Wang Shin Lei , Marissa J. Kilberg , Babette S. Zemel , Ronald C. Rubenstein , Clea Harris , Saba Sheikh , Andrea Kelly , Joseph M. Kindler
{"title":"胰腺不全性囊性纤维化年轻成人葡萄糖摄入后的骨代谢和肠促胰岛素激素","authors":"Wang Shin Lei , Marissa J. Kilberg , Babette S. Zemel , Ronald C. Rubenstein , Clea Harris , Saba Sheikh , Andrea Kelly , Joseph M. Kindler","doi":"10.1016/j.jcte.2022.100304","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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 <em>N</em>-terminal propeptide [P1NP]) during OGTT were computed.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/4c/main.PMC9467887.pdf","citationCount":"2","resultStr":"{\"title\":\"Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis\",\"authors\":\"Wang Shin Lei , Marissa J. Kilberg , Babette S. Zemel , Ronald C. Rubenstein , Clea Harris , Saba Sheikh , Andrea Kelly , Joseph M. Kindler\",\"doi\":\"10.1016/j.jcte.2022.100304\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>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 <em>N</em>-terminal propeptide [P1NP]) during OGTT were computed.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>\",\"PeriodicalId\":46328,\"journal\":{\"name\":\"Journal of Clinical and Translational Endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/4c/main.PMC9467887.pdf\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical and Translational Endocrinology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2214623722000126\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical and Translational Endocrinology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2214623722000126","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 2
摘要
肠道来源的肠促胰岛素激素,包括葡萄糖依赖的促胰岛素肽(GIP)和胰高血糖素样肽1 (GLP-1),通过促进胰岛素的产生来调节餐后葡萄糖代谢。GIP、GLP-1和胰岛素通过改变骨转换参与大量营养素摄入的急性骨抗吸收作用。囊性纤维化(CF)与外分泌胰腺功能不全(PI)有关,这扰乱了肠促胰岛素的反应。肠和骨之间的串扰(“肠-骨轴”)尚未在PI-CF中进行研究。本研究的目的是评估口服糖耐量试验(OGTT)期间骨代谢生物标志物的变化,并测试PI-CF患者肠促胰岛素和骨代谢生物标志物之间的关系。方法我们对14-30岁PI-CF患者(n = 23)先前获得的多样本OGTT血液标本进行了二次分析。计算OGTT期间胰岛素、肠促胰岛素和骨吸收生物标志物(1型胶原c端末端肽[CTX])和形成(I型前胶原n端前肽[P1NP])的变化。结果OGTT治疗120 min后sctx下降32% (P <0.001),但P1NP不变。从0到30分钟的GIP增加(rho = -0.48, P = 0.03)和从30到120分钟的GIP下降(rho = 0.62, P = 0.002)与0 - 120分钟的CTX下降相关。GLP-1和胰岛素的变化与CTX的变化无相关性,肠促胰岛素和胰岛素的变化与P1NP的变化无相关性。结论完整的GIP反应与葡萄糖摄入的骨抗吸收作用有关,表现为CTX的降低。由于肠促胰岛素激素可能促进CF中糖尿病和骨病的发展,因此在骨量达到峰值前后的几年里,CF中的“肠-骨轴”值得进一步关注。
Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis
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.