title: Effects of angiotensin II receptor blockade on cerebral, cardiovascular, counter-regulatory, and symptomatic responses during hypoglycaemia in patients with type 1 diabetes.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital - Hillerød, Denmark Louise.Faerch@regionh.dk.
authors: Louise H
authors: LH
authors: Færch
authors: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital - Hillerød, Denmark Department of Clinical Medicine, University of Copenhagen, Denmark.
authors: Birger
authors: B
authors: Thorsteinsson
authors: HIH Research Unit, Nordsjællands Hospital - Hillerød, Denmark Department of Health, University of Aarhus, Denmark.
authors: Lise
authors: L
authors: Tarnow
authors: NNF Centre for Basic Metabolic Research, Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Denmark.
authors: Jens Juul
authors: JJ
authors: Holst
authors: Clinic of Neurophysiology, The Neuroscience Centre, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors: Troels
authors: T
authors: Kjær
authors: Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital - Frederikssund, Denmark.
authors: Jørgen
authors: J
authors: Kanters
authors: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital - Frederikssund, Denmark Department of Cardiology, Bispebjerg Hospital, Copenhagen, Denmark.
authors: Charlotte
authors: C
authors: Larroude
authors: Xlab, Centre for Healthy Ageing, University of Copenhagen, Denmark.
authors: Flemming
authors: F
authors: Dela
authors: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands Hospital - Hillerød, Denmark Department of Clinical Medicine, University of Copenhagen, Denmark.
authors: Ulrik
authors: U
authors: Pedersen-Bjergaard
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004562:Electrocardiography; D004569:Electroencephalography; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011945:Receptors, Angiotensin / Q000378:metabolism*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001786:Blood Glucose; D011945:Receptors, Angiotensin
keywords: ATII receptor blocker; candesartan; high renin–angiotensin system activity; hypoglycaemia; type 1 diabetes