Modeling Insulin‐Glucose Dynamics during Insulin Induced Hypoglycemia. Evaluation of Glucose Counterregulation
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A dynamical network model of insulin‐glucose interactions in subjects with Type I Diabetes was developed and applied to data sets for 40 subjects. Each data set contained the amount of dextrose + insulin infused and blood glucose (BG) determinations, sampled every 5 minutes during a one‐hour standardized euglycemic hyperinsulinemic clamp and a subsequent one‐hour BG reduction to moderate hypoglycemic levels. The model approximated the temporal pattern of BG and on that basis predicted the counterregulatory response of each subject. The nonlinear fits explained more than 95% of the variance of subjects′ BG fluctuations, with a median coefficient of determination 97.7%. For all subjects the model‐predicted counterregulatory responses correlated with measured plasma epinephrine concentrations. The observed nadirs of BG during the tests correlated negatively with the model‐predicted insulin utilization coefficient (r = ‐0.51, p < 0.001) and counterregulation rates (r = ‐0.63, p < 0.001). Subjects with a history of multiple severe hypoglycemic episodes demonstrated slower onset of counterregulation compared to subjects with no such history (p < 0.03).
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The phenomenon of insulin action paradoxically increasing when glucose decreases under a given threshold has been described during hyperinsulinemic clamps in T1DM.
“This phenomenon has been described during hyperinsulemic clamps in T1DM. 9,10”
From The UVA/PADOVA Type 1 Diabetes Simulator: New Features (2014) · cites this paper as [9]
The Discussion (page unavailable) reports that, during hyperinsulinemic clamps in patients with type 1 diabetes, a lower glucose nadir was associated with faster model-estimated insulin utilization. It does not describe insulin action increasing within a patient as glucose crosses a particular threshold; the reported association is across subjects. (LLM, conf=0.85)
Experimental — accuracy not yet measuredWhen glucose falls below a given threshold, insulin sensitivity increases, resulting in enhanced glucose utilization and further reduction of plasma glucose.
“Results in T1DM subjects suggest that, when glucose falls below a given threshold, insulin sensitivity increases, resulting in an enhanced glucose utilization, which further reduces the plasma glucose level.4–6”
From The university of Virginia/Padova type 1 diabetes simulator matches the glucose traces of a clinical trial (2014) · cites this paper as [4]
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- Authors
- Kovatchev, B. P., Farhy, L. S., Cox, D. J., Straume, M., Yankov, V. I., Gonder-Frederick, L. A., & Clarke, W. L.
- Affiliations
- University of Virginia (US)
- Sofia University "St. Kliment Ohridski" (BG)
- Corresponding author
- Kovatchev, Boris P.
- Venue
- Computational and Mathematical Methods in Medicine
- Publisher
- Wiley
- Published
- 1998-10-21
- Volume
- 1
- Issue
- 4
- Pages
- 313-323
- ISSN
- 1748-670X (ISSN-L)
- 1748-6718
- OpenAlex
- W2099166298
- Cited by
- 17
- References
- 13
- Citations by year
- 2024: 1 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2012: 1
- FWCI
- 0.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Computational and Mathematical Methods in Medicine (publishedVersion, cc-by)
- Funders
- National Institutes of Health (ROl DK51562, R01 DK28288, RR00847, DIR-8920162, MM706)
- National Science Foundation (ROl DK51562, R01 DK28288, RR00847, DIR-8920162, MM706)
- Bulgarian Research Fund (ROl DK51562, R01 DK28288, RR00847, DIR-8920162, MM706)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- glucose-insulin dynamics, insulin-induced hypoglycemia, glucose counterregulation, type 1 diabetes, hyperinsulinemic-euglycemic clamp, dynamical network model, plasma epinephrine, insulin use
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