Reviews & Analysis

Fatty acid-binding proteins (FABPs) improve the solubility of fatty acids. Here, Hotamisligil and Bernlohr describe the structure and function of FABPs in the control of fatty acid metabolism and obesity. The authors focus on FABP4 and FABP5, the most abundant FABPs in adipose tissue, and discuss how targeting these proteins might be exploited to treat metabolic diseases.

Short-chain fatty acids (SCFA) are produced by the gut microbiota from indigestible food stuffs, and might have beneficial effects on metabolism and insulin sensitivity. Here, Canfora and colleagues discuss how SCFA can modulate energy homeostasis and metabolism in adipose tissue, muscle and the liver. The authors also discuss whether SCFA might be used to modulate glucose homeostasis in humans.

In a retrospective multicentre study of patients with type 1 diabetes mellitus, islet transplantation was associated with sustained HbA_1c levels of <7% and freedom from severe hypoglycaemia for 5 years in 60% of immunosuppressed recipients, including those with recurrent severe pretransplant hypoglycaemia. Will islet transplant utilization in patient care now expand?

Developmental exposure to endocrine disruptors is suspected to be one of the main factors responsible for the increased incidence of breast cancer in industrialized countries. New data published in the Journal of Clinical Endocrinology and Metabolism show that exposure to dichlorodiphenyltrichloroethane during fetal life is associated with an increased risk of breast cancer.

Patients with congenital generalized lipodystrophy (CGL) have a near total absence of body fat owing to mutations in genes involved in lipid storage. This Review describes the genetic pathophysiology of the four main forms of CGL and makes recommendations for their appropriate diagnosis and management. Specific therapies for CGL are currently limited, but the authors highlight novel drugs currently in development to treat this condition.

The long-term follow-up of the Veteran Affairs Diabetes Trial is important for researchers and clinicians. For the former, this study supports the conclusion that dysglycaemia causes cardiovascular outcomes; for the latter, it shows that in high-risk individuals, the benefits of lowering glucose are modest and take a long time to emerge.

Nicotinamide phosphoribosyltransferase (NAMPT) regulates the biosynthesis of nicotinamide adenine dinucleotide (NAD), levels of which are decreased in various metabolic disorders and during ageing. Here, Antje Garten and colleagues discuss the physiological functions of NAMPT and its relevance in various human diseases and conditions such as obesity, nonalcoholic fatty liver disease, type 2 diabetes mellitus, cancer and ageing.

Congenital hypogonadotropic hypogonadism (CHH)—a rare disorder caused by deficient production, secretion or action of gonadotropin-releasing hormone—results in an absence of puberty and infertility. Here, Ulrich Boehm and colleagues summarize approaches for the diagnosis and treatment of CHH in light of recent discoveries. This Consensus Statement differs from existing guidelines for the treatment of hypogonadism as it focuses exclusively on CHH.

Injectable testosterone esters and transdermal testosterone gels have generally been assumed to be equally safe and effective forms of testosterone-replacement therapy for male hypogonadism. Now, findings from a recent study suggest that transdermal testosterone gels are superior to injectable testosterone esters in terms of reducing cardiovascular events, all-cause hospitalizations and all-cause mortality.

Paracetamol is the most frequently used medication during pregnancy. Among concerns about its prenatal use, the association with failure of the testes to descend in neonates is the latest. A new study investigating the origin of this malformation reports that paracetamol can reduce testosterone levels in host mice transplanted with human fetal testis tissue.

Increased intake and reduced expenditure of energy results in obesity and must be appropriately controlled to prevent this disease state. In this Review, Denis Richard discusses how the central nervous system and peripheral signals from the gut interact to control energy homeostasis and thermogenesis of brown adipose tissue in states of obesity.

Attempts to prevent type 1 diabetes mellitus have been limited to interventions in patients who have already lost immune tolerance to pancreatic β cells. However, in a new report, orally administered insulin initiates immune protection in young children at increased risk of the disease.

Smoking cessation is associated with weight gain and an increased risk of developing type 2 diabetes mellitus (T2DM). A recent paper published in The Lancet Diabetes & Endocrinology suggests that weight gain and worsening glycaemia levels also occur when patients with established T2DM stop smoking, which highlights the need for careful monitoring of patients who stop smoking.

A recent study indicates that type 1 diabetes mellitus is associated with vascular brain lesions that affect cognition and might represent a target for preventive measures. This commentary discusses methods to ascertain vascular contributions to cerebral dysfunction in diabetes mellitus and indicates that we might only be seeing the tip of the iceberg.

Bariatric and metabolic surgeries are increasingly being used to treat patients with obesity, which is a major public health challenge. In this Review, Gema Frühbeck discusses the current body of evidence related to the outcomes of bariatric and metabolic surgery. Frühbeck suggests that a paradigm shift in eligibility and success criteria is required. She proposes that patient selection and follow-up should no longer focus solely on weight and BMI.

A new study suggests that an energy-dense dietary pattern that is high in saturated fat and low in fibre is associated with cardiovascular risk factors, but not incident cardiovascular disease, among people with severe obesity, which highlights the need for obesity prevention. Analysis of dietary patterns can bolster the evidence base for prevention-oriented dietary recommendations.

Fractures are associated with increased mortality in the general population. Now, a new study from a Danish national database has examined mortality after a fracture in patients with diabetes mellitus. Increased age, male sex, alcohol dependency, retinopathy, heart failure and use of glucocorticoids were associated with increased mortality; statin use was associated with a reduced risk of death.

Metformin is currently the first-line treatment option for patients with type 2 diabetes mellitus, yet its mechanism of action remains uncertain. A new study reveals the important role for the activation of a duodenal AMPK-dependent neuronal pathway in the acute antihyperglycaemic effect of metformin and the inhibition of hepatic glucose production.

In this Review, Joshua Farr and Sundeep Khosla discuss changes in bone architecture during growth, placing an emphasis on skeletal changes at the distal radius, a clinically relevant site of forearm fractures. The implications of these changes for fracture risk in adolescence and later in life, and the architectural changes in bone with ageing that might contribute to increased fracture risk are also discussed.

All women, regardless of ethnicity, geographic location or culture will transition through perimenopause. Many of the neurological symptoms that emerge during this transition are the result of estrogen depletion in the brain. In this Review, the authors discuss the neurological symptoms associated with perimenopause in the context of estrogen-mediated processes in the brain.