A Three-Arm Randomized Controlled Study Comparing Patient-Reported Outcomes in People With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion or Multiple Daily Injections.

BACKGROUND: The aim of this study was to compare patient-reported outcomes (PROs) in people with type 1 diabetes using either continuous subcutaneous insulin infusion (CSII) with two different insulin patch pumps or multiple daily injections (MDIs). MATERIALS AND METHODS: In this randomized three-arm study, people with type 1 diabetes on MDI therapy were included and used either MDI, the Accu-Chek Solo micropump system (Solo) or Omnipod for 26 weeks. From weeks 26 to 39, all participants used CSII with Solo. Patient-reported outcomes were assessed using the diabetes technology questionnaire (DTQ); in addition, HbA1c values were measured. RESULTS: Overall, 181 participants were randomized (61 MDI arm, 62 Solo arm, 58 Omnipod arm) and 142 completed the study. After 26 weeks in the study, the DTQ "change" score in the Solo group (105.9 [100.6-111.2]; baseline-adjusted mean [95% confidence interval]) was significantly higher than in the MDI group (94.8 [89.6-100.0]) (P = .001). The comparison between the Solo group (105.1 [99.1-111.1]) and the Omnipod group (108.7 [103.1-114.4]) showed no significant differences (P = .382). HbA1c increased by 0.2% ± 0.7% in the MDI group and decreased in both pump groups (Solo group -0.2% ± 0.8% and Omnipod group -0.1% ± 0.8%). Differences in HbA1c between the Solo group and the MDI group were significant (P = .009), but not between the Solo group and the Omnipod group (P = .896). CONCLUSIONS: This study showed that switching from MDI to CSII improves both psychosocial well-being and physiological outcomes. Furthermore, there were no substantial differences between the established and the recently released patch pump. Trial registration at www.clinicaltrials.gov is NCT03478969.

Concept and Implementation of a Novel Patch Pump for Insulin Delivery.

With the motivation to provide a small and discreet patch pump that complies with several customer needs, the recently CE-marked Accu-Chek® Solo micropump system was designed. The system consists of a tubeless insulin pump wirelessly controlled by the so-called diabetes manager. Via diabetes manager, basal rates and boluses are programmed; an integrated blood glucose meter and bolus calculator supports users in bolusing and offers several diary functions. The micropump features a quick bolus button for bolus initiation directly on the pump and is complemented by a disposable reservoir holding up to 200 U of rapid-acting insulin. The assembled pump is attached to the body via a pump holder containing soft cannula. The modular principle enables independent replacement of the single components if necessary.

Randomized Cross-Over Study Comparing Two Infusion Sets for CSII in Daily Life.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) therapy is a valuable option especially for people with type 1 diabetes. Although insulin infusion sets (IIS) are essential components of most insulin pump systems, only few studies have been conducted on their performance and safety. In this study 2 IIS with soft cannulas were compared. METHODS: In an open-label, randomized, crossover, multicenter 8-week study 80 type 1 diabetic subjects on CSII (20-74 years, mean 46.5 ± 12.9 years, 58.8% male) were enrolled to evaluate the use of 2 IIS. The Accu-Chek® FlexLink Plus (FL Plus) and the Accu-Chek® FlexLink infusion set (FL) were used 4 weeks each under real-life conditions at home. All patients had to record details about every IIS change in a diary. Insertion-related pain was assessed by means of a visual analogue scale (VAS). RESULTS: The mean pain noted during insertion was similar for both IIS (VAS 6.1 ± 6.4 mm for the FL Plus and 5.8 ± 6.3 mm for the FL, P = .92). 20.0% of the 895 IIS changes with FL Plus and 16.0% of the 854 with FL were unplanned. During the 4243 patient days of the study, 13 patients had adverse events. Among these, 2 serious adverse events occurred. Both serious events and 1 nonserious adverse event were considered as related to the IIS. Of the patients, 18.7% had kinked cannulas. Most patients were satisfied with both IIS. CONCLUSION: Both IIS are safe and effective. The 2 IIS did not differ from each other with respect to pain observed during insertion.

