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An evaluation of renin‐angiotensin system markers in youth with type 2 diabetes and associations with renal outcomes
Author(s) -
Dart Allison B.,
Wicklow Brandy,
Scholey James,
Sellers Elizabeth A.,
Dyck Justin,
Mahmud Farid,
Sochett Etienne,
Hamilton Jill,
BlydtHansen Tom,
Burns Kevin
Publication year - 2020
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.13081
Subject(s) - albuminuria , medicine , endocrinology , type 2 diabetes , renal function , diabetes mellitus , urine , glycemic , creatinine
Aims/hypothesis Youth with type 2 diabetes (T2D) have high rates of obesity, hypertension and suboptimal glycemic control. We hypothesized that renin‐angiotensin system (RAS) activation is present in youth with T2D and associated with poor glycemic control and renal outcomes. Methods Cross‐sectional analysis of 183 youth with T2D and 100 controls from the I mproving renal C omplications in A dolescents with T2D through RE search cohort. Diabetes youth stratified by urine albumin:creatinine ratio (ACR) < or ≥2 mg/mmol. RAS levels measured with enzyme‐linked immunosorbent assay (ELISA) and enzyme activities by synthetic substrates. In T2D, levels log transformed and Tobit linear regressions evaluated for associations with hemoglobin A1c (HbA1c), mean arterial pressure (MAP), estimated glomerular filtration rate (eGFR), ACR. Results Youth were 14 to 15 years, with diabetes duration 1.7 to 1.8 years; 21.3% albuminuria. Serum: differences in plasma renin activity (<0.0001), and angiotensin converting enzyme (ACE) activity ( P = .003) in T2D vs controls. Urine: higher ACE activity and ACE2 protein/activity (all P < .0001) in T2D, higher levels in T2D with albuminuria. Multivariable regressions: higher serum ACE activity (ß = 0.03, SE 0.01; P < .01), urine ACE activity (ß = 0.44, SE 0.18; P < .01), ACE2 (ß = 0.51, SE 0.19; P < .01) positively associated with HbA1c; urine angiotensinogen (AGT) negatively associated (ß = −0.28 [SE 0.06; P < .01]). Higher serum aldosterone (ß = 0.11 [SE 0.04; P < .01]) and urine AGT (ß = 0.32 [SE 0.07; P < .01]) significantly associated with ACR and urine ACE2 (ß = 0.21 [SE 0.13; P < .03]). No associations between RAS markers and eGFR/MAP. Conclusions/interpretation RAS activation present in youth with T2D and associated with higher HbA1c. Higher serum aldosterone and urine AGT associated with albuminuria. The prognostic significance of the combined effect of glycemia and RAS activation on renal outcomes requires additional investigation.