Accuracy of Continuous Glucose Monitoring before, during, and after Aerobic and Anaerobic Exercise in Patients with Type 1 Diabetes Mellitus

[EN] Continuous glucose monitoring (CGM) plays an important role in treatment decisions for patients with type 1 diabetes under conventional or closed-loop therapy. Physical activity represents a great challenge for diabetes management as well as for CGM systems. In this work, the accuracy of CGM in the context of exercise is addressed. Six adults performed aerobic and anaerobic exercise sessions and used two Medtronic Paradigm Enlite-2 sensors under closed-loop therapy. CGM readings were compared with plasma glucose during different periods: one hour before exercise, during exercise, and four hours after the end of exercise. In aerobic sessions, the median absolute relative difference (MARD) increased from 9.5% before the beginning of exercise to 16.5% during exercise (p < 0.001), and then decreased to 9.3% in the first hour after the end of exercise (p < 0.001). For the anaerobic sessions, the MARD before exercise was 15.5% and increased without statistical significance to 16.8% during exercise realisation (p = 0.993), and then decreased to 12.7% in the first hour after the cessation of anaerobic activities (p = 0.095). Results indicate that CGM might present lower accuracy during aerobic exercise, but return to regular operation a few hours after exercise cessation. No significant impact for anaerobic exercise was found.This project was partially supported by the Spanish Government through grants DPI2013-46982-C2-1-R, DPI2013-46982-C2-2-R, DPI2016-78831-C2-1-R, and DPI2016-78831-C2-2-R, and by the National Council of Technological and Scientific Development, CNPq Brazil through grants 202050/2015-7 and 207688/2014-1.Biagi, L.; Bertachi, A.; Quirós, C.; Giménez, M.; Conget, I.; Bondía Company, J.; Vehí, J. (2018). Accuracy of Continuous Glucose Monitoring before, during, and after Aerobic and Anaerobic Exercise in Patients with Type 1 Diabetes Mellitus. Biosensors. 8(1):1-8. https://doi.org/10.3390/bios8010022S188

Extensive assessment of blood glucose monitoring during postprandial period and its impact on closed-loop performance

[EN] Background: Closed-loop (CL) systems aims to outperform usual treatments in blood glucose control and continuous glucose monitors (CGM) are a key component in such systems. Meals represents one of the main disturbances in blood glucose control, and postprandial period (PP) is a challenging situation for both CL system and CGM accuracy. Methods: We performed an extensive analysis of sensor¿s performance by numerical accuracy and precision during PP, as well as its influence in blood glucose control under CL therapy. Results: During PP the mean absolute relative difference (MARD) for both sensors presented lower accuracy in the hypoglycemic range (19.4 ± 12.8%) than in other ranges (12.2 ± 8.6% in euglycemic range and 9.3 ± 9.3% in hyperglycemic range). The overall MARD was 12.1 ± 8.2%. We have also observed lower MARD for rates of change between 0 and 2 mg/dl. In CL therapy, the 10 trials with the best sensor spent less time in hypoglycemia (PG < 70 mg/dl) than the 10 trials with the worst sensors (2 ± 7 minutes vs 32 ± 38 minutes, respectively). Conclusions: In terms of accuracy, our results resemble to previously reported. Furthermore, our results showed that sensors with the lowest MARD spent less time in hypoglycemic range, indicating that the performance of CL algorithm to control PP was related to sensor accuracy.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has been partially supported by the Spanish Government through Grants DPI 2013-46982-C2-1-R, DPI 2016-78831-C2-1-R, DPI 2013-46982-C2-2-R, and DPI 2016-78831-C2-2-R, the National Council of Technological and Scientific Development, CNPq Brazil through Grants 202050/2015-7 and 207688/2014-1.Biagi, L.; Hirata-Bertachi, A.; Conget, I.; Quirós, C.; Giménez, M.; Ampudia-Blasco, F.; Rossetti, P.... (2017). Extensive assessment of blood glucose monitoring during postprandial period and its impact on closed-loop performance. Journal of Diabetes Science and Technology. 11(6):1089-1095. https://doi.org/10.1177/1932296817714272S10891095116Doyle, F. 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Time Lag of Glucose From Intravascular to Interstitial Compartment in Type 1 Diabetes. Journal of Diabetes Science and Technology, 9(1), 63-68. doi:10.1177/1932296814554797Keenan, D. B., Grosman, B., Clark, H. W., Roy, A., Weinzimer, S. A., Shah, R. V., & Mastrototaro, J. J. (2011). Continuous Glucose Monitoring Considerations for the Development of a Closed-Loop Artificial Pancreas System. Journal of Diabetes Science and Technology, 5(6), 1327-1336. doi:10.1177/193229681100500603Van Bon, A. C., Jonker, L. D., Koebrugge, R., Koops, R., Hoekstra, J. B. L., & DeVries, J. H. (2012). Feasibility of a Bihormonal Closed-Loop System to Control Postexercise and Postprandial Glucose Excursions. Journal of Diabetes Science and Technology, 6(5), 1114-1122. doi:10.1177/193229681200600516Rossetti, P., Quirós, C., Moscardó, V., Comas, A., Giménez, M., Ampudia-Blasco, F. J., … Vehí, J. (2017). Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target. Diabetes Technology & Therapeutics, 19(6), 355-362. doi:10.1089/dia.2016.0443Bailey, T., Zisser, H., & Chang, A. (2009). New Features and Performance of a Next-Generation SEVEN-Day Continuous Glucose Monitoring System with Short Lag Time. Diabetes Technology & Therapeutics, 11(12), 749-755. doi:10.1089/dia.2009.0075Zschornack, E., Schmid, C., Pleus, S., Link, M., Klötzer, H.-M., Obermaier, K., … Freckmann, G. (2013). Evaluation of the Performance of a Novel System for Continuous Glucose Monitoring. Journal of Diabetes Science and Technology, 7(4), 815-823. doi:10.1177/193229681300700403Pleus, S., Schmid, C., Link, M., Zschornack, E., Klötzer, H.-M., Haug, C., & Freckmann, G. (2013). Performance Evaluation of a Continuous Glucose Monitoring System under Conditions Similar to Daily Life. 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The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells

Type 1 diabetes mellitus (T1D) is due to autoimmune destruction of pancreatic beta-cells. Previously, we have shown that intravenously administered bone marrow-derived multipotent mesenchymal stromal cells (MSCs) allows pancreatic islet recovery, improves insulin secretion and reverts hyperglycemia in low doses streptozotocin (STZ)-induced diabetic mice. Here we evaluate whether insulin prophylaxis and the administration of a second dose of cells affect the antidiabetic therapeutic effect of MSC transplantation. Insulitis and subsequent elimination of pancreatic beta-cells was promoted in C57BL/6 mice by the injection of 40 mg/kg/day STZ for five days. Twenty-four days later, diabetic mice were distributed into experimental groups according to if they received or not insulin and/or one or two doses of healthy donor-derived MSCs. Three and half months later: glycemia, pancreatic islets number, insulinemia, glycated hemoglobin level and glucose tolerance were determined in animals that did not received exogenous insulin for the last 1.5 months. Also, we characterized MSCs isolated from mice healthy or diabetic. The therapeutic effect of MSC transplantation was observed in diabetic mice that received or not insulin prophylaxis. Improvements were similar irrespective if they received one or two doses of cells. Compared to MSCs from healthy mice, MSCs from diabetic mice had the same proliferation and adipogenic potentials, but were less abundant, with altered immunophenotype and no osteogenic potential

Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

BACKGROUND: Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. PRESENTATION: We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. IMPLICATIONS: We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. TESTING: Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis