Cited by 168Pancreatic function and diabetesDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and Research

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In Praise of the Hyperglycemic Clamp: A method for assessment of β-cell sensitivity and insulin resistance

Elahi, Dariush·1996·Diabetes Care

DOI 10.2337/diacare.19.3.278

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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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Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics
Karstoft, K., Mortensen, S. P., Knudsen, S. H., & Solomon, T. P. J. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00520.2014 · Cited by 32
“4 mmol/l was initiated (13); then the variable-rate glucose infusion was resumed aiming for the new target glucose level (hyperglycemia).”
Background
Effect of the urotensin‐II receptor antagonist palosuran on secretion of and sensitivity to insulin in patients with Type 2 diabetes mellitus
Sidharta, P. N., Rave, K., Heinemann, L., Chiossi, E., Krähenbühl, S., & Dingemanse, J. (2009) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2009.03480.x · Cited by 31
Measuring Insulin Resistance in Humans
Sharma, V. R., Matta, S. T., Haymond, M. W., & Chung, S. T. (2020) · Hormone Research in Paediatrics · doi:10.1159/000515462 · Cited by 30
Challenges in glucoCEST MR body imaging at 3 Tesla
Kim, M., Torrealdea, F. J., Adeleke, S. M., Rega, M., Evans, V., Beeston, T., Soteriou, K., Thust, S. C., Kujawa, A., Okuchi, S., et al. (2019) · Quantitative Imaging in Medicine and Surgery · doi:10.21037/qims.2019.10.05 · Cited by 29
Exendin-4 Pharmacodynamics: Insights from the Hyperglycemic Clamp Technique
Mager, D., Abernethy, D., Egan, J. M., & Elahi, D. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.069765 · Cited by 25
Self-citation
Association between insulin resistance indices and kidney stones: results from the 2015–2018 National Health and Nutrition Examination Survey
Shen, Y., Zhu, Z., Bi, X., Shen, Y., Shen, A., Deng, B., He, Y., Wang, W., & Ding, F. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1444049 · Cited by 27
Menopausal Hot Flash Frequency Changes in Response to Experimental Manipulation of Blood Glucose
Dormire, S. L., & Reame, N. K. (2003) · Nursing Research · doi:10.1097/00006199-200309000-00008 · Cited by 27
“Using the glucose clamp procedure of the methodology of the hyperglycemic glucose clamp (DeFronzo, Tobin, & Andres, 1979; Elahi, 1996; Fanelli, et al., 1998), a variable rate infusion of 20% dextrose maintained the blood glucose level above 130 mg/dl. Samples for blood glucose were drawn every 5…”
Method
Effects of treatment with metformin and/or sitagliptin on beta‐cell function and insulin resistance in prediabetic women with previous gestational diabetes
Daniele, G., Tura, A., Dardano, A., Bertolotto, A., Bianchi, C., Giusti, L., Kurumthodathu, J. J., & Prato, S. D. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13940 · Cited by 29
Triglycerides to High-Density Lipoprotein Cholesterol Ratio Is the Best Surrogate Marker for Insulin Resistance in Nonobese Middle-Aged and Elderly Population: A Cross-Sectional Study
Yang, Y., Wang, B., Yuan, H., & Li, X. (2021) · International Journal of Endocrinology · doi:10.1155/2021/6676569 · Cited by 32
Relationship between glycaemic variability and hyperglycaemic clamp-derived functional variables in (impending) type 1 diabetes
Belgian Diabetes Registry, Dalem, A. V., Demeester, S., Balti, E. V., Decochez, K., Weets, I., Vandemeulebroucke, E., de Velde, U. V., Walgraeve, A., Seret, N., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3761-y · Cited by 26
Obstructive Sleep Apnea, Glucose Tolerance, and β-Cell Function in Adults With Prediabetes or Untreated Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study
Mokhlesi, B., Tjaden, A. H., Temple, K. A., Edelstein, S. L., Sam, S., Nadeau, K. J., Hannon, T. S., Manchanda, S., Mather, K. J., Kahn, S. E., et al. (2021) · Diabetes Care · doi:10.2337/dc20-2127 · Cited by 27
“state (second phase) C-peptide was calculated as themeanof themeasurements at 100, 110,and120minof the clamp(20).”
Method
TyGIS: improved triglyceride-glucose index for the assessment of insulin sensitivity during pregnancy
Salvatori, B., Linder, T., Eppel, D., Morettini, M., Burattini, L., Göbl, C. S., & Tura, A. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01649-8 · Cited by 26
Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients
The Belgian Diabetes Registry, Vandemeulebroucke, E., Keymeulen, B., Decochez, K., Weets, I., Block, C. E. M. D., Féry, F., de Velde, U. V., Vermeulen, I., Pauw, P. E. M. D., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1569-3 · Cited by 27
“Relatives were prospectively followed (median [range]: 64[3–99] months) for glucose tolerance and diabetes onset (OGTT after 3, 9, 15, 18, 21, 27, 30, 33, 36, 42 and 48 months; glucose self-monitoring) and for beta cell function (hyperglycaemic clamp after 6, 12, 24, 36 and 48 months).”
Background
Association of TG / HDLC ratio trajectory and risk of type 2 diabetes: A retrospective cohort study in China
Zhang, Y., Qin, P., Lou, Y., Zhao, P., Li, X., Qie, R., Wu, X., Han, M., Huang, S., Zhao, Y., et al. (2020) · Journal of Diabetes · doi:10.1111/1753-0407.13123 · Cited by 25
Impact of family history of diabetes on the assessment of β-cell function
ALFORD, F. P., Henriksen, J. E., Rantzau, C., Vaag, A. A., Hew, L. F., Ward, G. M., & Beck‐Nielsen, H. (1998) · Metabolism · doi:10.1016/s0026-0495(98)90234-7 · Cited by 23
Effects of intracerebroventricular (ICV) olanzapine on insulin sensitivity and secretion in vivo: An animal model
Hahn, M., Chintoh, A. F., Remington, G. J., Teo, C., Mann, S. W., Arenovich, T., Fletcher, P. J., Lam, L., Nóbrega, J. N., Guenette, M. D., et al. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.07.011 · Cited by 22
Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets
Zawalich, W. S., Yamazaki, H., Zawalich, K. C., & Cline, G. W. (2004) · Journal of Endocrinology · doi:10.1677/joe.1.05832 · Cited by 21
“Qualitatively and quantitatively similar responses have been noted during in vivo hyperglycemic clamp studies in humans (Van Haeften et al. 1990, Elahi 1996 ) suggesting that the same biochemical processes operative in rat islets also play an important role in human islets.”
Glucose-induced desensitization of the pancreatic β-cell is species dependent
Zawalich, W. S., Bonnet-Eymard, M., & Zawalich, K. C. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.6.e917 · Cited by 22
Closed-Loop Insulin Delivery Utilizing Pole Placement to Compensate for Delays in Subcutaneous Insulin Delivery
Loutseiko, M., Voskanyan, G. R., Keenan, D. B., & Steil, G. M. (2011) · Journal of Diabetes Science and Technology · doi:10.1177/193229681100500605 · Cited by 22
Assessment of Insulin Sensitivity in Older Adults Using the Hyperglycemic Clamp Technique
Meneilly, G. S., & Elliott, T. G. (1998) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1998.tb01019.x · Cited by 21
Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio
Dalem, A. V., Demeester, S., Balti, E. V., Keymeulen, B., Gillard, P., Lapauw, B., Block, C. E. M. D., Abrams, P. J., Weber, E., Vermeulen, I., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0166702 · Cited by 23
The Artificial Pancreas: Is it Important to Understand How the β Cell Controls Blood Glucose?
Steil, G. M., & Grodsky, G. M. (2013) · Journal of Diabetes Science and Technology · doi:10.1177/193229681300700528 · Cited by 20
