{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:29:27Z","timestamp":1763490567762,"version":"3.45.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82474325"],"award-info":[{"award-number":["82474325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n The impact of sodium-glucose cotransporter-2 inhibitors (SGLT-2is), including dapagliflozin, on the renin-angiotensin-aldosterone system (RAAS) in type 2 diabetes mellitus (T2DM) patients remains controversial, as they may either activate or inhibit RAAS, subsequently influencing glucose metabolism and the accuracy of the aldosterone-to-renin ratio (ARR) in diagnosing primary aldosteronism (PA). However, the effects of SGLT-2is therapy on RAAS and their correlation with glucose metabolism have not been well studied.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A cohort of 147 patients with T2DM and hypertension was prospectively recruited and categorized into two groups: diabetic kidney disease group (DKD, n\u2009=\u200973) and non-DKD group (n\u2009=\u200974), based on diagnostic criteria for diabetic complications. Patients were prescribed 10 mg dapagliflozin daily for 3 months. The primary outcome measure was the change in renin (REN) levels during outpatient visits at baseline, 1 month, and 3 months. The secondary outcome was the change in other metabolic biomarkers from baseline to the 3-month visit. To evaluate the relationship between RAAS components and various glucose metabolism indicators, including HbA1c, FBG, CP, HOMA-\u03b2, HOMA-IR, and UACR, Spearman correlation and multiple linear regression analyses were conducted at baseline and 3-month visit.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After 3 months, the BMI, HbA1c, FBG, TG, TCHO, SBP, DBP, UACR, and HOMA-IR levels were significantly decreased, while Crea and HOMA-\u03b2 were significantly increased from the baseline in both groups. Additionally, the differences from the baseline in FBG (\u22122.64\u2009\u00b1\u20092.66 vs. \u22121.70\u2009\u00b1\u20091.92 mmol\/L) and UACR (\u2212355.01\u2009\u00b1\u20091534.12 vs. \u22124.66\u2009\u00b1\u20097.86 mg\/g) values were significantly higher in DKD group than those in non-DKD group. REN levels increased significantly from baseline at 1-month visit (4.15\u2009\u00b1\u20097.35 vs. 2.75\u2009\u00b1\u20098.03 ng\/L; DKD vs. non-DKD; between-group difference,\n p<\/jats:italic>\n \u2009<\u20090.05), while ARR values decreased significantly from baseline at 1-month visit (\u22120.70\u2009\u00b1\u20091.16 vs. \u22120.59\u2009\u00b1\u20091.19; between\u2011group difference,\n p<\/jats:italic>\n \u2009>\u20090.05) and 3-month visit (\u22120.45\u2009\u00b1\u20091.15 vs. \u22120.42\u2009\u00b1\u20091.07; between\u2011group difference,\n p<\/jats:italic>\n \u2009>\u20090.05) in both groups (within\u2011group change vs. baseline,\n p<\/jats:italic>\n \u2009<\u20090.017). Interestingly, no temporal differences were observed in ALD levels. REN levels returned to baseline after three months of treatment; yet the ARR, which was primarily influenced by REN, remained below its initial value. Multiple linear regression analysis revealed that a 100% increase in Log-ALD was associated with a 0.143 nmol\/L higher CP and a 15.8% higher HOMA-IR in DKD group(\n p<\/jats:italic>\n \u2009<\u20090.05). A 100% increase in Log-REN was associated with a 0.359 mg\/g lower UACR in DKD group and a 0.042 mmol\/L higher FBG in non-DKD group(\n p<\/jats:italic>\n \u2009<\u20090.01). These correlations were independent of the internal interactions of RAAS but were significantly attenuated after 3 months of treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The correlations between RAAS markers and glucose metabolism indices were significantly attenuated, potentially due to lowered blood glucose levels after SGLT\u20112is treatment. However, it is noteworthy that short-term therapy may elevate REN levels and reduce ARR, potentially resulting in false-negative outcomes in PA screening.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0336158","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:26:32Z","timestamp":1763490392000},"page":"e0336158","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of SGLT-2 inhibitors on renin-angiotensin-aldosterone system and their correlation with glucose metabolism in type 2 diabetes mellitus patients with hypertension: A prospective 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