Are New Ultra-Rapid-Acting Insulins Associated with Improved Glycemic Control and Reduced Hypoglycemia in Comparison to Conventional Rapid-Acting Insulins for Individuals with Type 1 and Type 2 Diabetes? A Systematic Review and Meta-Analysis.

Introduction: This study aimed to compare efficacy and safety of ultra-rapid-acting insulin analogs (URAIs; faster aspart [FAsp], ultra-rapid lispro [URLi], and technosphere insulin [TI]) with rapid-acting insulin analogs (RAI) in individuals with type 1 (T1D) or type 2 diabetes (T2D). Methods: Searching for randomized control trial comparing the effects of URAI versus RAI that lasted at least 12 weeks, we initially selected 15 studies for analysis. Three studies involving TI were excluded due to a high degree of heterogeneity. The final meta-analysis included only 12 studies with either FAsp or URLi. Results: Mealtime URAI significantly reduced overall early 1 h postprandial glycemia in individuals with T1D (-20.230 mg/dL [95% confidence interval, 95% CI -24.040 to -16.421]; P < 0.001; I2 = 33.42%) and those with T2D (-9.138 mg/dL [95% CI -12.612 to -5.663]; P < 0.001; I2 = 0%). However, the significant reduction in 2 h postprandial glucose remained only in individuals with T1D (-17.620 mg/dL [95% CI -26.047 to -9.193]; P < 0.001; I2 = 65.88%). These benefits were lost when URAI was administered postmeal. At 24-26 weeks, there was no significant difference in HbA1c between groups, but at 52 weeks, a slight reduction in HbA1c with mealtime URAI was observed (-0.080% [95% CI -0.147 to -0.013]; P = 0.019; I2 = 0%). No difference in weight or the rate of severe or confirmed hypoglycemia was observed. Only individuals with T1D showed a small, but significant increase in early 1-h hypoglycemia with URAI (1.468 [95% CI 1.235 to 1.747]; P < 0.001; I2 = 0%). Conclusion: Mealtime URAI improves 1 and 2 h postprandial glycemic control compared to RAI without increasing hypoglycemia or weight gain.

Ultrarapid Insulin Use Can Reduce Postprandial Hyperglycemia and Late Hypoglycemia, Even in Delayed Insulin Injections: A Connected Insulin Cap-Based Real-World Study.

Objectives: Reaching optimal postprandial glucose dynamics is a daily challenge for people with type 1 diabetes (T1D). This study aimed to analyze the postprandial hyperglycemic excursion (PHEs) and late postprandial hypoglycemia (LPH) risk according to prandial insulin time and type. Research Design and Methods: Real-world, retrospective study in T1D using multiple daily injections (MDI) analyzing 5 h of paired continuous glucose monitoring and insulin injections data collected from the connected cap Insulclock®. Meal events were identified using the rate of change detection methodology. Postprandial glucometrics and LPH (glucose <70 mg/dL 2-5 h after a meal) were evaluated according to insulin injection time and rapid (RI) or ultrarapid analog, Fiasp® (URI), use. Results: Meal glycemic excursions (n = 2488), RI: 1211, 48.7%; UR: 1277, 51.3%, in 82 people were analyzed according to injection time around the PHE: -45 to -15 min; -15 to 0 min; and 0 to +45 min. In 63% of the meals, insulin was injected after the PHE started. Lower PHE was observed with URI versus RI (glucose peak-baseline; mg/dL; mean ± standard deviation): 106.7 ± 35.2 versus 111.2 ± 40.3 (P = 0.003), particularly in 0/+45 injections: 111.6 ± 40.2 versus 118.1 ± 43.3; (P = 0.002). One third (29.1%) of participants added a second (correction) injection. The use of URI and avoiding a second injection were independently associated with less LPH risk, even in delayed injections (0/+45), (-36%, odds ratio [OR] 0.641; confidence interval [CI]: 0.462-0.909; P = 0.012) and -56% (OR 0.641; CI: 0.462-0.909 P = 0.038), respectively. Conclusions: URI analog use as prandial insulin reduces postprandial hyper- and hypoglycemia, even in delayed injections.

Autoimmune Diabetes From Childhood to Adulthood: The Role of Pancreatic Autoantibodies and HLA-DRB1 Genotype.

