title: Evaluating the cardiovascular effects of the thiazolidinediones and their place in the management of type 2 diabetes in relation to the metabolic syndrome.
abstract: BACKGROUND
  The aim of this work was to review evidence on the contribution of the metabolic syndrome to diabetes and atherosclerosis, to evaluate the effects of the thiazolidinediones (TZDs) on cardiovascular risk, and to assess the clinical use of TZDs and their associated risks and benefits.
  
  
  METHODS
  Participants were a multidisciplinary panel of experts in endocrinology, cardiology, and nephrology. Available studies on hyperglycemia, hyperinsulinemia, beta-cell function, dyslipidemia, obesity, hypertension, inflammation, endothelial dysfunction, and vascular reactivity were reviewed through presentations by the experts. Assessments were made regarding the associations between characteristics of the metabolic syndrome, type 2 diabetes, and cardiovascular disease, along with the place of TZDs in therapy and management of related adverse clinical events. A panel was convened in November 2002 to develop conclusions based on scientific evidence presented during the meeting. Summary statements were evaluated based on strength and clinical relevance of the data and approved by all panel members.
  
  
  CONCLUSIONS
  Many characteristics of the metabolic syndrome are present before diabetes develops that greatly contribute to the cardiovascular disease burden associated with the progression of diabetes, such as atherosclerosis and coronary artery disease. Insulin resistance is a fundamental component of the metabolic syndrome, and interventions to improve insulin sensitivity are associated with positive cardiovascular effects. From current experimental and clinical data, TZDs appear to reduce risk factors for future cardiovascular events in patients with type 2 diabetes. Study data up to 2 years have demonstrated that TZDs effectively maintain glycemic control in patients with type 2 diabetes, which is attributed to their insulin-sensitizing effects and preservation of beta-cell function. Potential adverse events of TZDs include weight gain and edema, which are generally manageable. Aside from improving insulin sensitivity, TZDs improve lipid profiles, favorably alter deposition of adipose tissue to the periphery rather than visceral areas, decrease markers of inflammation and endothelial dysfunction, and restore vascular reactivity. These pleiotropic effects have the potential to improve cardiovascular outcomes in patients with type 2 diabetes. Trials are underway to confirm this potentially beneficial addition to proven therapies for hypertension, dyslipidemia, and atherosclerosis.
authors: Clinical Associate Professor of Medicine, New York University School of Medicine, New York University, New York, New York.
authors: Andrew J
authors: AJ
authors: Drexler
authors: Richard W
authors: RW
authors: Nesto
authors: Martin J
authors: MJ
authors: Abrahamson
authors: George
authors: G
authors: Bakris
authors: David
authors: D
authors: Bell
authors: John
authors: J
authors: Brunzell
authors: Paresh
authors: P
authors: Dandona
authors: Jaime
authors: J
authors: Davidson
authors: Vivian
authors: V
authors: Fonseca
authors: Michael
authors: M
authors: Fowler
authors: Robert
authors: R
authors: Frye
authors: Thomas
authors: T
authors: Giles
authors: Steven
authors: S
authors: Haffner
authors: Norman
authors: N
authors: Hollenberg
authors: Willa
authors: W
authors: Hsueh
authors: Ronald
authors: R
authors: Law
authors: Jorge
authors: J
authors: Plutzky
authors: Robert
authors: R
authors: Ratner
authors: Jane
authors: J
authors: Reusch
authors: Andrew
authors: A
authors: Selwyn
authors: James
authors: J
authors: Sowers
authors: Kathleen
authors: K
authors: Wyne
authors: Lawrence H
authors: LH
authors: Young