Urine Albumin-to-Creatinine Ratio: A Marker of Early Endothelial Dysfunction in Youth

CONTEXT: The urine albumin-to-creatinine ratio (UACR) is a useful predictor of cardiovascular (CV) events in adults. Its relationship to vascular function in children is not clear. OBJECTIVE: We investigated whether UACR was related to insulin resistance and endothelial function, a marker of subclinical atherosclerosis, in adolescents across the spectrum of glucose regulation. PARTICIPANTS: Participants were 58 adolescents: 13 normal weight (NW), 25 overweight with normal glucose tolerance (OW-NGT), and 20 overweight with prediabetes (OW-PreD). INTERVENTIONS: Interventions included oral glucose tolerance test, hyperinsulinemic-euglycemic clamp with determination of insulin sensitivity (IS), endothelial function assessment by peripheral arterial tonometry determination of the reactive hyperemia index (RHI), body composition (dual-energy x-ray absorptiometry), and abdominal fat distribution (magnetic resonance imaging). PRIMARY OUTCOME MEASURE: Fasting UACR was determined. RESULTS: The 3 groups did not differ with respect to age, sex, or Tanner stage. The NW group had significantly lower percent body fat, higher IS (10.4 ± 0.9, 3.5 ± 0.6, and 2.1 ± 0.2 mg/kg/min per μU/mL; P < .001), and higher RHI (1.84 ± 0.1, 1.56 ± 0.1, and 1.56 ± 0.1, P = .04) than the OW-NGT and OW-PreD groups, respectively. lnUACR was related to percent body fat (r = 0.4, P = .001), RHI (r = -0.33, p = .01), and IS (r = -0.27, P = .043). In multiple regression analysis with lnUACR as the dependent variable and RHI, percent body fat, age, sex, race, systolic blood pressure, cholesterol, glycated hemoglobin, and IS as independent variables, RHI (β = -0.3, P = .045) and sex (β = 0.31, P = .06) contributed to the variance in UACR (R(2) = 0.35, P = .02). CONCLUSIONS: UACR is an early marker of endothelial dysfunction in youth, independent of glycemia. Endothelial dysfunction may mediate the link between obesity-related insulin resistance and early microalbuminuria.