CONTEXT: Autoimmune diabetes can develop at any age, but unlike early-onset diabetes, adult onset is less well documented. We aimed to compare, over a wide age range, the most reliable predictive biomarkers for this pathology: pancreatic-autoantibodies and HLA-DRB1 genotype. METHODS: A retrospective study of 802 patients with diabetes (aged 11 months to 66 years) was conducted. Pancreatic autoantibodies at diagnosis: insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GADA), islet tyrosine phosphatase 2 autoantibodies (IA2A), and zinc transporter-8 autoantibodies (ZnT8A) and HLA-DRB1 genotype were analyzed. RESULTS: Compared with early-onset patients, adults had a lower frequency of multiple autoantibodies, with GADA being the most common. At early onset, IAA was the most frequent in those younger than 6 years and correlated inversely with age; GADA and ZnT8A correlated directly and IA2A remained stable.The absence of HLA-DRB1 risk genotype was associated with higher age at diabetes onset (27.5 years; interquartile range [IQR], 14.3-35.7), whereas the high-risk HLA-DR3/DR4 was significantly more common at lower age (11.9 years; IQR, 7.1-21.6). ZnT8A was associated with DR4/non-DR3 (odds ratio [OR], 1.91; 95% CI, 1.15-3.17), GADA with DR3/non-DR4 (OR, 2.97; 95% CI, 1.55-5.71), and IA2A with DR4/non-DR3 and DR3/DR4 (OR, 3.89; 95% CI, 2.28-6.64, and OR, 3.08; 95% CI, 1.83-5.18, respectively). No association of IAA with HLA-DRB1 was found. CONCLUSION: Autoimmunity and HLA-DRB1 genotype are age-dependent biomarkers. Adult-onset autoimmune diabetes is associated with lower genetic risk and lower immune response to pancreatic islet cells compared with early-onset diabetes.

Efficacy of a Connected Insulin Pen Cap in People With Noncontrolled Type 1 Diabetes: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To assess the efficacy of the insulin pen cap Insulclock on improving glycemic control, treatment adherence, and user satisfaction in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: This multicenter, open-label, randomized controlled trial comprised a 4-week run-in phase and a 6-week double-arm phase in which participants were randomly assigned into an active or masked mode. RESULTS: Fifty-five participants were evaluable (active group, n = 26, masked group, n = 29). The increase in time in range was higher in the active versus masked group (5.2% vs. -0.8%; P = 0.016). The active group showed a higher reduction in mean glucose, glucose management indicator, time above range, and high blood glucose index. On-time insulin doses increased in the active group and decreased in the masked group. CONCLUSIONS: Insulclock system use was associated with improved glycemic control, glycemic variability, hyperglycemia risk, and treatment adherence in people with uncontrolled type 1 diabetes.

Incidence of diabetes mellitus and associated risk factors in the adult population of the Basque country, Spain.

The aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11-9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846-0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.

CNN Based Detectors on Planetary Environments: A Performance Evaluation.

An essential characteristic that an exploration robot must possess is to be autonomous. This is necessary because it will usually do its task in remote or hard-to-reach places. One of the primary elements of a navigation system is the information that can be acquired by the sensors of the environment in which it will operate. For this reason, an algorithm based on convolutional neural networks is proposed for the detection of rocks in environments similar to Mars. The methodology proposed here is based on the use of a Single-Shot-Detector (SSD) network architecture, which has been modified to evaluate the performance. The main contribution of this study is to provide an alternative methodology to detect rocks in planetary images because most of the previous works only focus on classification problems and used handmade feature vectors.

Coasting in live-bearing fish: the drag penalty of being pregnant.

Swimming performance of pregnant live-bearing fish is presumably constrained by the additional drag associated with the reproductive burden. Yet, it is still unclear how and to what extent the reproductive investment affects body drag of the females. We examined the effect of different levels of reproductive investment on body drag. The biggest measured increase in body volume due to pregnancy was about 43%, linked to a wetted area increase of about 16% and 69% for the frontal area. We printed three-dimensional models of live-bearing fish in a straight body posture representing different reproductive allocation (RA) levels. We measured the drag and visualized the flow around these models in a flow tunnel at different speeds. Drag grew in a power fashion with speed and exponentially with the increase of RA, thus drag penalty for becoming thicker was relatively low for low speeds compared to high ones. We show that the drag increase with increasing RA was most probably due to bigger regions of flow separation behind the enlarged belly. We suggest that the rising drag penalty with an increasing RA, possibly together with pregnancy-related negative effects on muscle- and abdominal bending performance, will reduce the maximum swimming speed.

Why do placentas evolve? Evidence for a morphological advantage during pregnancy in live-bearing fish.

A live-bearing reproductive strategy can induce large morphological changes in the mother during pregnancy. The evolution of the placenta in swimming animals involves a shift in the timing of maternal provisioning from pre-fertilization (females supply their eggs with sufficient yolk reserves prior to fertilization) to post-fertilization (females provide all nutrients via a placenta during the pregnancy). It has been hypothesised that this shift, associated with the evolution of the placenta, should confer a morphological advantage to the females leading to a more slender body shape during the early stages of pregnancy. We tested this hypothesis by quantifying three-dimensional shape and volume changes during pregnancy and in full-grown virgin controls of two species within the live-bearing fish family Poeciliidae: Poeciliopsis gracilis (non-placental) and Poeciliopsis turneri (placental). We show that P. turneri is more slender than P. gracilis at the beginning of the interbrood interval and in virgins, and that these differences diminish towards the end of pregnancy. This study provides the first evidence for an adaptive morphological advantage of the placenta in live-bearing fish. A similar morphological benefit could drive the evolution of placentas in other live-bearing (swimming) animal lineages.

