Reviews & Analysis

Raised levels of aldosterone, but also concentrations within the normal range are associated with elevated blood pressure. The authors of this Review assess evidence for the role of aldosterone in the development and maintenance of hypertension, including experimental and clinical studies, and discuss the genetic and environmental mechanisms that underlie its effects.

Type 2 diabetes mellitus is a complex disease with a heterogeneous genetic and environmental background. Three relatively infrequent polymorphisms in genes of the insulin signaling pathway modulate the risk of type 2 diabetes mellitus and cardiovascular diseases related to insulin resistance in specific subgroups of individuals. This article discusses the role of these variants and demonstrates how difficult it is to ascertain the contribution of relatively infrequent genetic variants on disease susceptibility.

Amiodarone is widely used for treating cardiac arrhythmias, but is associated with various adverse effects. This Review discusses how the treatment can affect thyroid function, leading to amiodarone-induced hypothyroidism or hyperthyroidism. It compares outcomes with dronedarone, a structurally similar anti-arrhythmic drug that does not contain iodine and may have fewer and less serious adverse effects.

Depression, anxiety and diabetes-specific distress are common and serious comorbid health problems in type 2 diabetes mellitus that often remain unrecognized and thus untreated. Widely used guidelines have therefore recommended assessments of emotional well-being in type 2 diabetes mellitus. The present Review discusses whether there is evidence to support this recommendation.

Multiple sclerosis and type 1 diabetes mellitus are seemingly very different autoimmune diseases. However, this Review discusses recent studies in genetics, epidemiology and immunology that have uncovered many features common to both disorders. Overlaps between T1DM and MS might lead to similar strategies in preventing and treating these debilitating conditions.

Estrogen therapy can reduce cognitive decline in aging women. However, the beneficial effects of estrogen on cognition are apparent only when treatment is initiated around the time of menopause; the same effect is not detected when estrogen therapy is started years later. The 'critical period' hypothesis attempts to explain this discrepancy. Here, Barbara Sherwin reviews studies in which the timing of estrogen therapy was provided and asks whether their findings support the critical period hypothesis.

Regulation of systemic phosphate homeostasis is strictly controlled by a limited number of factors, including FGF23 (a bone-derived protein) and Klotho (a membrane-bound protein). Dysregulation of FGF23 and Klotho is associated with altered phosphate turnover in several acquired and genetic human diseases. The endocrine effects of the FGF23–Klotho axis in normal physiology and disease are described by the author of this Review.

The metabolic syndrome is a complex disorder that consists of an accumulation of visceral fat tissue, dyslipidemia, insulin resistance and hypertension, and can lead to type 2 diabetes mellitus and cardiovascular disease. This article reviews the mechanisms that underlie the metabolic syndrome, focusing on the role of testosterone. The potential of testosterone substitution therapy to treat patients with the metabolic syndrome is also discussed.

The global burden of microvascular disease associated with type 2 diabetes mellitus continues to escalate. Furthermore, conventional standards of care do not completely abolish the risk of diabetic retinopathy, nephropathy or neuropathy in affected individuals. In this Review, the authors highlight the issue of residual microvascular risk and discuss intensive treatment with statins and/or fibrates to target atherogenic dyslipidemia, a potential trigger of the microvascular complications that can develop in patients with type 2 diabetes mellitus.

Biochemical control cannot be achieved by the use of somatostatin analogs alone in a large number of patients with acromegaly. Combination therapy with somatostatin analogs and the growth-hormone-receptor antagonist pegvisomant is, however, highly effective at normalizing levels of insulin-like growth factor I. In this Review, the efficacy and safety of somatostatin analog–pegvisomant combination therapy as a potential tool for the medical management of patients with acromegaly is discussed.

The Diabetes Control and Complications Trial (DCCT) was a landmark study that evaluated intensive versus conventional insulin therapy in patients with type 1 diabetes mellitus; the Epidemiology of Diabetes Interventions and Complications (EDIC) study continues to follow the same cohort of patients. Many of the key contributions that the DCCT and EDIC have made to our understanding of type 1 diabetes mellitus are discussed by the authors of this Review.

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.