Qualitative analysis of subcutaneous Lispro and regular insulin injections for stress hyperglycemia: A pilot numerical study

Richard J. Strilka, Scott Armen, Matthew C. Indeck

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Increased glucose variability (GV) is an independent risk factor for mortality in the critically ill; unfortunately, the optimal insulin therapy that minimizes GV is not known. We simulate the glucose-insulin feedback system to study how stress hyperglycemia (SH) states, taken to be a non-uniform group of physiologic disorders with varying insulin resistance (IR) and similar levels of hyperglycemia, respond to the type and dose of subcutaneous (SQ) insulin. Two groups of 100 virtual patients are studied: those receiving and those not receiving continuous enteral feeds. Stress hyperglycemia was facilitated by doubling the gluconeogenesis rate and IR was stepwise varied from a borderline to a high value. Lispro and regular insulin were simulated with dosages that ranged from 0 to 6 units; the resulting GV was analyzed after each insulin injection. The numerical model used consists of a set of non-linear differential equations with two time delays and five adjustable parameters. The results show that regular insulin decreased GV in both patient groups and rarely caused hypoglycemia. With continuous enteral feeds and borderline to mild IR, Lispro showed minimal effect on GV; however, rebound hyperglycemia that increased GV occurred when the IR was moderate to high. Without a nutritional source, Lispro worsened GV through frequent hypoglycemia episodes as the injection dose increased. The inferior performance of Lispro is a result of its rapid absorption profile; half of its duration of action is similar to the glucose ultradian period. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units, and if such dynamics are present, their clinical effects should be evaluated.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalJournal of Theoretical Biology
Volume356
DOIs
StatePublished - Sep 7 2014

Fingerprint

Insulin Lispro
Insulin
hyperglycemia
Qualitative Analysis
qualitative analysis
Hyperglycemia
Glucose
Numerical Study
Injection
insulin
injection
glucose
Injections
insulin resistance
Insulin Resistance
hypoglycemia
enteral feeding
Hypoglycemia
Small Intestine
dosage

All Science Journal Classification (ASJC) codes

  • Applied Mathematics
  • Statistics and Probability
  • Modeling and Simulation
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

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abstract = "Increased glucose variability (GV) is an independent risk factor for mortality in the critically ill; unfortunately, the optimal insulin therapy that minimizes GV is not known. We simulate the glucose-insulin feedback system to study how stress hyperglycemia (SH) states, taken to be a non-uniform group of physiologic disorders with varying insulin resistance (IR) and similar levels of hyperglycemia, respond to the type and dose of subcutaneous (SQ) insulin. Two groups of 100 virtual patients are studied: those receiving and those not receiving continuous enteral feeds. Stress hyperglycemia was facilitated by doubling the gluconeogenesis rate and IR was stepwise varied from a borderline to a high value. Lispro and regular insulin were simulated with dosages that ranged from 0 to 6 units; the resulting GV was analyzed after each insulin injection. The numerical model used consists of a set of non-linear differential equations with two time delays and five adjustable parameters. The results show that regular insulin decreased GV in both patient groups and rarely caused hypoglycemia. With continuous enteral feeds and borderline to mild IR, Lispro showed minimal effect on GV; however, rebound hyperglycemia that increased GV occurred when the IR was moderate to high. Without a nutritional source, Lispro worsened GV through frequent hypoglycemia episodes as the injection dose increased. The inferior performance of Lispro is a result of its rapid absorption profile; half of its duration of action is similar to the glucose ultradian period. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units, and if such dynamics are present, their clinical effects should be evaluated.",
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Qualitative analysis of subcutaneous Lispro and regular insulin injections for stress hyperglycemia : A pilot numerical study. / Strilka, Richard J.; Armen, Scott; Indeck, Matthew C.

In: Journal of Theoretical Biology, Vol. 356, 07.09.2014, p. 192-200.

Research output: Contribution to journalArticle

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