Reviews & Analysis

A massive prospective study that assessed the association between consumption of cereals and mortality has concluded that cereal fibre is a component of whole grains that is potentially protective. This focus on cereal fibre is not fully consonant with plant and human biology and might distract from the aspect of most importance in prediction of chronic disease—the whole grain and its myriad bioactive phytochemical constituents.

The use of antibiotics has improved the health of millions of individuals. However, in a new study by Boursi et al. an important and surprising hypothesis is presented: treating infections with repeated antibiotic therapy in early life can increase the risk of developing diabetes mellitus in adulthood.

Whole-exome sequencing (WES) can effectively sequence >90% of the coding DNA in an individual, and reveal potential disease-causing genetic variants. In this Review, de Bruin and Dauber discuss the use of WES in the field of endocrinology, how this technique can reveal new insights into both rare and common disorders, and its future use in a clinical environment.

Osteoporosis is a process operative in almost all individuals past middle age and results in fractures in a large proportion of men and women. In this Review, Ian Reid reflects on the nature of the osteoporotic process and its implications for treatment indications, and considers the pros and cons of available interventions to reduce fracture risk.

Although reported to improvein vitrofertilization outcomes, androgen supplementation of women with low functional ovarian reserve (LFOR) has remained controversial. In this Review, Aya Shohat-Tal and colleagues discuss genetic variants and polymorphisms associated with inefficient metabolism of dehydroepiandrosterone (DHEA) to testosterone and how, following DHEA supplementation, the hormonal profiles of hypoandrogenic women reflect their ability to metabolize DHEA to testosterone.

Thyroid hormones regulate many metabolic and developmental processes, including key functions in the brain, and mutations in a transporter specific for thyroid hormone lead to severe neurological impairment. In this Review, Bernal and colleagues discuss the physiological importance and clinical implications of thyroid hormone transport, with a particular focus on brain development.

Disorders of sex development (DSDs) are caused by a broad range of genetic changes, but can be difficult to diagnose. In the past few years, advances have been made in molecular diagnostics that could affect the diagnosis of DSDs. This Review analyses the contribution of molecular biology techniques to the diagnosis and management of DSDs, as well as discussing advances in these techniques.

Gonadotropin-releasing hormone analogues (GnRHa) can improve adult height prospects in children with central precocious puberty (CPP). A recent report demonstrates that 50 mg histrelin subcutaneous implants are safe and effective when used yearly. However, questions remain regarding the use of GnRHa in girls with idiopathic CPP, who experience a slow progressive form of puberty.

Low doses of two commonly used dietary emulsifiers—carboxymethylcellulose and polysorbate-80—are reported to induce low-grade inflammation, metabolic disorders and increases in body weight in mice. These emulsifiers also promote colitis in mice that are susceptible to this disorder. Interestingly, changes in the gut microbiota were both necessary and sufficient to induce the metabolic alterations.

For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women with gestational diabetes mellitus is highly relevant.

Epicardial adipose tissue is a multifaceted fat depot with unique metabolic, thermogenic and mechanical properties. Here, Gianluca Iacobellis reviews the pathophysiology of this distinctive fat depot with regard to its function in health and disease, as well as addressing a role for epicardial fat as a biomarker for cardiometabolic disease and measuring the efficacy of treatments that target metabolic diseases.

Islet α cells produce glucagon, which is an important regulator of blood glucose levels under fasting conditions. Dysregulated glucagon secretion is a hallmark of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Here, Campbell and Drucker review current understanding of α cells, as well as glucagon secretion and action in normal physiology and in diabetes mellitus. The consequences of selectively enhancing or attenuating glucagon action for the treatment of T1DM and T2DM are also addressed.

Over the past decade, several multikinase inhibitors have shown considerable effectiveness against metastatic radioiodine-refractory thyroid cancers in early stage clinical trials. On the basis of some remarkable results in a phase III clinical trial, lenvatinib now joins sorafenib as another multikinase inhibitor approved by the FDA for this disease.

Type 1 diabetes mellitus (T1DM) is associated with coeliac disease; however, whether coeliac disease influences the risk of microvascular complications in patients with T1DM is unclear. Now, in a new study, coeliac disease has been identified as a risk factor for retinopathy and nephropathy in patients who also have T1DM.

Obesity is associated with inflammatory responses in the brain, particularly the hypothalamus, which could open up new therapeutic targets. This Review will discuss the innate immune response in the hypothalamic neuron–glial circuit to obesity and associated metabolic disorders and propose corresponding strategies for treating obesity.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cancer. In this Perspectives article, Xilin Yang and colleagues discuss risk factors (subphenotypes) for cancer in Chinese patients with T2DM, which can lead to drug-subphenotype interactions. The authors also propose plausible biological links between T2DM and cancer and underlying the drug-subphenotype interactions.

In a prospective study of patients with type 1 diabetes mellitus, leisure time physical activity of low intensity at baseline (versus high intensity) was associated with the development and progression of nephropathy. This finding is consistent with previous reports that exercise delays the progression of chronic kidney disease in people with or without diabetes mellitus.

The role of prolactin in processes such as lactation and reproduction is well established. However, in the past few years, numerous novel functions for this hormone have been elucidated. In this Review, Bernard and colleagues discuss these newly described functions for prolactin, in particular, the mechanisms underlying infertility associated with hyperprolactinaemia, and the discovery of a mutation in the gene that encodes the prolactin receptor.

The aetiology of type 2 diabetes mellitus (T2DM) involves interactions between genetic, developmental and lifestyle environmental risk factors, which are partly influenced by epigenetic processes. Multhaup and colleagues have combined genome-wide analysis with analyses of an animal model of insulin resistance and tissues from individuals with obesity obtained before and after gastric bypass surgery to identify novel potential pathways that contribute to T2DM pathogenesis.

A large meta-analysis of 52 observational studies, conducted in multiple countries, suggests that menopausal hormone therapy (MHT) increases the risk of ovarian cancer. Should women who are taking MHT, either as estrogen alone or as estrogen combined with a progestogen, and their doctors be worried?