Metformin Improves Cardiac and Aortic Parameters in Adolescents with Type 1 Diabetes

Purpose: People with type 1 diabetes (T1D) have higher rates of cardiovascular disease (CVD) despite modern advances in glucose control. While insulin resistance (IR) is known to relate to CVD in type 2 diabetes, less is understood about IR in T1D-related CVD. We previously found vascular and cardiac dysfunction, including left ventricular (LV) dyssynchrony, in adolescents with T1D. In the Effects of MEtformin on caRdiovascular function in AdoLescents with type 1 Diabetes (EMERALD) study, we also showed that metformin improves BMI, body composition, insulin sensitivity, arterial stiffness, and carotid intimal media thickness in T1D adolescents. We hypothesized that metformin, with insulin-sparing effects, would improve echocardiographically-assessed cardiac and aortic health. Methods: 43 T1D youth ages 12-21 years (mean age 16.8 ± 2.5 years, HbA1c 8.6 ± 1.5%, BMI 25.1 ± 4.3 kg/m2, diabetes duration 7.7 ± 4.2 years) from the EMERALD study who were randomized to 3 months of either 1000 mg BID of metformin (n=23) or placebo (n=20) had echocardiograms with speckle tracking to evaluate traditional echocardiographic measures, cardiac strain and synchrony, and aortic root diameter at baseline and 3 months. One-way ANOVA and paired t-tests were utilized to assess the impacts of metformin. Results: LV diameter (4.45 ± 0.47 vs. 4.26 ± 0.50 cm, p = 0.019) at end-diastole and at end-systole (2.89 ± 0.39 vs. 2.69 ± 0.36 cm, p = 0.022) and LV dyssynchrony (98.0 ± 36.9 vs. 81.7 ± 27.5 milliseconds, p = 0.014) showed significant improvement within the metformin group. Aortic root diameter (2.51 ± 0.39 vs. 2.73 ± 0.28 cm, p = 0.042) was also significantly lower in the metformin vs. placebo group post-treatment. Conclusions: Metformin may be beneficial in improving or reversing early cardiovascular changes in T1D detectable by echocardiogram. A better understanding of T1D-related CVD and the benefits of improving insulin action in T1D longer-term should be investigated further as a target for new treatment modalities. Disclosure A. Nguyen: None. U. Truong: None. M. Schafer: None. A. Baumgartner: None. A. J. Barker: None. K. S. Hunter: None. D. Burkett: None. J. E. Reusch: Advisory Panel; Self; Medtronic. K. J. Nadeau: None. Funding American Diabetes Association (7-11-CD-08 to K.J.N.)