Reviews & Analysis

This Review focuses on new findings regarding the role of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue and skeletal metabolism and summarizes the emerging role of PPARγ as an integral part of a complex circadian regulatory system that modulates food storage, energy consumption and skeletal metabolism.

Combination therapy with vitamins B₆, B₉ and B₁₂ is a therapeutic intervention to decrease levels of plasma homocysteine and the risk of cardiovascular disease. However, a recent trial found that cosupplementation with these vitamins exacerbated the decline in renal function and increased the risk of vascular disease in patients with diabetic nephropathy. Confidence in this high-dose vitamin supplement is shaken.

Case reports published over 100 years ago suggested that high-dose sodium salicylate could reduce the symptoms of type 2 diabetes mellitus, but adverse affects precluded clinical use. Now, results from the TINSAL-T2D study that used salsalate, a salicylate prodrug, provide renewed hope for NSAID treatment of type 2 diabetes mellitus.

Lowering blood pressure to normal levels, below those currently recommended, does not reduce the risk of cardiovascular disease events in patients with type 2 diabetes mellitus. Nor does treating dyslipidemia with fibrate and statin combination therapy reduce the risk of cardiovascular disease events more than treatment with statin alone.

A new study shows that serum vitamin D concentration is inversely associated with HbA_1c levels among adults in the US aged 35–74 years, in line with results from other observational studies. Should adults with diabetes mellitus or at risk of developing this disease take vitamin D to improve glycemia or reduce this risk?

Developments in treatment modalities and assays over the past 10 years warranted a new consensus on the criteria for cure of acromegaly, which was reached at a meeting of the Acromegaly Consensus Group, in April 2009. The novel consensus statement highlights current analytical pitfalls and the need to optimize disease control in acromegaly.

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.

Microvascular complications in diabetes mellitus are driven by chronic hyperglycemia. Their correlation with HbA_1c levels is considered useful; however, unlike the direct information provided by glucose, HbA_1c values reflect glycemic and nonglycemic factors. The author of this Perspective delineates the prominent roles of genetic and ethnic factors in determining HbA_1c variance and questions the usefulness of HbA_1clevels as a diagnostic tool for diabetes mellitus and prediabetes.

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.

A review of amputation rates in England documents that in patients without diabetes mellitus amputation rates seem to be falling, but not in patients with diabetes mellitus. The burden of foot disease in patients with diabetes mellitus is rising but evidence suggests this increase might be masking improvements in the quality of its management.

Appropriate diagnosis and clinical management of patients with acute suppurative thyroiditis, an endocrine emergency, presents a major challenge, with no consensus guidelines currently available. Could the novel algorithm proposed by John Paes and colleagues provide a solution?

To successfully tailor glycemic therapies to each patient with type 2 diabetes mellitus, the heterogeneity of the clinical features, pathogenesis and causative genetic factors of this disorder must be considered. A new study has summarized the potential of individualized treatment for type 2 diabetes mellitus on the basis of phenotypes and genotypes.

A recent article by Bushnell et al. confirms and reassures what neuroendocrine tumor specialists have witnessed and believed for some time: radionuclide therapy using somatostatin analogs labeled with radioactive yttrium-90 alleviates symptoms of metastatic neuroendocrine tumors, reduces or stabilizes tumor burden and improves quality of life.

Evidence indicates that flutamide, a specific and potent androgen-receptor blocker, when given in low dose (∼1 mg/kg daily), confers a first-choice balance between antiandrogenic efficacy and hepatic safety for women and adolescent girls with hirsutism or other androgen-related symptoms.

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.

The contribution of secondary causes to low bone mass in postmenopausal women with osteoporosis is unknown. A study by Cerdá Gabaroi et al. aimed to fill this gap. While the researchers found a high prevalence of secondary causes, the importance of clinical risk factors should not be underestimated in the primary care setting.

To address concerns about the long-term safety of using dopamine agonists to treat patients with hyperprolactinemia Valassi and colleagues carried out a systematic review of the literature. Although the results show no increased risk of valvular heart disease, lengthy prospective follow-up studies are needed in patients requiring long-term high dose regimens.