Insulin resistance and obesity affect monocyte-derived dendritic cell phenotype and function.

AIM: Cardiovascular disease (CVD) is prevalent in women after menopause, which may be associated with obesity, insulin resistance and metaflammation. Despite the recognized role of immunological mechanisms in vascular remodeling, the role of dendritic cells (DCs) is still unclear. The aim was to characterize monocyte-derived DCs (Mo-DC) in post-menopausal patients with type 2 diabetes (T2DM) and obese woman, without clinical manifestations of atherosclerosis. METHODS: Obese post-menopausal women with or without T2DM were enrolled and were compared to age-matched healthy women. DCs obtained from patients were phenotypically and functionally characterized by flow cytometry and mixed lymphocyte reaction. MRNA integrins expression was assessed by real time RT-PCR; circulating fetuin-A and adiponectin levels were measured by ELISA. RESULTS: Phenotypic dysregulation of Mo-DC reported was related to a defective allogenic lymphocyte stimulation and to an increased mRNA of CD11c, CD18 and DC-SIGN/CD209 which regulate their adhesion to vascular wall cells. Fetuin-A and adiponectin levels were significantly altered and negatively correlated. Hyperglycaemia significantly impaired CD14+ transdifferentiation into Mo-DC. CONCLUSIONS: These data show a dysfunction of Mo-DCs obtained from precursors isolated from T2DM obese post-menopausal woman without any documented clinical CV event. Association of obesity to diabetes seems to worsen DC's phenotype and function and increase vascular inflammation.

Role of insulin in the type 2 diabetes therapy: past, present and future.

CONTEXT: Since 2006 a relevant number of therapeutical algorithms for the management of type 2 diabetes have been proposed, generating a lively debate in the scientific community, particularly on the ideal timing for introduction of insulin therapy and on which drug should be preferred as add-on therapy in patients failing to metformin. At the moment, there is no real consensus. The aim of the present review is to summarize established knowledge and areas for debate with respect to insulin therapy in type 2 diabetes. EVIDENCE ACQUISITION: In type 2 diabetic patients, insulin represents a therapy with a long and well-established history, but, considering the modern insulin therapy, several points must be carefully examined. The role played by the introduction of insulin analogues, the choice of insulin regimens, the ongoing debate on insulin and cancer, the cardiovascular effects of insulin, the role of insulin on ß-cell protection and the actual clinical perspective in the treatment of the disease. Nevertheless, still many exciting expectations exist: the new insulin analogues, the technological options, the inhaled and oral insulin and the issue of transplantation. CONCLUSIONS: Although insulin is the more potent hypoglicemic agent, the availability of a wider spectrum of therapeutic agents, many of which are better tolerated than insulin, has reduced the field of application for insulin treatment; presently, insulin is used only in those who cannot maintain an adequate glycemic control with other drugs. Furthermore, a lively research activity is currently ongoing, in order to make insulin therapy even safer and simpler for patients.