Abstract
Our knowledge and understanding of the role played by peroxisome proliferator-activated γ receptors in physiology and pathophysiology has expanded dramatically over the past 5 years. Originally described as having important functions in adipogenesis and glucose homeostasis, their pharmacologic agonists, the thiazolidinediones, were introduced as antihyperglycemic, insulin-sensitizing agents for the management of type 2 diabetes mellitus. However, it was to some degree inevitable that the thiazolidinediones would be rapidly recognized as having vasculoprotective properties beyond glycemic control that might also be beneficial. First, diabetic complications are vascular in nature, the earliest feature of these is endothelial dysfunction. Second, it is being increasingly appreciated that these complications develop through inflammatory and procoagulant pathways in which increased oxidative stress is considered a major etiologic mechanism, and which are closely linked to the presence of insulin resistance, visceral obesity, and hyperglycemia. Early appreciation that the thiazolidinediones have antioxidant, anti-inflammatory, anti-procoagulant, and antiproliferative properties in addition to their insulin-sensitizing, anti-lipotoxic properties created a marriage of investigative pathways that has not only led to a very large body of literature on the pleiotropic effects of thiazolidinediones, but also to the development of new understandings of the connections between insulin resistance, obesity, and hyperglycemia and the onset of vascular disease. Understandably, most of the focus has been directed at the macrovascular complications of diabetes, since these are the major causes of morbidity and mortality in this population. However, there is evidence that these agents may have benefits for the microvascular complications as well, and their potential role for cardiovascular disease prevention in non-diabetic patients with the metabolic syndrome is a logical extension of the work performed in diabetes. The recently reported results of the effects of pioglitazone versus placebo on cardiovascular events in patients with type 2 diabetes support the contention that these agents have vasculoprotective effects.
| Original language | English |
|---|---|
| Pages (from-to) | 25-36 |
| Number of pages | 12 |
| Journal | Treatments in Endocrinology |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 23 2006 |
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ASJC Scopus subject areas
- Endocrinology
Cite this
Thiazolidinediones : Beyond glycemic control. / Reynolds, Kathryn; Goldberg, Ronald B.
In: Treatments in Endocrinology, Vol. 5, No. 1, 23.01.2006, p. 25-36.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thiazolidinediones
T2 - Beyond glycemic control
AU - Reynolds, Kathryn
AU - Goldberg, Ronald B
PY - 2006/1/23
Y1 - 2006/1/23
N2 - Our knowledge and understanding of the role played by peroxisome proliferator-activated γ receptors in physiology and pathophysiology has expanded dramatically over the past 5 years. Originally described as having important functions in adipogenesis and glucose homeostasis, their pharmacologic agonists, the thiazolidinediones, were introduced as antihyperglycemic, insulin-sensitizing agents for the management of type 2 diabetes mellitus. However, it was to some degree inevitable that the thiazolidinediones would be rapidly recognized as having vasculoprotective properties beyond glycemic control that might also be beneficial. First, diabetic complications are vascular in nature, the earliest feature of these is endothelial dysfunction. Second, it is being increasingly appreciated that these complications develop through inflammatory and procoagulant pathways in which increased oxidative stress is considered a major etiologic mechanism, and which are closely linked to the presence of insulin resistance, visceral obesity, and hyperglycemia. Early appreciation that the thiazolidinediones have antioxidant, anti-inflammatory, anti-procoagulant, and antiproliferative properties in addition to their insulin-sensitizing, anti-lipotoxic properties created a marriage of investigative pathways that has not only led to a very large body of literature on the pleiotropic effects of thiazolidinediones, but also to the development of new understandings of the connections between insulin resistance, obesity, and hyperglycemia and the onset of vascular disease. Understandably, most of the focus has been directed at the macrovascular complications of diabetes, since these are the major causes of morbidity and mortality in this population. However, there is evidence that these agents may have benefits for the microvascular complications as well, and their potential role for cardiovascular disease prevention in non-diabetic patients with the metabolic syndrome is a logical extension of the work performed in diabetes. The recently reported results of the effects of pioglitazone versus placebo on cardiovascular events in patients with type 2 diabetes support the contention that these agents have vasculoprotective effects.
AB - Our knowledge and understanding of the role played by peroxisome proliferator-activated γ receptors in physiology and pathophysiology has expanded dramatically over the past 5 years. Originally described as having important functions in adipogenesis and glucose homeostasis, their pharmacologic agonists, the thiazolidinediones, were introduced as antihyperglycemic, insulin-sensitizing agents for the management of type 2 diabetes mellitus. However, it was to some degree inevitable that the thiazolidinediones would be rapidly recognized as having vasculoprotective properties beyond glycemic control that might also be beneficial. First, diabetic complications are vascular in nature, the earliest feature of these is endothelial dysfunction. Second, it is being increasingly appreciated that these complications develop through inflammatory and procoagulant pathways in which increased oxidative stress is considered a major etiologic mechanism, and which are closely linked to the presence of insulin resistance, visceral obesity, and hyperglycemia. Early appreciation that the thiazolidinediones have antioxidant, anti-inflammatory, anti-procoagulant, and antiproliferative properties in addition to their insulin-sensitizing, anti-lipotoxic properties created a marriage of investigative pathways that has not only led to a very large body of literature on the pleiotropic effects of thiazolidinediones, but also to the development of new understandings of the connections between insulin resistance, obesity, and hyperglycemia and the onset of vascular disease. Understandably, most of the focus has been directed at the macrovascular complications of diabetes, since these are the major causes of morbidity and mortality in this population. However, there is evidence that these agents may have benefits for the microvascular complications as well, and their potential role for cardiovascular disease prevention in non-diabetic patients with the metabolic syndrome is a logical extension of the work performed in diabetes. The recently reported results of the effects of pioglitazone versus placebo on cardiovascular events in patients with type 2 diabetes support the contention that these agents have vasculoprotective effects.
UR - http://www.scopus.com/inward/record.url?scp=30744471644&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30744471644&partnerID=8YFLogxK
U2 - 10.2165/00024677-200605010-00004
DO - 10.2165/00024677-200605010-00004
M3 - Article
C2 - 16396516
AN - SCOPUS:30744471644
VL - 5
SP - 25
EP - 36
JO - Treatments in Endocrinology
JF - Treatments in Endocrinology
SN - 1175-6349
IS - 1
ER -