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

Hypoglycemia, Type 1 Diabetes

Type 1 diabetes, Hypoglycaemia, genetic susceptibility, Renin angiotensin system activity

Hypothesis: Treating patients with type 1 diabetes with a certain antihypertensive drug preserve cerebral function during hypoglycaemia. Background: Studies have found that certain genetic variations leaves a subject with type 1 diabetes more prone to hypoglycaemia. It it thought to be a decline in cognition during hypoglycaemia that leaves them at risk of severe hypoglycaemia. The idea is tha when you suppress the genetic phenotype with a well known antihypertensive drug an improvement in cognition will occur and this will remove the patients tendency to severe hypoglycaemia. Methods: The investigators want to explore whether the cerebral function is improved during hypoglycaemia in subjects with type 1 diabetes and the above mentioned genetic variation when treated with the antihypertensive drug Candesartan.

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.

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