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. 2023 May 10:14:1103251.
doi: 10.3389/fendo.2023.1103251. eCollection 2023.

Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes

Lijun Zhao  1   2 , Yutong Zou  2 , Yucheng Wu  2 , Linli Cai  2 , Yuancheng Zhao  2 , Yiting Wang  2 , Xiang Xiao  2 , Qing Yang  2 , Jia Yang  2 , Honghong Ren  2 , Nanwei Tong  3 , Fang Liu  2
Affiliations

Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes

Lijun Zhao et al. Front Endocrinol (Lausanne). .

Abstract

Background: Obesity often initiates or coexists with metabolic abnormalities. This study aimed to investigate the pathological characteristics and the independent or mutual relations of obesity and metabolic abnormalities with end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) and associated diabetic kidney disease (DKD).

Methods: A total of 495 Chinese patients with T2D and biopsy-confirmed DKD between 2003 and 2020 were enrolled in this retrospective study. The metabolic phenotypes were based on the body weight index (BMI)-based categories (obesity, BMI ≥ 25.0 kg/m2) and metabolic status (metabolically unhealthy status, ≥ 1 criterion National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) excluding waist circumference and hyperglycemia) and were categorized into four types: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO). The pathological findings were defined by the Renal Pathology Society classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) for ESKD.

Results: There are 56 (11.3%) MHNO patients, 28 (5.7%) MHO patients, 176 (35.6%) MUNO patients, and 235 (47.5%) MUO patients. The high prevalence of the Kimmelstiel-Wilson nodule and severe mesangial expansion were associated with obesity, whereas severe IFTA was related to metabolically unhealthy status. In the multivariate analysis, the adjusted HR (aHR) was 2.09 [95% confidence interval (CI) 0.99-4.88] in the MHO group, 2.16 (95% CI 1.20-3.88) in the MUNO group, and 2.31 (95% CI 1.27-4.20) in the MUO group compared with the MHNO group. Furthermore, the presence of obesity was insignificantly associated with ESKD compared with non-obese patients (aHR 1.22, 95% CI 0.88-1.68), while the metabolically unhealthy status was significantly associated with ESKD compared to the metabolically healthy status in the multivariate analysis (aHR 1.69, 95% CI 1.10-2.60).

Conclusion: Obesity itself was insignificantly associated with ESKD; however, adding a metabolically unhealthy status to obesity increased the risk for progression to ESKD in T2D and biopsy-proven DKD.

Keywords: diabetic kidney disease; end-stage kidney disease; metabolic phenotype; prognostic factor; type 2 diabetes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of patients in this study.
Figure 2
Figure 2
Survival rate of end-stage kidney disease in all patients with type 2 diabetes according to the metabolic phenotype (A), obesity or not (B), metabolically healthy status (C), or according to the number of metabolic abnormalities except for diabetes (D).
See this image and copyright information in PMC

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