Key result
Type 2 diabetes in youth was associated with higher plasma renin and ACE activity compared to controls (P<0.01), and RAS markers were positively associated with HbA1c and albuminuria.
Why the study?
Youth with type 2 diabetes have high rates of obesity, hypertension, and suboptimal glycemic control, but whether renin-angiotensin system activation is present and associated with poor glycemic control and renal outcomes remained to be determined.
Are renin-angiotensin system (RAS) markers activated in youth with type 2 diabetes and associated with glycemic control and renal outcomes?
Cross-Sectional (n=283)
Are renin-angiotensin system (RAS) markers activated in youth with type 2 diabetes and associated with glycemic control and renal outcomes?
RAS activation is present in youth with type 2 diabetes and is associated with poorer glycemic control and albuminuria, suggesting a potential early pathway for renal complications.
Supports RAS activation in youth T2D; leaves open whether blockade alters glycemic or renal trajectories.
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 Improving renal Complications in Adolescents with T2D through REsearch 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.
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Dart et al. (2020) conducted a cross-sectional in Type 2 diabetes (n=283). Type 2 diabetes vs. Controls was evaluated on Renin-angiotensin system (RAS) marker levels and their association with glycemic control and renal outcomes. Type 2 diabetes in youth was associated with higher plasma renin and ACE activity compared to controls (P<0.01), and RAS markers were positively associated with HbA1c and albuminuria.
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