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Sponsored by: |
Shanghai Jiao Tong University of Medicine |
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Information provided by: | Shanghai Jiao Tong University School of Medicine |
ClinicalTrials.gov Identifier: | NCT00361023 |
Angiotensin type-1 receptor (AT1R) blockers (ARBs) have been recognized recently as regulators of glucose and lipid metabolism in adipocytes and adipose tissue.Moreover 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.
Condition | Intervention |
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Type 2 Diabetes Diabetic Nephropathy |
Drug: losartan |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Effects of Angiotensin Type 1 Receptor Blockade With Losartan on Insulin Sensitivity and Secretion in Subjects With Type 2 Diabetes and Nephropathy |
Estimated Enrollment: | 25 |
Study Start Date: | January 2006 |
Estimated Study Completion Date: | July 2006 |
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 sensitivity.Angiotensin 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.
Ages Eligible for Study: | 17 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Study ID Numbers: | LISS |
Study First Received: | August 1, 2006 |
Last Updated: | August 4, 2006 |
ClinicalTrials.gov Identifier: | NCT00361023 |
Health Authority: | China: State Food and Drug Administration |
Angiotensin type 1 receptor blocker (ARB) losartan type 2 diabetes insulin sensitivity and secretion glucose metabolism |
Losartan Diabetic Nephropathies Metabolic Diseases Diabetes Mellitus Endocrine System Diseases Angiotensin II Insulin |
Urologic Diseases Diabetes Mellitus, Type 2 Kidney Diseases Endocrinopathy Glucose Metabolism Disorders Metabolic disorder Diabetes Complications |
Angiotensin II Type 1 Receptor Blockers Molecular Mechanisms of Pharmacological Action Therapeutic Uses Cardiovascular Agents |
Anti-Arrhythmia Agents Antihypertensive Agents Pharmacologic Actions |