Assistant Professor Wake Forest School of Medicine, Brenner Children's Hospital Wake Forest School of Medicine Winston Salem, North Carolina, United States
Background: Type 1 diabetes (T1D) increases the risk of cardiovascular (CV) disease and chronic kidney disease. Altered vascular function is an early marker of CV disease and is associated with worse kidney function, but whether changes in kidney function precede changes in CV health in patients with T1D is unclear.
Objective: To determine if the change in kidney function predicts increased blood pressure (BP) and worse vascular function in youth with T1D, especially those with overweight/obesity.
Design/Methods: Prospective cohort of 294 participants with T1D in the SEARCH for Diabetes in Youth Study. We estimated glomerular filtration rate (eGFR) using the creatinine-based full age spectrum equation, calculated morning urine albumin-to-creatinine ratios (ACR), and measured BP and vascular function via pulse wave velocity (PWV) and augmentation index (AIx) at two separate study visits (mean 4.6 years apart, SD ±1.1). We defined high BP as ≥90th %ile for age/sex/height (<13 years) and ≥120/80 mmHg (≥13 years). We used multivariable regression models to estimate the associations of the annualized change in eGFR and ACR with the annualized change in outcomes. Directed acyclic graphs informed model adjustment sets, and we assessed effect modification by overweight/obesity.
Results: Mean age was 18.4 ±4.5 years, 44.2% were female, 69.7% were White, and 42.2% had overweight/obesity. A 1 ml/min/1.73 m2/year decrease in eGFR was associated with 14% increased odds of high BP (OR 1.14, 95% CI 1.04 to 1.25), adjusted for sex, family history of CV disease, BP medications, and change in age, height, T1D duration, A1c, and AIx. Compared to those with overweight/obesity, participants with normal BMI demonstrated a mildly stronger association (1.25, 1.1 to 1.42 vs. 1.08, 0.94 to 1.25, interaction p=0.13). A 1 mg/g/year increase in ACR was associated with increased AIx (β: 0.013 %/year, 95% CI 0.001 to 0.025), adjusted for sex, family history of CV disease, site, dyslipidemia, and the change age, height, T1D duration, A1c, mean arterial pressure, and inflammatory markers. Overweight/obesity did not modify this association. Conclusion(s): Among participants with T1D, worsening kidney function over time was associated with developing high BP and altered vascular function, particularly in those with a normal BMI. Further investigations are warranted to elucidate how kidney function affects CV health in T1D and the role of obesity.
Authors/Institutions: Andrew M. South, Wake Forest School of Medicine, Winston Salem, North Carolina, United States; Joseph Rigdon, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States; Amy Mottl, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States; Dana Dabelea, University of Colorado Health, Aurora, Colorado, United States; Santica M. Marcovina, University of Washington, Seattle, Washington, United States; Catherine Pihoker, University of Washington School of Medicine, Seattle, Washington, United States; Elaine Urbina, Cincinnati Children's Hospital, Cincinnati, Ohio, United States; Elizabeth T. Jensen, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States