Effects of Losartan on Insulin Sensitivity and Secretion in Type 2 Diabetes and Nephropathy

This study has been completed.
Sponsor:
Information provided by:
Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier:
NCT00361023
First received: August 1, 2006
Last updated: August 4, 2006
Last verified: January 2006
  Purpose

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
Type 2 Diabetes
Diabetic Nephropathy
Drug: losartan

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Angiotensin Type 1 Receptor Blockade With Losartan on Insulin Sensitivity and Secretion in Subjects With Type 2 Diabetes and Nephropathy

Resource links provided by NLM:


Further study details as provided by Shanghai Jiao Tong University School of Medicine:

Estimated Enrollment: 25
Study Start Date: January 2006
Estimated Study Completion Date: July 2006
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 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.

  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fasting plasma glucose (FPG) level of 3.3-9.0mmol/L
  • 2h plasma glucose level of 7.5-13 mmol/L
  • Body mass index (BMI) of 22 kg/m2
  • Two occasions of a ratio of urinary albumin to urinary creatinine≥300 or 24 hours urinary protein concentration is >150mg.
  • Informed consent

Exclusion Criteria:

  • Type1 diabetes or nondiabetic renal disease
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00361023

Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
Investigators
Principal Investigator: Hui M Jin, MD Shanghai NO.3 people's Hospital
Principal Investigator: Hui M Jin, MD Shanghai No.3 people's hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00361023     History of Changes
Other Study ID Numbers: LISS
Study First Received: August 1, 2006
Last Updated: August 4, 2006
Health Authority: China: Food and Drug Administration

Keywords provided by Shanghai Jiao Tong University School of Medicine:
Angiotensin type 1 receptor blocker (ARB)
losartan
type 2 diabetes
insulin sensitivity and secretion
glucose metabolism

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Kidney Diseases
Insulin Resistance
Diabetic Nephropathies
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Hyperinsulinism
Diabetes Complications
Insulin
Losartan
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014