title: Addressing the insulin secretion defect: a logical first-line approach.
abstract: The pathogenesis of type 2 diabetes has been an area of intense investigation, considerable controversy, and continuing discovery. It is now clear that this is a heterogeneous condition both phenotypically and genotypically, and that acquired reversible abnormalities/risk factors also play an important role. Currently, type 2 diabetes can be viewed as developing in genetically susceptible individuals, who, because of impaired beta-cell function, are incapable of increasing their insulin release appropriately to compensate for reduced insulin sensitivity which is acquired through life for various reasons (eg, obesity, aging, physical inactivity, drug use, or diet). As our knowledge of the interplay of these elements increases, there will be important consequences regarding the choice of the most appropriate therapeutic approach for individual patients. This review will analyze issues pertaining to the interaction of reduced insulin sensitivity and impaired beta-cell function in type 2 diabetes, specifically: which is the primary genetic factor, which is more important in determining hyperglycemia, what is the most important site affected by impaired beta-cell function and insulin sensitivity, and which, if any, should be the preferential target for therapeutic intervention.
authors.affiliation: Department of Medicine, University of Rochester, NY, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Gerich
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds