Pub Date : 2024-06-06DOI: 10.1038/s41574-024-00993-x
Daniela Esposito, Cesar Luiz Boguszewski, Annamaria Colao, Maria Fleseriu, Federico Gatto, Jens Otto Lunde Jørgensen, Oskar Ragnarsson, Diego Ferone, Gudmundur Johannsson
Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications. Patients with acromegaly are commonly affected by diabetes mellitus, which occurs as a complication of growth hormone hypersecretion. This Review discusses the pathophysiology of diabetes mellitus in acromegaly and explores management options in these patients.
{"title":"Diabetes mellitus in patients with acromegaly: pathophysiology, clinical challenges and management","authors":"Daniela Esposito, Cesar Luiz Boguszewski, Annamaria Colao, Maria Fleseriu, Federico Gatto, Jens Otto Lunde Jørgensen, Oskar Ragnarsson, Diego Ferone, Gudmundur Johannsson","doi":"10.1038/s41574-024-00993-x","DOIUrl":"10.1038/s41574-024-00993-x","url":null,"abstract":"Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications. Patients with acromegaly are commonly affected by diabetes mellitus, which occurs as a complication of growth hormone hypersecretion. This Review discusses the pathophysiology of diabetes mellitus in acromegaly and explores management options in these patients.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":31.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1038/s41574-024-01006-7
Javier Butragueño, Jonatan R. Ruiz
Anti-obesity medications based on incretin hormones have advanced weight control and metabolic health in individuals with obesity. The long-term success of obesity therapeutics could be facilitated by exercise, a vital metabolic ally in enhancing treatment efficacy.
{"title":"Metabolic alliance: pharmacotherapy and exercise management of obesity","authors":"Javier Butragueño, Jonatan R. Ruiz","doi":"10.1038/s41574-024-01006-7","DOIUrl":"10.1038/s41574-024-01006-7","url":null,"abstract":"Anti-obesity medications based on incretin hormones have advanced weight control and metabolic health in individuals with obesity. The long-term success of obesity therapeutics could be facilitated by exercise, a vital metabolic ally in enhancing treatment efficacy.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":31.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-28DOI: 10.1038/s41574-024-00996-8
Andreas L. Birkenfeld, Viswanathan Mohan
Current guidelines for the delay and prevention of type 2 diabetes mellitus recommend for people with prediabetes to lose at least 7% of their body weight. Here, we advocate to use glycaemic remission as a goal of prevention in people with prediabetes and those who are at high risk for type 2 diabetes mellitus.
{"title":"Prediabetes remission for type 2 diabetes mellitus prevention","authors":"Andreas L. Birkenfeld, Viswanathan Mohan","doi":"10.1038/s41574-024-00996-8","DOIUrl":"10.1038/s41574-024-00996-8","url":null,"abstract":"Current guidelines for the delay and prevention of type 2 diabetes mellitus recommend for people with prediabetes to lose at least 7% of their body weight. Here, we advocate to use glycaemic remission as a goal of prevention in people with prediabetes and those who are at high risk for type 2 diabetes mellitus.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":31.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-21DOI: 10.1038/s41574-024-01002-x
Shimona Starling
{"title":"Obesity dysregulates a pituitary–liver axis through disruption of the unfolded protein response","authors":"Shimona Starling","doi":"10.1038/s41574-024-01002-x","DOIUrl":"10.1038/s41574-024-01002-x","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":40.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-20DOI: 10.1038/s41574-024-00990-0
Zunair Ahmad, Wahab Kahloan, Evan D. Rosen
Interferon regulatory factors (IRFs) comprise a family of nine transcription factors in mammals. IRFs exert broad effects on almost all aspects of immunity but are best known for their role in the antiviral response. Over the past two decades, IRFs have been implicated in metabolic physiology and pathophysiology, partly as a result of their known functions in immune cells, but also because of direct actions in adipocytes, hepatocytes, myocytes and neurons. This Review focuses predominantly on IRF3 and IRF4, which have been the subject of the most intense investigation in this area. IRF3 is located in the cytosol and undergoes activation and nuclear translocation in response to various signals, including stimulation of Toll-like receptors, RIG-I-like receptors and the cGAS–STING pathways. IRF3 promotes weight gain, primarily by inhibiting adipose thermogenesis, and also induces inflammation and insulin resistance using both weight-dependent and weight-independent mechanisms. IRF4, meanwhile, is generally pro-thermogenic and anti-inflammatory and has profound effects on lipogenesis and lipolysis. Finally, new data are emerging on the role of other IRF family members in metabolic homeostasis. Taken together, data indicate that IRFs serve as critical yet underappreciated integrators of metabolic and inflammatory stress. Interferon regulatory factors (IRFs) are well known as mediators of the antiviral response but there is growing appreciation of their role in metabolism. This Review discusses the current understanding of IRFs as metabolic regulators, with a particular focus on IRF3 and IRF4.
