to assess changes in biomarkers of bone metabolism during oral glucose tolerance testing (OGTT) and to test associations between incretins and biomarkers of bone metabolism in individuals with PI-CF.

Methods: We performed a secondary analysis of previously acquired blood specimens from multi-sample OGTT from individuals with PI-CF ages 14-30 years (n = 23). Changes in insulin, incretins, and biomarkers of bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) and formation (procollagen type I N-terminal propeptide [P1NP]) during OGTT were computed.

Results: CTX decreased by 32% by min 120 of OGTT (P < 0.001), but P1NP was unchanged. Increases in GIP from 0 to 30 mins (rho = -0.48, P = 0.03) and decreases in GIP from 30 to 120 mins (rho = 0.62, P = 0.002) correlated with decreases in CTX from mins 0-120. Changes in GLP-1 and insulin were not correlated with changes in CTX, and changes in incretins and insulin were not correlated with changes in P1NP.

Conclusions: Intact GIP response was correlated with the bone anti-resorptive effect of glucose ingestion, represented by a decrease in CTX. Since incretin hormones might contribute to development of diabetes and bone disease in CF, the "gut-bone axis" warrants further attention in CF during the years surrounding peak bone mass attainment.

Keywords: Bone; CF, cystic fibrosis; CTX, C-terminal telopeptide of type 1 collagen; Cystic Fibrosis; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide-1; Incretins; Nutrition; OGTT; OGTT, oral glucose tolerance test; P1NP, procollagen type I N-terminal propeptide; PI, pancreatic insufficiency.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Changes in glucose, insulin, GLP-1, and GIP during OGTT in youth with PI- CF. Vertical bands represent the 95% confidence interval. OGTT, oral glucose tolerance test; CF, cystic fibrosis.
Fig. 2
Fig. 2
CTX (top) and P1NP (bottom) %Δ during OGTT in youth with PI-CF. Vertical bands represent the 95% confidence interval. *Significantly different than minute 0. %Δ, percent change; CTX, C-terminal telopeptide of type 1 collagen.
Fig. 3
Fig. 3
Associations between %Δ in GIP and CTX during OGTT in youth with PI-CF. %Δ, percent change; CTX, C-terminal telopeptide of type 1 collagen.
See this image and copyright information in PMC

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