Insulin Resistance Targeted Panel

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Insulin Resistance Targeted Panel

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About Insulin Resistance

Insulin resistance is a critical pathophysiological state underlying several chronic conditions, including type-2 diabetes, cardiovascular disease (CVD), hypertension, and polycystic ovarian syndrome. Insulin resistance is evident when glucose builds up in the bloodstream instead of being absorbed by the body’s cells. It is a result of a diminished response to the hormone insulin at the whole body, organ, or cellular level.

A panel of biomarkers comprised of a small organic acid (α-hydroxybutyric acid (AHB)), 2 lipids (oleic acid and linoleoylglycero-phosphocholine (LGPC)) and insulin assesses insulin resistance with a single fasting blood sample and may have value as an early indicator of risk for the development of prediabetes and type-2 diabetes.1

Metabolomics reveals biological insights otherwise unseen. For a successful metabolomics study, both small molecule discovery and the ability to dig deeper into specific biomarkers of interest are needed to uncover actionable insights that propel new therapeutic developments. A specific combination of liquid chromatography-mass spectrometry (LC-MS) technology and biochemical expertise is required to identify these biomarkers of interest and develop assays that are sensitive enough to explore them fully.

At Metabolon, we understand the crucial role insulin resistance plays in diabetes, and we’ve established best-in-class expertise to detect metabolites reflective of this condition. This panel focuses on metabolites involved in insulin resistance and their metabolic pathways and can be used to track biomarkers and enhance biological understanding across preclinical and clinical research.

Insulin Resistance Targeted Panel for Clinical Use—Quantose® IR

The Quantose® IR test score was developed to estimate the value obtained from the hyperinsulinemic euglycemic clamp, the gold standard for determining insulin sensitivity, within a prospective, observational cohort study of 1277 clinically healthy, non- diabetic people recruited from 13 European countries.2 It is the first and only test to be clinically developed and validated using the clamp.

The Insulin Resistance cut-off of 63 was defined by the top tertile of scores from the European study.2 Concentrations of the panel biomarkers are measured by clinical chemistry (insulin) and mass spectrometric (UHPLC-MS/MS) based quantitation and then combined to generate the Quantose® IR Score.

The Quantose® IR Score is based on a linear regression algorithm utilizing the quantitative measures (natural log transformed) of AHB, oleate, LGPC, and insulin and was designed to estimate the natural log of the Mwbm (insulin-induced glucose infusion rate normalized by whole body mass) from the hyperinsulinemic euglycemic clamp procedure.2 Fasting plasma levels of AHB, LGPC, oleate, and insulin individually correlate significantly with Mwbm.2,3 The algorithm score is then converted to the Quantose® IR score within a range of 1 to 120 by an arithmetic calculation where higher scores denote greater Insulin Resistance.

Insulin Resistance Panel Details

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LLOQ*
Metabolite EDTA Plasma
2-Hydroxybutyric acid 0.500 µg/mL
Oleic acid 10.0 µg/mL
LGPC 2.50 µg/mL
Insulin 2 µg/mL
*Lower Limit of Quantitation (LLOQ) varies for each sample type.

Analysis Method and Instrumentation:
LC-MS/MS (Agilent 1290 UHPLC/Sciex QTrap 5500)

Sample Type and Required Amounts
Sample Type Sample Requirements
Fasting EDTA Plasma 0.5 mL
Others on request

Versions of this panel are available for Research Use Only or Clinical Use.

Clinical Use Panel Interpretive Information

It is recommended that the Quantose® IR test be administered to patients with relatively stable weight (+/- 3 lbs. over one month) and before and after diet and exercise programs.

In a 12-week, 70 subject study, the Quantose® IR measurement demonstrated fluctuations in individual analytes in subjects experiencing active weight loss. Further studies are required to more fully understand potential correlations between active weight loss, Insulin Resistance and the Quantose® IR measurement. In a situation when a patient is experiencing active weight loss, clinicians should interpret the Quantose® IR test results with caution (Metabolon data on file).

