Department of Pediatrics and Child Health, University of Manitoba, Children's Hospital Research Institute of Manitoba, Diabetes Research Envisioned and Accomplished in Manitoba Research Team, Winnipeg, Manitoba, Canada.
Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Pediatr Diabetes. 2020 Nov;21(7):1102-1109. doi: 10.1111/pedi.13081. Epub 2020 Aug 25.
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.
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.
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.
目的/假设：患有 2 型糖尿病（T2D）的年轻人肥胖、高血压和血糖控制不佳的发生率很高。我们假设肾素-血管紧张素系统（RAS）的激活存在于患有 T2D 的年轻人中，并与血糖控制不佳和肾脏结局有关。
横断面分析来自改善青少年 2 型糖尿病肾脏并发症的研究队列中的 183 名患有 T2D 的年轻人和 100 名对照者。根据尿白蛋白：肌酐比（ACR）将糖尿病青少年分为<或≥2mg/mmol。使用酶联免疫吸附测定（ELISA）测量 RAS 水平，并使用合成底物测量酶活性。在 T2D 中，水平进行对数转换，使用 Tobit 线性回归评估与血红蛋白 A1c（HbA1c）、平均动脉压（MAP）、估计肾小球滤过率（eGFR）、ACR 的关联。
青少年年龄为 14 至 15 岁，糖尿病病程为 1.7 至 1.8 年；21.3%的白蛋白尿。血清：与对照组相比，T2D 中的血浆肾素活性（<0.0001）和血管紧张素转换酶（ACE）活性（P =.003）存在差异。尿液：T2D 中 ACE 活性和 ACE2 蛋白/活性更高（均 P < .0001），白蛋白尿患者中更高。多变量回归：血清 ACE 活性（β=0.03，SE 0.01；P < .01）、尿液 ACE 活性（β=0.44，SE 0.18；P < .01）、ACE2（β=0.51，SE 0.19；P < .01）与 HbA1c 呈正相关；尿液血管紧张素原（AGT）呈负相关（β=-0.28[SE 0.06；P < .01]）。血清醛固酮（β=0.11[SE 0.04；P < .01]）和尿液 AGT（β=0.32[SE 0.07；P < .01]）与 ACR 和尿液 ACE2 显著相关（β=0.21[SE 0.13；P < .03]）。RAS 标志物与 eGFR/MAP 之间无关联。
结论/解释：T2D 患者中存在 RAS 激活，与较高的 HbA1c 相关。较高的血清醛固酮和尿液 AGT 与白蛋白尿有关。血糖和 RAS 激活对肾脏结局的综合影响的预后意义需要进一步研究。
