Review Articles in 2021

This article discusses trends in human reproductive behaviour and health that are associated with infertility. These changes have occurred over a period of only a couple of generations, so environmental factors are suggested to have a role.

This Review highlights results from large randomized clinical trials performed during the period 2017–2020 and Mendelian randomization studies on vitamin D levels. Together, findings indicate that vitamin D supplementation alone in vitamin D-replete adults does not provide health benefits; however, vitamin D deficiency should always be corrected.

Imaging modalities are now available that enable non-invasive quantitative measurements of liver fat content. This Review highlights the various modalities and their use in clinical trials, discusses the clinical importance of hepatic steatosis for progression of nonalcoholic fatty liver disease and proposes how the new modalities might be used going forward.

S-nitrosylation is a key molecular mechanism in the regulation of insulin signalling. This Review explores the role of S-nitrosylation throughout the life cycle of insulin, in both metabolic health and disease.

This Review explains core concepts in artificial intelligence (AI) and machine learning for endocrinologists. AI applications in endocrine cancer diagnostics are highlighted as well as research challenges and future directions for the field.

This Review summarizes adaptive immune cell dysregulation in obesity and type 2 diabetes mellitus (T2DM). Under-appreciated comorbidities of obesity and T2DM (oral cavity inflammation, neuroinflammation and dysbiosis) are considered, and previous clinical trials of anti-inflammatory therapies for T2DM are discussed.

There is growing evidence that fat accumulation in the pancreas can have consequences for metabolic health. This Review discusses the methods for detecting pancreatic fat and the potential causes and pathogenic consequences of pancreatic fat accumulation.

Within the pancreatic islets of Langerhans, endocrine cells are heterogeneous in terms of transcriptional profile, protein expression and the regulation of hormone release. This Review describes how endocrine cell heterogeneity, particularly of β-cells, affects the regulation of hormone secretion within pancreatic islets.

This Review highlights the ontogeny of thermogenic adipocytes, regulation of the adipose tissue microenvironment and inter-organ communication between adipose and other tissues. In addition, activation of thermogenic adipose tissue in humans and animal models is discussed, as well as the therapeutic potential of thermogenic adipose tissue.

Melanin-concentrating hormone (MCH) integrates physiological functions and mood states associated with energy and glucose homeostasis. In this Review, Al-Massadi et al. describe how MCH regulates the hedonic component of food intake and discuss its potential as a therapeutic target.

This Review outlines the pathogenesis of skeletal fragility in patients with type 2 diabetes mellitus, and discusses potential therapeutic approaches to the management of increased fracture risk in these patients. The evidence that skeletal fragility should now be included in the list of well-recognized diabetic complications is also summarized.

The cellular consequences of dysfunctional autophagy contribute to numerous diseases. In this Review, Kitada and Koya consider the relationship between impaired autophagy and age-related metabolic derangements, including insulin resistance, type 2 diabetes mellitus and sarcopenic obesity, and discuss candidate autophagy-based therapies.

Anterior pituitary tumours (APTs) are usually benign but sometimes exhibit aggressive behaviour. In very rare cases, they metastasize and are termed pituitary carcinomas. Here, the authors provide an overview of APTs and pituitary carcinomas, including their epidemiology, diagnosis, predictive markers, and current and emerging therapeutic approaches.

In children, growth hormone deficiency (GHD) results in growth failure and has multiple different causes. This Review discusses the diagnosis of GHD in children and highlights advances in management, including transitional care.

Although sexual dimorphism of the liver is well known, its contribution to non-alcoholic fatty liver disease (NAFLD) is often overlooked. Here, Lefebvre and Staels discuss liver sexual dimorphism in the context of increasingly accurate studies of cellular modifications in NAFLD.

It is 100 years since the famous experiments that identified insulin and showed that this protein could be used to treat people with type 1 diabetes mellitus. This Review charts the developments in insulin research over the past century and highlights future directions for this field.

The expression of growth differentiation factor 15 (GDF15) is increased under conditions of cellular stress as well as by metformin and exercise. This Review highlights mechanisms of GDF15 production and secretion, GDF15 signalling, and the relevance of GDF15 in obesity and metabolic diseases.

Transgender and gender-diverse (TGD) youth are increasingly seeking medical services to bring their physical sex characteristics into alignment with their gender identity. This Review highlights advances in our understanding of TGD youth, the challenges of providing gender-affirming care and research priorities.

Sex differences can have important implications in research and medical care. This Review will outline our understanding on sex differences, and will offer strategies that, if implemented, will provide information with which to personalize and improve health care for all people.

Bariatric surgery is linked with adverse effects on mental health in some patients. This Review summarizes how gut physiology changes after surgery and considers how alterations in gut-derived hormones, microbiota and bile acids can affect gut–brain signalling, with potential consequences for mood and behaviour.