Review Articles in 2010

Patients with phenylketonuria develop almost normally if diagnosed neonatally and treated by diet; however, executive dysfunction remains. This Review discusses the disorder's diagnosis, the outcome of traditional treatment by dietary restriction and outlines new treatment possibilities, including tetrahydrobiopterin and other chaperone proteins, enzymatic treatment, large neutral amino acid supplementation and possibly gene therapy.

Obesity is affecting an increasing proportion of children globally. A multifactorial approach to encouraging young people to be physically active is urgently needed to counteract the obesity epidemic. This Review describes the context of the relationship between obesity and physical inactivity in children, and provides suggestions for a way forward.

A comprehensive program of lifestyle modification, comprised of diet, physical activity and behavior therapy, is the cornerstone of treatment for individuals with overweight or obesity. This article reviews options for lifestyle modification and pharmacotherapy for obesity and concludes with an examination of genes that contribute to obesity, which may yield new targets for pharmacologic intervention and ultimately gene therapy.

Systemic medications that target glycemic control and coexisting conditions in diabetes mellitus can have beneficial or deleterious effects on the onset or progression of diabetic retinopathy. This article reviews current knowledge of the ocular-specific effects of systemic medications commonly used by patients with diabetes mellitus, including those directed at control of hyperglycemia, dyslipidemia, hypertension, cardiac disease, anemia, inflammation and cancer.

This Review addresses the relative roles of growth hormone and IGF 1 in mediating their biological effects, as well as the clinical outcome of inappropriate growth hormone signaling. Furthermore, it summarizes novel information provided by transgenic mouse models and mutagenesis studies on the roles and mechanisms of activation of the growth hormone receptor in the context of related class 1 cytokine receptors.

The development of molecular breast cancer therapies in the past few decades has considerably improved treatment of the disease. This Review chronicles these advances and discusses future treatment targets, namely steroid sulfatase and 17β-hydroxysteroid dehydrogenase type 1 (in estrogen-dependent breast cancers), and treatment strategies, including combinatory therapies and the use of techniques such as RNA silencing and functional genomics.

A local autocrine axis exists in the testes that regulates spermatogenesis. In this Review, Cheng and Mruk review findings from the past decade that support the presence and reveal the importance of this axis, which is an emerging target for male contraceptive development.

Graves disease, toxic adenoma and toxic multinodular goiter differ in their clinical presentation and cardiovascular implications. In this Review, establishing the etiology of hyperthyroidism is highlighted as a prerequisite for correct treatment of both the disease and the associated cardiovascular complications.

The gastrointestinal tract is an important source of endocrine signals. Gut hormones such as glucagon-like peptide 1, peptide YY, and islet amyloid polypeptide act in an integrated fashion to modulate appetite and energy expenditure. This Review addresses the physiological roles of gut hormones and discusses their potential as targets for the development of novel treatments for obesity, on the basis of pharmacological mimicry of the hormonal milieu after bariatric surgery.

Peroxisome proliferator-activated receptor α (PPARα) activation attenuates or inhibits several mediators of vascular damage, which indicates that PPARα could potentially be targeted by therapies to prevent microvascular disease in patients with diabetes. This Review focuses on the role of PPARα activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPARα agonists.

Falls and fall-related injuries, such as fractures, are often the cause of pain, functional impairments, reduced quality of life and excess health-care costs and mortality among older adults. This Review focuses on evidence-based physical therapy approaches for the prevention of falls and fractures, including exercise, vibration training and improvement of safety at home and during periods of mobility, and highlights the benefits of multifaceted intervention strategies.

With the increase in life expectancy of patients with cystic fibrosis, so has the prevalence of cystic fibrosis-related diabetes mellitus risen in the past decades. The authors of this Review address cystic fibrosis-specific diagnostic approaches and stress the need for a strong evidence base to guide the management of patients with cystic fibrosis-related diabetes mellitus and its complications.

An increased incidence of malformations of the genital tract, and neoplasms of the testis, uterus, and breast has been observed during the past half century following the introduction of endocrine disrupting chemicals into the environment. This Review discusses the theoretical underpinnings and corresponding evidence connecting development and carcinogenesis. The data gathered thus far linking exposure to these chemicals to cancer warrant action to protect public health.

Pregnancy is an immunological balancing act in which major changes in the mother's immune system occur that prevent rejection of the fetus that bears paternal antigens. This Review discusses the immunological mechanisms involved in such tolerance of the fetus, and highlights how these mechanisms may explain the clinical changes in autoimmune thyroid disease during and after pregnancy.

The six major apolipoprotein B (apoB) dyslipoproteinemias can be specifically identified according to a diagnostic algorithm based on levels of total cholesterol, triglycerides and apoB. The authors of this Review delineate the characteristic apoB phenotype of the major apoB dyslipoproteinemias and their underlying pathophysiology and provide a treatment plan which aims at a reduction of atherogenic apoB particles—in particular, remnants and LDL particles—rather than plasma lipid levels.

Insulin replacement therapy in type 1 diabetes mellitus (T1DM) leads to peripheral hyperinsulinemia, which is associated with potentially serious metabolic complications, such as increased hypoglycemia, weight gain and postprandial hyperglucagonemia. This Review discusses adjunctive therapies to minimize these complications in patients with T1DM, with a focus on the islet amyloid polypeptide analog pramlintide.

Several independent studies have shown the presence of functional brown adipose tissue in adult humans. Its innate ability to expend energy via heat production is a feature that could be used to develop new regimens to treat obesity and type 2 diabetes mellitus. This Review outlines the current knowledge on the transcriptional regulation and development of brown adipose tissue and addresses possible targets that may be useful for the expansion and/or activation of brown adipose tissue by pharmacological means.

Enteroviruses are believed to contribute to the pathogenesis of type 1 diabetes mellitus. This Review discusses the interplay between infection with enteroviruses, the immune system and host genes, as an improved knowledge of the mechanisms involved could uncover preventive strategies for type 1 diabetes mellitus.

The autoimmune polyglandular syndromes (APS), a combination of endocrine and nonendocrine autoimmune diseases, differ in their component diseases and in the immunologic features of their pathogenesis. This Review discusses the genetic basis of the three main syndromes—APS-1, APS-2 and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) syndrome—with an emphasis on the mechanisms of autoimmunity, and presents currently available treatment strategies for their underlying autoimmune disorders.

Antiobesity drugs are chosen for their ability to suppress food intake or body weight, with little regard for the psychological factors that influence consumption and weight gain. This Review argues that selective pharmacological targeting of specific emotional and motivational processes that govern appetite and eating may improve outcomes for weight reduction and improved self-control over consumption.