[The glitazones].
BACKGROUND
Type 2 diabetes mellitus is one of the biggest public health problem, responsible of major complications. The treatment of hyperglycaemia has been based on lifestyle changes, diet and physical exercise, and oral antidiabetic drugs for reducing the microangiopathic complications and the high cardiovascular risk of these patients. For decades we used sulfonylureas, metformin and alpha glucosidases inhibitors. However these drugs have no effect on muscle insulin resistance, high levels of free fatty acids, lipotoxicity and progressive pancreatic beta-cell loss.


METHODS
Thiazolidine-diones or glitazones are the pharmacological ligands of peroxisome proliferator activated receptor gamma mainly expressed in the white adipose tissue. New adipocytes are recruited with, finally, a decrease of free fatty acids, of some cytokines, of muscle and liver insulin resistance. The hypoglycaemic effect is moderate but more pronounced in association with other oral antidiabetic drugs. Long-term studies will possibly confirm the beneficial effects on the beta-cell loss and some cardiovascular parameters in type 2 diabetes and the metabolic syndrome.


CONCLUSIONS
Glitazones enrich the treatment of type 2 diabetes allowing new and synergistic combinations for more precocious and efficient strategies. Moreover their action on peroxisome proliferator activated receptor opens on new therapeutics for cancer, immunology, rheumatology, and infection.
Halimi
S
S
Département d'urologie, néphrologie et endocrinologie, UF diabétologie 11 A, centre hospitalier universitaire de Grenoble, BP 217, 38043 Grenoble cedex 09, France. shalimi@chu-grenoble.fr <shalimi@chu-grenoble.fr>
D017667:Adipocytes / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000209:etiology; D007333:Insulin Resistance; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
D016207:Cytokines; D045162:Thiazolidinediones