8073 Association Between Serum GDF15 Level And Metabolic Parameters in Severely Obese Men Undergoing Weight Loss From Lifestyle Intervention

Abstract

Disclosure: S. Bathina: None. V. Fuenmayor Lopez: None. M. Prado: None. G. Colleluori: None. D.T. Villareal: None. R.C. Villareal: None.

Background: Growth Differentiation factor (GDF-15), member of TGF-β superfamily was identified as marker of aging, frailty, and metabolic disorders. Several clinical studies demonstrated an association between GDF15 with obesity and cardiovascular disease. However, information on the changes in GDF15 and its relationship to changes in metabolic and body composition parameters in the population of severely obese subjects undergoing weight loss (WL) remains lacking. Objective: The objective of this study is to evaluate the influence of WL on serum GDF15 level and its relationship to glucometabolic parameters in severely obese hypogonadal men. Method: Data from 116 severely obese (BMI ≥35 kg/m²) hypogonadal men participating in an ongoing clinical trial of WL from lifestyle intervention±anastrozole, aged 35-65 years old (NCT03490513) were analyzed. Hemoglobin A1C (A1C) was measured by HPLC, lipid profile by colorimetric method (except LDL was calculated), testosterone (T) and estradiol (E2) LC-MS and GDF-15 by ELISA. Body composition was measured by DXA. Results: The mean age of the participants was 51.4±7.6 years with mean BMI 41.8 ±5.4 kg/m². At baseline, serum GDF15 positively correlated with age (r=0.25, p=0.01), fasting blood glucose (r=0.29, p=0.004) and A1C (r=0.39, p<0.001) but no correlation was found for lipid parameters and with T and E2. GDF15 was negatively correlated with total lean mass (r= -0.23, p=0.03), appendicular lean mass (r= -0.30, p=0.02), and fat-free mass (r= -0.22, p=0.03), but positively correlated with visceral adipose tissue volume (r=0.22, p=0.03). Average WL was 4.2±4.7% and 5.8±8.5% at 6months (6M) and 12 months (12M), respectively. Overall GDF15 levels increased by 9.4±84.7% at 6M and 18.4±128.0% at 12M. At 12M, changes in GDF15 levels positively correlated with changes in A1C (r= 0.26, p<0.05), and negatively with changes in total cholesterol (r= -0.30, p=0.05), Triglycerides (r= -0.35, p=0.02) and E2 (r=-0.31, p=0.028). For LDL cholesterol changes, a negative correlation with GDF15 changes was observed at 6M (r= -0.27, p=0.047). There was no correlation between changes in GDF15 with changes in body weight and changes in body composition parameters. A comparison for those with significant WL (≥5%) vs. those with less WL showed that at 6M, GFD15 levels were reduced among those with WL of ≥5% (-19.5±42.3%) vs <5% (+19.8±93.9%), p=0.07, and at 12M (≥5% (-29.5±38.7) vs <5% (+0.61±69%), p<0.1). Conclusion: We demonstrated that changes in serum GDF15 in severely obese men undergoing WL was associated with alteration in cardiometabolic parameters. Our results show a new perspective on the potential role of GDF15 in cardiometabolic disorders associated with severe obesity. Aside from GDF15 used as a biomarker for health, it may also be used as target for drug development in modifying potential cardiometabolic complications in severe obesity.

Presentation: 6/1/2024