Flash Glucose-Sensing Technology as a Replacement for Blood Glucose Monitoring for the Management of Insulin-Treated Type 2 Diabetes: a Multicenter, Open-Label Randomized Controlled Trial

Introduction Glycemic control in participants with insulin-treated diabetes remains challenging. We assessed safety and efficacy of new flash glucose-sensing technology to replace self-monitoring of blood glucose (SMBG). Methods This open-label randomized controlled study (ClinicalTrials.gov, NCT02082184) enrolled adults with type 2 diabetes on intensive insulin therapy from 26 European diabetes centers. Following 2 weeks of blinded sensor wear, 2:1 (intervention/control) randomization (centrally, using biased-coin minimization dependant on study center and insulin administration) was to control (SMBG) or intervention (glucose-sensing technology). Participants and investigators were not masked to group allocation. Primary outcome was difference in HbA1c at 6 months in the full analysis set. Prespecified secondary outcomes included time in hypoglycemia, effect of age, and patient satisfaction. Results Participants (n = 224) were randomized (149 intervention, 75 controls). At 6 months, there was no difference in the change in HbA1c between intervention and controls: −3.1 ± 0.75 mmol/mol, [−0.29 ± 0.07% (mean ± SE)] and −3.4 ± 1.04 mmol/mol (−0.31 ± 0.09%) respectively; p = 0.8222. A difference was detected in participants aged <65 years [−5.7 ± 0.96 mmol/mol (−0.53 ± 0.09%) and −2.2 ± 1.31 mmol/mol (−0.20 ± 0.12%), respectively; p = 0.0301]. Time in hypoglycemia <3.9 mmol/L (70 mg/dL) reduced by 0.47 ± 0.13 h/day [mean ± SE (p = 0.0006)], and <3.1 mmol/L (55 mg/dL) reduced by 0.22 ± 0.07 h/day (p = 0.0014) for intervention participants compared with controls; reductions of 43% and 53%, respectively. SMBG frequency, similar at baseline, decreased in intervention participants from 3.8 ± 1.4 tests/day (mean ± SD) to 0.3 ± 0.7, remaining unchanged in controls. Treatment satisfaction was higher in intervention compared with controls (DTSQ 13.1 ± 0.50 (mean ± SE) and 9.0 ± 0.72, respectively; p < 0.0001). No serious adverse events or severe hypoglycemic events were reported related to sensor data use. Forty-two serious events [16 (10.7%) intervention participants, 12 (16.0%) controls] were not device-related. Six intervention participants reported nine adverse events for sensor-wear reactions (two severe, six moderate, one mild). Conclusion Flash glucose-sensing technology use in type 2 diabetes with intensive insulin therapy results in no difference in HbA1c change and reduced hypoglycemia, thus offering a safe, effective replacement for SMBG

A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area

Tn this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications hi reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny wit-bin HG 9 (Rosser et al. 2000) with the deepest branching defined by alleles T (Haplogroup Eu 10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, xvith a high rate of male gene flow in the Turkish Greek area

Population Physiology: Leveraging Electronic Health Record Data to Understand Human Endocrine Dynamics

Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR) data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i) aggregation of the population can obscure or generate a signal, (ii) there is often no control population with a well understood health state, and (iii) diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI), did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube) fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly predict the difference between the general uncontrolled population and a subpopulation whose feeding was controlled

Closed-loop insulin delivery for treatment of type 1 diabetes

Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.Supported by the Juvenile Diabetes Research Foundation (#22-2006-1113, #22-2007-1801, #22-2009-801), Diabetes UK (BDA07/0003549, BDA07/0003551), European Commission Framework Programme 7 (247138), NIDDK (DK085621), and NIHR Cambridge Biomedical Research Centre

Optical Drug Monitoring: Photoacoustic Imaging of Nanosensors to Monitor Therapeutic Lithium in Vivo

Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes