Uma S Unni, Fernando Bril, John P Mugler, Rickey E Carter, Ananda Basu, Rita Basu
{"title":"肝糖原在2型糖尿病夜间糖异生中的作用。","authors":"Uma S Unni, Fernando Bril, John P Mugler, Rickey E Carter, Ananda Basu, Rita Basu","doi":"10.1210/clinem/dgaf044","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Higher gluconeogenesis (GNG) contributes to higher nocturnal endogenous glucose production (EGP) in type 2 diabetes (T2D). Studies using 13C magnetic resonance spectroscopy (MRS) have confirmed lower hepatic glycogen content in subjects with T2D than in subjects with no diabetes (ND).</p><p><strong>Objective: </strong>We determined the role of glycogen loading (GL) vs nonglycogen loading (NGL) on the contribution of GNG to nocturnal EGP in T2D.</p><p><strong>Methods: </strong>In total, 14 subjects with T2D and 15 matched subjects with ND were studied on 2 occasions, with GL (60% carbohydrate) vs NGL (40% carbohydrate) isocaloric meals for 3 days, in random order in the overnight state. [6,6-2H2] glucose was infused to measure EGP, deuterium labelled water was used to measure GNG, and 13C MRS scans were performed in fed and fasted states to measure hepatic glycogen content.</p><p><strong>Results: </strong>Hepatic glycogen content and nocturnal EGP were higher (P < .05) in GL vs NGL in both cohorts. The % GNG to EGP averaged ∼50% in subjects with ND throughout the night after both meals. In contrast, % GNG to nocturnal EGP in T2D was lower with GL vs NGL and matched the pattern observed in subjects with ND with GL lowering overnight rates of GNG in subjects with T2D.</p><p><strong>Conclusion: </strong>Selective targeting of GNG at night with appropriate medications could reduce nocturnal and early morning fasting hyperglycemia and hepatic insulin resistance in people with T2D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"2790-2799"},"PeriodicalIF":5.1000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448574/pdf/","citationCount":"0","resultStr":"{\"title\":\"Role of Hepatic Glycogen on Nocturnal Gluconeogenesis in Type 2 Diabetes Mellitus.\",\"authors\":\"Uma S Unni, Fernando Bril, John P Mugler, Rickey E Carter, Ananda Basu, Rita Basu\",\"doi\":\"10.1210/clinem/dgaf044\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>Higher gluconeogenesis (GNG) contributes to higher nocturnal endogenous glucose production (EGP) in type 2 diabetes (T2D). Studies using 13C magnetic resonance spectroscopy (MRS) have confirmed lower hepatic glycogen content in subjects with T2D than in subjects with no diabetes (ND).</p><p><strong>Objective: </strong>We determined the role of glycogen loading (GL) vs nonglycogen loading (NGL) on the contribution of GNG to nocturnal EGP in T2D.</p><p><strong>Methods: </strong>In total, 14 subjects with T2D and 15 matched subjects with ND were studied on 2 occasions, with GL (60% carbohydrate) vs NGL (40% carbohydrate) isocaloric meals for 3 days, in random order in the overnight state. [6,6-2H2] glucose was infused to measure EGP, deuterium labelled water was used to measure GNG, and 13C MRS scans were performed in fed and fasted states to measure hepatic glycogen content.</p><p><strong>Results: </strong>Hepatic glycogen content and nocturnal EGP were higher (P < .05) in GL vs NGL in both cohorts. The % GNG to EGP averaged ∼50% in subjects with ND throughout the night after both meals. In contrast, % GNG to nocturnal EGP in T2D was lower with GL vs NGL and matched the pattern observed in subjects with ND with GL lowering overnight rates of GNG in subjects with T2D.</p><p><strong>Conclusion: </strong>Selective targeting of GNG at night with appropriate medications could reduce nocturnal and early morning fasting hyperglycemia and hepatic insulin resistance in people with T2D.</p>\",\"PeriodicalId\":50238,\"journal\":{\"name\":\"Journal of Clinical Endocrinology & Metabolism\",\"volume\":\" \",\"pages\":\"2790-2799\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448574/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Endocrinology & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1210/clinem/dgaf044\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"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 Endocrinology & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1210/clinem/dgaf044","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Role of Hepatic Glycogen on Nocturnal Gluconeogenesis in Type 2 Diabetes Mellitus.
Context: Higher gluconeogenesis (GNG) contributes to higher nocturnal endogenous glucose production (EGP) in type 2 diabetes (T2D). Studies using 13C magnetic resonance spectroscopy (MRS) have confirmed lower hepatic glycogen content in subjects with T2D than in subjects with no diabetes (ND).
Objective: We determined the role of glycogen loading (GL) vs nonglycogen loading (NGL) on the contribution of GNG to nocturnal EGP in T2D.
Methods: In total, 14 subjects with T2D and 15 matched subjects with ND were studied on 2 occasions, with GL (60% carbohydrate) vs NGL (40% carbohydrate) isocaloric meals for 3 days, in random order in the overnight state. [6,6-2H2] glucose was infused to measure EGP, deuterium labelled water was used to measure GNG, and 13C MRS scans were performed in fed and fasted states to measure hepatic glycogen content.
Results: Hepatic glycogen content and nocturnal EGP were higher (P < .05) in GL vs NGL in both cohorts. The % GNG to EGP averaged ∼50% in subjects with ND throughout the night after both meals. In contrast, % GNG to nocturnal EGP in T2D was lower with GL vs NGL and matched the pattern observed in subjects with ND with GL lowering overnight rates of GNG in subjects with T2D.
Conclusion: Selective targeting of GNG at night with appropriate medications could reduce nocturnal and early morning fasting hyperglycemia and hepatic insulin resistance in people with T2D.
期刊介绍:
The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.