News & Views in 2015

A new study shows that low and high maternal levels of free T₄ during pregnancy are associated with reduced IQ and cortex and grey matter volumes in offspring. Do these findings herald change for the clinical management of pregnant women with borderline low or high normal levels of T₄?

Exercise training has positive effects on disease risk and health outcomes through mechanisms that have not been fully characterized. Newly published data reveal that a single bout of exercise regulates the phosphoproteome via activation of a global network of kinases and 5′-AMP-activated protein kinase substrates — targets with therapeutic potential for chronic metabolic diseases.

Finnish women <60 years old have an increased risk of death from cardiac events or stroke within a year of stopping hormone-replacement therapy (HRT), compared with women who have not had HRT and with those on current therapy. The safety of the practice of annual discontinuation of HRT should be questioned.

A recent US study comparing different drugs for ovarian stimulation in women with unexplained infertility demonstrates that letrozole is less effective than gonadotropins or clomiphene; however, the primary end point for the study was not efficacy but, rather, multiple pregnancy rates. This study confirms, yet again, that gonadotropins are associated with unacceptably high rates of multiple births.

Lysosomal acid lipase deficiency can lead to liver failure and early death. A recently published placebo-controlled trial shows that enzyme-replacement therapy improves plasma levels of lipids and aminotransferases, and reduces liver fat content. However, the effect on clinical end points and an appropriate indication for treatment remain to be established.

The past decade has witnessed incredible advances in the field of reproductive endocrinology. The use of new genetic and genomic tools has had a particular impact, leading to advances in our understanding, diagnosis and treatment of reproductive endocrine disorders, particularly those related to the neuroendocrine control of reproduction and ovarian biology.

The past decade has seen exciting progress in the field of thyroid disease, especially in the evaluation of thyroid nodules, the genomic characterization of carcinomas and the treatment of carcinomas after surgery. An improved understanding of hyperthyroidism during pregnancy, as well as the causes of 'low T₃ syndrome' and consumptive hypothyroidism have also been achieved.

The mechanistic link between the FTO locus and risk of obesity has remained elusive. However, a new study presents compelling evidence suggesting that the browning of white adipocytes into beige adipocytes (together with regulation of thermogenesis), might be an important and potentially modifiable pathway for development of obesity therapeutics.

In an analysis of data from NHANES spanning from 1999 to 2010, Tuot et al. address two linked questions. Which patients with diabetes mellitus and renal insufficiency are reasonable candidates for metformin therapy and how does this treatment depend on the approach used to measure renal function?

The past 10 years have seen substantial advances in many areas of paediatric endocrinology. Major progress has been made in our understanding of the aetiology of many disorders with the advent of next-generation sequencing. Furthermore, the introduction of novel therapies has revolutionized clinical management.

Antisense oligonucleotides have proven effective at preventing protein synthesis as a result of their on-target specificity. Recent data from several clinical trials including a phase I trial targeting Lp(a), published in The Lancet, highlight the therapeutic potential of antisense oligonucleotides in regulating plasma lipid levels.

Our understanding of bone biology and the subsequent development of therapies to treat bone diseases have both expanded greatly in the past 30 years. This article reviews some of the key advances made in these fields during the past decade.

Over the past decade, the growing epidemic of type 2 diabetes mellitus (T2DM) and its associated complications has presented both challenges and opportunities. Progress has been made in incretin-based therapies, bariatric surgeries and inhibiting renal glucose reabsorption; however, long-term safety and efficacy studies are required. Advances in the prevention of macrovascular complications of T2DM from ongoing clinical trials are expected soon.

In a new study published in The Lancet Diabetes & Endocrinology, metformin use is associated with significantly increased all-cause mortality in patients with type 2 diabetes mellitus and stage 5 chronic kidney disease (CKD). The findings support current recommendations that metformin should not be used in patients with stage 5 CKD.

In a new trial, provision of antenatal dietary and lifestyle advice to pregnant women who are obese is associated with modest improvements in maternal diet. This intervention is, however, inadequate to affect pregnancy and birth outcomes, and challenges the notion that limiting gestational weight gain can improve pregnancy outcomes.

A recent study shows that preceding teriparatide treatment with 2 years of denosumab treatment leads to lower BMD after 4 years than either administering these interventions in the opposite order or combining them initially. However, BMD measurements could be biased in favour of using teriparatide first, owing to the time required for completion of secondary mineralization.

Liraglutide is an agonist of glucagon-like receptor-1, which is a component of an important biological system that inhibits food intake and enhances insulin secretion from the pancreas in the presence of glucose. This drug can therefore facilitate weight loss and glucose control at the same time.

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.

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.