Glucagon Resistance in Individuals With Obesity and Hepatic Steatosis Can Be Measured Using the GLUSENTIC Test and Index.

Diabetes Pub Date : 2024-10-01 DOI:10.2337/db23-0858

Sasha A S Kjeldsen, Michael M Richter, Nicole J Jensen, Malin S D Nilsson, Niklas Heinz, Janus D Nybing, Frederik H Linden, Erik Høgh-Schmidt, Mikael P Boesen, Thomas L Andersen, Helle H Johannesen, Samuel A J Trammell, Trisha J Grevengoed, Sten Madsbad, Hendrik Vilstrup, Frank Vinholt Schiødt, Andreas Møller, Elias B Rashu, Kirsten Nørgaard, Signe Schmidt, Lise L Gluud, Steen B Haugaard, Jens J Holst, Jørgen Rungby, Nicolai J Wewer Albrechtsen

{"title":"Glucagon Resistance in Individuals With Obesity and Hepatic Steatosis Can Be Measured Using the GLUSENTIC Test and Index.","authors":"Sasha A S Kjeldsen, Michael M Richter, Nicole J Jensen, Malin S D Nilsson, Niklas Heinz, Janus D Nybing, Frederik H Linden, Erik Høgh-Schmidt, Mikael P Boesen, Thomas L Andersen, Helle H Johannesen, Samuel A J Trammell, Trisha J Grevengoed, Sten Madsbad, Hendrik Vilstrup, Frank Vinholt Schiødt, Andreas Møller, Elias B Rashu, Kirsten Nørgaard, Signe Schmidt, Lise L Gluud, Steen B Haugaard, Jens J Holst, Jørgen Rungby, Nicolai J Wewer Albrechtsen","doi":"10.2337/db23-0858","DOIUrl":null,"url":null,"abstract":"Increased plasma levels of glucagon (hyperglucagonemia) promote diabetes development but are also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, which consists of 2 study days: a glucagon injection and measurements of plasma amino acids and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The δ-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (P = 0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (P < 0.0001) but not T1D (P > 0.99). In contrast, glucagon-induced glucose increments were similar in control participants and participants with MASLD (P = 0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1716-1727"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2337/db23-0858","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

Increased plasma levels of glucagon (hyperglucagonemia) promote diabetes development but are also observed in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This may reflect hepatic glucagon resistance toward amino acid catabolism. A clinical test for measuring glucagon resistance has not been validated. We evaluated our glucagon sensitivity (GLUSENTIC) test, which consists of 2 study days: a glucagon injection and measurements of plasma amino acids and an infusion of mixed amino acids and subsequent calculation of the GLUSENTIC index (primary outcome measure) from measurements of glucagon and amino acids. To distinguish glucagon-dependent from insulin-dependent actions on amino acid metabolism, we also studied patients with type 1 diabetes (T1D). The δ-decline in total amino acids was 49% lower in MASLD following exogenous glucagon (P = 0.01), and the calculated GLUSENTIC index was 34% lower in MASLD (P < 0.0001) but not T1D (P > 0.99). In contrast, glucagon-induced glucose increments were similar in control participants and participants with MASLD (P = 0.41). The GLUSENTIC test and index may be used to measure glucagon resistance in individuals with obesity and MASLD.

Article highlights:

查看原文本刊更多论文

肥胖症和肝脂肪变性患者的胰高血糖素抵抗可通过 GLUSENTIC 试验和指数进行测量。

血浆中胰高血糖素水平的升高（高胰高血糖素血症）会促进糖尿病的发展，但在代谢功能障碍相关性脂肪性肝病（MASLD）患者中也能观察到。这可能反映了肝脏对氨基酸分解代谢的胰高血糖素抵抗。测量胰高血糖素抵抗的临床测试尚未得到验证。我们对胰高血糖素敏感性（GLUSENTIC）测试进行了评估，该测试包括两个研究日：注射胰高血糖素并测量血浆氨基酸；输注混合氨基酸，然后根据胰高血糖素和氨基酸的测量值计算 GLUSENTIC 指数（主要结果测量值）。为了区分胰高血糖素依赖型和胰岛素依赖型对氨基酸代谢的作用，我们还对 1 型糖尿病（T1D）患者进行了研究。在外源性胰高血糖素作用下，MASLD 患者氨基酸总量的δ-下降率降低了 49%（P=0.01），计算得出的 GLUSENTIC 指数降低了 34%（P0.99）。相比之下，胰高血糖素诱导的葡萄糖增量在对照组和 MASLD 中相似（p=0.41）。GLUSENTIC测试和指数可用于测量肥胖症和MASLD患者的胰高血糖素抵抗。

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