TY - JOUR
T1 - Elevated serum uric acid is associated with greater risk for hypertension and diabetic kidney diseases in obese adolescents with type 2 diabetes
T2 - An observational analysis from the treatment options for type 2 diabetes in adolescents and youth (today) study
AU - for the TODAY Study Group
AU - Bjornstad, Petter
AU - Laffel, Lori
AU - Lynch, Jane
AU - El ghormli, Laure
AU - Weinstock, Ruth S.
AU - Tollefsen, Sherida E.
AU - Nadeau, Kristen J.
N1 - Funding Information:
This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health grant numbers T32-DK-063687, K23-DK- 116720, U01-DK-61212, U01-DK-61230, U01- DK-61239, U01-DK-61242, and U01-DK-61254; from National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR-00036 (Washington University in St. Louis School of Medicine), M01-RR- 00043-45 (Children's Hospital Los Angeles), M01-RR-00069 (University of Colorado Denver), M01-RR-00084 (Children's Hospital of Pittsburgh), M01-RR-01066 (Massachusetts General Hospital), M01-RR-00125 (Yale University), and M01-RR-14467 (University of Oklahoma Health Sciences Center); and from National Center for Research Resources Clinical and Translational Science Awards grant numbers UL1-RR- 024134 (Children's Hospital of Philadelphia), UL1-RR-024139 (Yale University), UL1-RR- 024153 (Children's Hospital of Pittsburgh), UL1-RR-024989 (Case Western Reserve University), UL1-RR-024992 (Washington University in St. Louis), UL1-RR-025758 (Massachusetts General Hospital), and UL1-RR-025780 (University of Colorado Denver).
Funding Information:
The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the respective Tribes and the Indian Health Service. Funding. This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health grant numbers T32-DK-063687, K23-DK-116720, U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254; from National Center for Research Resources General Clinical Research Centers Program grant numbers M01-RR-00036 (Washington University in St. Louis School of Medicine), M01-RR-00043-45 (Children’s Hospital Los Angeles), M01-RR-00069 (University of Colorado Denver), M01-RR-00084 (Children’s Hospital of Pittsburgh), M01-RR-01066 (Massachusetts General Hospital), M01-RR-00125 (Yale University), and M01-RR-14467 (University of Oklahoma Health Sciences Center); and from National Center for Research Resources Clinical and Translational Science Awards grant numbers UL1-RR-024134 (Children’s Hospital of Philadelphia), UL1-RR-024139 (Yale University), UL1-RR-024153 (Children’s Hospital of Pittsburgh), UL1-RR-024989 (Case Western Reserve University), UL1-RR-024992 (Washington University in St. Louis), UL1-RR-025758 (Massachusetts General Hospital), and UL1-RR-025780 (University of Colorado Denver).
Publisher Copyright:
© 2019 by the American Diabetes Association.
PY - 2019
Y1 - 2019
N2 - 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. Wehypothesized 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 ≥130/80mmHgand elevated UAE asUACR ≥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, HbA1c, 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 elevatedUAE. Research is needed to determine whether SUA-lowering therapies can impede development of diabetic kidney disease and hypertension in T2D youth.
AB - 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. Wehypothesized 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 ≥130/80mmHgand elevated UAE asUACR ≥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, HbA1c, 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 elevatedUAE. Research is needed to determine whether SUA-lowering therapies can impede development of diabetic kidney disease and hypertension in T2D youth.
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U2 - 10.2337/dc18-2147
DO - 10.2337/dc18-2147
M3 - Article
C2 - 30967435
AN - SCOPUS:85066457061
SN - 0149-5992
VL - 42
SP - 1120
EP - 1128
JO - Diabetes care
JF - Diabetes care
IS - 6
ER -