Local heating of the skin around the infusion site significantly reduced postprandial BG by enhancing insulin absorption. The heating device was well tolerated, and it could facilitate development of closed-loop systems.

Background: Currently, two systems for continuous tissue glucose monitoring (CGM) (Dexcom® G5 [DG5] and FreeStyle Libre [FL]) are intended to replace blood glucose monitoring (BGM) and, according to manufacturer labeling, are distributed as such in some jurisdictions, including the United States and the European Union.Methods: The measurement performance of these two systems in comparison with a BGM system was analyzed in a 14-day study with 20 participants comprising study site visits, which included phases of induced rapid glucose changes, and home use phases. Performance analysis was mainly based on deviations between CGM readings and BGM results. Sensor-to-sensor precision was also analyzed.Results: Approximately 25% of DG5 and FL results showed differences from BGM results exceeding 15 mg/dL or 15% (at glucose concentration below or above 100 mg/dL, respectively) at times of therapeutic decisions, and ∼5% of differences exceeded 30 mg/dL or 30%. Performance was different depending on the setting (study site visits, home use phases, and phases of induced rapid glucose changes). In consensus error grid (CEG) analysis, both systems showed >99.5% of results within the clinically acceptable zones A and B.Conclusions: In this study, both systems showed deviations from blood glucose (BG) measurements, the current standard approach in diabetes therapy. Although a large percentage of results was found in CEG zones A and B, for approximately one in four therapeutic decisions, CGM and BG readings differed by at least 15 mg/dL or 15%. Such deviations should be taken into account when using CGM systems.

Background: Continuous interstitial glucose monitoring (CGM) systems often provide glucose trend indicators (e.g., arrows) in addition to current glucose values. These indicators are recommended to be used in therapeutic decisions, because they are ascribed predictive qualities by CGM system manufacturers and expert committees. This study assessed how reliably trend indicators match future glucose change, because such information is missing.Methods: In a clinical trial, two different CGM systems were used by 20 participants, with two sensors of each system per patient. Participants used the systems for 14 days with three study site visits (48 h each). During study site visits, glucose trend indicators, as displayed by the CGM systems, were recorded at least once per hour during daytime and once at night in a diary. In addition, CGM data were downloaded from the devices.Trend indicators were compared with glucose change calculated from CGM data >30 min after recording the trend indicator.Results: Approximately 60% of trend indicators matched the glucose change calculated from CGM data. More than 10% of trend indicators differed by at least two trend indicator categories. Focusing on trend indicators recorded around carbohydrate (CHO) intake and insulin deliveries resulted in approximately half of trend indicators matching the calculated glucose change.Conclusions: Trend indicators do not always match future glucose change, especially within the first few hours after CHO intake and insulin deliveries. Manufacturers' labeling and recommendations should reflect this, so that CGM users can make informed decisions.

Insulin pumps are used by many patients with diabetes to manage their diabetes therapy. Adequate handling of the systems is important to avoid errors. In this study, one aspect of device handling-the number of steps required to operate the system-was evaluated for different insulin pump systems. Specific tasks that are usually performed by insulin pump users were simulated and all necessary actions were documented. Differences between the required numbers of steps strongly depended on the specific task. So did the level of guidance for these tasks provided by the systems. Results of this study provide an overview of this particular aspect of insulin pump handling rather than a general advice.

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Resistance to current treatment regimens such as radiation therapy remains a major concern in oncology and may be caused by defects in apoptosis programs. Since “Inhibitor of apoptosis proteins” (IAPs), which are expressed at high levels in many tumors, block apoptosis at the core of the apoptotic machinery by inhibiting caspases, therapeutic modulation of IAPs could target a key control point in resistance. Here, we report for the first time that full length or mature Smac, an inhibitor of IAPs, significantly enhanced γ-irradiation-induced apoptosis and reduced clonogenic survival in neuroblastoma, glioblastoma or pancreatic carcinoma cells. Notably, Smac had no impact on DNA damage/DNA repair, activation of NF-κB, upregulation of p53 and p21 proteins or cell cycle arrest following γ-irradiation indicating that Smac did not alter the initial damage and/or cellular stress response. Smac enhanced activation of caspase-2, -3, -8 and -9, loss of mitochondrial membrane potential and cytochrome c release upon γ-irradiation. Inhibition of caspases also blocked γ-irradiation-induced mitochondrial perturbations, indicating that Smac facilitated caspase activation, which in turn triggered a mitochondrial amplification loop. Interestingly, mitochondrial perturbations were completely blocked by the broad range caspase inhibitor zVAD.fmk or the relatively selective caspase-2 inhibitor zVDVAD.fmk, whereas caspase-8 or caspase-3 inhibitors only inhibited the increased drop of mitochondrial membrane potential provided by Smac, suggesting that caspase-2 was acting upstream of mitochondria upon γ-irradiation. In conclusion, our findings provide evidence that targeting IAPs, e.g. by Smac agonists, is a promising strategy to enhance radiosensitivity in human cancers.

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