Cognitive Function and Electrocardiogram (ECG) During Hypoglycemia and Blockade of the Renin-angiotensin System

We will include 25 type 1 diabetic patients from our outpatient clinic. They are already genotyped from another trial.

Each patient goes through two cycles with hyperinsulinemic glucose clamp induced hypoglycemia. The study is double blinded, randomised and placebocontrolled so the patients receive both Candesartan and placebo but in different cycles.

In each cycle patients will receive either Candesartan or placebo for 7 days. After 8 days patients undergo a hypoglycaemic clamp during which primary and secondary endpoints will be measured.

In the hyperinsulinemic hypoglycaemic clamp the patients will undergo an adjustment period towards euglycaemia. A period of approximately 1 hour of euglycemia, an hour of hypoglycemia and a period of recovery towards euglycemia. In each of these glycemic states primary and secondary outcomes will be measured.

Inclusion criteria

• Type 1 diabetes
• Danish spoken and written
• RAS activity score>7 - diabetes duration > 5 years
• not pregnant and safe anticonception
• Signed informed consent.

Exclusion criteria

• Treatment with an ACE blocker
• An ARB og a renin blocker
• Treatment with other antihypertensive drugs
• Severe diabetic late complications
• Renal impairment
• Pregnancy and breastfeeding
• Previous reactions to study medication
• Heart insufficiency (NYHA 3-4)\\
• Known ischaemic heart disease
• Epilepsy
• Alcohol and drug abuse
• Suspicion of non-compliance,
• Plasma potassium < 3.5 mmol/l or >5.0 mmol/l.