title: Thiazolidinediones may not reduce diabetes incidence in type 1 diabetes.
abstract: Thiazolidinediones improve glycemic control by reducing insulin resistance. Some studies have demonstrated that troglitazone had a preventative effect on diabetes in NOD (non-obese diabetic) mice. One of the mechanisms proposed for the prevention of diabetes by thiazolidinediones is an effect on T-helper 1/T-helper 2 (Th1/Th2) balance. In this article, we attempted to clarify whether pioglitazone is also effective in preventing diabetes as compared to metformin, which has no immunological effect. Female NOD mice were administered pioglitazone or metformin orally, and the insulitis score, cytokines secreted from splenocytes, cytokine expression levels in the pancreas, and the incidence of diabetes after acceleration by cyclophosphamide were analyzed. We could not find any advantage of pioglitazone in preventing Th1 skewing and the development of diabetes over metformin. Therefore, further research should take place before the application of thiazolidinediones to human slowly progressive insulin-dependent diabetes mellitus (SPIDDM) patients.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Shigihara
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okubo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity; D015994:Incidence; D007515:Islets of Langerhans / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D000077205:Pioglitazone; D011897:Random Allocation; D013154:Spleen / Q000166:cytology / Q000276:immunology; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D045162:Thiazolidinediones; D003520:Cyclophosphamide; D008687:Metformin; D000077205:Pioglitazone