Blood Glucose Control Using a Novel Continuous Blood Glucose Monitor and Repetitive Intravenous Insulin Boluses: Exploiting Natural Insulin Pulsatility as a Principle for a Future Artificial Pancreas

The aim of this study was to construct a glucose regulatory algorithm by employing the natural pulsatile pattern of insulin secretion and the oscillatory pattern of resting blood glucose levels and further to regulate the blood glucose level in diabetic pigs by this method. We developed a control algorithm based on repetitive intravenous bolus injections of insulin and combined this with an intravascular blood glucose monitor. Four anesthetized pigs were used in the study. The animals developed a mildly diabetic state from streptozotocin pretreatment. They were steadily brought within the blood glucose target range of 4.5–6.0 mmol/L in 21 to 121 min and kept within that range for 128 to 238 min (hypoglycemic values varied from 2.9 to 51.1 min). The study confirmed our hypotheses regarding the feasibility of this new principle for blood glucose control, and the algorithm was constantly improved during the study to produce the best results in the last animals. The main obstacles were the drift of the IvS-1 sensor and problems with the calibration procedure, which calls for an improvement in the sensor stability before this method can be applied fully in new studies in animals and humans

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM

Rapid declines in systolic blood pressure are associated with an increase in pulse transit time

Background The correlation between pulse transit time and blood pressure has been proposed as a route to measure continuous non-invasive blood pressure. We investigated whether pulse transit time trends could model blood pressure trends during episodes of rapid declines in blood pressure. Methods From the Medical Information Mart for Intensive Care waveform database we identified substantial blood pressure reductions. Pulse transit time was calculated from the R-peak of the electrocardiogram to the peak of the arterial pulse waveform. The time-series were processed with a moving average filter before comparison. Averaged, continuous heart rate was also analysed as a control. The intra-individual association between variables was assessed per subject using linear regression. Results In the 511 patients included we found a median correlation coefficient between blood pressure and pulse transit time of -0.93 (IQR -0.98 to -0.76) with regression slopes of -1.23 mmHg/ms (IQR -1.73 to -0.81). The median correlation coefficient between blood pressure and heart rate was 0.46 (IQR -0.16 to 0.83). In supplementary analysis, results did not differ substantially when widening inclusion criteria, but the results were not always consistent within subjects across episodes of hypotension. Conclusions In a large cohort of critically ill patients experiencing episodes of rapid declines in systolic blood pressure, there was a moderate-strong intra-individual correlation between averaged systolic blood pressure and averaged pulse transit time. Our findings encourage further investigation into using the pulse transit time for non-invasive real-time detection of hypotension

A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction

Background: The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle. Results: Pulmonary hypertension was induced by lowering the FiO2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm5 to 504 (191) dyns/cm5, with a lowering of FiO2 from 0.30 to 0.15 (0.024). The animals’ individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered. Conclusions: We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible, although this was not studied in this work

Rapid declines in systolic blood pressure are associated with an increase in pulse transit time.

BackgroundThe correlation between pulse transit time and blood pressure has been proposed as a route to measure continuous non-invasive blood pressure. We investigated whether pulse transit time trends could model blood pressure trends during episodes of rapid declines in blood pressure.MethodsFrom the Medical Information Mart for Intensive Care waveform database we identified substantial blood pressure reductions. Pulse transit time was calculated from the R-peak of the electrocardiogram to the peak of the arterial pulse waveform. The time-series were processed with a moving average filter before comparison. Averaged, continuous heart rate was also analysed as a control. The intra-individual association between variables was assessed per subject using linear regression.ResultsIn the 511 patients included we found a median correlation coefficient between blood pressure and pulse transit time of -0.93 (IQR -0.98 to -0.76) with regression slopes of -1.23 mmHg/ms (IQR -1.73 to -0.81). The median correlation coefficient between blood pressure and heart rate was 0.46 (IQR -0.16 to 0.83). In supplementary analysis, results did not differ substantially when widening inclusion criteria, but the results were not always consistent within subjects across episodes of hypotension.ConclusionsIn a large cohort of critically ill patients experiencing episodes of rapid declines in systolic blood pressure, there was a moderate-strong intra-individual correlation between averaged systolic blood pressure and averaged pulse transit time. Our findings encourage further investigation into using the pulse transit time for non-invasive real-time detection of hypotension

Visualisation of Limb Movements by Accelerometers in Sedated Patients

The prognostication of neurological outcome in sedated ICU patients is challenging. Multiple clinical scoring schemes and examinations are used, where different motoric responses are important input variables. Accelerometery is a well-known technology widely applied in different fields of research and everyday electronic products. In medical research, accelerometers have been used in longitudinal epidemiological studies of physical activity and health as well as in ICU studies on the topic of activity, sleep and agitation monitoring. Similarly, accelerometric information could be a candidate to improve future neurological prognostication schemes. To the best of our knowledge, including a systematic review from 2015 [1], there are no published articles on automatic motion registration from ICU patients in connection to neurologic outcome prognosticatio

MOESM1 of A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction

Additional file 1: Table S1. Arterial and mixed venous blood gases at baseline and pulmonary hypertension