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

Front Endocrinol (Lausanne). 2023 May 10:14:1103251. doi: 10.3389/fendo.2023.1103251. eCollection 2023.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Weight
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / epidemiology
  • Humans
  • Kidney Failure, Chronic* / complications
  • Kidney Failure, Chronic* / epidemiology
  • Obesity / complications
  • Obesity / epidemiology
  • Obesity, Metabolically Benign* / epidemiology
  • Phenotype
  • Retrospective Studies
  • Risk Factors

Grants and funding

This study was supported by the National Natural Science Foundation of China [Grant numbers 81970626 and 82100756], the Key Research and Development Project of Sichuan Science and Technology Department [Grant number 19ZDYF1273], and the Postdoctoral Research Foundation of Sichuan University [Grant number 2021SCU12029]. The funding source played no role in study design, data analysis, and manuscript writing or submission.