Environmental factors, in particular viral infections, are thought to have an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The COVID-19 pandemic reinforced this hypothesis as many observational studies and meta-analyses reported a notable increase in the incidence of T1DM following infection with SARS-CoV-2 as well as an association between SARS-CoV-2 infection and the risk of new-onset T1DM. Experimental evidence suggests that human β-cells express SARS-CoV-2 receptors and that SARS-CoV-2 can infect and replicate in β-cells, resulting in structural or functional alterations of these cells. These alterations include reduced numbers of insulin-secreting granules, impaired pro-insulin (or insulin) secretion, and β-cell transdifferentiation or dedifferentiation. The inflammatory environment induced by local or systemic SARS-CoV-2 infection might result in a set of signals (such as pro-inflammatory cytokines) that lead to β-cell alteration or apoptosis or to a bystander activation of T cells and disruption of peripheral tolerance that triggers autoimmunity. Other mechanisms, such as viral persistence, molecular mimicry and activation of endogenous human retroviruses, are also likely to be involved in the pathogenesis of T1DM following SARS-CoV-2 infection. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies. Many studies identified an increase in the incidence of type 1 diabetes mellitus (T1DM) during the COVID-19 pandemic, but other reports do not support this association. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies.
{"title":"The relationship between SARS-CoV-2 infection and type 1 diabetes mellitus","authors":"Cyril Debuysschere, Magloire Pandoua Nekoua, Enagnon Kazali Alidjinou, Didier Hober","doi":"10.1038/s41574-024-01004-9","DOIUrl":"10.1038/s41574-024-01004-9","url":null,"abstract":"Environmental factors, in particular viral infections, are thought to have an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The COVID-19 pandemic reinforced this hypothesis as many observational studies and meta-analyses reported a notable increase in the incidence of T1DM following infection with SARS-CoV-2 as well as an association between SARS-CoV-2 infection and the risk of new-onset T1DM. Experimental evidence suggests that human β-cells express SARS-CoV-2 receptors and that SARS-CoV-2 can infect and replicate in β-cells, resulting in structural or functional alterations of these cells. These alterations include reduced numbers of insulin-secreting granules, impaired pro-insulin (or insulin) secretion, and β-cell transdifferentiation or dedifferentiation. The inflammatory environment induced by local or systemic SARS-CoV-2 infection might result in a set of signals (such as pro-inflammatory cytokines) that lead to β-cell alteration or apoptosis or to a bystander activation of T cells and disruption of peripheral tolerance that triggers autoimmunity. Other mechanisms, such as viral persistence, molecular mimicry and activation of endogenous human retroviruses, are also likely to be involved in the pathogenesis of T1DM following SARS-CoV-2 infection. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies. Many studies identified an increase in the incidence of type 1 diabetes mellitus (T1DM) during the COVID-19 pandemic, but other reports do not support this association. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 10","pages":"588-599"},"PeriodicalIF":31.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334121","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 : 2024-06-17DOI: 10.1038/s41574-024-01005-8
Henriett Butz, Attila Patócs, Peter Igaz
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies. Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. This Review outlines ncRNA biology, before discussing research findings on ncRNAs in endocrine tumours and their potential utility as biomarkers, ending with an outlook for future studies.
{"title":"Circulating non-coding RNA biomarkers of endocrine tumours","authors":"Henriett Butz, Attila Patócs, Peter Igaz","doi":"10.1038/s41574-024-01005-8","DOIUrl":"10.1038/s41574-024-01005-8","url":null,"abstract":"Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies. Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. This Review outlines ncRNA biology, before discussing research findings on ncRNAs in endocrine tumours and their potential utility as biomarkers, ending with an outlook for future studies.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 10","pages":"600-614"},"PeriodicalIF":31.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333658","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 : 2024-06-17DOI: 10.1038/s41574-024-01010-x
Marily Theodoropoulou, Stephan Petersenn, Philippe Chanson, Gerald Raverot
The recent Consensus Statement on the diagnosis and management of prolactin-secreting pituitary adenomas (prolactinomas) drew attention to molecular pathogenetic mechanisms. We comment that somatic screening for SF3B1 hotspot variants in select cases might alert to aggressive tumour behaviour and prompt the timely management and intense follow up of these challenging tumours.
