Griffin Tomás P, Islam Md Nahidul, Blake Liam, Bell Marcia, Griffin Matthew D, O'Shea Paula M
Centre for Diabetes, Endocrinology and Metabolism, Saolta University Health Care Group (SUHCG), Galway University Hospitals, Galway, Ireland.
Regenerative Medicine Institute at CÚRAM SFI Research Centre, School of Medicine, National University of Ireland Galway (NUIG), Galway, Ireland.
Horm Metab Res. 2019 Feb;51(2):91-99. doi: 10.1055/a-0794-7026. Epub 2018 Dec 6.
The aldosterone to renin ratio (ARR) is recommended for case detection of primary aldosteronism (PA). Several factors including medications can undermine its diagnostic accuracy. The objective was to explore the effect of Sodium Glucose Co-Transporter-2 Inhibition on the ARR in patients with type 2 diabetes mellitus (T2DM) who were prescribed a Sodium Glucose Co-Transporter-2 Inhibitor (SGLT-2i) as part of routine clinical care. The primary outcomes were intra-individual changes in aldosterone, renin and ARR. Participants were recruited at routine diabetes outpatient visits as part of a prospective longitudinal study. Eligible participants were prescribed standard doses of empagliflozin and sampled at baseline (pre-SGLT-2i) and at their next routine outpatient visit (post-SGLT-2i). After a mean of 198 (±87) days on SGLT-2i treatment (n=20), there was a significant reduction in HbA, BMI, eGFR and serum triglycerides and a significant increase in serum creatinine and sodium. Compared with baseline, there was a significant increase in median direct renin concentration (mIU/l) [40.3 (6.2-249.5) vs. 70.2 (7.0, 551.0) (p=0.005)] and no significant change in median plasma aldosterone concentration (pmol/l) [296 (101, 685) vs. 273 (101, 794) (p=0.541)] with a significant reduction in median ARR (pmol/mIU) [6.9 (0.6-70.7) vs. 5.3 (0.2-39.3) (p=0.007)]. The proportion of participants with a screen positive ARR decreased from 20% (pre-SGLT-2i) to 5% (post-SGLT-2i) (p=0.248). Although performed in a relatively small cohort of medically complex patients, the study indicates that SGLT-2i therapy has the potential to cause false-negative screening for PA in the setting of T2DM. Future confirmatory studies should include patients with confirmed PA.
醛固酮与肾素比值（ARR）被推荐用于原发性醛固酮增多症（PA）的病例检测。包括药物在内的多种因素会削弱其诊断准确性。本研究目的是探讨在接受钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）治疗作为常规临床护理一部分的2型糖尿病（T2DM）患者中，SGLT-2抑制剂对ARR的影响。主要结局指标是个体内醛固酮、肾素和ARR的变化。作为一项前瞻性纵向研究的一部分，参与者在糖尿病门诊常规就诊时被招募。符合条件的参与者接受标准剂量的恩格列净治疗，并在基线（开始使用SGLT-2i之前）和下次常规门诊就诊时（开始使用SGLT-2i之后）进行采样。在接受SGLT-2i治疗平均198（±87）天后（n = 20），糖化血红蛋白、体重指数、估算肾小球滤过率和血清甘油三酯显著降低，血清肌酐和钠显著升高。与基线相比，直接肾素浓度中位数（mIU/l）显著升高[40.3（6.2 - 249.5）对70.2（7.0，551.0）（p = 0.005）]，血浆醛固酮浓度中位数（pmol/l）无显著变化[296（101，685）对273（101，794）（p = 0.541）]，ARR中位数（pmol/mIU）显著降低[6.9（0.6 - 70.7）对5.3（0.2 - 39.3）（p = 0.007）]。ARR筛查阳性的参与者比例从20%（开始使用SGLT-2i之前）降至5%（开始使用SGLT-2i之后）（p = 0.248）。尽管该研究是在相对较小的患有复杂疾病的患者队列中进行的，但表明SGLT-2i治疗在T2DM患者中可能导致PA筛查出现假阴性结果。未来的验证性研究应纳入确诊为PA的患者。
