Several large-scale prospective studies have convincingly demonstrated that the microvascular complications, and the associated morbidity and mortality, from diabetes are attenuated by strict glycemic control. For patients with type 1 diabetes, insulin replacement therapy is the mainstay of treatment, while nonpharmacologic approaches such as dietary restrictions and exercise (which improves insulin sensitivity) are often the “first line of defense” for type 2 diabetes. Most patients with type 2 diabetes eventually require therapeutic intervention to reduce hyperglycemia. Glycemic control is assessed clinically by measuring the percentage of glycosylated hemoglobin, also known as HbA1C, which is formed by nonenzymatic addition of glucose moieties to hemoglobin in red cells. Unlike blood glucose levels, HbA1C is a measure of glycemic control over long periods of time (2–3 months) and is relatively unaffected by day-to-day variations. The ADA recommends maintenance of HbA1C levels at less than 7% to reduce the risk for long-term complications. In addition, diabetics need to maintain LDL and HDL cholesterol and triglycerides at optimal levels to reduce the risk for macrovascular complications. The adoption of a healthy and active lifestyle remains one of the best defenses against this modern day scourge.
Type1diabetesisanautoimmunediseasecharacterizedbyprogressivedestructionofisletbetacells,leadingtoabsoluteinsulindeficiency.BothautoreactiveTcellsandautoantibodiesareinvolved.
Type2diabetesiscausedbyinsulinresistanceandbetacelldysfunction,resultinginrelativeinsulindeficiency.Autoimmunityisnotinvolved.
Obesityhasanimportantrelationshipwithinsulinresistance(andhencetype2diabetes),mediatedbyvariousfactors,includingexcessfreefattyacids,aberrantlevelsofadipokines,andanalteredinflammatorymilieuwithinadiposetissue.
Monogenicformsofdiabetesareuncommonandarecausedbysingle-genedefectsthatresultinprimarybetacelldysfunctionorleadtoabnormalitiesofinsulin–insulinreceptorsignaling.
Thelong-termcomplicationsofdiabetesaresimilarinalltypesandaffectmainlybloodvessels,andthekidneys,nerves,andeyes.Thedevelopmentofthesecomplicationsisattributedtothreeunderlyingmechanisms:formationofAGEs,activationofPKC,anddisturbancesinpolyolpathwaysleadingtooxidativestress.
http://ebooksmedicine.net
Pancreatic neuroendocrine tumors (PanNETs), also known as islet cell tumors, are rare in comparison with tumors of the exocrine pancreas, accounting for only 2% of all pancreatic neoplasms. PanNETs are most common in adults and may be single or multifocal; when they are malignant, the liver is the most common site of metastases. These tumors have a propensity to elaborate pancreatic hormones, but some are nonfunctional. The latter typically are larger at the time of diagnosis, since they come to clinical attention later in their natural history than functional PanNETs, which often present with symptoms related to excessive hormone production. All PanNETs, with the exception of insulinomas (see later), are regarded as having malignant potential, and in fact, 60% to 90% of PanNETs manifest with overtly malignant features of biologic aggressiveness, such as invasion into local tissues or distant metastases. The tumors frequently have mutations in tumor suppressor genes MEN1 and PTEN, or inactivating mutations in genes (e.g. ATRX) whose products maintain telomere length.