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The Key Advances in Endocrinology collection offers a unique series of specially commissioned ‘Year in Review’ articles that highlight the key discoveries made each year. In these articles, leading experts in the field describe their pick of the top 3–8 key advances of the year, outlining their clinical impact and implications for current and future research.
Metabolic diseases emerged as important risk factors for severe COVID-19, but the mechanisms responsible remained unclear for some time. The severity of metabolic diseases was also associated with worse outcomes in patients with COVID-19, forcing clinicians to adjust their thinking on which patients with metabolic disease, but without COVID-19, to prioritize for treatment during and immediately after the pandemic.
The development and application of effective immunotherapies for type 1 diabetes mellitus has lagged behind our ability to identify and stage individuals in pre-clinical stages of disease. This Year in Review addresses advances in immunotherapy aimed towards prevention and our readiness to roll out screening in the broader population.
Owing to the strong association of non-alcoholic fatty liver disease with obesity and cardiometabolic disease, in 2020 experts controversially proposed to rename this condition as ‘metabolic associated fatty liver disease’. Additional studies have elucidated new genetic and dietary modifiers of this disease. This knowledge is essential to improve diagnosis, risk-stratification and treatment.
Heart failure and chronic kidney disease are frequent causes of morbidity and mortality in people with type 2 diabetes mellitus. Cardiovascular outcome trials have confirmed benefits of sodium–glucose co-transporter 2 inhibitors on cardiovascular events, cardiovascular deaths, hospitalization for heart failure and renal outcomes. These benefits now extend to people with and without type 2 diabetes mellitus.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by reproductive and metabolic disturbances. Androgen excess is a hallmark of PCOS, driving many of the phenotypic features. In 2020, several findings highlight altered metabolic pathways as an underlying biological mechanism in PCOS. These findings add to our understanding of the complex interaction between metabolic homeostasis and reproduction.
Neuroendocrine neoplasms are derived from the diffuse endocrine system and represent a spectrum of tumours with a diverse range of molecular abnormalities, functionality and anatomical locations. Here, some key advances in molecular diagnosis, functional imaging and therapeutic strategies that have been published in 2020 are discussed.
Exercise is a potent modulator of intestinal microbiota composition and function. In 2019, several studies uncovered biologically important links between skeletal muscle and the gut microbiota, revealing how the gut bacteria respond to an exercise challenge and have reciprocal roles in fuel availability, muscle function and endurance performance.
Pancreatic islets, which are critical for glucose homeostasis, are endocrine microorgans embedded in the exocrine pancreas; their location has often limited studying their function. In 2019, advances in islet biology were achieved with new technologies extending findings from several decades ago and with conceptual advances built on findings from other fields.
Feeding is regulated by defined neuronal pathways and circulating factors that ensure homeostatic balance is maintained. However, many emotion-affective pathways are also involved in communicating positive and negative valence on feeding behaviour. In 2019, several seminal discoveries were made that illuminate the complex interaction between homeostatic and hedonic feeding control mechanisms.
Multikinase inhibitors are effective treatments for thyroid cancers, acting primarily as antiangiogenic agents. This year, advances have been made in selective targeting of RET and BRAF in patients with medullary and anaplastic thyroid cancers, respectively. However, Hürthle cell carcinomas have a unique genomic landscape with no dominant truncal drivers, precluding simplistic approaches to therapeutic targeting.
Personalized, or precision, medicine in type 2 diabetes mellitus is becoming a reality with new insights into the contributions of subgroup analyses. The roadmap to future implementation must take into account individual and subgroup variability in genetic architecture, environment, clinical measures, lifestyle, cost-effectiveness and treatment burden.
In 2018, more than 4,000 publications were dedicated to the study of the gut microbiota, and an important proportion investigated cardiometabolic disorders associated with overweight and obesity. Novel mechanisms and strategies have emerged, some of which were focused not only on specific bacteria or nutrients, but also on new metabolites.
Circadian rhythm research is beginning to show how rhythms sustain health. Genome-wide transcriptome, metabolome and proteome studies have improved our understanding of circadian regulation. This knowledge is leveraged for behavioural interventions that optimize daily rhythms, the timing of drug delivery and the targeting of clock components to prevent or treat chronic diseases.
A key component in the development from fatty liver to hepatocellular carcinoma (HCC) is the appearance of nonalcoholic steatohepatitis (NASH). The precise cellular processes that trigger the advancement of NASH towards HCC are not well understood. In 2018, three key papers were published that help us better understand these processes.
Cancer cells consume and utilize glucose at a higher rate than normal cells. However, some microenvironments limit the availability of nutrients and glucose. In 2018, researchers found that tumours depend on a variety of different nutrient sources, both locally and systemically, to overcome metabolic limitations and promote tumour progression and metastasis.
The pathophysiology of coronavirus disease 19 (COVID-19) and diabetes mellitus are interlinked, and diabetes mellitus is associated with severe COVID-19 outcomes. This Review highlights new advances in diabetes mellitus and COVID-19, considering disease mechanisms and clinical management of patients with diabetes mellitus in the ongoing pandemic.
This Review examines the evidence that β-cells are active participants in the dialogue with the immune system during the development of type 1 diabetes mellitus. The authors suggest that therapies targeting β-cell health, vitality and function might prove essential, in combination with immunotherapy, to change the course of events leading to β-cell destruction.
Sodium–glucose cotransporter type 2 inhibitors (SGLT2is) are used for the treatment of type 2 diabetes mellitus. This Review provides an in-depth overview of the role of SGLT2is as glucose-lowering agents and as cardiovascular and renal protective agents.
The adrenal glands are a source of androgens that all share an oxygen atom on carbon 11 (termed 11-oxyandrogens). This Review focuses on the rapidly expanding knowledge regarding the implications of 11-oxyandrogens in human physiology and disease.
During the past 5 years, a number of notable research advances have been reported for neuroendocrine cancers of the gastrointestinal tract. This Review provides an up-to-date summary of the research advances that have improved the clinical management of these cancers.