Prevention of type 2 diabetes: insulin resistance and beta-cell function.
Type 2 diabetes is increasing worldwide in epidemic proportions. Its associated morbidity and mortality is imposing a major burden on the health care system. Based on a better understanding of the pathophysiology of glucose intolerance, clinical trials on the prevention of diabetes have been performed. It has now been demonstrated that diet and exercise, metformin, acarbose, and troglitazone can prevent or at least delay the development of diabetes in subjects with impaired glucose tolerance (IGT). It is now generally accepted that insulin resistance and beta-cell dysfunction are major factors involved in the development of diabetes. The relative contribution of insulin resistance versus beta-cell dysfunction on the pathogenesis of diabetes has aroused much debate. These two processes should be studied in relation to one another: their relationship is best described as hyperbolic in nature. When this relationship is taken into consideration, it becomes evident that subjects at risk of developing type 2 diabetes have beta-cell dysfunction before they develop glucose intolerance. Insulin resistance may be mostly explained by the presence of obesity and accelerate the progression to diabetes in subjects with the propensity to beta-cell failure. By the time hyperglycemia occurs, impairment in both insulin sensitivity and insulin secretion are present. There are still few data on insulin sensitivity and insulin secretion from the trials on the prevention of diabetes. The few data that we do have suggest that most interventions mostly have an effect on insulin resistance. By reducing insulin resistance, they protect and preserve the beta-cell function. No intervention has yet shown any direct effect on beta-cell function.
Chiasson
J-L
JL
Research Centre-CHUM-Hôtel-Dieu, 3850 St. Urbain St., Rm. 8-202, Montreal (Quebec) H2W 1T7, Canada. jean.louis.chiasson@umontreal.ca
Rabasa-Lhoret
Rémi
R
D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000517:prevention & control*; D018149:Glucose Intolerance / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*
D007328:Insulin