Plasma Uric Acid (PUA), Renal Hemodynamic Function, and Arterial Stiffness at the Extremes of T1D Duration-Adolescents vs. Adults with T1D for =50 Years
Bibliographic record
Abstract
Higher PUA levels are associated with renal vasoconstriction, renin angiotensin aldosterone system (RAAS) activation and vascular stiffness, however the timeline for these associations in T1D is not clear. Our aim was to compare adolescents vs. young adults vs. adults with ≥50 years of T1D from the Canadian Study of Longevity to determine the relationship between PUA and changes in renal hemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of diabetes duration. PUA, GFRinulin, 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±1.9 years), 52 young adults (25.6±5.5 years) and 66 older adults (65.7±7.5 years). PUA levels were highest in the cohort with the longest T1D duration: 197±44 in adolescents vs. 264±82µmol/L in older adults (p<0.001). While PUA levels did not associate with renal hemodynamic parameters in adolescents or young adults, higher PUA correlated with lower GFR in older adults, even after correcting for age, HbA1c and gender (β=-2.12±0.56, p=0.0003). Higher PUA correlated with lower carotid AIx (β=-1.67±0.58, p=0.02) in adolescents, indicating greater compliance. In contrast, PUA correlated with higher cfPWV (less compliance, p=0.03) and higher plasma renin (p=0.03) in adults with ≥50 years of T1D. The relationship between higher PUA with lower GFR, increased arterial stiffness and RAAS activation was observed only in adults with longstanding T1D. T1D may modify the association between PUA, renal hemodynamic function and RAAS activation, leading to renal vasoconstriction and ischemia. Further work is required to determine whether pharmacological PUA lowering prevents injurious hemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes. Disclosure Y. Lytvyn: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. M. Farooqi: None. V.S. Lai: None. J.M. Tse: None. L. Cham: None. L. Lovblom: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. E.B. Sochett: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".