Dataset Information

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

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.

SUBMITTER: Lei WS

PROVIDER: S-EPMC9467887 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Lei Wang Shin WS Kilberg Marissa J MJ Zemel Babette S BS Rubenstein Ronald C RC Harris Clea C Sheikh Saba S Kelly Andrea A Kindler Joseph M JM

Journal of clinical & translational endocrinology 20220903

<h4>Background</h4>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 b ...[more]

PMID: 36110921

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Project description:BackgroundStudies in adults indicate that macronutrient ingestion yields an acute anti-resorptive effect on bone, reflected by decreases in C-terminal telopeptide (CTX), a biomarker of bone resorption, and that gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), facilitate this response. There remain knowledge gaps relating to other biomarkers of bone turnover, and whether gut-bone cross-talk is operative during the years surrounding peak bone strength attainment. This study first, describes changes in bone resorption during oral glucose tolerance testing (OGTT), and second, tests relationships between changes in incretins and bone biomarkers during OGTT and bone micro-structure.MethodsWe conducted a cross-sectional study in 10 healthy emerging adults ages 18-25 years. During a multi-sample 2-hour 75 g OGTT, glucose, insulin, GIP, GLP-1, CTX, bone-specific alkaline phosphatase (BSAP), osteocalcin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL), sclerostin, and parathyroid hormone (PTH) were assayed at mins 0, 30, 60, and 120. Incremental areas under the curve (iAUC) were computed from mins 0-30 and mins 0-120. Tibia bone micro-structure was assessed using second generation high resolution peripheral quantitative computed tomography.ResultsDuring OGTT, glucose, insulin, GIP, and GLP-1 increased significantly. CTX at min 30, 60, and 120 was significantly lower than min 0, with a maximum decrease of about 53 % by min 120. Glucose-iAUC0-30 inversely correlated with CTX-iAUC0-120 (rho = -0.91, P < 0.001), and GLP-1-iAUC0-30 positively correlated with BSAP-iAUC0-120 (rho = 0.83, P = 0.005), RANKL-iAUC0-120 (rho = 0.86, P = 0.007), and cortical volumetric bone mineral density (rho = 0.93, P < 0.001).ConclusionsGlucose ingestion yields an anti-resorptive effect on bone metabolism during the years surrounding peak bone strength. Cross-talk between the gut and bone during this pivotal life stage requires further attention.

Project description:BackgroundPost-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear.MethodsTo understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF).ResultsHypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120-210) minutes following initial meal ingestion. Hypoglycemia[+] and hypoglycemia[-] groups did not differ in gender, age, lung function, HbA1c, or BMI. While 11/14 hypoglycemia[-] individuals displayed normal glucose tolerance (NGT), only 2/9 hypoglycemia[+] had NGT. Peak glucose was higher in hypoglycemia[+] vs hypoglycemia[-]. Compared to hypoglycemia[-] NGT, hypoglycemia[+] exhibited lower early-phase insulin secretion (ISR-AUC0-30min). ISR-AUC120-180min was not different in hypoglycemia[+] vs hypoglycemia[-] with abnormal glucose tolerance (AGT); however, glucose-AUC120-180min was lower in hypoglycemia[+] vs hypoglycemia[-] AGT. After adjusting for glucose-AUC, hypoglycemia[+] subjects tended to have higher ISR-AUC120-180min than hypoglycemia[-] AGT. Glucagon concentration did not differ between groups. Lower GLP-1-AUC30min and AUC180min and higher GIP-AUC30min were present in hypoglycemia[+] individuals.ConclusionHypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC30min), and possibly late compensatory hyperinsulinemia. Further study is required to understand whether absence of glucagon difference in the hypoglycemia[+] individuals signals counterregulatory impairment, to delineate the role of incretins in hypoglycemia, and to determine the relationship of hypoglycemia to emergence of CFRD.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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