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.
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