Reviews & Analysis

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.

Until recently, weight loss has been viewed as the principal determinant of success in obesity reduction. This Review details a growing body of evidence that links adoption of a healthy lifestyle (but minimal or no weight loss) with appreciable reductions in obesity, in particular abdominal obesity, and related cardiometabolic risk.

Glucose control does not have a clear cardiovascular benefit in people with established, long-duration diabetes mellitus; however, it reduces the risk of diabetes-related eye disease and kidney disease, myocardial infarction and mortality in those with recent-onset diabetes mellitus. Here, the author discusses the relationship between blood glucose level and cardiovascular disease and compares the cardiovascular effects of various glucose-lowering drugs and strategies.

Sleep curtailment, which has become a common behavior in modern society, and sleep disorders, such as obstructive sleep apnea, might have detrimental effects on endocrine functions and glucose metabolism. This review discusses the role of sleep loss and poor-quality sleep in the development of obesity and diabetes mellitus, and highlights the importance of screening for sleep problems in patients with endocrine and metabolic disorders.

Carcinoid tumors are characterized by their ability to secrete hormones, such as serotonin, tachykinins and other mediators that might contribute to carcinoid syndrome. The authors of this Review describe the incidence and prevalence of carcinoid tumor related fibrosis, which is a major complication of this syndrome, and explore the role of potential causative agents.

Incretin-based drugs have several advantages over commonly used antidiabetic agents, including a glucose-dependent mechanism of action and no risk of weight gain. However, their long-term efficacy, safety and durability are yet to be established. This Review summarizes the available data on the mechanisms of action of currently used and emerging incretin-based agents.

Obesity is associated with a systemic, chronic, inflammatory response that involves the production of various cytokines, such as tumor necrosis factor and interleukins. Several interleukins, in particular IL-6 and IL-1, have been suggested to contribute to the development of insulin resistance and type 2 diabetes mellitus, by acting both on insulin signaling pathways and on pancreatic beta and alpha cells. This article provides insights into the latest findings regarding the role of these interleukins in the pathology and physiology of obesity-related insulin resistance and type 2 diabetes mellitus.

Trans fatty acids, which are largely consumed from partially hydrogenated vegetable oils, adversely affect circulating lipid and lipoprotein levels and endothelial function, trigger systemic inflammation, and might increase visceral adiposity, body weight, and insulin resistance. The authors provide an overview of these adverse effects and their relationships with clinical endpoints, with a focus on potential effects on insulin resistance and diabetes.

Chronic hyperglycemia in diabetes mellitus can lead to erythropoietic stress and subsequent anemia, which might contribute to diabetes-related complications. The authors of this Review discuss the various causes of diabetes-related anemia and current guidelines on its correction, and emphasize the role of screening and monitoring for this preventable condition in patients with diabetes mellitus.

Innate immunity and inflammatory mediators have been suggested to have a much broader role in type 1 diabetes mellitus than initially assumed. Inflammation might contribute to early induction and amplification of the immune assault against pancreatic β-cells and, at later stages, to the stabilization and maintenance of insulitis. This review summarizes the latest findings that demonstrate the role of inflammation in the different phases of the course of type 1 diabetes mellitus.