Elevated Serum Uric Acid Is Associated With Greater Risk for Hypertension and Diabetic Kidney Diseases in Obese Adolescents With Type 2 Diabetes: An Observational Analysis From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study

Abstract

Objective: Elevated serum uric acid (SUA) is increasingly recognized as a risk factor for kidney disease in adults with diabetes, but data in youth are limited. We hypothesized that elevated SUA predicts development of elevated urinary albumin excretion (UAE) and hypertension over time in teens with type 2 diabetes (T2D).

Research design and methods: Serum creatinine, cystatin C, SUA, and the urine albumin-to-creatinine ratio (UACR) were assessed in 539 obese youth, ages 12-17 years, with T2D duration <2 years at baseline in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Estimated glomerular filtration rate (eGFR) was calculated using creatinine and cystatin C. Hypertension was defined as systolic or diastolic blood pressure ≥130/80 mmHg and elevated UAE as UACR ≥30 mg/g. Cox proportional hazards models evaluated the relationship between SUA and outcome variables longitudinally over an average follow-up of 5.7 years, adjusting for age, sex, race/ethnicity, BMI, HbA_1c, eGFR, ACE inhibitor/angiotensin receptor blocker use, and TODAY treatment group assignment.

Results: At baseline, hyperuricemia (≥6.8 mg/dL) was present in 25.6% of participants, hypertension in 18.7%, and elevated UAE in 6.1%. During follow-up of up to 7 years, hypertension developed in 37.4% and UAE in 18.0%. Higher baseline SUA increased the risk of incident hypertension (hazard ratio [HR] 1.19, 95% CI 1.03-1.38, per 1 mg/dL increase in SUA) and elevated UAE (HR 1.24, 95% CI 1.03-1.48) in adjusted models.

Conclusions: Hyperuricemia was common in youth with T2D. Higher baseline SUA independently increased the risk for onset of hypertension and elevated UAE. Research is needed to determine whether SUA-lowering therapies can impede development of diabetic kidney disease and hypertension in T2D youth.

Trial registration: ClinicalTrials.gov NCT00081328.

Figure 1

Forest plot portraying the HR, 95% CI, and P value of the association between baseline SUA or hyperuricemia and incident hypertension (A) or elevated UAE (UACR ≥30 mg/g) (B) in adjusted models over time in TODAY. All models were adjusted for baseline eGFR, age, HbA_1c, BMI, antihypertensive medication use, sex, race/ethnicity, and randomized treatment group assignment.

Figure 2

Forest plot portraying the HR, 95% CI, and P value of the association between baseline SUA or hyperuricemia and incident elevated UAE (UACR ≥30 mg/g) stratified by sex (A) and race/ethnicity (B) in adjusted models over time in TODAY. All models were adjusted for baseline eGFR, age, HbA_1c, BMI, antihypertensive medication use, sex (for model B), and race/ethnicity (for model A).