title: Association between regional cerebral blood flow during hypoglycemia and genetic and phenotypic traits of the renin-angiotensin system.
abstract: The risk of severe hypoglycemia in patients with type I diabetes and high basal activity in the renin-angiotensin system (RAS) is significantly higher than in patients with low basal RAS activity. In healthy men, we tested the hypothesis that differences in spontaneous RAS activity are associated with differences in cerebral activity responses during mild hypoglycemia. A total of 10 healthy men with high and 10 with low spontaneous RAS activity were selected. An H(2)(15)O-PET (H(2)(15)O-positron emission tomography) study was conducted with a series of six scans, i.e., two during normoglycemia, two during hypoglycemia, and two after hypoglycemia. The mean plasma glucose concentration was similar in both the groups (i.e., 2.1 mmol/L (s.d.: 0.4) in the low RAS group and 2.2 mmol/L (s.d.: 0.4) in the high RAS group (P=0.47)). The high RAS group has lower cerebral activity in the frontal area and a higher cerebral activity in the entorhinal area that expanded to include the parahippocampal gyrus after hypoglycemia. Our findings suggest that the high RAS group to a lesser extent than the low RAS group activates areas involving executive function that may explain the correlation between high basal RAS activity and risk of severe hypoglycemia in type I diabetes.
authors: Department of Cardiology and Endocrinology, Endocrinology Section, Hillerød Hospital, Hillerød, Denmark. ligri@noh.regionh.dk
authors: Lise Grimmeshave
authors: LG
authors: Bie-Olsen
authors: Ulrik
authors: U
authors: Pedersen-Bjergaard
authors: Troels Wesenberg
authors: TW
authors: Kjaer
authors: Markus Nowak
authors: MN
authors: Lonsdale
authors: Ian
authors: I
authors: Law
authors: Birger
authors: B
authors: Thorsteinsson
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D044139:Receptor, Angiotensin, Type 2; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A