1195-P: Metformin and Growth Differentiation Factor 15 (GDF-15) in Youth with Type 2 Diabetes

Abstract

Metformin is the only approved oral therapy in youth with type 2 diabetes (T2D-Y) but its molecular mechanisms remain controversial. Recent data links metformin-induced weight loss with increased levels of a peptide hormone, growth differentiation factor 15 (GDF15). Yet high GDF15 is linked to high stress and lipolysis and its value in T2D-Y is known. We compared fasting GDF15 in 32 T2D-Y not on metformin to 15 matched peers without diabetes and determined the change in GDF15 in 19 T2D-Y after 3 months of metformin (metformin only, n=13 and metformin + liraglutide, n=6). Youth were 15.5 ± 2.6 years (mean ± SD), 64% female, 78% African American with similar BMI 39 ± 7 kg/m2). T2D-Y had higher HbA1c (6.9 ± 1.1 vs. 5.6 ± 0.3%, P 0.2). GDF15 increased ≥2-fold in 6 of 18 T2D-Y (Figure). Overall, GDF15 correlated with age (r=0.4, P=0.01) but the change in GDF15 did not correlate with changes in glucose, weight, blood pressure, inflammatory markers, sex or treatment group. GDF15 was highly variable and not associated with cardiometabolic markers in youth. GDF15 markedly increased in a small subset of youth, but the determinants and implications of this change remain to be elucidated. Changes in GDF15 may have no association with metformin action. Disclosure S. Matta: None. M. W. Haymond: Advisory Panel; Self; Daiichi Sankyo, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Stock/Shareholder; Self; Xeris Pharmaceuticals, Inc. S. T. Chung: None. C. K. Cravalho: None. A. Villalobos-perez: None. L. Mabundo: None. V. R. Sharma: None. M. Walter: None. J. M. Dawson: None. A. Zenno: None. A. B. Courville: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases