Pharmacology of Intravenous Insulin Administration: Implications for Future Closed-Loop Glycemic Control by the Intravenous/Intravenous Route

Skjærvold, Nils Kristian; Lyng, Oddveig; Spigset, Olav; Aadahl, Petter

doi:10.1089/dia.2011.0118

Cited by 15 publications

(11 citation statements)

References 11 publications

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“…The animals were anaesthetized and euthanized as described in earlier studies (Skjaervold et al, 2012(Skjaervold et al, , 2013. A central venous line was established via the left internal jugular vein and an arterial line via the left external carotid artery, respectively, for monitoring, glucose bolus administration and blood sampling.…”

Section: The Animal Modelmentioning

confidence: 99%

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

Fougner¹,

Kölle²,

Skjærvold³

et al. 2016

MIC

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Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC) glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP) sensor sites, as an alternative to the SC location.Intraarterial (IA) and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70-360 mg/dL (approximately 3.8-20 mmol/L). Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing.The time delay in glucose excursions from central circulation (IA) to IP sensor location was found to be in the range 0-26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s), and the time constant was found to be 0.5-10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min).IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies.This study may provide a benchmark for future, rapid IP glucose sensors.

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Section: The Animal Modelmentioning

confidence: 99%

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

Fougner¹,

Kölle²,

Skjærvold³

et al. 2016

MIC

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“…In animals 2–4, the rate of decrease (RD) from the first insulin bolus until the 6.0 mmol/L limit was reached was relatively high, from 0.064 to 0.077 (mmol/L)/min. (As a comparison, we found the maximum RD to be approximately 0.1 (mmol/L)/min after a single bolus dose of insulin in our earlier experiments [23]. ) After reaching the target range, the animals were kept under glycemic control ( T ctrl ) from 128 to 238 minutes.…”

Section: Resultsmentioning

confidence: 93%

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

Skjærvold

Østling

Hjelme

et al. 2013

International Journal of Endocrinology

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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.

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“…It is beyond the scope of this exploratory study to speculate regarding the physiological origin of these oscillations. However, based on our previous studies on the effect of intravenous insulin boluses on BGL changes in pigs, where the effect of each bolus has an approximately 15-min BGL-lowering effect [ 19 ], the fastest oscillations are unlikely to be caused by the pulsatile oscillation release by the beta-cells. The two slowest effects, in contrast, could be caused by such pulsatility.…”

Section: Resultsmentioning

confidence: 99%

Some oscillatory phenomena of blood glucose regulation: An exploratory pilot study in pigs

2018

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It is well-known that blood glucose oscillates with a period of approximately 15 min (900 s) and exhibits an overall complex behaviour in intact organisms. This complexity is not thoroughly studied, and thus, we aimed to decipher the frequency bands entailed in blood glucose regulation. We explored high-resolution blood glucose time-series sampled using a novel continuous intravascular sensor in four pigs under general anaesthesia for almost 24 hours. In all time series, we found several interesting oscillatory components, especially in the 5000–10000 s, 500–1000 s, and 50–100 s regions (0.0002–0.0001 Hz, 0.002–0.001 Hz, and 0.02–0.01 Hz). The presence of these oscillations is not permanent, as they come and go. This is the first report of glucose oscillations in the 50–100 s range. The origin of these oscillations and their role in overall blood glucose regulation is unknown. Although the sample size is small, we believe this finding is important for our understanding of glucose regulation and perhaps for our understanding of general homeostatic regulation in intact organisms.

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Pharmacology of Intravenous Insulin Administration: Implications for Future Closed-Loop Glycemic Control by the Intravenous/Intravenous Route

Cited by 15 publications

References 11 publications

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

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

Some oscillatory phenomena of blood glucose regulation: An exploratory pilot study in pigs

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