Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00361023
Status:
COMPLETED
Last Update Posted:
2006-08-07
First Post:
2006-08-01
Brief Title:
Effects of Losartan on Insulin Sensitivity and Secretion in Type 2 Diabetes and Nephropathy
Sponsor:
Shanghai Jiao Tong University School of Medicine
Organization:
Shanghai Jiao Tong University School of Medicine
Study Overview
Official Title:
Effects of Angiotensin Type 1 Receptor Blockade With Losartan on Insulin Sensitivity and Secretion in Subjects With Type 2 Diabetes and Nephropathy
Status:
COMPLETED
Status Verified Date:
2006-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Angiotensin type-1 receptor AT1R blockers ARBs have been recognized recently as regulators of glucose and lipid metabolism in adipocytes and adipose tissueMoreover telmisartan and irbesartan have been recognized recently as regulators of glucose metabolism For ARB losartan the results were controversial To confirm its effect on glucose metabolism we designed and performed a prospective randomized and controlled study in subjects with type 2 diabetes and nephropathy
Detailed Description:
Angiotensin II AngII the main effector peptide of the rennin-angiotensin system RAS is implicated in the development of vascular cardiac and renal pathologies Several lines of evidence have suggested that AngII can impair insulin sensitivityAngiotensin type-1 receptor AT1R blockers ARBs have been recognized recently as regulators of glucose and lipid metabolism in adipocytes and adipose tissue Recent clinical trials suggest that blockade of the RAS either by inhibiting the angiotensin-converting enzyme ACE or by blocking AT1R may substantially lower the risk for type 2 diabetes In the Heart Outcomes Prevention Evaluation HOPE trial there was 34 reduction in relative risk for the development of type 2 diabetes Similarly in the Intervention For Endpoint Reduction in Hypertension study LIFE the incidence of type 2 diabetes was reduced by 25 in the losartan group compared with other antihypertensive therapies Previous study demonstrated that AT1R blockade improved insulin sensitivity in animal models of insulin resistance The underlying mechanism of the insulin sensitizing and anti-diabetic effect of ARBs is incompletely clear
The nuclear hormone receptor peroxisome proliferator activated receptor- PPAR-γ plays an important role in the regulation of insulin sensitivity Several studies have shown the ARBs telmisartan and irbesartan potently induces PPAR-γ activity promoting PPAR-γ-dependent differentiation in adipocytes However not all ARBs own PPAR-γ activating properties In vitro studies have shown that significant differences among PPAR-γ activating ARBs are likely caused by their physicochemical properties and high lipophilicity is required to obtain sufficiently high penetration rates to bind to intracellular PPAR-γ Losartan at high concentrations could activate PPAR-γ and behaved like partial PPAR-γ agonists Nevertheless the results of losartan on insulin sensitivity remain controversial
To elucidate the underlying effects of losartan on insulin sensitivity we investigated the effects of losartan on insulin sensitivity and secretion in patients with type 2 diabetes and nephropathy
The nuclear hormone receptor peroxisome proliferator activated receptor- PPAR-γ plays an important role in the regulation of insulin sensitivity Several studies have shown the ARBs telmisartan and irbesartan potently induces PPAR-γ activity promoting PPAR-γ-dependent differentiation in adipocytes However not all ARBs own PPAR-γ activating properties In vitro studies have shown that significant differences among PPAR-γ activating ARBs are likely caused by their physicochemical properties and high lipophilicity is required to obtain sufficiently high penetration rates to bind to intracellular PPAR-γ Losartan at high concentrations could activate PPAR-γ and behaved like partial PPAR-γ agonists Nevertheless the results of losartan on insulin sensitivity remain controversial
To elucidate the underlying effects of losartan on insulin sensitivity we investigated the effects of losartan on insulin sensitivity and secretion in patients with type 2 diabetes and nephropathy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None