Test Scores REFERENCE INTERVALS
AHB 1.92 to 7.37 μg/mL Oleate 25.9 to 114 μg/mL
LGPC 7.60 to 25.4 μg/mL Insulin 3.13 to 21.3 μU/mL

Patients with a Quantose® IR Score of 63 or higher are defined as insulin resistant. This cut-off is defined by the top tertile of scores from a study of 1277 hyperinsulinemic glycemic clamp values of clinically healthy, non-diabetic people recruited from 13 European countries.2 Quantose® IR test score reference intervals were established using 456 non-diabetic subjects at risk for diabetes (IFG, IGT, and/or FINDRISC score > 12).

Delivering Absolute Quantification for Research and Biomarker Analysis

Our readily available or custom developed quantitative assays help you achieve your research and biomarker validation objectives with precise and fully validated methods. Our targeted assays and panels cover >1,000 metabolites and lipids across a wide range of biochemical classes, metabolic pathways, and physiological processes, and they can be customized to best fit any application.

Insulin Resistance Targeted Panel Applications

Diabetes

Diabetes is a serious metabolic condition affecting more than 37 million Americans and 460 million people worldwide according to the most recent report from the Centers for Disease Control. Despite being a worldwide epidemic, much remains unknown about individual risk factors for diabetes development, and research is currently being done to identify new and effective treatments for diabetes at all stages. By facilitating the assessment of specific metabolic pathways impacted by diabetes, targeted metabolomics can be a critical tool used to identify biomarkers of disease development for early intervention and novel targets to control disease progression, as well for the development of new pharmaceuticals with specific mechanisms of action.

Diabetes
Cardiovascular Disease

Cardiovascular Diseases

Heart disease is a leading cause of death worldwide, and there are numerous factors that lead to this and other cardiovascular diseases (CVD). Metabolomics can illuminate cardiovascular disease at multiple levels. In preclinical studies, such as with cardiomyocytes or heart tissue from model organisms, understanding mitochondrial function, energetics, and redox status can drive critical insights into disease mechanisms. In human studies, metabolomics offers the opportunity to account for well-established CVD risk factors such as cholesterol and complex lipids, while simultaneously profiling thousands of other biochemicals in an unbiased fashion to enable the discovery of novel disease mechanisms and biomarkers.

Liver

The liver is the single most important regulator of metabolic homeostasis at the organismal level in vertebrates and performs multiple crucial biological functions, such as detoxification of xenobiotics, protein metabolism, degradation of waste products, vitamin storage, and bile acid production. As the incidence of certain liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) continue to rise, researchers and healthcare providers can look to Metabolon to provide much-needed diagnostic and prognostic indicators to better understand the molecular mechanisms underpinning pathological processes. The Targeted Assay team at Metabolon has developed many assays that can provide insights into the liver, such as assessment of energy homeostasis (Branched-Chain Amino Acids Assay, Central Carbon Assay, Free Fatty Acid Assay, Beta-Hydroxybutyrate Assay, Salivary Glucose Assay), liver health (Bile Acid Assay, Expanded Glucose Tolerance Assay, Insulin Resistance Assay, Impaired Glucose Tolerance Panel), and liver function (Bile Acids Assay, C4 Assay).
liver

Big Insights with Metabolon

Cited in over 3,000 publications, we help scientists and manufacturers gain greater insight into their studies through metabolomics. See how our approach can become a successful part of your workflow.

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References

1. Cobb J, Gall W, Adam KP, et al. A novel fasting blood test for insulin resistance and prediabetes. J Diabetes Sci Technol. 2013;7(1):100-110. Published 2013 Jan 1. doi:10.1177/193229681300700112

2. Cobb J, Eckhart A, Perichon R, et al. A novel test for IGT utilizing metabolite markers of glucose tolerance. J Diabetes Sci Technol. 2015;9(1):69-76. doi:10.1177/1932296814553622

3. Gall WE, Beebe K, Lawton KA, et al. alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One. 2010;5(5):e10883. Published 2010 May 28. doi:10.1371/journal.pone.0010883