Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.

Diabetes Pub Date : 2024-10-01 DOI:10.2337/db24-0305

Magnus F G Grøndahl, Andreas H Lange, Malte P Suppli, Jonatan I Bagger, Mira Thing, Lise L Gluud, Dea H Kofod, Mads Hornum, Gerrit van Hall, Samuel A J Trammell, Trisha J Grevengoed, Bolette Hartmann, Jens J Holst, Tina Vilsbøll, Mikkel B Christensen, Asger B Lund, Filip K Knop

{"title":"Glucagon Clearance Is Decreased in Chronic Kidney Disease but Preserved in Liver Cirrhosis.","authors":"Magnus F G Grøndahl, Andreas H Lange, Malte P Suppli, Jonatan I Bagger, Mira Thing, Lise L Gluud, Dea H Kofod, Mads Hornum, Gerrit van Hall, Samuel A J Trammell, Trisha J Grevengoed, Bolette Hartmann, Jens J Holst, Tina Vilsbøll, Mikkel B Christensen, Asger B Lund, Filip K Knop","doi":"10.2337/db24-0305","DOIUrl":null,"url":null,"abstract":"It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1641-1647"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417434/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2337/db24-0305","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A-C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.

Article highlights:

查看原文本刊更多论文

慢性肾病患者的胰高血糖素清除率降低，但肝硬化患者的清除率保持不变。

目前还不完全清楚哪些器官负责排出人体内的胰高血糖素，胰高血糖素排出障碍可能是慢性肝病和慢性肾病（CKD）中出现高胰高血糖素血症的原因之一。在此，我们评估了外源性胰高血糖素在第 4 期慢性肾脏病患者（16 人）、Child-Pugh A-C 肝硬化患者（16 人）和匹配的对照组患者（16 人）中，在输注胰高血糖素（4 纳克/千克/分钟）60 分钟之前、期间和之后的动力学和代谢效应。与肝硬化患者（19.7 [18.1;21.3] mL/kg/min，P < 0.001）和对照组患者（20.4 [18.1;22.7] mL/kg/min，P < 0.001）相比，慢性肾功能衰竭患者的胰高血糖素平均代谢清除率（14.0 [95% CI 12.2;15.7] mL/kg/min）明显较低。与肝硬化患者（5.7 [5.2;6.3] 分钟，P = 0.002）和对照组患者（5.7 [5.2;6.3] 分钟，P < 0.001）相比，慢性肾脏病组患者的胰高血糖素半衰期明显延长（7.5 [6.9;8.2] 分钟）。外源性胰高血糖素对血浆葡萄糖、氨基酸或甘油三酯的影响在不同组间没有差异。总之，慢性肾脏病（而非肝硬化）会导致胰高血糖素清除率显著下降，从而支持肾脏是人体清除胰高血糖素的主要部位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes

自引率

0.00%

发文量