Nonlinear Metabolic Effect of Insulin Across the Blood Glucose Range in Patients with Type 1 Diabetes Mellitus
Open accessAbstract
Background: For insulin therapy to successfully maintain blood glucose (BG) levels of patients with type 1 diabetes mellitus (T1DM) in normoglycemia, it is necessary to understand if the metabolic effect of insulin across the BG range is linear or not. Methods: We assess the ability of insulin to lower BG in patients with T1DM in hypoglycemia and hyperglycemia. The net metabolic effect of insulin, defined as the total effect resulting from both reduced endogenous glucose production and increased glucose uptake, was used to define the insulin effectiveness (IE), a measure that indicates the amplitude of glucose lowering that a unit of active insulin can achieve at a given BG level. The IE was assessed in hypoglycemia and hyperglycemia through two separate studies. In the first study, patients were subjected to a hyperinsulinemic euglycemic and hypoglycemic glucose clamp. In the second study, another group of patients were clamped at a hyperglycemic level. Results: The IE increased by 75% when BG dropped from 90 to 50 mg/dl at a steady rate of 1 mg/d1/min and decreased by 10% when BG was increased from 100 to 200 mg/d1. Conclusions: The net metabolic effect of insulin is nonlinear across the BG range and is amplified in hypoglycemia and dampened in hyperglycemia. Most importantly, the BG lowering per unit of insulin is accelerated when falling into hypoglycemia. The understanding of the accelerated risk for hypoglycemia with falling glucose levels will help the design of more robust hypoglycemia prevention and detection systems.
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Recent studies have provided new insights into nonlinearities of insulin action in the hypoglycemic range and into glucagon kinetics as it relates to response to hypoglycemia.
“Recently new data and models have become available on hypoglycemia 5 and counterregulation. 6,7”
From The UVA/PADOVA Type 1 Diabetes Simulator: New Features (2014) · cites this paper as [6]
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- Authors
- Chan, A., Heinemann, L., Anderson, S. M., Breton, M. D., & Kovatchev, B. P.
- Affiliations
- University of Virginia Health System (US)
- Profil Institute for Metabolic Research (DE)
- Corresponding author
- Chan, Alice
- Venue
- Journal of Diabetes Science and Technology
- Publisher
- SAGE Publications
- Published
- 2010-07
- Volume
- 4
- Issue
- 4
- Pages
- 873-881
- ISSN
- 1932-2968 (ISSN-L)
- PMC
- PMC2909519
- OpenAlex
- W2131590286
- Cited by
- 13
- References
- 20
- Citations by year
- 2026: 2 · 2024: 1 · 2020: 1 · 2015: 4 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Diabetes Science and Technology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health (5r01dk051562-23)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK 51562, R01DK085623)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, blood glucose, hypoglycemia, hyperglycemia, endogenous glucose production, glucose uptake, hyperinsulinemic-euglycemic clamp, hypoglycemic clamp, hyperglycemic clamp, hypoglycemia prevention
- MeSH terms
- Adult, Algorithms, Blood Glucose, Diabetes Mellitus, Type 1, Female, Glucose, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Male, Middle Aged, Glucose Clamp Technique, Treatment Outcome, Nonlinear Dynamics
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