Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications.
Type 2 diabetes primarily develops from pathogenic defects in the mechanisms of insulin secretion and hepatic and peripheral insulin action. The consequent disruption of normal glucose metabolism involves a number of organ systems and is ultimately manifested in fasting and daytime hyperglycemia. Chronically elevated blood glucose concentrations determine the progression of the disease by further exacerbating insulin resistance and causing beta-cell exhaustion in addition to decreasing their responsiveness to glucose. The beta-cell secretory dysfunction is characterized by the lack of the early phase of glucose-induced insulin secretion and the insufficient and delayed late phase of secretion. Glycemic levels in patients with type 2 diabetes are directly related to the risk of developing microvascular and macrovascular complications, the main cause of the morbidity and mortality associated with this disease. The goal of treatment is to decrease the risk and delay the progression of these complications by improving glycemic control. Current oral antidiabetic agents, used as monotherapy or in combination, include traditional insulin secretagogues, insulin sensitizers and inhibitors of carbohydrate absorption. A greater understanding of the pathophysiology of type 2 diabetes and recent findings on the significance of meal-related glycemia to overall glycemic control are expanding the therapeutic options for treating this disease.
Porte
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University of California and VA San Diego Healthcare System, 111G, Diabetes and Metabolism Division, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. dporte@ucsd.edu
D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin