Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage
Abstract
Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance.
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Insulin resistance can be measured using numerous direct and indirect techniques, including homeostatic model assessment, quantitative insulin sensitivity check index, and oral glucose tolerance test-related measures comprising area under the curve for glucose and insulin.
“IR can be measured using numerous direct and indirect techniques, including homeostatic model assessment, quantitative insulin sensitivity check index and oral glucose tolerance test-related measures comprising area under the curve for glucose and insulin (Muniyappa et al., 2008).”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Muniyappa et al., 2008
Indirect measures based on fasting or post glucose-load blood glucose and insulin levels lack accuracy and reliability and are inadequate for clinical purposes and mechanistic research where insulin resistance is a primary study outcome.
“These are based on fasting or post glucose-load blood glucose and insulin levels, yet lack accuracy and reliability and are inadequate for clinical purposes and mechanistic research where IR is a primary study outcome (Muniyappa et al., 2008).”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Muniyappa et al., 2008
The euglycaemic-hyperinsulinaemic clamp is considered the reference standard to directly measure insulin sensitivity in research settings and can be used to define a specific cut-off level for insulin resistance.
“The euglycaemic-hyperinsulinaemic clamp is considered the reference standard to directly measure IS in research settings and can be used to define a specific cut-off level for IR (Muniyappa et al., 2008).”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Muniyappa et al., 2008
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- Authors
- Muniyappa, R., Lee, S., Chen, H., & Quon, M. J.
- Affiliations
- National Institutes of Health (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-01
- Volume
- 294
- Issue
- 1
- Pages
- E15-E26
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2164418602
- Cited by
- 1,643
- References
- 12
- Citations by year
- 2026: 77 · 2025: 121 · 2024: 132 · 2023: 99 · 2022: 82 · 2021: 88 · 2020: 71 · 2019: 70 · 2018: 54 · 2017: 101 · 2016: 80 · 2015: 116 · 2014: 110 · 2013: 124 · 2012: 73
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin sensitivity, insulin resistance, in vivo evaluation, insulin suppression test, minimal model analysis, intravenous glucose tolerance test, QUICKI, HOMA, diabetes mellitus, obesity, metabolic syndrome
- MeSH terms
- Animals, Blood Glucose, Homeostasis, Humans, Insulin Resistance, Models, Biological, Glucose Clamp Technique, Glucose Intolerance
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