Pathophysiology of type 2 diabetes: rationale for different oral antidiabetic treatment strategies.
Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Both insulin resistance and beta-cell failure are genetically determined to some extent; however, environmental factors contribute to exacerbate both abnormalities. Type 2 diabetic individuals are also characterised by reduced beta-cell mass likely due to increased cellular apoptosis. The early use of insulin therapy in type 2 diabetes may prove beneficial to prevent further beta-cell loss and need for exogenous insulin. Treatment options with oral agents are quite diverse, including insulin sensitizers, alpha-glucosidase inhibitors, and beta-cell secretagogues. Although in recent years the emphasis on initial therapy has been shifting from insulin secretagogues to insulin sensitizers such as metformin and thiazolidinediones, questions remain as to genetic and/or phenotypic factors may dictate a different choice of the first antidiabetic drug to be used. It is not totally clear whether monotherapy should be pursued until the maximally effective dose of a given drug or combination therapy should be used to target distinct pathogenic defects in a single patient. Individual phenotypic and genetic characterisation of the patients may help to solve this conundrum, eventually providing tailored treatment algorithms.
Giorgino
Francesco
F
Dipartimento dell'Emergenza e dei Trapianti di Organi - Sezione di Medicina Interna, Endocrinologia e Malattie Metaboliche, Università degli Studi di Bari, Piazza Giulio Cesare 11, I-70124 Bari, Italy. f.giorgino@endo.uniba.it
Laviola
Luigi
L
Leonardini
Anna
A
D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014280:Triglycerides; D005934:Glucagon