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Are Your Patients Insulin Resistant? 4 Ways To Test

Written By
Dr.
Eve Henry
MD

Why This Was Updated?

Our specialists regularly review advancements in health and wellness, ensuring our articles are updated with the newest information as it becomes accessible.
Medically Reviewed by

Type II diabetes is a profound global health problem associated with tremendous disease and disability worldwide. The WHO estimates that in 2019 alone, diabetes was the direct cause of 1.5 million deaths.

Functional Medicine practitioners understand the importance of focusing on the root cause of cellular imbalances that lead to devastating diseases such as diabetes.

Abnormalities in cellular glucose metabolism can be detected in blood work more than a decade before one develops diabetes. Insulin resistance (IR) marks the beginning of these metabolic changes and can be detected via blood work, glucose tolerance tests, or continuous glucose monitors. IR occurs when the liver, muscle, and adipose cells become less sensitive to insulin and do not rapidly remove glucose from the blood. The presence of IR correlates with numerous detrimental metabolic changes such as an increase in small dense LDL particles, increased inflammatory markers, and an increase in systolic blood pressure.

Below we highlight some of the lab-based biomarkers a clinician can use to identify early changes in glucose metabolism and help a patient avoid the dangerous metabolic path towards diabetes.

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Ways To Test Insulin Resistance:

Below are some of the most important tests for assessing insulin resistance:

Hemoglobin A1c

Using the volume of glycosylation on red blood cells, the Hemoglobin A1c test (HbA1c) gives a rough estimate of glucose levels during the life of the red blood cell (approximately three months). An HbA1c level between 5.7% and 6.4% is considered diagnostic for pre-diabetes. HbA1c level at 6.5% or above is consistent with a diagnosis of diabetes. Β 

HbA1c is a well-established and popular method for diagnosing pre-diabetes. Studies have found the HbA1c test to be significantly more sensitive to detecting early abnormalities in glucose metabolism than fasting glucose levels. Β 

HbA1c is helpful and sensitive for early changes in glucose metabolism because it catches the rise in blood sugar people experience after large meals. One of the earliest changes in pre-diabetes is the loss of an effective early-phase insulin release that helps prevent a large postprandial (after you eat) glucose spike. These large glucose peaks after meals increase red blood cell glycosylation and push up the HbA1c score, and measures of fasting blood glucose do not catch this early change in glucose metabolism.

Note: Any disorder that changes the size of the red blood cell or alters the rate of red blood cell turnover will significantly decrease the accuracy of HbA1c as a proxy for blood sugar levels. Barring known pathologies of hemoglobin, there are also people in whom the rate of glycosylation may be faster or slower than average, which will alter the accuracy of the HbA1c.

Fasting Insulin

Measuring insulin levels after an overnight fast is a practicable and effective proxy for detecting insulin resistance. As the body becomes less effective at metabolizing glucose, insulin levels begin to rise. Research has shown a considerable correlation between fasting insulin levels and insulin action as measured by the gold standard glucose clamp technique. Normal fasting insulin reference ranges are quite broad, 2.6-24.9 mcIU/ml, but research has correlated fasting insulin levels over 7 as being associated with a significant increase in future risk of metabolic syndrome and type II diabetes. Β 

In healthy subjects, increased fasting insulin levels, even in the setting of normal fasting glucose levels, corresponded to insulin resistance. This correlation ends when glucose dysfunction advances and the pancreas stops producing elevated insulin levels even in the setting of hyperglycemia. Β 

HOMA-IR Score

HOMA-IR stands for the Homeostasis Model Assessment of Insulin Resistance and uses a validated mathematical model to create a score that can be used to determine insulin resistance. The score is based on inputs of a fasting plasma glucose and fasting plasma insulin. You can download a calculator to automatically compute the score from the University of Oxford.

One of the challenges of the HOMA-IR score has been the lack of validated cutoffs for various populations. In the last five years, numerous studies have been published outlining cutoff values for insulin resistance in specific populations. Although specific cutoffs may vary by demographics, a HOMA-IR score of less than 1 is generally considered very insulin sensitive. A cutoff of 2.9 is used for significant insulin resistance.

As a simple and relatively easy to access marker, the HOMA-IR score is considered one of the best and most extensively validated assessments of IR and gives an accurate physiological assessment of glucose homeostasis.

