Review Articles in 2010

Adipose tissue transplantation is increasingly being explored as a treatment strategy for metabolic disease—to promote the beneficial metabolic effects of subcutaneous white adipose tissue and brown adipose tissue, as well as those of adipose-derived stem cells. This Review summarizes the current available data on the biology of different adipose tissue depots and conceptualizes the future of adipose tissue transplantation and ongoing research.

The secretion of the SPARC protein by adipose tissue has been associated with obesity, insulin resistance and diabetes-related complications. Kos and Wilding discuss the effects of SPARC in the extracellular matrix and its role in subcutaneous adipose tissue fibrosis. They further discuss the effects of leptin, inflammation and hypoxia in the development of SPARC-mediated fibrosis and the possible contributions of this process to the pathology of obesity and obesity-related metabolic complications.

Clinicians and patients with type 1 diabetes mellitus eagerly await the successful use of stem cell-derived β cells in clinical practice. This Review provides a summary of current strategies to obtain cells which express insulin from different progenitor sources and highlights the main pathways and genes involved, as well as the different approaches for the modulation of the immune response in patients with type 1 diabetes mellitus.

Interleukin 1 (IL-1) has important functions in innate and adaptive immunity. Blocking IL-1 action has clinical efficacy in many inflammatory diseases, including type 2 diabetes mellitus. Here, the authors review the mechanisms of IL-1 action that lead to β-cell failure and the rationale for use of IL-1 antagonists in type 1 diabetes mellitus.

Improved hygiene has reduced childhood exposure to environmental microbes, a change that could partly explain the increased incidence of autoimmune diseases, such as type 1 diabetes mellitus, now reported in the developed world. Such exposure to microbes seems to promote development of a healthy immune system; in experimental animal models, administration of microbes or their components can inhibit autoimmune diabetes. This finding raises the possibility of a future vaccine against type 1 diabetes mellitus.

Immune therapies that induce or, in the case of established type 1 diabetes mellitus (T1DM), restore immune tolerance to target autoantigens hold potential to cure T1DM whilst avoiding the need for chronic immunosuppression. This Review discusses different immune therapies for T1DM and, in particular, focuses on two promising strategies in clinical development—the use of candidate autoantigens and anti-CD3 monoclonal antibodies—that aim to restore immune tolerance.

Stereotactic radiosurgery can be performed to control tumor growth and hypersecretion of pituitary tumors, which are the most frequent type of intercranial tumors and lead to high rates of morbidity and mortality. Results of long-term studies of this treatment are discussed in this Review, with recommendations for therapeutic management.

Adipocytes store energy and regulate themselves depending on the environment. Clinical studies suggest that excess macronutrient intake may induce cellular lipid loading and promote signs of inflammatory stress, which ultimately leads to metabolic dysfunction. This Review discusses how lipid mediators may act on important immune receptors to induce low-grade tissue inflammation, which leads to adipocyte and metabolic dysfunction in obesity.

Diabetic angiopathy is among the most serious consequences of diabetes mellitus owing to its impact on quality of life, morbidity, mortality and burden to health-care systems. This Review discusses data that support a role of dysregulation of components of the complement system and the tumor necrosis factor superfamily in the development of diabetic angiopathy.

Mounting evidence suggests that gastrointestinal surgical procedures, such as gastric bypass, can induce long-term remission of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Here, Rubino and colleagues provide an overview of the use of 'metabolic surgery' for patients with T2DM and discuss the implications for future research. The authors hypothesize that the gastrointestinal tract might have a key role in the pathophysiology of T2DM and obesity.

Osteomyelitis is one of the most feared complications of ulcers associated with the foot in diabetes mellitus as it greatly increases the risk of a lower-extremity amputation. As no generally agreed protocol exists, the management of this condition is also one of the most controversial. This Review discusses the available data on surgical versus primarily nonsurgical management of osteomyelitis as a complication of the diabetic foot.

Hereditary hemochromatosis is a genetic condition leading to iron overload that can have detrimental effects on glucose metabolism and other organ systems. This review summarizes the epidemiology of hereditary hemochromatosis and iron overload and discusses possible pathophysiologic mechanisms whereby iron excess can have toxic effects on β cells.