Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)

The CACTI cohort is being followed for progression of coronary artery calcification (CAC) for development of clinical CVD and participants have been characterized during the baseline examination (4/00-3/02) and two follow-up re-examinations 3 and 6 years later. We are proposing assess a subset of this population to determine vasodilatory reserve as it relates to early coronary atherosclerosis in T1D. In the CACTI Study sought to determine the relationship between risk factors for CAD and coronary arterial calcification in T1D subjects compared to an age and gender matched control cohort. The trial identified CAC as a high risk marker of CAD and was more extensive in diabetic patients.

T1D patients have more CAC than nondiabetic controls but they also appear to have more impaired coronary vasoreactive function. Impaired response to acetylcholine testing and adenosine vasodilation are reported in diabetic subjects. The relationship between coronary microvascular dysfunction and diabetic cardiomyopathy is supported by observation of similar microvascular abnormalities. Endothelial dysfunction not only precedes and predicts clinical macrovascular disease, but also is an independent prognostic marker of adverse long-term cardiovascular outcomes. Significantly greater CAC in T1D was also noted than in non-DM subjects. There is also a greater rate of increase noted in the CACTI cohort.

Myocardial Flow Reserve by MRI: Myocardial perfusion distribution and myocardial blood flow reserve can be simultaneously assessed using a MRI first-pass Gd contrast injection approach. Rapid MR imaging (MRI) during the first pass injection of Gd compounds is used to assess myocardial perfusion with a spatial resolution of 2-3 mm, and to detect any regional impairments of myocardial blood flow (MBF) that may lead to ischemia. The myocardial perfusion reserve (MPR) is a useful concept for quantifying the vasodilator response. The perfusion reserve can be estimated from the ratio of MBFs during vasodilation and at baseline, similar to that described by labeled microspheres. Assessment of myocardial blood flow and flow reserve by cardiac MR is a robust technique. There is a relationship between CAC and hyperemic flow reserve, although it may be more or less strong depending upon the methodology employed. However, CAC is still a marker of the atherosclerotic process and this process appears to be more aggressive in T1D. The investigation of MBF reserve as a marker of early or more aggressive vasculopathy is important, especially in a disease with significant morbidity and mortality from cardiovascular events.

Regadenoson Vasodilation: Regadenoson is a selective A2A adenosine receptor agonist FDA released as a pharmacologic vasodilator in nuclear stress myocardial perfusion imaging (MPI). It has a higher affinity for A2A receptors than adenosine and is a more potent coronary vasodilator. Adenosine infusion is the gold standard for both invasive and non-invasive assessment of myocardial blood flow reserve, yet regadenoson with potentially greater coronary arterial vasodilation and a simple bolus injection is an ideal agent with which to study differences in CFR between different disease states. Limited data is published on the utility of regadenoson in invasive assessment of CFR and no data are published regarding the utility of this agent in assessing the hyperemic myocardial blood flow response with respect to cardiac MRI.

Research Design and Methods POPULATION CACTI Diabetes Study: We propose to recruit subjects from the CACTI cohort into this sub-study by focusing on individuals completing 6-yr follow-up.