Oral Glucose Tolerance

A two-hour oral glucose tolerance test is one of the most sensitive measures of early glucose dysregulation. Two-hour glucose tests require a significant investment in patient time but can be a fantastic tool in identifying early glucose dysregulation. The test consists of a fasting glucose blood test followed by consumption of a 75mg glucose drink and then subsequent blood draws for glucose levels at 30, 60, and 120 minutes. The test is considered abnormal if the glucose is greater than 140 two hours after the drink has been consumed. An abnormality of the two-hour glucose tolerance test is a strong indicator of a problem with glucose metabolism and is associated with an increased risk of cardiovascular disease and all-cause mortality . While this test does not directly measure insulin levels, it provides valuable real-time feedback on glucose tolerance.

Intervening Early Β 

We owe it to our patients to screen for evidence of glucose dysregulation as early as possible. Even the earliest form of glucose dysregulation - where only the oral glucose tolerance test is abnormal - can be intervened upon by lifestyle interventions to prevent the onset of diabetes.

Teaching patients how to follow a whole foods lower carbohydrate diet can profoundly impact reducing glucose dysregulation. Intermittent fasting as well as increasing muscle mass, have been shown to decrease markers of insulin resistance and prevent the progression from insulin resistance to diabetes. Continuous glucose monitors are another fantastic tool that patients can use to learn how their specific physiology responds to their diet. Once you identify the problem, there are so many ways to help patients take control of their metabolic health.

Type II diabetes is a significant global health concern associated with considerable health challenges worldwide. The WHO estimates that in 2019 alone, diabetes was the direct cause of 1.5 million deaths.

Functional Medicine practitioners focus on understanding the underlying factors that may contribute to cellular imbalances associated with conditions like diabetes.

Changes in cellular glucose metabolism can be observed in blood work many years before diabetes develops. Insulin resistance (IR) is an early indicator of these metabolic changes and can be identified through blood work, glucose tolerance tests, or continuous glucose monitors. IR occurs when the liver, muscle, and adipose cells become less responsive to insulin, affecting glucose removal from the blood. The presence of IR is associated with various metabolic changes such as an increase in small dense LDL particles, increased inflammatory markers, and higher systolic blood pressure.

Below we highlight some of the lab-based biomarkers that may help clinicians identify early changes in glucose metabolism and support patients in maintaining metabolic health.

[signup]

Ways To Test Insulin Resistance:

Below are some of the important tests for assessing insulin resistance:

Hemoglobin A1c

Using the volume of glycosylation on red blood cells, the Hemoglobin A1c test (HbA1c) provides an estimate of average glucose levels over the life of the red blood cell (approximately three months). An HbA1c level between 5.7% and 6.4% may indicate pre-diabetes. An HbA1c level at 6.5% or above is consistent with a diagnosis of diabetes. Β 

HbA1c is a widely used method for assessing glucose metabolism. Studies have found the HbA1c test to be more sensitive in detecting early changes in glucose metabolism than fasting glucose levels. Β 

HbA1c is useful for identifying early changes in glucose metabolism because it reflects the rise in blood sugar after meals. One of the early changes in pre-diabetes is the reduced effectiveness of early-phase insulin release, which helps manage postprandial (after eating) glucose spikes. These glucose peaks can increase red blood cell glycosylation and raise the HbA1c score, while fasting blood glucose measures may not detect this early change.

Note: Any condition that affects the size of red blood cells or alters their turnover rate can impact the accuracy of HbA1c as an indicator of blood sugar levels. Additionally, individual variations in glycosylation rates can affect the accuracy of the HbA1c.

Fasting Insulin

Measuring insulin levels after an overnight fast can be a practical method for assessing insulin resistance. As the body becomes less efficient at metabolizing glucose, insulin levels may rise. Research has shown a correlation between fasting insulin levels and insulin action as measured by the glucose clamp technique. Normal fasting insulin reference ranges are broad, 2.6-24.9 mcIU/ml, but research suggests that fasting insulin levels over 7 may be associated with an increased risk of metabolic syndrome and type II diabetes. Β 

In healthy individuals, increased fasting insulin levels, even with normal fasting glucose levels, may indicate insulin resistance. This correlation may change as glucose metabolism becomes more impaired and the pancreas produces less insulin despite high blood sugar levels. Β 

HOMA-IR Score

HOMA-IR stands for the Homeostasis Model Assessment of Insulin Resistance and uses a mathematical model to create a score that can help assess insulin resistance. The score is based on fasting plasma glucose and fasting plasma insulin levels. A calculator to compute the score is available from the University of Oxford.

One challenge with the HOMA-IR score is the lack of universally validated cutoffs for different populations. Recent studies have proposed cutoff values for insulin resistance in specific populations. While cutoffs may vary, a HOMA-IR score of less than 1 is generally considered to indicate high insulin sensitivity, while a score of 2.9 or higher may suggest significant insulin resistance.

