Objective
This project will: (1) investigate a potential treatment target (i.e., glycemic variability) for cardiovascular risk reduction in T1D and (2) determine the cardiovascular effects of artificial pancreas technology, a therapy that directly addresses this target.
Background Rationale
Glycemic variability is a proposed risk factor for the substantial excess rate of cardiovascular disease (CVD) in people with type 1 diabetes (T1D), but the pathophysiology driving this relationship is poorly-understood and treatment options are limited. Closed-loop artificial pancreas technology is a tool with proven ability to reduce glycemic variability in T1D, but its potential cardiovascular benefits have not been investigated. This study will examine mechanisms whereby glycemic variability contributes to CVD in people with T1D and examine the cardiovascular effects of reducing glycemic variability by treatment with closed-loop artificial pancreas technology.
Description of Project
Numerous studies indicate that type 1 diabetes (T1D) shortens lifespan by ~8-13 years compared to the general population. Cardiovascular disease (CVD) is a key contributor to this, as CVD events occur more than a decade earlier in people with T1D than in the general population. Controlling blood glucose, blood pressure, and cholesterol are the best available strategies for CVD risk reduction in T1D, but substantial residual risk remains. Glycemic variability (GV) is a proposed risk factor for the excess CVD rate in T1D, but the pathophysiology driving this relationship is poorly-understood and treatment options are limited. This study will (1) clarify how GV contributes to CVD in T1D and (2) determine the cardiovascular effects of artificial pancreas technology, a therapy with proven ability to reduce GV in T1D.
Anticipated Outcome
We anticipate that glycemic variability contributes to CVD in T1D by increasing inflammation and endothelial dysfunction while simultaneously reducing cardiac micro- and macrovascular function. We also anticipate that reducing glycemic variability will improve these parameters.
Relevance to T1D
Epidemiological data indicate that type 1 diabetes (T1D) shortens lifespan by ~8-13 years compared to the general population. Similarly, cardiovascular disease (CVD) events occur more than a decade earlier in people with T1D than in the general population. Glycemic control and LDL reduction are the best available strategies for CVD risk reduction in T1D, but substantial residual risk remains. Glycemic variability (GV) is a proposed risk factor for the excess CVD rate in T1D, but the pathophysiology driving this relationship is poorly-understood and treatment options are limited. Successful completion of this study will: (1) identify pathways whereby GV contributes to CVD in T1D; (2) impact clinical care by identifying a potential treatment target (i.e., GV reduction) that may decrease CVD in T1D; and (3) provide a strong basis for continued examination of a therapy (i.e., AP technology) that directly addresses this target.