Growth Differentiation Factor (Gdf)-15 And Metabolic Outcomes: The Aric Study

Introduction: Mechanistic studies suggest an involvement of growth differentiation factor 15 (GDF-15) in metabolic dysregulation. However, the potential utility of GDF-15 as a marker of diabetes or metabolic syndrome (MetS) risk remains unclear, especially in older adults. Hypothesis: GDF-15 is positively associated with biomarkers of hyperglycemia, diabetes, and MetS. Methods: We conducted a cross-sectional analysis of older adults who attended visit 6 (2016-2017) of the Atherosclerosis Risk in Communities (ARIC) Study. GDF-15 was measured using electrochemiluminescence immunoassay (Elecsys, Roche Diagnostics). Linear regression was used to assess continuous outcomes after appropriate transformations, and multivariable-adjusted odds of diabetes or MetS by quartiles of GDF-15 were derived using logistic regression. Results: Among 3,792 participants (mean age 80 years, 59% women, 23% blacks and 77% whites), higher GDF-15 concentrations (per 1-unit increase in ln[GDF-15]) were associated with higher levels of fasting plasma glucose (mg/dL) (adjusted β coefficient : 10.98, 95% CI:8.86 - 13.09) and HbA 1C (%)(0.41, 95% CI: 0.35 - 0.48). Higher GDF-15 was associated with greater odds of diabetes (adjusted odds ratio [OR]: 5.81 for highest vs. lowest GDF-15 quartile, 95% CI 4.43-7.61) and of MetS syndrome (adjusted OR: 2.57, 95% CI 2.01-3.20) among individuals without diabetes (Figure). Conclusions: In this sample of older adults, elevated GDF-15 was strongly associated with diabetes and metabolic syndrome. These data strongly suggest that GDF-15 could be a robust biomarker of adverse metabolic states.