BACKGROUND: Insulin resistance and hyperglycemia characterize type 2 diabetes mellitus. Type 2 diabetes mellitus is usually accompanied by concomitant disorders, such as dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones are antidiabetic drugs that increase insulin sensitivity by activating the peroxisome proliferator-activated receptor gamma. There is evidence that thiazolidinediones exert a number of pleiotropic effects that may play an important role in the treatment of type 2 diabetes mellitus. OBJECTIVE: The purpose of the present article was to review the 'pleiotropic' effects of thiazolidinediones (i.e., their effects beyond glucose lowering). METHODS: The study involved searching PubMed up to February 2008 using relevant keywords. CONCLUSIONS: Thiazolidinediones favorably alter fat distribution and improve cardiovascular risk factors, such as blood pressure, inflammation markers and uric acid and they may also delay the progression of atherosclerosis. The effects on the lipid profile differ between the two thiazolidinediones studied with pioglitazone having more positive effects compared with rosiglitazone. Furthermore, thiazolidinediones improve diabetic complications, such as diabetic nephropathy and non-alcoholic fatty liver disease. Thiazolidinediones may also play a role in other diseases, such as polycystic ovary syndrome. These pleiotropic effects may prove to be clinically relevant. There has been recent debate about the possible differences between the two thiazolidinediones in terms of cardiovascular disease outcome. In this context, differences in the lipid effects between the two drugs may be relevant.
BACKGROUND:Insulin resistance and hyperglycemia characterize type 2 diabetes mellitus. Type 2 diabetes mellitus is usually accompanied by concomitant disorders, such as dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones are antidiabetic drugs that increase insulin sensitivity by activating the peroxisome proliferator-activated receptor gamma. There is evidence that thiazolidinediones exert a number of pleiotropic effects that may play an important role in the treatment of type 2 diabetes mellitus. OBJECTIVE: The purpose of the present article was to review the 'pleiotropic' effects of thiazolidinediones (i.e., their effects beyond glucose lowering). METHODS: The study involved searching PubMed up to February 2008 using relevant keywords. CONCLUSIONS:Thiazolidinediones favorably alter fat distribution and improve cardiovascular risk factors, such as blood pressure, inflammation markers and uric acid and they may also delay the progression of atherosclerosis. The effects on the lipid profile differ between the two thiazolidinediones studied with pioglitazone having more positive effects compared with rosiglitazone. Furthermore, thiazolidinediones improve diabetic complications, such as diabetic nephropathy and non-alcoholic fatty liver disease. Thiazolidinediones may also play a role in other diseases, such as polycystic ovary syndrome. These pleiotropic effects may prove to be clinically relevant. There has been recent debate about the possible differences between the two thiazolidinediones in terms of cardiovascular disease outcome. In this context, differences in the lipid effects between the two drugs may be relevant.
