Milestone |

Diabetes

2021 marks the centenary of the discovery of insulin. Since that landmark discovery, huge advances have taken place in our understanding of the pathogenesis of type 1 diabetes and type 2 diabetes, as well as improvements in the treatment of patients with diabetes. This Milestone timeline highlights some of the key advances that have occurred in diabetes research over the past 100 years — from the development of synthetic insulin to new drug classes and technologies for the management of diabetes.

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Timeline

2021 marks the centenary of the discovery of insulin. Since that landmark discovery, huge advances have taken place in our understanding of the pathogenesis of type 1 diabetes and type 2 diabetes, as well as improvements in the treatment of patients with diabetes. This Milestone timeline highlights some of the key advances that have occurred in diabetes research over the past 100 years — from the development of synthetic insulin to new drug classes and technologies for the management of diabetes.

Milestones |

Milestones

Milestones |

Main collection: Free to access for 6 months

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.

Review Article | | Nature Reviews Endocrinology

This Review highlights the research advances, advantages and challenges in several different strategies for generating functional β-cells for therapeutic use in diabetes mellitus. In addition, scalable bioengineering processes are also discussed for the realization of the therapeutic potential of derived β-cells.

Review Article | | Nature Reviews Endocrinology

Metabolically-mature human islet-like organoids generated from induced pluripotent stem cells are able to recapitulate insulin-responsive pancreatic islet function and avoid immunologic cell death in diabetic mouse transplantation models.

Article | | Nature

Further reading: Research and Reviews articles

Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.

Article | Open Access | | Nature Communications

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Article | Open Access | | Nature Communications

The early identification of metabolic disorders could improve or prevent overt disease. Here the authors show that the circulating concentration of hyocholic acid (HCA) species is decreased in the context of obesity and diabetes and increased after gastric bypass surgery in humans, and further that serum HCA species are predictive of metabolic outcomes in healthy individuals.

Article | Open Access | | Nature Communications

The soluble bioactive form of the transmembrane protein fibronectin type III domain containing 4 (sFNDC4) has anti-inflammatory effects and improves insulin sensitivity. Here the authors show that liver derived sFNDC4 signals through adipose tissue GPCR GPR116 to promote insulin-mediated glucose uptake.

Article | Open Access | | Nature Communications

Type 2 diabetes (T2D) is prevalent in populations worldwide, however, mostly studied in European and mixed-ancestry populations. Here, the authors perform a genome-wide association study for T2D in over 5,000 sub-Saharan Africans and identify a locus, ZRANB3, that is specific for this population.

Article | Open Access | | Nature Communications

Type 1 as well as type 2 diabetes are characterized by a loss of insulin-producing β-cells. Here the authors show that the FDA-approved drug neratinib has beneficial effects on β-cell survival, insulin secretion, and glycemic control in mouse models of diabetes.

Article | Open Access | | Nature Communications

Chen et al. show that a prior history of hyperglycaemia can induce persistent DNA methylation changes at key CpGs to facilitate metabolic memory (the effect of early metabolic control on risk of developing diabetic complications later in life) and trigger diabetic complications, through modifying enhancer activity at myeloid and other cells.

Article | | Nature Metabolism

Yu et al. report a preparation that enables transplantation of pancreatic islets underneath the skin and achieves long-term euglycaemia in several preclinical models of type 1 diabetes, thus providing a simple method that might enable a more widespread adoption of islet transplantation in the clinic.

Letter | | Nature Metabolism

The CTLA-4–Ig fusion protein (abatacept) can have beneficial effects in autoimmune disease. Walker and colleagues show in mouse and human type 1 diabetes that abatacept targets pathogenic follicular helper T cells, and the frequencies of these cells at baseline can be used to stratify treatment responses in patients.

Article | | Nature Immunology

This Primer by Umpierrez and colleagues reviews the epidemiology, pathophysiology, diagnosis and management of diabetic ketoacidosis, the most common acute hyperglycaemic emergency in people with diabetes mellitus. Additionally, the authors also discuss different strategies that can be implemented to prevent recurrent diabetic ketoacidosis episodes.

Primer | | Nature Reviews Disease Primers

This Review summarizes the physiological functions, pharmacology and clinical studies of G protein-coupled receptors that are specific for lipid metabolite ligands. The challenges associated with the clinical development of therapeutics for type 2 diabetes mellitus that target these G protein-coupled receptors are also discussed.

Review Article | | Nature Reviews Endocrinology

This Review highlights the evidence from clinical trials that diet-induced weight loss interventions can be used to treat type 2 diabetes mellitus. The composition of the diet and the importance of physical exercise programmes are discussed. Lifestyle interventions for prevention of type 2 diabetes mellitus are also considered.

Review Article | | Nature Reviews Endocrinology

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.

Review Article | | Nature Reviews Endocrinology

This Review focuses on the current understanding of the molecular and cellular pathology of diabetic retinopathy. The primary focus is on the cellular signalling between the neuronal and vascular retina that promotes formation of the inner blood–retinal barrier of the retinal vasculature as an important point of intervention.

Review Article | | Nature Reviews Endocrinology