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.
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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.
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.
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.
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.
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
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.
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