Reviews & Analysis

Clinical and experimental studies suggest that early life experiences, perhaps spanning multiple generations, affect lifelong risk of metabolic dysfunction through epigenetic mechanisms. Data published in 2011 suggest that epigenetic analysis could potentially have utility as a marker of early metabolic pathology and might enable early life prophylaxis.

Research in 2011 regarding β-cell destruction, early immunointervention trials and development of late complications in type 1 diabetes mellitus have highlighted the heterogeneity of this disease. Patient phenotyping should be performed for the implementation of tailored therapies, especially taking into account the age at which the disease is diagnosed.

Polycystic ovary syndrome (PCOS) is a complex genetic disease that affects approximately 7% of women of reproductive age worldwide. From novel pathways implicated in the etiology of PCOS through genome-wide association to characterization of the reproductive and metabolic changes that occur in ageing women with PCOS, the year 2011 has seen a number of studies published that highlight the intricacies of this condition.

With primary aldosteronism now widely acknowledged as common and associated with both hypertension-related and non-hypertension-related pathology, research interest into its causes and consequences continues to grow. In 2011, major breakthroughs occurred in understanding the role and nature of underlying genetic disturbances and elucidating the pathophysiology of its cardiovascular sequelae.

Over the past decade, investigators have actively searched for safer therapeutic approaches to replace or complement the use of bisphosphonates and/or parathyroid hormone, exploring both antiresorptive and osteoanabolic pathways. Besides marked progress in basic research, the year 2011 has seen several compounds for the treatment of osteoporosis enter or progress within clinical trials.

The complex relationship between pregnancy and thyroid function, and its clinical effect on mother and baby, continued to stimulate research in 2011. Key advances were made on three important issues: how long maternal thyroid function affects fetal thyroid hormone levels; whether thyroid autoimmunity affects pregnancy outcome; and the prevalence of permanent hypothyroidism after postpartum thyroiditis.

In April 2011, the International Olympic Committee determined that women with hyperandrogenism and androgen levels above the lower limit of the male range cannot compete against other women. This attempt to implement a 'level playing field' has received much criticism. But is it justified?

Advanced imaging techniques can identify pancreatic features that are characteristic of diabetes subtypes and can help guide molecular and genetic investigations. This Review describes pancreatic imaging in monogenic diabetes mellitus, focusing on the characteristic imaging findings in patients with subtypes of this disease, and relates these features to imaging findings in other exocrine and endocrine pancreatic disorders. The potential of advanced imaging techniques to reveal novel aspects of the pathogenesis and pathophysiology of monogenic diabetes mellitus that are relevant for progression to β-cell disease is also discussed.

Diabetes mellitus diagnosed during the first 2 years of life differs from the disease in older children regarding its causes, clinical characteristics, treatment options and needs in terms of education and psychosocial support. This Review summarized the current knowledge on the clinical management of diabetes mellitus in infants, including diagnostic and therapeutic approaches, ongoing diabetes care and quality control.

Insulin resistance is a characteristic feature of type 2 diabetes mellitus. The activation of SIRT1, a deacetylase, is reported to be very beneficial for the treatment of type 2 diabetes mellitus in animal models. Recent reports reveal the mechanisms by which insulin signaling might be targeted by SIRT1.

Extensive reference data sets of pediatric bone density measurements are now available, together with equations to translate BMD into relevant Z-scores and correct for abnormal stature. So now is the right time to ask: are you thinking about bone density in children correctly?

A recent report has identified uroguanylin as an endocrine signal that exerts a physiological role in energy homeostasis, adding another factor to the gut–brain axis. From a clinical point of view, several observations highlight the uroguanylin–guanylyl cyclase C pathway as a potential therapeutic target for the development of antiobesity drugs.

Adipokines are emerging as key molecules linking obesity to breast cancer and are found in the tumor microenvironment. This Review discusses the role of peritumoral stroma, adipose tissue and secreted adipokines in breast cancer biology, focusing on leptin and the crosstalk between leptin and estrogen signaling. Research fromin vitroand animal studies on how leptin is involved in the pathogenesis and progression of breast cancer is discussed, along with the potential future use of leptin and its receptor as therapeutic targets in patients with breast cancer.

Does untreated celiac disease associated with type 1 diabetes mellitus worsen microvascular outcomes? Previous studies have concluded that a gluten-free diet offers no major benefit for glycemic control, whereas Leeds and colleagues provide preliminary data to the contrary. The question awaits a long-term prospective study or a clinical trial.

There is an epidemic of type 2 diabetes mellitus in nearly every nation in the world. This Review gives an overview of the current trends of the diabetes epidemic in a world scenario and discusses the associated major risk factors, particularly genetic and epigenetic factors. The potential impact of the use of HbA_1cas an alternative diagnostic tool on global diabetes surveillance is also discussed.

Dose-response studies with patient-specific outcomes rather than surrogate measures of efficacy are needed to determine the benefits of vitamin D supplementation in the elderly. A novel study from Australia now casts doubt on the usefulness of intermittent, high-dose vitamin D supplementation as a strategy to reduce falls and fractures.

After short introductions into the physiology of aromatase and chemical characteristics of aromatase inhibitors, this Review focuses on the efficacy and safety of aromatase inhibitors in the pediatric population, in particular for the treatment of hyperestrogenism, hyperandrogenism, pubertal gynecomastia, and short stature and/or delayed puberty.

Recent studies suggest previously unrecognized complications of hyponatremia, including falls, osteoporosis and fractures, and show that hyponatremia can have direct effects on bone, mainly via activation of osteoclasts. Here, the emerging relationship between hyponatremia and bone is reviewed, with special emphasis on possible mechanisms, unanswered questions and clinical implications.

This Review discusses the emerging concept that resistance to the metabolic adverse effects of lifestyle factors is mediated by an adaptive response to cellular stress, counteracting mechanisms that otherwise lead to impaired insulin signaling and β cell failure. This response exhibits characteristics of hormesis, originally described in toxicology, whereby exposure of cells, tissues or organisms to low levels of toxin induces resistance to higher toxin concentrations.

Primary aldosteronism is a common, but often overlooked, cause of arterial hypertension. Recent guidelines by the Japanese Endocrine Society should improve detection of this surgically curable disorder, but their endorsement of a 'confirmatory' test in patients with a positive aldosterone-to-renin ratio must be viewed with caution.