Field potential signature of distinct multicellular activity patterns in the mouse hippocampus.

Cognitive functions go along with complex patterns of distributed activity in neuronal networks, thereby forming assemblies of selected neurons. To support memory processes, such assemblies have to be stabilized and reactivated in a highly reproducible way. The rodent hippocampus provides a well studied model system for network mechanisms underlying spatial memory formation. Assemblies of place-encoding cells are repeatedly activated during sleep-associated network states called sharp wave-ripple complexes (SPW-Rs). Behavioral studies suggest that at any time the hippocampus harbors a limited number of different assemblies that are transiently stabilized for memory consolidation. We hypothesized that the corresponding field potentials (sharp wave-ripple complexes) contain a specific signature of the underlying neuronal activity patterns. Hence, they should fall into a limited number of different waveforms. Application of unbiased sorting algorithms to sharp wave-ripple complexes in mouse hippocampal slices did indeed reveal the reliable recurrence of defined waveforms that were robust over prolonged recording periods. Single-unit discharges tended to fire selectively with certain SPW-R classes and were coupled above chance level. Thus, field SPW-Rs of different waveforms are directly related to the underlying multicellular activity patterns that recur with high fidelity. This direct relationship between the coordinated activity of distinct groups of neurons and macroscopic electrographic signals may be important for cognition-related physiological studies in humans and behaving animals.

Dynamics of input patterns modulate the behavior of a model of olfactory bulb function.

Input patterns to the olfactory bulb are dynamic and change in an odor-specific manner as measured by selective calcium imaging of olfactory bulb input. To our knowledge, none of the published models of olfactory bulb function uses dynamic input patterns. Therefore we tested how dynamic input alters the behavior of a simple model consisting of two layers. The membrane potential of the first-layer neurons, integrate-and-fire neurons corresponding to mitral cells, was modulated with a subthreshold oscillation at respiration frequency. The membrane potential of the second-layer neurons was used to discriminate input patterns. We implemented oscillating input with amplitudes and latencies different for each mitral cell. Not only varying the input amplitudes but also de-synchronizing the input, and varying the relation between latency and input amplitude, individually changed the model's performance significantly. The discrimination time was affected more easily than the number of second-layer neurons that can differentiate an odor pair. Increasing the de-synchronization, i.e., the spread of latency values, reduced the differences in response time between strong and weak stimulus pairs without reducing the number of reacting cells. Input phase relative to the subthreshold oscillation altered the effect of de-synchronization. Thus dynamic input changes performance parameters of models of olfactory information processing that can be verified experimentally.

Second harmonic imaging of intrinsic signals in muscle fibers in situ.

We use second harmonic generation (SHG) imaging to study and quantify a strong intrinsic SHG signal in skeletal muscle fiber preparations and single isolated myofibrils. The intrinsic signal follows the striation pattern of the muscle cells and is positioned at the sarcomeric location of the myosin filaments. Interestingly, the signal is enhanced at the region where the myosin heads are located on the myosin filaments. As the intrinsic signal reflects the subcellular structure in an accurate way, SHG can be used for noninvasive high resolution structural imaging without exogenous labels in living muscle cells. This may be very important for detecting changes in myofibrillar organization occurring under pathophysiological conditions, e.g., in cardiac and skeletal myopathies. Due to the strong dependency of SHG on orientation and symmetries of the tissue, it may allow the study of dynamic interactions between the contractile proteins actin and myosin during force production and muscle shortening. Furthermore, SHG imaging can be combined with other nonlinear microscopical techniques, such as laser scanning multiphoton fluorescence microscopy, to simultaneously measure other dynamic cellular processes, representing a complementary method and extending the range of nonlinear microscopical methods.