Glucose Optimisation With Angiotensin II Antagonist Losartan (GOAAL)

• Insulin sensitivity assessed with hyperinsulinaemic isoglycaemic glucose clamp(GDR)
  

• Fasting serum glucose
  
• Fasting serum insulin
  
• HOMA-IR
  
• C-peptide
  
• High sensitivity C-reactive protein
  
• Lipids (Triglycerides, Total-cholesterolHDL-cholesterol, LDL-cholesterol)
  
• Adipocytokines etc.(Adiponectin, leptin, resistin, TNF-a, PAI-1 activity, ghrelin)
  
• Serum uric acid
  
• Catecholamines
  
• Baroreflex sensitivitiy
  
• Heart rate variability
  
• Microalbuminuria
  

Patients with hypertension have an increased prevalence of insulin resistance and an increased risk of developing diabetes mellitus with ageing. Different antihypertensive regimens have varying effects on glucose metabolism and the development of diabetes mellitus. In a double-blind,randomized cross-over study we aim to compare the metabolic effects of 10 mg amlodipine and 100 mg losartan + 5 mg amlodipine in patients with hypertension and other risk factors for the metabolic syndrome.

After a 4-week open label amlodipine 5 mg run-in period, all hypertensive patient will be randomized to additional treatment with either amlodipine 5 mg or losartan 100 mg for 8 weeks. At the end of this 8-week treatment-period we will do a physical examination, laboratory-tests, hyperinsulinaemic isoglycaemic glucose clamp, heart rate variability and baroreflex sensitivity measurements. Following this is a 4-week wash-out phase where the subjects continue open label 5 mg amlodipine, before crossed over to the opposite treatment regimen for another 8 week before the final examination.