Background-The matrix metalloproteinases (MMPs) contribute to regional remodeling after prolonged periods of ischemia and reperfusion (I/R), but specific MMP types activated during this process remain poorly understood. A novel class, the membrane-type MMPs (MT-MMPs), has been identified in the myocardium, but activity of these MMP types has not been assessed in vivo, particularly during I/R. Methods and Results-Pigs (30 kg, nϭ8) were instrumented with microdialysis catheters to measure MT1-MMP activity in both ischemic and nonischemic (remote) myocardium. A validated MT1-MMP fluorogenic substrate was infused through the microdialysis system, and changes in fluorescence were reflective of MT1-MMP activity at steady state, during ischemia (90 minutes), and during reperfusion (120 minutes). At peak ischemia, MT1-MMP activity was increased by Ͼ40% in the ischemic region, with no change in the remote region, which persisted with reperfusion (PϽ0.05). After I/R, MT1-MMP abundance was increased by Ͼ50% (PϽ0.05). Differential centrifugation revealed that the endosomal fraction (which contains subcellular organelles) within the ischemic myocardium was associated with a Ͼ135% increase in MT1-MMP (PϽ0.05). Furthermore, in an isolated left ventricular myocyte model of I/R, hypoxia (simulated ischemia) induced a Ͼ70% increase in MT1-MMP abundance in myocytes, and confocal microscopy revealed MT1-MMP internalization during this time period and reemergence to the membrane with reperfusion. Conclusions-These unique results demonstrate that a specific MMP type, MT1-MMP, is increased in abundance and activity with I/R and is likely attributed, at least in part, to changes in intracellular trafficking.

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Real-time continuous glucose monitoring (rtCGM) can directly improve patient outcomes, including decreased health care system utilization and associated costs. The purpose of this study was to evaluate the clinical benefits of rtCGM use in a high-risk, under-resourced cohort of adolescents and young adults (AYA) with type 1 diabetes (T1D) who had no prior access to rtCGM. The effects of rtCGM use on hemoglobin A1c (A1c) and the frequency of health care events (i.e., diabetes-related emergency room (ER) visits, hospitalizations, emergency medical services (EMS), and after-hour emergency calls) were evaluated regarding payor costs in 33 AYA with ≥70% rtCGM use. Secondary aims included the evaluation of a phone-based pattern management intervention. The frequency of health care events decreased at 12 and 24 weeks for all participants, and there was no significant difference by treatment group. We estimated that the use of rtCGM in this cohort results in a projected annualized cost-savings of $195,943 to $294,864 or 43–65% per year based on Medicare or list pricing for rtCGM, respectively. Results also revealed improvements in A1c at 12 weeks for all study participants, but this was not maintained at 24 weeks for the phone-based pattern management intervention group. Our findings suggest that rtCGM may be an effective tool for reducing diabetes-related events and underscores the importance of access. Future studies are needed to further examine tailored interventions and support to optimize rtCGM use and glycemic health in high-risk AYA.

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