Reviews & Analysis

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.

Statins might exert diabetogenic effects, potentially increasing insulin resistance and worsening glucose control. However, patients with diabetes mellitus are at high or very high cardiovascular risk and, thus, statin use is strongly recommended. Adding ezetimibe to statins might be helpful in achieving lipid targets and reducing cardiovascular risk without adversely affecting glucose metabolism.

Metabolites have emerged as central regulators of biological function, but understanding mechanisms of metabolite regulation has proven challenging. In 2021 we have seen discoveries in the field of metabolite signalling motivated by a combination of scientific intuition and the elegant deployment of new technologies.

In 2021, several discoveries shed light on the pathomechanisms of β-cell failure during the initiation and progression of diabetes mellitus, and validated novel molecular targets for intervention. Moreover, the field of stem-cell-derived replacements for β-cells is rapidly advancing. These advances bring us closer to therapies to protect and/or regenerate β-cell mass.

Physical activity stimulates tissue crosstalk and provides powerful protection against cardiometabolic disease. This past year, several studies have expanded our knowledge of the secreted molecules regulated by physical activity, uncovered new circuits of cell and tissue crosstalk and provided fundamental insights into the mechanisms that underlie the cardiometabolic benefits of exercise.

Obesity and impaired metabolic health are important risk factors for severe COVID-19. Novel data indicate that these risk factors might also promote vaccine-breakthrough SARS-CoV-2 infections in fully vaccinated people. Here, these relationships are discussed and post-acute sequelae of COVID-19 that are related to obesity and impaired metabolic health are addressed.

In 2021, clinical trials reported the promising effects of incretins and a new class of dual glucagon-like peptide 1–glucose-dependent insulinotropic peptide receptor agonists in preventing and treating type 2 diabetes mellitus and obesity. These ‘twincretins’ will transform the prevention of obesity and type 2 diabetes mellitus and the care of people with these conditions.

Achondroplasia is the most common skeletal dysplasia and is characterized by various lifelong clinical, functional and psychosocial challenges for affected individuals. This first International Consensus Statement on the care of children and adults with achondroplasia aims to facilitate the global standardization and improvement of achondroplasia clinical care.

The investigation of age-induced disease progression in humans is time consuming and resource intensive. One burning question for the exploration of human metabolic ageing is how similar metabolic changes over a lifetime are between humans and mice. A recent study highlights similarities and disparities between these species throughout their lifespan.

Time-restricted feeding (TRF) has shown many health benefits in different organisms, but its effect on lifespan is unknown. A new study showed that a novel intermittent TRF (iTRF) dietary regimen can extend the healthy lifespan of Drosophila. A clock-dependent nightly rise in autophagy drives the lifespan benefits of iTRF.

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.

By mapping the spatial organization of adipose tissue, Bäckdahl and colleagues identify adipocyte progenitor structures as well as three subclasses of adipocytes with different molecular functions, including insulin sensitivity and leptin signalling.

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.

The effects of the gut microbiota on human health are tremendous. Now, a study on the microbiota of wild mice sheds light on how the microorganisms that inhabit the gut between birth and weaning determine resistance to weight gain during adulthood.

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.