Yuliya Lytvyn1, Petter Bjornstad2,3, Julie A Lovshin4, Sunita K Singh1, Genevieve Boulet4, Mohammed A Farooqi4, Vesta Lai1, Josephine Tse1, Leslie Cham1, Leif E Lovblom5, Alanna Weisman4, Hillary A Keenan6, Michael H Brent7, Narinder Paul8, Vera Bril9,10, Andrew Advani11, Etienne Sochett12, Bruce A Perkins4, David Z I Cherney1. 1. Department of Medicine, Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 2. Department of Pediatrics, Division of Endocrinology, University of Colorado School of Medicine, Aurora, Colorado. 3. Department of Medicine, Division of Nephrology, University of Colorado School of Medicine. 4. Department of Medicine, Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 5. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. 6. Research Division, Joslin Diabetes Center, Boston, Massachusetts. 7. Department of Ophthalmology and Vision Sciences, Department of Medicine, University of Toronto, Ontario, Canada. 8. Joint Department of Medical Imaging, Division of Cardiothoracic Radiology, University Health Network, Toronto, Ontario, Canada. 9. Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada. 10. Department of Neuroscience Research, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. 11. Department of Medicine, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 12. Division of Pediatric Endocrinology, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
Abstract
AIMS: To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS: PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS: PUA was highest in patients with the longest T1D duration: 197 ± 44 μmol/L in adolescents versus 264 ± 82 μmol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (β = -2.12 ± 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (β = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. CONCLUSIONS: The relationship between higher PUA with lower GFR, increased arterial stiffness and renin angiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.
AIMS: To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS:PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS:PUA was highest in patients with the longest T1D duration: 197 ± 44 μmol/L in adolescents versus 264 ± 82 μmol/L in older adults (P < 0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, glycated haemoglobin and sex (β = -2.12 ± 0.56; P = 0.0003), but not in adolescents or young adults. Higher PUA correlated with lower carotid AIx (β = -1.90, P = 0.02) in adolescents. In contrast, PUA correlated with higher cfPWV (P = 0.02) and higher plasma renin (P = 0.01) in older adults with T1D. CONCLUSIONS: The relationship between higher PUA with lower GFR, increased arterial stiffness and reninangiotensin aldosterone system (RAAS) activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal haemodynamic function and RAAS activation, leading to renal vasoconstriction and ischaemia. Further work must determine whether pharmacological PUA-lowering prevents or reverses injurious haemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.
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