{"title":"Evidence for somatic mutation screening on aggressive prolactinomas","authors":"Marily Theodoropoulou, Stephan Petersenn, Philippe Chanson, Gerald Raverot","doi":"10.1038/s41574-024-01010-x","DOIUrl":"10.1038/s41574-024-01010-x","url":null,"abstract":"The recent Consensus Statement on the diagnosis and management of prolactin-secreting pituitary adenomas (prolactinomas) drew attention to molecular pathogenetic mechanisms. We comment that somatic screening for SF3B1 hotspot variants in select cases might alert to aggressive tumour behaviour and prompt the timely management and intense follow up of these challenging tumours.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 10","pages":"565-566"},"PeriodicalIF":31.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334125","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 : 2024-06-10DOI: 10.1038/s41574-024-01000-z
Béatrice Bouvard, Guillaume Mabilleau
Bone resorption follows a circadian rhythm, with a marked reduction in circulating markers of resorption (such as carboxy-terminal telopeptide region of collagen type I in serum) in the postprandial period. Several gut hormones, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and GLP2, have been linked to this effect in humans and rodent models. These hormones are secreted from enteroendocrine cells in the gastrointestinal tract in response to a variety of stimuli and effect a wide range of physiological processes within and outside the gut. Single GLP1, dual GLP1–GIP or GLP1–glucagon and triple GLP1–GIP–glucagon receptor agonists have been developed for the treatment of type 2 diabetes mellitus and obesity. In addition, single GIP, GLP1 and GLP2 analogues have been investigated in preclinical studies as novel therapeutics to improve bone strength in bone fragility disorders. Dual GIP–GLP2 analogues have been developed that show therapeutic promise for bone fragility in preclinical studies and seem to exert considerable activity at the bone material level. This Review summarizes the evidence of the action of gut hormones on bone homeostasis and physiology. This Review summarizes the evidence regarding the actions of gut hormones on bone homeostasis and physiology. The potential implications for the development of future therapeutics to treat bone fragility are considered.
{"title":"Gut hormones and bone homeostasis: potential therapeutic implications","authors":"Béatrice Bouvard, Guillaume Mabilleau","doi":"10.1038/s41574-024-01000-z","DOIUrl":"10.1038/s41574-024-01000-z","url":null,"abstract":"Bone resorption follows a circadian rhythm, with a marked reduction in circulating markers of resorption (such as carboxy-terminal telopeptide region of collagen type I in serum) in the postprandial period. Several gut hormones, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and GLP2, have been linked to this effect in humans and rodent models. These hormones are secreted from enteroendocrine cells in the gastrointestinal tract in response to a variety of stimuli and effect a wide range of physiological processes within and outside the gut. Single GLP1, dual GLP1–GIP or GLP1–glucagon and triple GLP1–GIP–glucagon receptor agonists have been developed for the treatment of type 2 diabetes mellitus and obesity. In addition, single GIP, GLP1 and GLP2 analogues have been investigated in preclinical studies as novel therapeutics to improve bone strength in bone fragility disorders. Dual GIP–GLP2 analogues have been developed that show therapeutic promise for bone fragility in preclinical studies and seem to exert considerable activity at the bone material level. This Review summarizes the evidence of the action of gut hormones on bone homeostasis and physiology. This Review summarizes the evidence regarding the actions of gut hormones on bone homeostasis and physiology. The potential implications for the development of future therapeutics to treat bone fragility are considered.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 9","pages":"553-564"},"PeriodicalIF":31.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301151","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 : 2024-06-06DOI: 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":"20 9","pages":"541-552"},"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":"20 9","pages":"505-506"},"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":"20 8","pages":"441-442"},"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":"20 7","pages":"385-385"},"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}
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