The Association Among Uric Acid, Renal Hemodynamics, and Arterial Stiffness Over the Natural History of Type 1 Diabetes
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- The authors performed this study to determine the timeline of associations between elevated plasma uric acid (PUA) concentrations and renal vasoconstriction, renin angiotensin–aldosterone system (RAAS) activation, and vascular stiffness. PUA levels were associated with age and duration of type 1 diabetes. GFR was lower in association with higher PUA among older adults (but not adolescents or young adults), after adjusting for age, HbA1c, and gender. While adolescents with elevated PUA had lower carotid augmentation index scores, carotid femoral pulse wave velocity and plasma renin were higher in older adults who had elevated PUA levels.
- The results indicate that the duration of type 1 diabetes influences the relationship between PUA levels and renal and cardiac function.
abstract
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Access this abstract nowAIMS
Higher plasma uric acid (PUA) concentrations are associated with renal vasoconstriction, renin angiotensin aldosterone system (RAAS) activation and vascular stiffness, however the timeline for these associations in type 1 diabetes (T1D) is not clear. We aimed to compare the changes in such associations over a wide range of T1D duration.
MATERIALS AND METHODS
PUA, glomerular filtration rate (GFRINULIN ), effective renal plasma flow (ERPFPAH ), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), plasma renin and aldosterone were measured during a euglycemic clamp in participants with T1D: 27 adolescents (age 16.8±1.9yrs), 52 young adults (25.6±5.5yrs) and 66 older adults (65.7±7.5yrs).
RESULTS
PUA was highest in patients with the longest T1D duration: 197±44 in adolescents vs. 264±82μmol/L in older adults (p<0.001). Higher PUA correlated with lower GFR only in older adults, even after correcting for age, HbA1c 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 RAAS activation was observed only in older adults with longstanding T1D. T1D duration may modify the association between PUA, renal hemodynamic function and RAAS activation, leading to renal vasoconstriction and ischemia. Further work must determine whether pharmacological PUA lowering prevents or reverses injurious hemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes.
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Additional Info
The Association Between Uric Acid, Renal Hemodynamics and Arterial Stiffness Over the Natural History of Type 1 Diabetes
Diabetes Obes Metab 2019 Feb 13;[EPub Ahead of Print], Y Lytvyn, P Bjornstad, JA Lovshin, SK Singh, G Boulet, MA Farooqi, V Lai, J Tse, L Cham, LE Lovblom, A Weisman, HA Keenan, MH Brent, N Paul, V Bril, A Advani, E Sochett, BA Perkins, DZI CherneyFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.