The Impact of GLP-1 Receptor Agonists on Patients with Diabetes on Insulin Therapy

Objective: The clinical benefit of adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal-bolus or very high dose insulin regimens is unclear. This study investigated the impact of adding a GLP-1RA to a spectrum of insulin regimens (basal, basal-bolus, and U-500) to determine the impact on hemoglobin A1c (HbA1c), weight loss, and total daily insulin dose (TDD) over the course of 12 months. Methods: A retrospective chart review was conducted on 113 participants with type 2 diabetes mellitus using insulin therapy. Each participant\u27s HbA1c, body weight, and TDD were recorded prior to initiation of GLP-1RA therapy and at the 3, 6, and 12-month time points while on combination therapy. Results: Across all participants, the HbA1c values decreased significantly from a baseline of 8.9 (74 mmol/mol) ± 0.14% to 8.2 (66 mmol/mol) ± 0.14% (P\u3c.01) in the first 3 months, 8.0 (64 mmol/mol) ± 0.12% (P\u3c.01) at 6 months, to 8.3 (67 mmol/mol) ± 0.14% (P\u3c.01) at 12 months. There was no significant decrease in weight or TDD with the addition of a GLP-1RA overall or in different insulin groups. However, there was a clinically significant decrease in weight over the study duration. Conclusion: The results of this study suggest that adding a GLP-1RA to various insulin regimens may help to achieve glycemic goals while avoiding the less desirable side effects of weight gain and increasing insulin regimens. However, the expected weight loss and decrease in TDD may not be as sizable in the clinical setting. Abbreviations: DCOE = Diabetes Center of Excellence; DM = diabetes mellitus; GLP-1RA = glucagon-like peptide-1 receptor agonist; HbA1c = hemoglobin A1c; RCT = randomized controlled trial; TDD = total daily dose

Balancing with Vibration: A Prelude for “Drift and Act” Balance Control

Stick balancing at the fingertip is a powerful paradigm for the study of the control of human balance. Here we show that the mean stick balancing time is increased by about two-fold when a subject stands on a vibrating platform that produces vertical vibrations at the fingertip (0.001 m, 15–50 Hz). High speed motion capture measurements in three dimensions demonstrate that vibration does not shorten the neural latency for stick balancing or change the distribution of the changes in speed made by the fingertip during stick balancing, but does decrease the amplitude of the fluctuations in the relative positions of the fingertip and the tip of the stick in the horizontal plane, A(x,y). The findings are interpreted in terms of a time-delayed “drift and act” control mechanism in which controlling movements are made only when controlled variables exceed a threshold, i.e. the stick survival time measures the time to cross a threshold. The amplitude of the oscillations produced by this mechanism can be decreased by parametric excitation. It is shown that a plot of the logarithm of the vibration-induced increase in stick balancing skill, a measure of the mean first passage time, versus the standard deviation of the A(x,y) fluctuations, a measure of the distance to the threshold, is linear as expected for the times to cross a threshold in a stochastic dynamical system. These observations suggest that the balanced state represents a complex time–dependent state which is situated in a basin of attraction that is of the same order of size. The fact that vibration amplitude can benefit balance control raises the possibility of minimizing risk of falling through appropriate changes in the design of footwear and roughness of the walking surfaces

The importance of pheochromocytoma case detection in patients with neurofibromatosis type 1: A case report and review of literature

Neurofibromatosis type 1 is a complex, multi-system genetic disorder that is associated with an increased prevalence of pheochromocytoma and paraganglioma compared to the general population, 1.0%–5.7% versus 0.2%–0.6%, respectively. A delay in pheochromocytoma and paraganglioma diagnosis or undiagnosed pheochromocytoma and paraganglioma, as seen in normotensive and asymptomatic patients, may portend a significant morbidity and mortality risk due to excess catecholamine secretion. Currently, there are no generally accepted guidelines of screening for pheochromocytoma and paragangliomas in asymptomatic individuals of this population with approaches and practices varying considerably between physicians. Emerging data suggest benefit in routine pheochromocytoma and paraganglioma screening of all individuals with neurofibromatosis type 1. Herein, we present a case to highlight how routine case detection screening would have identified pheochromocytoma earlier in an active duty military member

Vibration–induced enhancement of stick balancing skill as a function of vibration-induced amplitude lowering.

<p>a) and b) show the same data plotted in two different ways. Data is obtained from three subjects using three different vibration frequencies (15 Hz, 25 Hz, 50 Hz) on three different days. Relative survival is the same as defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007427#pone-0007427-g003" target="_blank">Figure 3</a>. The ‘% decrease amplitude’ is calculated from the standard deviation of in the presence and absence of vibration, where is defined in the legend to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007427#pone-0007427-g007" target="_blank">Figure 7</a>.</p

Effect of vibration on neural latency for stick balancing skill.

<p>The cross–correlation function, for stick balancing is measured in the absence of vibration (top panels) and in the presence of vibration (bottom panels). Data is shown for two subjects having different skill levels: in the absence of vibration s for the subject on the left (33.2 s in presence of vibration) and 23.2 s for the subject on the right (45.5 s in presence of vibration).</p

Effect of vibration on the distribution of the changes in speed made by the fingertip during stick balancing.

<p>High speed motion capture cameras were used to measure the distribution, , of the changes in speed, , of the movements of the fingertip in the presence (red •) and absence (black •) of vibration, where is the standard deviation. Data is shown for the same subject: the 50 Hz vibration experiment was done 2 days after the 25 Hz vibration experiment. The broadening of is consistent with the increase in stick balancing skill that the subject experienced: s in the absence of 25 Hz vibration and s in the absence of 50 Hz vibration. The sampling frequency was 500 Hz.</p

Effects of parametric excitation on the dynamics of a simple “drift and act” controller.

<p>a) Graphical representation of a simple realization of the feedback function that produces a limit cycle oscillation in (2) in the absence of parametric excitation and noisy perturbations, where and , , , and . The displacement from the upright position, , grows when and decreases when . b) Periodic parametric excitation is turned on at the . The effect is to decrease the amplitude of the limit cycle oscillation. Parameters are and .</p

Effect of vibration amplitude and frequency on the mean stick balancing time.

<p>a) shows the effect of 0.001 m vertical vibration at the fingertip on relative survival and b) shows the effects of whole body vibration on relative survival using a vibrating platform which vibrated the body in a way that did not produce detectable vertical vibrations at the fingertip. The relative survival is the mean stick survival time, , measured for stick balancing in the presence of vibration divided by that obtained in the absence of vibration. In a) the shape of the symbol indicates the vibration frequency; 15 Hz (), 25 Hz () and 50 Hz (), and filled symbols indicate a statistically significant enhancement in stick balancing skill (). In b) the relative survival of subjects () was not significantly enhanced by whole body vibration ( in all cases).</p

Vibration enhances stick balancing skill.

<p>The survival fraction represents the fraction of stick balancing trials for which the stick was still balanced at time (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007427#s4" target="_blank">METHODS</a> for more details): ‘’ means no vibration and ‘’ means with vibration. The survival fraction is determined using stick balancing trials and the mean survival time, , is used as a measure of stick balancing skill. Here a 50 Hz, 0.001 m peak–to–peak amplitude vibration at the fingertip approximately doubles the mean survival time (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007427#pone-0007427-g003" target="_blank">Figure 3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007427#pone-0007427-t001" target="_blank">Table 1</a> for summary of results).</p