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Metabolomics and Glucose Intolerance—Diving Deeper into this Diabetes Driver

Metabolomics and Glucose Intolerance

Humans derive energy from food, which is broken down (digested) in the stomach by acids and enzymes. Digestion releases glucose from food. Glucose then travels to your intestine where it is absorbed into the bloodstream. Glucose tolerance is defined as a body’s ability to absorb glucose. Under physiologic conditions, blood glucose levels consistently lie within a normal range. The pancreas monitors these levels and releases insulin when blood glucose is too high. Insulin helps to move those glucose molecules from the blood into cells. A breakdown in this process is known as glucose intolerance. Here, the ability to absorb glucose becomes impaired, causing the blood glucose levels to remain too high as glucose can’t move into cells.

Glucose intolerance has many implications for overall health, with one of the most well-known being diabetes. In type 2 diabetes the pancreas is no longer able to make enough insulin to meet the body’s needs which results in excess glucose in the blood. Too much glucose in the blood for a long period can also increase the risk of heart disease, kidney disease, and nerve damage. 

The Glucose Tolerance Test

Current testing strategies for understanding glucose tolerance involves a fasted blood test and then another blood test after glucose is consumed. This is commonly referred to as the glucose tolerance test. It provides baseline glucose levels and monitors how well the body is removing glucose from the blood. Typically, a result above 140 mg/dL indicates prediabetes, and a level above 200 mg/dL suggests diabetes.1

While the glucose tolerance test is the currently accepted standard for measuring how well the body is processing glucose and if someone might have glucose intolerance, it does have limitations. Firstly, there is a tendency to diagnose patients as diabetic after an abnormal glucose test without considering other factors that may be contributing to their inability to process glucose.2 False positives are particularly prevalent when testing for gestational diabetes.3 These false positives can lead to ineffective treatments that do not address the appropriate underlying cause. Another limitation of the glucose tolerance test is a lack of standards for using the test in older patients. As we age, our ability to process glucose naturally declines, however, guidelines for interpreting the test do not account for this.4 This could be leading to increased rates of diabetes diagnosis in older people who are processing glucose appropriately for their age.

Beyond Glucose Level Testing

In light of these limitations, other testing strategies need to be explored to truly understand how glucose is being processed. Simply testing glucose levels in the blood does not illuminate all of the potential failure points along these complex biochemical processes. One way to get a deeper picture is to examine the small molecules or metabolites involved in these pathways. Metabolomic analysis can identify other diagnostic biomarker signatures that can distinguish between diabetes or other underlying causes of high blood glucose levels. A study conducted in 2014 identified 23 candidate biomarkers for impaired glucose tolerance, all of which were involved in the biochemical pathways that allow us to process glucose. This metabolomic test identified impaired glucose tolerance in over 1000 nondiabetic patients. Early intervention through diet and lifestyle changes can help patients with impaired glucose tolerance avoid progressing to type 2 diabetes. Additionally, this alternative metabolite-based test only requires one blood draw, making it a more convenient testing strategy.5

Additional discoveries continue to be made that can provide more insight into how glucose is processed and how lifestyle and environmental factors influence overall health. A study published in 2022 examined the effect that exercise has on metabolism. Exercise stimulated the production of the metabolite N-lactoyl-phenylalanine (Lac-Phe) which suppresses feeding and obesity. Increasing the amount of Lac-Phe in mice also helped to improve their glucose homeostasis.6 The results suggest that additional research into the Lac-Phe mediating pathways could illuminate more about how exercise influences health and our ability to regulate glucose levels.

There is still much to be explored in terms of identifying metabolomic signatures of glucose intolerance. A better understanding of the small molecules involved in these biochemical pathways and the discovery of new biomarkers could offer alternative ways to identify the causes of glucose intolerance. Metabolon’s deep scientific expertise can help you design and execute a metabolomic study examining glucose intolerance utilizing our suite of solutions for glucose research, such as our Glucose Tolerance Metabolites Targeted Panel, Impaired Glucose Tolerance Targeted Panel, Insulin Resistance Targeted Panel, or our Salivary Glucose Single Analyte Assay. Learn more about our portfolio here.


Our team is made up of over 45 PhDs, has been published 3,000+ times, and is committed to hard work, excellence, and success through collaboration. With over 1,300 clients and 10,000 projects, Metabolon has been a trusted partner of researchers for over two decades.


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