Authors: Anna Köttgen; Eva Albrecht; Alexander Teumer; Veronique Vitart; Jan Krumsiek; Claudia Hundertmark; Giorgio Pistis; Daniela Ruggiero; Conall M O'Seaghdha; Toomas Haller; Qiong Yang; Toshiko Tanaka; Andrew D Johnson; Zoltán Kutalik; Albert V Smith; Julia Shi; Maksim Struchalin; Rita P S Middelberg; Morris J Brown; Angelo L Gaffo; Nicola Pirastu; Guo Li; Caroline Hayward; Tatijana Zemunik; Jennifer Huffman; Loic Yengo; Jing Hua Zhao; Ayse Demirkan; Mary F Feitosa; Xuan Liu; Giovanni Malerba; Lorna M Lopez; Pim van der Harst; Xinzhong Li; Marcus E Kleber; Andrew A Hicks; Ilja M Nolte; Asa Johansson; Federico Murgia; Sarah H Wild; Stephan J L Bakker; John F Peden; Abbas Dehghan; Maristella Steri; Albert Tenesa; Vasiliki Lagou; Perttu Salo; Massimo Mangino; Lynda M Rose; Terho Lehtimäki; Owen M Woodward; Yukinori Okada; Adrienne Tin; Christian Müller; Christopher Oldmeadow; Margus Putku; Darina Czamara; Peter Kraft; Laura Frogheri; Gian Andri Thun; Anne Grotevendt; Gauti Kjartan Gislason; Tamara B Harris; Lenore J Launer; Patrick McArdle; Alan R Shuldiner; Eric Boerwinkle; Josef Coresh; Helena Schmidt; Michael Schallert; Nicholas G Martin; Grant W Montgomery; Michiaki Kubo; Yusuke Nakamura; Toshihiro Tanaka; Patricia B Munroe; Nilesh J Samani; David R Jacobs; Kiang Liu; Pio D'Adamo; Sheila Ulivi; Jerome I Rotter; Bruce M Psaty; Peter Vollenweider; Gerard Waeber; Susan Campbell; Olivier Devuyst; Pau Navarro; Ivana Kolcic; Nicholas Hastie; Beverley Balkau; Philippe Froguel; Tõnu Esko; Andres Salumets; Kay Tee Khaw; Claudia Langenberg; Nicholas J Wareham; Aaron Isaacs; Aldi Kraja; Qunyuan Zhang; Philipp S Wild; Rodney J Scott; Elizabeth G Holliday; Elin Org; Margus Viigimaa; Stefania Bandinelli; Jeffrey E Metter; Antonio Lupo; Elisabetta Trabetti; Rossella Sorice; Angela Döring; Eva Lattka; Konstantin Strauch; Fabian Theis; Melanie Waldenberger; H-Erich Wichmann; Gail Davies; Alan J Gow; Marcel Bruinenberg; Ronald P Stolk; Jaspal S Kooner; Weihua Zhang; Bernhard R Winkelmann; Bernhard O Boehm; Susanne Lucae; Brenda W Penninx; Johannes H Smit; Gary Curhan; Poorva Mudgal; Robert M Plenge; Laura Portas; Ivana Persico; Mirna Kirin; James F Wilson; Irene Mateo Leach; Wiek H van Gilst; Anuj Goel; Halit Ongen; Albert Hofman; Fernando Rivadeneira; Andre G Uitterlinden; Medea Imboden; Arnold von Eckardstein; Francesco Cucca; Ramaiah Nagaraja; Maria Grazia Piras; Matthias Nauck; Claudia Schurmann; Kathrin Budde; Florian Ernst; Susan M Farrington; Evropi Theodoratou; Inga Prokopenko; Michael Stumvoll; Antti Jula; Markus Perola; Veikko Salomaa; So-Youn Shin; Tim D Spector; Cinzia Sala; Paul M Ridker; Mika Kähönen; Jorma Viikari; Christian Hengstenberg; Christopher P Nelson; James F Meschia; Michael A Nalls; Pankaj Sharma; Andrew B Singleton; Naoyuki Kamatani; Tanja Zeller; Michel Burnier; John Attia; Maris Laan; Norman Klopp; Hans L Hillege; Stefan Kloiber; Hyon Choi; Mario Pirastu; Silvia Tore; Nicole M Probst-Hensch; Henry Völzke; Vilmundur Gudnason; Afshin Parsa; Reinhold Schmidt; John B Whitfield; Myriam Fornage; Paolo Gasparini; David S Siscovick; Ozren Polašek; Harry Campbell; Igor Rudan; Nabila Bouatia-Naji; Andres Metspalu; Ruth J F Loos; Cornelia M van Duijn; Ingrid B Borecki; Luigi Ferrucci; Giovanni Gambaro; Ian J Deary; Bruce H R Wolffenbuttel; John C Chambers; Winfried März; Peter P Pramstaller; Harold Snieder; Ulf Gyllensten; Alan F Wright; Gerjan Navis; Hugh Watkins; Jacqueline C M Witteman; Serena Sanna; Sabine Schipf; Malcolm G Dunlop; Anke Tönjes; Samuli Ripatti; Nicole Soranzo; Daniela Toniolo; Daniel I Chasman; Olli Raitakari; W H Linda Kao; Marina Ciullo; Caroline S Fox; Mark Caulfield; Murielle Bochud; Christian Gieger Journal: Nat Genet Date: 2012-12-23 Impact factor: 38.330