Three-dimensional analysis of the fast-start escape response of the least killifish, Heterandria formosa.

Fish make C-starts to evade predator strikes. Double-bend (DB) C-starts consist of three stages: Stage 1, in which the fish rapidly bends into a C-shape; Stage 2, in which the fish bends in the opposite direction; and a variable Stage 3. In single-bend (SB) C-starts, the fish immediately straightens after Stage 1. Despite fish moving in three-dimensional (3D) space, fast-start responses of adult fish have mainly been studied in a horizontal plane. Using automated 3D tracking of multi-camera high-speed video sequences, we show that both SB and DB fast-starts by adult female least killifish (Heterandria formosa) often contain a significant vertical velocity component, and large changes in pitch (DB up to 43 deg) and roll (DB up to 77 deg) angles. Upwards and downwards elevation changes are correlated with changes in pitch angle of the head; movement in the horizontal plane is correlated with changes in yaw angle of the head. With respect to the stimulus, escape heading correlates with the elevation of the fish at the onset of motion. Irrespective of the initial orientation, fish can escape in any horizontal direction. In many cases, the centre of mass barely accelerates during Stage 1. However, it does accelerate in the final direction of the escape in other instances, indicating that Stage 1 can serve a propulsive role in addition to its preparatory role for Stage 2. Our findings highlight the importance of large-scale 3D analyses of fast-start manoeuvres of adult fish in uncovering the versatility of fish escape repertoire.

Hummingbird wing efficacy depends on aspect ratio and compares with helicopter rotors.

Hummingbirds are the only birds that can sustain hovering. This unique flight behaviour comes, however, at high energetic cost. Based on helicopter and aeroplane design theory, we expect that hummingbird wing aspect ratio (AR), which ranges from about 3.0 to 4.5, determines aerodynamic efficacy. Previous quasi-steady experiments with a wing spinner set-up provide no support for this prediction. To test this more carefully, we compare the quasi-steady hover performance of 26 wings, from 12 hummingbird taxa. We spun the wings at angular velocities and angles of attack that are representative for every species and measured lift and torque more precisely. The power (aerodynamic torque × angular velocity) required to lift weight depends on aerodynamic efficacy, which is measured by the power factor. Our comparative analysis shows that AR has a modest influence on lift and drag forces, as reported earlier, but interspecific differences in power factor are large. During the downstroke, the power required to hover decreases for larger AR wings at the angles of attack at which hummingbirds flap their wings (p < 0.05). Quantitative flow visualization demonstrates that variation in hover power among hummingbird wings is driven by similar stable leading edge vortices that delay stall during the down- and upstroke. A side-by-side aerodynamic performance comparison of hummingbird wings and an advanced micro helicopter rotor shows that they are remarkably similar.

Wingbeat kinematics and motor control of yaw turns in Anna's hummingbirds (Calypte anna).

The biomechanical and neuromuscular mechanisms used by different animals to generate turns in flight are highly variable. Body size and body plan exert some influence, e.g. birds typically roll their body to orient forces generated by the wings whereas insects are capable of turning via left-right wingbeat asymmetries. Turns are also relatively brief and have low repeatability, with almost every wingbeat serving a different function throughout the change in heading. Here we present an analysis of Anna's hummingbirds (Calypte anna) as they fed continuously from an artificial feeder revolving around the outside of the animal. This setup allowed for examination of sustained changes in yaw without requiring any corresponding changes in pitch, roll or body position. Hummingbirds sustained yaw turns by expanding the wing stroke amplitude of the outer wing during the downstroke and by altering the deviation of the wingtip path during both downstroke and upstroke. The latter led to a shift in the inner-outer stroke plane angle during the upstroke and shifts in the elevation of the stroke plane and in the deviation of the wingtip path during both strokes. These features are generally more similar to how insects, as opposed to birds, turn. However, time series analysis also revealed considerable stroke-to-stroke variation. Changes in the stroke amplitude and the wingtip velocity were highly cross-correlated, as were changes in the stroke deviation and the elevation of the stroke plane. As was the case for wingbeat kinematics, electromyogram recordings from pectoral and wing muscles were highly variable, but no correlations were found between these two features of motor control. The high variability of both kinematic and muscle activation features indicates a high level of wingbeat-to-wingbeat adjustments during sustained yaw. The activation timing of the muscles was more repeatable than the activation intensity, which suggests that the former may be constrained by harmonic motion and that the latter may play a large role in kinematic adjustments. Comparing the revolution frequency of the feeder with measurements of free flight yaws reveals that feeder tracking, even at one revolution every 2 s, is well below the maximum yaw capacity of the hummingbirds.