Diabetes Mellitus, Hypertension
Conditions
Brief summary
This study was designed to evaluate the effect of ARB in improving insulin secretion in patients with type 2 diabetes. The investigators also aimed to evaluate if there are potential synergisms between ARB and DPP4 inhibitors in improving insulin secretion and urinary albumin secretion in diabetic patients.
Detailed description
Angiotensin II has been reported to insulin secretion in beta cells. Angiotensin II indirectly improves insulin secretion in beta cells via vasoconstriction and reduced islet blood flow. Chronic exposure to high glucose or high fat increases expression of AT1R (angiotensin type 1 receptor), leading to reactive oxidative stresses, inflammation, and apoptosis in beta cells, finally decreased insulin formation and secretion. Some studies showed the beneficial effect of blocking AT1R on insulin secretion and beta cell proliferation in animal models using angiotensin receptor blocker (ARB). Furthermore, 26 weeks of valsartan treatment improved insulin secretion in humans with impaired glucose regulation.
Interventions
DRUGFimasartan
16 weeks of fimasartan vs. amlodipine followed by 2 weeks of wash-out period, then crossover
DRUGAmlodipine
16 weeks of fimasartan vs. amlodipine followed by 2 weeks of wash-out period, then crossover
Sponsors
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Aged 20\ 80 years * Type 2 diabetic patients diagnosed more than 6 months ago * HbA1c ≤8.5% at screening * No change of OAD within the 3 months before screening * SBP \<140 mmHg and DBP \<90 mmHg with anti-hypertensive drug at screening * SBP ≥140 mmHg or DBP ≥80 mmHg without anti-hypertensive drug at screening
Exclusion criteria
* Type 1 diabetic patients or active insulin treatment at screening * Treatment with ARB or ACEi within 1 month prior to screening * Uncontrolled hypertension with SBP \>170 mmHg or DBP \>100 mmHg * Pregnancy or lactation * Elevated liver enzyme (AST or ALT \> 3 times the UNL) or elevated serum Cr (≥1.5 mg/dL in men and 1.4 mg/dL in women)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Insulinogenic index | 16 week |
Secondary
| Measure | Time frame |
|---|---|
| HOMA β-cell function | 16 week |
| Insulin resistance | 16 week |
| Urinary albumin creatinine ratio, urinary protein creatinine ratio | 16 week |
Countries
South Korea
Outcome results
None listed