Sodium-dependent glucose transporter 2 inhibitor alleviates renal lipid deposition and improves renal oxygenation levels in newly diagnosed type 2 diabetes mellitus patients: a randomized controlled trial

Li Zhang; Tongdan Wang; Yan Kong; Haizhen Sun; Yuling Zhang; Junmei Wang; Zhida Wang; Shan Lu; Pei Yu; Saijun Zhou

doi:10.1186/s13098-023-01236-1

Sodium-dependent glucose transporter 2 inhibitor alleviates renal lipid deposition and improves renal oxygenation levels in newly diagnosed type 2 diabetes mellitus patients: a randomized controlled trial

Diabetol Metab Syndr. 2023 Dec 7;15(1):256. doi: 10.1186/s13098-023-01236-1.

Authors

Li Zhang^#¹, Tongdan Wang^#¹, Yan Kong^#¹, Haizhen Sun¹, Yuling Zhang¹, Junmei Wang¹, Zhida Wang¹, Shan Lu¹, Pei Yu², Saijun Zhou³

Affiliations

¹ NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Beichen District, No.6 North Huanrui Rd, Tianjin, 300134, China.
² NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Beichen District, No.6 North Huanrui Rd, Tianjin, 300134, China. yupei@tmu.edu.cn.
³ NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Beichen District, No.6 North Huanrui Rd, Tianjin, 300134, China. zhousaijun@tmu.edu.cn.

^# Contributed equally.

Abstract

Background: Sodium-dependent glucose transporter 2 inhibitor (SGLT2i) has the advantages of effectively lowering blood glucose levels and improving renal outcomes in diabetic patients. This study evaluated the effect of canagliflozin on intrarenal lipid content and oxygenation in newly diagnosed type 2 diabetes mellitus (T2DM) patients.

Methods: A total of 64 newly diagnosed T2DM patients with normal renal function were randomly divided into canagliflozin (n = 33) and glimepiride control (n = 31) groups. All patients underwent functional magnetic resonance imaging (fMRI) scanning to assay patients' intrarenal lipid content and oxygenation level before and after 24 weeks of treatment. Furthermore, the relationship between body mass index and intrarenal lipid content in T2DM patients was analyzed and the correlation between changes in intrarenal lipid content and improvements in renal hypoxia was further assessed.

Results: The canagliflozin group had a greater decrease in body weight and blood uric acid level than the glimepiride group (all P < 0.05). The intrarenal lipid content could be significantly reduced after canagliflozin treatment for 24 weeks. The R2* values, a parameter for quantifying the oxygen content in tissues and is inversely related to the oxygen content, of the renal cortex and medulla in the canagliflozin group decreased from the baseline by 6.40% (P < 0.01) and 12.09% (P = 0.000007), respectively. In addition, the degree of reduction of fat fraction (ΔFF) in the kidneys of the canagliflozin group was correlated with the degree of improvement of oxygenation level (ΔR2*) in the renal cortex (r = 0.422, P = 0.014).

Conclusions: The early renal protective effect of SGLT2i in newly diagnosed T2DM patients may be partly attributed to the amelioration of renal hypoxia via the alleviation of ectopic lipid deposition in the kidneys.

Trial registration: Chu Hsien-I Memorial Hospital of Tianjin Medical University (ChiCTR2000037951).

Keywords: Canagliflozin; Hypoxia; Intrarenal lipid content; Renal oxygenation level; Type 2 diabetes.

Abstract

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