{"title":"Transcriptional control of metabolism by interferon regulatory factors","authors":"Zunair Ahmad, Wahab Kahloan, Evan D. Rosen","doi":"10.1038/s41574-024-00990-0","DOIUrl":"10.1038/s41574-024-00990-0","url":null,"abstract":"Interferon regulatory factors (IRFs) comprise a family of nine transcription factors in mammals. IRFs exert broad effects on almost all aspects of immunity but are best known for their role in the antiviral response. Over the past two decades, IRFs have been implicated in metabolic physiology and pathophysiology, partly as a result of their known functions in immune cells, but also because of direct actions in adipocytes, hepatocytes, myocytes and neurons. This Review focuses predominantly on IRF3 and IRF4, which have been the subject of the most intense investigation in this area. IRF3 is located in the cytosol and undergoes activation and nuclear translocation in response to various signals, including stimulation of Toll-like receptors, RIG-I-like receptors and the cGAS–STING pathways. IRF3 promotes weight gain, primarily by inhibiting adipose thermogenesis, and also induces inflammation and insulin resistance using both weight-dependent and weight-independent mechanisms. IRF4, meanwhile, is generally pro-thermogenic and anti-inflammatory and has profound effects on lipogenesis and lipolysis. Finally, new data are emerging on the role of other IRF family members in metabolic homeostasis. Taken together, data indicate that IRFs serve as critical yet underappreciated integrators of metabolic and inflammatory stress. Interferon regulatory factors (IRFs) are well known as mediators of the antiviral response but there is growing appreciation of their role in metabolism. This Review discusses the current understanding of IRFs as metabolic regulators, with a particular focus on IRF3 and IRF4.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":31.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.1038/s41574-024-00992-y
Henning Tim Langer, Maria Rohm, Marcus DaSilva Goncalves, Lykke Sylow
Ground-breaking discoveries have established 5′-AMP-activated protein kinase (AMPK) as a central sensor of metabolic stress in cells and tissues. AMPK is activated through cellular starvation, exercise and drugs by either directly or indirectly affecting the intracellular AMP (or ADP) to ATP ratio. In turn, AMPK regulates multiple processes of cell metabolism, such as the maintenance of cellular ATP levels, via the regulation of fatty acid oxidation, glucose uptake, glycolysis, autophagy, mitochondrial biogenesis and degradation, and insulin sensitivity. Moreover, AMPK inhibits anabolic processes, such as lipogenesis and protein synthesis. These findings support the notion that AMPK is a crucial regulator of cell catabolism. However, studies have revealed that AMPK’s role in cell homeostasis might not be as unidirectional as originally thought. This Review explores emerging evidence for AMPK as a promoter of cell survival and an enhancer of anabolic capacity in skeletal muscle and adipose tissue during catabolic crises. We discuss AMPK-activating interventions for tissue preservation during tissue wasting in cancer-associated cachexia and explore the clinical potential of AMPK activation in wasting conditions. Overall, we provide arguments that call for a shift in the current dogma of AMPK as a mere regulator of cell catabolism, concluding that AMPK has an unexpected role in tissue preservation. This Review discusses the role of AMPK in cancer cachexia and metabolic dysfunction, including discussion of how targeting AMPK might be an option to preserve muscle and adipose tissue mass.
{"title":"AMPK as a mediator of tissue preservation: time for a shift in dogma?","authors":"Henning Tim Langer, Maria Rohm, Marcus DaSilva Goncalves, Lykke Sylow","doi":"10.1038/s41574-024-00992-y","DOIUrl":"10.1038/s41574-024-00992-y","url":null,"abstract":"Ground-breaking discoveries have established 5′-AMP-activated protein kinase (AMPK) as a central sensor of metabolic stress in cells and tissues. AMPK is activated through cellular starvation, exercise and drugs by either directly or indirectly affecting the intracellular AMP (or ADP) to ATP ratio. In turn, AMPK regulates multiple processes of cell metabolism, such as the maintenance of cellular ATP levels, via the regulation of fatty acid oxidation, glucose uptake, glycolysis, autophagy, mitochondrial biogenesis and degradation, and insulin sensitivity. Moreover, AMPK inhibits anabolic processes, such as lipogenesis and protein synthesis. These findings support the notion that AMPK is a crucial regulator of cell catabolism. However, studies have revealed that AMPK’s role in cell homeostasis might not be as unidirectional as originally thought. This Review explores emerging evidence for AMPK as a promoter of cell survival and an enhancer of anabolic capacity in skeletal muscle and adipose tissue during catabolic crises. We discuss AMPK-activating interventions for tissue preservation during tissue wasting in cancer-associated cachexia and explore the clinical potential of AMPK activation in wasting conditions. Overall, we provide arguments that call for a shift in the current dogma of AMPK as a mere regulator of cell catabolism, concluding that AMPK has an unexpected role in tissue preservation. This Review discusses the role of AMPK in cancer cachexia and metabolic dysfunction, including discussion of how targeting AMPK might be an option to preserve muscle and adipose tissue mass.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":31.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140953923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-14DOI: 10.1038/s41574-024-00999-5
Claire Greenhill
{"title":"The role of brown adipose tissue in metabolic health","authors":"Claire Greenhill","doi":"10.1038/s41574-024-00999-5","DOIUrl":"10.1038/s41574-024-00999-5","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":40.5,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140919696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-13DOI: 10.1038/s41574-024-00994-w
Ravi Savarirayan
The first precision therapy for children with achondroplasia, vosoritide, is now approved in many regions, including Australia, the USA, the European Union and Japan. This article discusses the recent trial results for this therapy regarding growth and the co-morbidities associated with achondroplasia and considers the rationale for its clinical use.
{"title":"Advances in the management of achondroplasia","authors":"Ravi Savarirayan","doi":"10.1038/s41574-024-00994-w","DOIUrl":"10.1038/s41574-024-00994-w","url":null,"abstract":"The first precision therapy for children with achondroplasia, vosoritide, is now approved in many regions, including Australia, the USA, the European Union and Japan. This article discusses the recent trial results for this therapy regarding growth and the co-morbidities associated with achondroplasia and considers the rationale for its clinical use.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":null,"pages":null},"PeriodicalIF":31.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}