EMERALD: Effects of Metformin on Cardiovascular Function in Adolescents With Type 1 Diabetes

Diabetes is increasingly common among youth, forecasting early complications. Type 1 (T1D)
cause early heart disease, shortening lifespan despite modern improvements in control of
blood sugars and other risk factors for heart disease. Poor insulin action, otherwise known
as insulin resistance (IR), is the main factor causing heart disease in type 2 diabetes
(T2D), but the cause of increased heart disease in T1D is unclear. IR may contribute to heart
disease in T1D as in T2D, as the investigators and others have found the presence of IR in
T1D. Much less is known about IR in T1D, but a better understanding of its role in T1D is
critical to understanding causes of heart disease in T1D. The investigators long-term goal is
to understand the early causes of heart disease in diabetes so that we can prevent it. The
investigators unique initial findings suggest that even reasonably well-controlled, normal
weight, T1D youth are IR. The IR appears directly related to the heart, blood vessel, and
exercise defects, but in a pattern that appears very different from T2D. The goals of this
study are to determine the unique heart, blood vessel and insulin sensitivity abnormalities
in T1D youth, and determine whether metformin improves these abnormalities. A clear
understanding of these factors will help determine the causes, and what treatments could help
each abnormality.

Hypothesis 1: Metformin will improve insulin function and mitochondrial function in T1D.

Hypothesis 2: Metformin will improve vascular and cardiac function in T1D.

All measures will be performed twice, before and after a 3-month randomized,
placebo-controlled design where subjects are randomized to either metformin or placebo. The
independent impact of insulin action as well as glucose levels, BMI, T1D duration, and gender
on baseline outcomes and the impact of changes in insulin action, glucose levels and BMI on
response to metformin will also be examined to help customize future strategies to prevent
heart disease in T1D. This study will advance the field by providing new information about
the role of poor insulin action in the heart disease of T1D, and whether improving insulin
action in T1D is helpful. If a focus on directly improving insulin action in T1D youth is
supported by our studies, the clinical approach to T1D management may significantly change.