title: Age is a determinant of acute hemodynamic responses to hyperglycemia and angiotensin II in humans with uncomplicated type 1 diabetes mellitus.
abstract: Hyperglycemia is associated with hemodynamic changes in type 1 diabetes (DM), acting in part through renin-angiotensin system activation. Since aging is associated with vascular dysfunction in DM, we hypothesized that acute hemodynamic responses to clamped hyperglycemia and infused ANG II would be exaggerated in older adults compared with a group of adolescent/young adults with type 1 DM. Renal hemodynamic function, blood pressure, and arterial stiffness were assessed in adolescent/young adults (n = 34; mean age: 18 +/- 3 yr) and older adults (n = 32; mean age: 45 +/- 9 yr). Studies were performed during clamped euglycemia (4-6 mmol/l) and hyperglycemia (9-11 mmol/l). Renal and systemic hemodynamic responses to ANG II were measured during clamped euglycemia in diabetic subjects. ANG II responses were also assessed in a cohort of non-DM subjects (n = 97; mean age: 26; age range: 18-40 yr). Older DM adults exhibited higher baseline blood pressure, arterial stiffness, and renal vascular resistance, and lower glomerular filtration rate (GFR) and effective renal plasma flow, compared with adolescent/young DM adults (P < 0.05). Clamped hyperglycemia was associated with exaggerated peripheral and renal hemodynamic responses uniquely in older DM adults; only GFR increased in adolescent/young DM adults. ANG II infusion also produced exaggerated vasoconstrictive responses in older DM adults vs. adolescent/young DM adults (P < 0.05). The independent effect of age on hemodynamic responses to hyperglycemia and ANG II was confirmed using multivariate regression analysis in DM subjects (P < 0.05), and results were still significant when participants were matched for DM duration. Age-related alterations in hemodynamic function and ANG II response were not observed in healthy non-DM control subjects. Acute hemodynamic responses to clamped hyperglycemia and ANG II were exaggerated in older subjects with type 1 DM, highlighting an important interaction between age and factors that contribute to the pathogenesis of acute vascular dysfunction in DM.
authors.affiliation: Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada. david.cherney@uhn.on.ca
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
authors.forename: Heather N
authors.initials: HN
authors.lastname: Reich
authors.forename: Judith A
authors.initials: JA
authors.lastname: Miller
authors.forename: Vesta
authors.initials: V
authors.lastname: Lai
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Maria G
authors.initials: MG
authors.lastname: Dekker
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bradley
authors.forename: James W
authors.initials: JW
authors.lastname: Scholey
authors.forename: Etienne B
authors.initials: EB
authors.lastname: Sochett
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000187:drug effects*; D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015309:Glucose Clamp Technique; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D011141:Polyuria; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013894:Thirst / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000804:Angiotensin II