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.