As a simple and accessible marker, the HOMA-IR score is considered a valuable tool for assessing insulin resistance and provides insights into glucose homeostasis.

Oral Glucose Tolerance

A two-hour oral glucose tolerance test is a sensitive measure of early glucose dysregulation. This test requires a time investment but can be useful in identifying early glucose metabolism issues. It involves a fasting glucose test, followed by a 75mg glucose drink, and subsequent blood draws at 30, 60, and 120 minutes. The test is considered abnormal if glucose levels exceed 140 two hours after the drink. An abnormal result may indicate issues with glucose metabolism and is associated with an increased risk of cardiovascular concerns and all-cause mortality . While this test does not directly measure insulin levels, it provides valuable feedback on glucose tolerance.

Intervening Early Β 

It is important to screen for early signs of glucose dysregulation. Even early forms of glucose dysregulation, where only the oral glucose tolerance test is abnormal, may be addressed through lifestyle changes to support metabolic health.

Encouraging patients to consider a whole foods, lower carbohydrate diet may help in managing glucose levels. Intermittent fasting and increasing muscle mass have been associated with reduced markers of insulin resistance and may help in maintaining metabolic health. Continuous glucose monitors can be useful tools for patients to understand how their bodies respond to different foods. Identifying potential issues allows for various strategies to support patients in managing their metabolic health.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
Learn More

Lab Tests in This Article

(n.d.). Retrieved from https://www.who.int/news-room/fact-sheets/detail/diabetes

Adam G Tabak, M. J. (2009, July 8). The Lancet. Retrieved from Science Direct: https://www.sciencedirect.com/science/article/pii/S014067360960619X

Altuntaş, Y. (2019, Aug). Postprandial Reactive Hypoglycemia. Retrieved from US National Library of Medicine National Institutes of Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192270/

Amy T. Hutchison, P. R. (n.d.). 724 Obesity | VOLUME 27 | NUMBER 5 | MAY 2019 www.obesityjournal.org Obesity Time-Restricted Feeding Improves Glucose Tolerance in Men at Risk for Type 2 Diabetes: A Randomized Crossover Trial. Retrieved from Online Library: https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.22449

B J Gould, S. J. (2007, April). Investigation of the mechanism underlying the variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia. Retrieved from Pubmed.gov: https://pubmed.ncbi.nlm.nih.gov/9101100/

Bhawna Singh, A. S. (2010, May). Surrogate markers of insulin resistance: A review. Retrieved from US National Library of Medicine National Institutes of Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083884/

Bhawna Singh, A. S. (2010, May). Surrogate markers of insulin resistance: A review. Retrieved from US National Library of Medicine National Institutes of Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083884/

Consensus Development Conference on Insulin Resistance. 5-6 November 1997. American Diabetes Association. (1998, Feb). Retrieved from Pubmed.gov: https://pubmed.ncbi.nlm.nih.gov/9540000/

D. R. Matthews, J. P. (1985, July). Homeostasis model assessment: insulin resistance and Ξ²-cell function from fasting plasma glucose and insulin concentrations in man. Retrieved from Springer Link: https://link.springer.com/article/10.1007%2FBF00280883

Diabetes. (2021, April 13). Retrieved from World Health Organization: https://www.who.int/news-room/fact-sheets/detail/diabetes

J Tuomilehto, J. L.-P.-K. (2001, May). Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. Retrieved from Pubmed.gov: https://pubmed.ncbi.nlm.nih.gov/11333990/

Ki-Chul C Sung, M.-H. H.-J. (2011, Nov). Elevated fasting insulin predicts the future incidence of metabolic syndrome: a 5-year follow-up study. Retrieved from Cardiovascular Diabetology: https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-10-108

Lan T. Ho-Pham, U. D. (2017, Aug 17). Discordance in the diagnosis of diabetes: Comparison between HbA1c and fasting plasma glucose. Retrieved from PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182192

Qing Qiao, J. M. (2004, June). Two prospective studies found that elevated 2-hr glucose predicted male mortality independent of fasting glucose and HbA1c. Retrieved from Pubmed.gov: https://pubmed.ncbi.nlm.nih.gov/15246127/

Robert M. Cohen, S. H. (2010, Dec). HbA1c for the Diagnosis of Diabetes and Prediabetes: Is It Time for a Mid-Course Correction? Retrieved from US National Library of Medicine National Institutes of Health: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999978/

Sungwoo Hong, Y. C.-S. (2017, Nov 30). Relative muscle mass and the risk of incident type 2 diabetes: A cohort study. Retrieved from PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188650

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