Effects of angiotensin II receptor blockade on cerebral, cardiovascular, counter-regulatory, and symptomatic responses during hypoglycaemia in patients with type 1 diabetes

J Renin Angiotensin Aldosterone Syst. 2015 Dec;16(4):1036-45. doi: 10.1177/1470320314529356. Epub 2014 Jul 27.

Abstract

Introduction: High spontaneous activity of the renin-angiotensin system (RAS) results in more pronounced cognitive impairment and more prolonged QTc interval during hypoglycaemia in type 1 diabetes. We tested whether angiotensin II receptor blockade improves cerebral and cardiovascular function during hypoglycaemia.

Methods: Nine patients with type 1 diabetes and high spontaneous RAS activity were included in a double-blind, randomised, cross-over study on the effect of angiotensin II receptor antagonist (candesartan 32 mg) or placebo for one week on cognitive function, cardiovascular parameters, hormonal counter-regulatory response, substrate mobilisation, and symptoms during hypoglycaemia induced by two hyperinsulinaemic, hypoglycaemic clamps.

Results: Compared to placebo, candesartan did neither change performance of the cognitive tests nor the EEG at a plasma glucose concentration of 2.6±0.2 mmol/l. During candesartan treatment, the QT interval in the ECG was not affected. No effect of candesartan was observed in the hormonal counter-regulatory responses, in substrate concentrations, or in symptom scores. A 36% reduced glucose infusion rate during hypoglycaemia with candesartan was observed.

Conclusion: In conclusion candesartan has no effect on cerebral function during mild experimental hypoglycaemia in subjects with type 1 diabetes and high RAS activity. Candesartan may reduce glucose utilisation or increase endogenous glucose production during hypoglycaemia.

Keywords: ATII receptor blocker; candesartan; high renin–angiotensin system activity; hypoglycaemia; type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Blood Glucose / metabolism
  • Brain / drug effects*
  • Brain / physiopathology
  • Cardiovascular System / drug effects*
  • Cardiovascular System / physiopathology
  • Cognition / drug effects
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Electrocardiography
  • Electroencephalography
  • Female
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / complications
  • Hypoglycemia / drug therapy*
  • Hypoglycemia / physiopathology
  • Male
  • Middle Aged
  • Receptors, Angiotensin / metabolism*

Substances

  • Angiotensin Receptor Antagonists
  • Blood Glucose
  • Receptors, Angiotensin