Review Articles

Early foundations of the metabolic syndrome may be laid as a consequence of changes in dietary supply to the rapidly growing fetus and/or postnatal offspring. This review highlights fetal developmental plasticity in cellular homeostasis that may manifest in adult life as the metabolic syndrome particularly if followed by a period of accelerated postnatal growth.

This review discusses newly recommended screening approaches for childhood acute malnutrition in low-income settings, using mid-upper arm circumference or weight for height Z-score and inspection for presence of bipedal edema. A treatment algorithm is provided to guide management of children with severe acute malnutrition and systemic complications who require inpatient therapy and for those with uncomplicated severe or moderate acute malnutrition who can be treated in the community using recently developed ready-to-use-therapeutic foods or other appropriately designed food blends.

Congenital adrenal hyperplasia (CAH) is a disorder of cortisol biosynthesis that is usually caused by a mutation in the gene that encodes steroid 21-hydroxylase. As this abnormality can lead to fatal shock, hyponatremia and hyperkalemia in early infancy, many countries include tests for CAH in their neonatal screening program. The author of this article provides an overview of the currently used methodologies for neonatal CAH screening and discusses their efficiency, limitations and cost-effectiveness.

Aromatase deficiency is an extremely rare syndrome that is characterized by congenital estrogen deprivation. Early diagnosis is a key consideration, and estrogen therapy should be initiated as soon after puberty as possible in order to avoid the skeletal complications associated with this disorder. Here, Rochira and Carani review the presentation, diagnosis and treatment of aromatase deficiency in men.

Mutations in a number of genes have been identified in patients as the primary genetic cause of idiopathic hypogonadotropic hypogonadism. These genes encode proteins that regulate gonadotropin-releasing hormone (GnRH) neuron development, migration from the nasal placode to the hypothalamus, GnRH secretion or GnRH action. This Review discusses genes associated with hypogonadotropic disorders and the molecular mechanisms by which mutations in these genes may result in idiopathic hypogonadotropic hypogonadism.

Very little is known about how the changes in body composition that occur around the time of menopause might affect subsequent risk of new-onset diabetes mellitus, as well as the management of pre-existing disease, in postmenopausal women. Here, Emily D. Szmuilowicz and colleagues discuss the potential relationship between menopause, diabetes mellitus and the use of postmenopausal hormone therapy.

The progressive increase in the incidence of both type 1 diabetes mellitus (T1DM) and T2DM, which is associated with changing environmental conditions, highlights overlapping clinical and pathogenetic features of these diabetes stereotypes. The article proposes that the common thread is a proinflammatory environment that activates innate immunological and inflammatory pathways, which lead to β-cell dysfunction in T2DM, insulin resistance in both T1DM and T2DM, and enhanced adaptive immunity that kills β cells in T1DM.

When patients treated with HMG-CoA reductase inhibitors exhibit residual risk—including low levels of high-density lipoprotein cholesterol and elevated triglycerides—adjunctive therapy with a fibric-acid derivative (i.e. fibrate) may be appropriate. However, given the prospect of statin–fibrate-associated myopathy, major factors affecting the question of which fibrate to choose in this setting have not been systematically evaluated. This article discusses available pharmacokinetic, pharmacodynamic, clinical pharmacologic, and postmarketing surveillance issues that may inform such decision making.

Currently, controversy reigns over the effects of different antidiabetic agents on cardiovascular outcomes in type 2 diabetes mellitus (T2DM). This article reviews the findings of recent cardiovascular outcome trials that assessed the safety of various glucose-lowering strategies. Multifactorial interventions to improve glycemic control, hypertension, and dyslipidemia enhance survival and reduce macrovascular events in T2DM. Insulin-sensitization regimens may be preferred in patients with T2DM who have coronary disease.

