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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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Shah, S. S., Ramirez, C. E., Powers, A. C., Yu, C., Shibao, C. A., & Luther, J. M. (2016) · Metabolism · doi:10.1016/j.metabol.2016.02.011 · Cited by 14
“The hyperglycemic clamp method further allows the analysis of late-phase insulin secretion and the response to non-glucose stimuli, such as L-Arginine [25].”
InfluentialTime-dependent Mechanisms in Beta-cell Glucose Sensing
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“The combination of translocation and the memory effect gives a nearly linear increase in insulin release after the first phase, when the glucose concentration is held constant [8, 9, 20, 53].”
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“The use of the hyperglycemic clamp technique [32] in the current study enables a mechanistic explanation for the observed improvements in glucose regulation in this and other lifestyle intervention studies.”
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“Feasibility of the more invasive and laborious hyperglycemic clamp technique, the gold standard technique to assess both insulin sensitivity and b-cell function precluded us from using it in our study (Elahi 1996).”
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“Tissue insulin sensitivity can also be estimated from the hyperglycaemic clamp,using the ratio of glucose metabolism to plasma insulin concentration or insulin sensitivity indices, for example (DeFronzo et al., 1979; Elahi, 1996; Mitrakou et al., 1992).”
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Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods
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“Simplified indices such as homeostasis model of insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) are more convenient but are influenced by factors including insulin levels, renal function, and metabolic status, which restrict their predictive performance [3–7].”
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“Euglycemic clamp is the gold standard for measuring IR; however, due to the sophisticated procedures, it is not ideal to utilize it as a routine screening item for admission and inappropriate for large-scale investigations (22).”
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“M was expressed per kg body weight, corrected for urinary glucose loss, and divided by the mean insulin concentration at these same time points (I).(26-28) This calculated M/I term was used as the measurement of insulin sensitivity.”
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“- 257 - 적용하는데 있어서 실용적이지 못하다는 한계가 있다 (Elahi, 1996).”
Rave, K., Sidharta, P. N., Dingemanse, J., Heinemann, L., & Roggen, K. (2010) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2009.0103 · Cited by 4
“8 In addition, the amount of glucose infused during glucose clamps provides a measure of INS sensitivity.”
Can technological solutions for diabetes replace islet cell function?
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“The derivative term is also significant in that it effectively mimics first phase insulin response by increasing insulin secretion proportional to the rate of glucose rise seen in the first minutes following a meal.(23,24,80) The terms K p , K I and K D are tuning parameters called gain and their value determines the…”
BackgroundMechanism-Based Modeling of the Glucose-Insulin Regulation during Clinical Provocation Experiments
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“The hyperglycemic glucose clamp (HGC) technique provides a highly reproducible method of assessing ß-cell sensitivity to glucose following a controlled hyperglycemic stimulus (7).”
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“The hyperinsulinemic euglycemic clamp (HEC) technique is regarded as the gold standard for assessing IR; however, its clinical application is limited by its invasiveness, high cost, and complex procedure (9).”
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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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