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In Praise of the Hyperglycemic Clamp: A method for assessment of β-cell sensitivity and insulin resistance
Abstract
The most widely used methods for the assessment of beta-cell response and peripheral tissue sensitivity to insulin include the oral glucose tolerance test (OGTT), the frequently sampled intravenous glucose tolerance test, and the hyperinsulinemiceuglycemic clamp technique. During an OGTT, glucose levels increase after a variable lag period, then reach a peak and fall variably among individuals. The response even varies in the same subject upon repeat testing. A more reproducible glucose curve is achieved with an intravenous glucose tolerance test in which the plasma glucose levels rise rapidly to a very high level and fall exponentially. In neither of the two methods is a steady-state glucose level achieved. In the hyperinsulinemic-euglycemic clamp technique, a steady-state glucose level can be maintained at any level of hyperinsulinemia. However, an assessment of beta-cell sensitivity is not obtained. The less used hyperglycemic clamp technique can assess beta-cell sensitivity as well as peripheral tissue sensitivity. Moreover, a measure of glucose effectiveness or non-insulin-mediated glucose uptake can also be determined. With this technique the beta-cells of all subjects are stimulated with the same arterial glucose concentration, thus enabling assessment of beta-cell response to identical plasma glucose levels. Comparison of responses to stable hyperglycemic stimuli can be made in glucose-tolerant and -intolerant states with the addition of various substances, either alone or in combination. The use of the hyperglycemic clamp and several of its variant forms is reviewed as an alternative method for assessment of glucose homeostasis.
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“Although not as accurate as euglycemic hyperinsulinemic clamps for measuring insulin sensitivity, GIR during steady-state hyperglycemia (i.e., 60–90 min) allows a fairly good direct measurement of insulin sensitivity (34).”
From Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods (2023) · cites this paper as [34]
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Feasibility of Automating Insulin Delivery for the Treatment of Type 1 Diabetes
Steil, G. M., Rebrin, K., Darwin, C. H., Hariri, F., & Saad, M. F. (2006) · Diabetes · doi:10.2337/db06-0419 · Cited by 473
Hanson, R. L., Pratley, R. E., Bogardus, C., Narayan, K. M. V., Roumain, J. M. L., Imperatore, G., Fagot-Campagna, A., Pettitt, D. J., Bennett, P. H., & Knowler, W. C. (2000) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a010187 · Cited by 463
“While these methods have been used widely, alternate methods such as the hyperglycemic "clamp" may be superior, particularly for assessing insulin secretion (28).”
MethodAge-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk
Chia, C. W., Egan, J. M., & Ferrucci, L. (2018) · Circulation Research · doi:10.1161/circresaha.118.312806 · Cited by 454
“The insulin response to square-wave–induced hyperglycemia is bimodal: there is a first-phase insulin secretion that occurs during the first 10 minutes with a peak response at ≈4 minutes; then, plasma insulin level falls reaching a nadir at ≈10 minutes; next, the second insulin secretion phase begins and insulin levels…”
BackgroundClosed-loop insulin delivery-the path to physiological glucose control.
Steil, G., Panteleon, A., & Rebrin, K. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2003.08.011 · Cited by 325
Hyperglycemia Associated With Pasireotide: Results From a Mechanistic Study in Healthy Volunteers
Henry, R. R., Ciaraldi, T. P., Armstrong, D. A., Burke, P., Ligueros‐Saylan, M., & Mudaliar, S. R. D. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1771 · Cited by 256
Metadata
- Authors
- Elahi, D.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- Elahi, Dariush
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 1996-03-01
- Volume
- 19
- Issue
- 3
- Pages
- 278-286
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2027219674
- Cited by
- 168
- References
- 0
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 10 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 4.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P60AG012583, P60 AG12583)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- hyperglycemic clamp, insulin resistance, glucose homeostasis, oral glucose tolerance test, intravenous glucose tolerance test, hyperinsulinemic-euglycemic clamp, glucose effectiveness
- MeSH terms
- Insulin Secretion, Adult, Aged, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin, Insulin Resistance, Islets of Langerhans, Middle Aged, Models, Biological, Glucose Clamp Technique
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