Relevance of GDF15 as a biomarker for clinical outcomes after bariatric surgery

Bariatric surgery (BS) is the most effective long-term approach for weight loss and improvement of obesity-related comorbidities. Growth differentiation factor 15 (GDF15), a cytokine that enhances insulin sensitivity and reduces food intake, is a promising therapeutic target for obesity. This study assessed changes in circulating GDF15 levels in obesity and following BS, examining their associations with anthropometric, clinical, and biochemical parameters. Circulating GDF15 levels were measured in normal-weight individuals and patients with obesity before BS and at 3, 6 and 12 months post-surgery. Correlation analyses and linear mixed models were used to investigate variations in circulating GDF15 levels and to identify variables associated with GDF15 concentration. Circulating GDF15 levels were elevated in patients with obesity compared to normal-weight individuals and were higher in men than in women. In the combined cohort of obese and normal-weight individuals, circulating GDF15 levels positively correlated with weight, BMI, fat mass, glucose markers, C-reactive protein, transaminases, triglycerides, urea, creatinine and uric acid, and negatively correlated with apolipoprotein A and total, HDL and LDL cholesterol. In the obese cohort, however, circulating GDF15 levels showed a negative correlation with fat mass, while other associations persisted. After BS, circulating GDF15 levels significantly decreased, particularly in patients with hypertension or type 2 diabetes (T2D). One year post-surgery, ΔGDF15 was negatively associated with BMI and positively with excess weight loss and excess BMI loss. In conclusion, BS significantly reduces circulating GDF15 levels, particularly in patients with hypertension or T2D, indicating an association with clinical improvement after BS.