Although previous studies unequivocally demonstrated that type 2 diabetes mellitus (T2DM) has a strong genetic component, the genes that contribute to the risk of this disease were largely unknown until recently, owing to the complexity of genetic and environmental interactions that are involved in T2DM. Genome-wide association studies, which provide global searches throughout the entire genome, have greatly improved our understanding of the genetic background of diabetes mellitus. Here, the authors discuss the currently available findings of diabetes-related genome-wide association studies and examine the utility of the genetic loci identified in these studies as predictors of T2DM.

Whilst less than 5% of pituitary tumors are familial, identification of familial pituitary tumor syndromes is important owing to the associated pathologies that might occur and the important implications for family members. Advances have been made in our understanding of these syndromes in the past decade and four genes have now been identified as being associated with familial pituitary tumors:MEN1, CDKN1B, PRKAR1A and AIP. This article reviews the current state of knowledge of familial pituitary tumor syndromes.

Noninvasive imaging modalities are increasingly used to study various aspects of diabetes mellitus. The authors of this article focus on the application of MRI, a modality that can provide not only anatomical and functional but also molecular information, for monitoring islet transplantation. Potential causes of islet graft failure, and novel technologies for the simultaneous imaging and delivery of experimental therapies to prevent such failure are also discussed.

The role of sex steroids in the regulation of bone metabolism has been extensively studied in women; however, less is known about their skeletal effects in men. On the basis of associations between serum estradiol levels, bone metabolism and fracture risk in adult men and skeletal symptoms in young men with estrogen resistance or aromatase deficiency, the authors suggest a crucial role for estradiol in regulating skeletal growth and health in men.

An organism's ability to adjust its phenotypic development to the environment is partly determined by epigenetic changes that are established in early life and modulate gene expression during development and maturity. A mismatch between the inducing and the mature environment may result in inappropriate patterns of epigenetic marks and of gene expression that increase the organism's susceptibility to chronic noncommunicable disease. The authors review the relationships between environmental influences during mammalian development, epigenetic changes and metabolic and cardiovascular diseases, and discuss the implications for prevention and treatment.

Physical or emotional effects that potentially threaten homeostasis activate various compensatory mechanisms coordinated by the stress system. This article provides an overview of the conceptual evolution and current understanding of homeostasis and stress, the main effectors and targets of the stress response and the effects of stress on the organism.

Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs, such as octreotide, is a promising option for the treatment of somatostatin-receptor-positive endocrine tumors. Here, van Essen et al. evaluate data from preliminary studies of PRRT, and discuss the pros and cons of this approach. The authors propose that PRRT might soon become the treatment of choice for patients with metastatic or inoperable endocrine tumors.

Nonvasive imaging of insulin-producing β cells, although not currently used in clinical practice, is a useful tool that can complement information gained by other methods to assess the insulin secretory response in patients with diabetes mellitus and in people at high risk of developing this condition. This Review discusses the currently available methods for noninvasive imaging and quantification of insulin-producing β cells.

SIRT1, a mammalian sirtuin that is known to be involved in the regulation of lifespan, DNA damage response and carcinogenesis, is also likely to influence insulin action. Moreover, increasing evidence suggests that decreased SIRT1 expression or activity might contribute to the pathogenesis of insulin-resistance-related diseases. This review explores the effects of SIRT1 on adiponectin and inflammation, the role of SIRT1 in insulin signaling, and the relationship between SIRT1 and mitochondrial function, which is a potential link with insulin resistance.

This article provides an overview of the pathogenesis, diagnosis and management of Graves orbitopathy (GO), an inflammatory eye disease commonly associated with Graves disease. In the past few years, advances have been made regarding both the pathogenesis and the management of this condition, including an improved understanding of the role of TSH receptors and insulin-like growth factor I receptors in the development of GO, the publication of evidence-based guidelines on its diagnosis and management, and promising results from preliminary studies on novel treatment strategies.

Down syndrome can be associated with major impairments in skeletal maturation and bone mass accrual, which increases the risk of fragility fractures. Here, the authors outline various endocrine and metabolic factors that could contribute to suboptimal bone health in children and adolescents with Down syndrome, review indications and limitations of bone density measurement in children and discuss available therapeutic strategies to improve bone health in such patients.