Glucose effectiveness, but not insulin sensitivity, is improved after short-term interval training in individuals with type 2 diabetes mellitus: a controlled, randomised, crossover trial
Karstoft, K., Clark, M. A., Jakobsen, I., Knudsen, S. H., van Hall, G., Pedersen, B. K., & Solomon, T. P. J. (2017) · Diabetologia · doi:10.1007/s00125-017-4406-0 · Cited by 21
Estimating insulin secretion in youth using simple indices derived from the oral glucose tolerance test
Henderson, M., Baillargeon, J., RABASA-LHORET, R. P. R., Chiasson, J. L., Hanley, J., & Lambert, M. A. (2012) · Diabetes & Metabolism · doi:10.1016/j.diabet.2012.02.002 · Cited by 18
Acute and chronic effects of glucose and carbachol on insulin secretion and phospholipase C activation: studies with diazoxide and atropine
Yamazaki, H., Philbrick, W. M., Zawalich, K. C., & Zawalich, W. S. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00149.2005 · Cited by 17
Signal transduction in pancreatic beta -cells Regulation of insulin secretion by information flow in the phospholipase C Protein kinase C pathway
Zawalich, W. S. (1997) · Frontiers in bioscience · doi:10.2741/a180 · Cited by 17
Association of Habitual Daily Physical Activity With Glucose Tolerance and β-Cell Function in Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes From the Restoring Insulin Secretion (RISE) Study
Temple, K. A., Tjaden, A. H., Atkinson, K. M., Barengolts, E., Hannon, T. S., Mather, K. J., Utzschneider, K. M., Edelstein, S. L., Ehrmann, D. A., Mokhlesi, B., et al. (2019) · Diabetes Care · doi:10.2337/dc19-0538 · Cited by 16
Resistive Training Improves Insulin Sensitivity after Stroke
Ivey, F. M., & Ryan, A. S. (2013) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2012.12.014 · Cited by 15
Metabolic Features of Individuals with Obesity Referred for Bariatric and Metabolic Surgery: a Cohort Study
Li, M., Liu, Y., Jin, L., Zeng, N., Wang, L., Zhao, K., Lv, H., Zhang, M., Xu, W., Zhang, P., et al. (2019) · Obesity Surgery · doi:10.1007/s11695-019-04067-0 · Cited by 15
Pancreatic β-Cell Dysfunction Is Associated with Nonalcoholic Fatty Liver Disease
Chen, X., Xiao, J., Pang, J., Chen, S., Wang, Q., & Ling, W. (2021) · Nutrients · doi:10.3390/nu13093139 · Cited by 16
“Second, we assessed the β-cell function of DI based on the HOMA2 model, which was simple and easy-to-use, but less accurate in reflecting β-cell function compared to other indices derived from the glucose challenge test and hyperglycemic clamp method (the gold standard) [33].”
Method
Prediction of Diabetic Kidney Disease in Newly Diagnosed Type 2 Diabetes Mellitus
Mu, X., Wu, A., Hu, H., Zhou, H., & Yang, M. (2023) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s417300 · Cited by 14
Relationship between four visceral obesity indices and prediabetes and diabetes: a cross-sectional study in Dalian, China
Liu, Y., Jiang, H., Luo, L., & Gao, Z. (2024) · BMC Endocrine Disorders · doi:10.1186/s12902-024-01718-x · Cited by 15
“However, the benchmark for assessing insulin resistance—the high insulin-normal glucose clamp technique—is impractical for large sample populations because of its expensive price, invasive nature, and lengthy duration [17].”
Background
Insulin secretion and IP levels in two distant lineages of the genusMus: comparisons with rat islets
Zawalich, W. S., Zawalich, K. C., Tesz, G. J., Sterpka, J., & Philbrick, W. M. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e720 · Cited by 14

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
DOI: 10.2337/diacare.19.3.278
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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In Praise of the Hyperglycemic Clamp: A method for assessment of β-cell sensitivity and insulin resistance

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