Investigating the role of GDF-15 in diabetes and obesity: A comprehensive analysis of a cohort from the KEDP-study

Introduction: Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β (TGF-β) superfamily, is expressed in various tissues and is produced during stressful conditions such as inflammation and oxidative stress. It has recently gained attention as a potential diagnostic and prognostic marker for metabolic disorders. However, little is known about the GDF-15 protein expression in diabetes and obesity, particularly across various ethnicities, age groups, and genders. This study investigated the association between GDF-15 plasma levels, diabetes mellitus, and obesity in individuals of various ages, ethnic groups, and genders. Methods We measured plasma GDF-15 concentrations in 2,083 participants from the Kuwait Diabetes Epidemiology Programme (KDEP) study cohort. The cohort included information on a anthropometric clinical, biochemical, and glycemic markers. The phenotype data were analyzed using multivariate regression analysis. Results The average plasma GDF-15 concentration across the study cohort was significantly higher in males than in females (580.6 ng/L vs. 519.3 ng/L, p < 0.001) and in those who were > 50 years old than those < 50 years of age (781.4 ng/L vs. 563.4 ng/L, p < 0.001). Participants from Arab ethnic backgrounds had higher GDF-15 levels than South Asians and Southeast Asians (597.0 vs 514.9 and 509.9 ng/L, p < 0.001). Furthermore, GDF-15 levels were significantly higher in obese individuals, in diabetic individuals, and in insulin resistant individuals. GDF-15 levels were positively corrrelated with BMI, hip and waist circumferences, blood pressure readings, and glycemic indices, including insulin and triglyceride levels, while they were negatively correlated with HDL. Conclusion The observed findings on the associations between higher levels of GDF-15 and increased age, diabetes, obesity, and insulin resistance suggest that GDF-15 may have particular utility as a valuable biomarker for metabolic disorders, especially in older age groups, among males, and within specific ethnic groups.