# Different association of GDF15 and FGF21 with glycemic status and aging in the context of obesity

## TL;DR

This study finds that GDF15 and FGF21 levels rise with obesity, diabetes, and aging, with GDF15 more linked to aging and FGF21 to metabolic issues.

## Contribution

The FGF21/adiponectin ratio is proposed as a novel biomarker for detecting type 2 diabetes.

## Key findings

- GDF15 and FGF21 levels increase with obesity, impaired glucose tolerance, and type 2 diabetes.
- GDF15 is more strongly associated with aging, while FGF21 is more related to metabolic status.
- The FGF21/adiponectin and GDF15/adiponectin ratios are effective biomarkers for T2D detection.

## Abstract

Growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) are stress-induced cytokines increased in age-related and metabolic disorders. The aim of the present study was to analyze the association between circulating concentrations of GDF15 and FGF21 in obesity and type 2 diabetes (T2D) in the context of aging. Serum samples from 405 participants (33 with normal weight and normoglycemia (NG), 156 with obesity and NG, 157 with obesity and impaired glucose tolerance (IGT), and 59 with obesity and T2D) aged 47 ± 13 years, were recruited to study the serum GDF15 and FGF21 concentrations and their relationship with obesity, T2D, and aging. Adipokines (leptin and adiponectin) and other cardiometabolic risk factors were also measured. The circulating concentrations of GDF15 and FGF21 were significantly increased with obesity and further increased with IGT and T2D. Both GDF15 and FGF21 showed positive associations with glucose (r = 0.25, P < 0.001 and r = 0.40, P < 0.001, respectively) and insulin (r = 0.16, P < 0.01 and r = 0.27, P < 0.001, respectively) levels. Similarly, GDF15 and FGF21 were positively correlated with age (r = 0.55, P < 0.001 and r = 0.15, P < 0.01, respectively). Interestingly, the FGF21/adiponectin and GDF15/adiponectin ratios emerged as good biomarkers for the presence of T2D (AUC = 0.807 and 0.779, respectively). Our findings support that obesity, T2D, and aging increase the concentrations of both GDF15 and FGF21. Furthermore, GDF15 concentrations are more associated with aging while FGF21 levels are more related to the metabolic status. Finally, we propose the FGF21/adiponectin ratio as a novel biomarker for the detection of the presence of T2D.

The online version contains supplementary material available at 10.1007/s11357-025-01830-3.