Effects of Losartan on Insulin Sensitivity and Secretion in Type 2 Diabetes and Nephropathy
Information source: Shanghai Jiao Tong University of Medicine
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes; Diabetic Nephropathy
Intervention: losartan (Drug)
Sponsored by: Shanghai Jiao Tong University of Medicine
Official(s) and/or principal investigator(s):
Hui M Jin, MD, Principal Investigator, Affiliation: Shanghai NO.3 people's Hospital
Hui M Jin, MD, Principal Investigator, Affiliation: Shanghai No.3 people's hospital
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.
Official title: Effects of Angiotensin Type 1 Receptor Blockade With Losartan on Insulin Sensitivity and Secretion in Subjects With Type 2 Diabetes and Nephropathy
Study design: Treatment, Randomized, Open Label, Placebo Control, Parallel Assignment, Safety/Efficacy Study
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
Minimum age: 17 Years.
Maximum age: N/A.
- 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
- Type1 diabetes or nondiabetic renal disease
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Starting date: January 2006
Ending date: July 2006
Last updated: August 4, 2006