Description
Impaired glucose tolerance (IGT) refers to a condition in which the body cannot metabolize and regulate glucose properly.

Quantose Glucose Tolerance Test is a laboratory test offered by Labtech Diagnostics. According to the technical information dossier, QUANTOSE™ IGT reflects the degree of impaired glucose tolerance in an individual. Assessment of several biomarkers are converted into a risk score by a proprietary algorithm, and higher scores are intended to represent higher risk of impaired glucose tolerance.

Policy 

Quantose Impaired Glucose Tolerance (IGT) test is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY at this point of time because of  a lack of valid scientific evidence. 

Policy Guideline 
There is no established guideline regarding the test from any professional association and regulatory agencies. 

There is no valid study to justify the medical necessity of the test. The only study has conflict of interest and potential of commercial bias.  

Rationale 
Diabetes is a major health concern in the United States. According to the Centers for Disease Control and Prevention:  

• Prevalence: In 2018, 34.2 million Americans, or 10.5% of the population, had diabetes. Approximately 90% – 95% of these cases are Type 2.
• Undiagnosed: Of the 34.2 million, 26.9 million were diagnosed, and 7.3 million were undiagnosed.
• Prevalence in seniors: The percentage of Americans age 65 and older remains high, at 26.8%, or 12 million seniors (diagnosed and undiagnosed).
• New Cases: 1.5 million Americans are diagnosed with diabetes every year.
• Prediabetes: In 2018, 88 million Americans age 18 and older had prediabetes, a condition in which blood glucose levels are higher than normal but are not high enough for a diagnosis of diabetes. People with prediabetes are at increased risk for developing Type 2 diabetes and for heart disease and stroke. Other names for prediabetes are impaired glucose tolerance and impaired fasting glucose.
• Deaths: Diabetes remains the seventh-leading cause of death in the United States in 2017, with 83,564 death certificates listing it as the underlying cause of death, and a total of 270,702 death certificates listing diabetes as an underlying or contributing cause of death.
• Multiple comorbidities such as cardiovascular disease (including hyperlipidemia, coronary artery disease, and stroke), renal disease, (chronic renal insufficiency, dialysis and transplantation), infections, malignancy, and functional impairment are associated with uncontrolled diabetes.
• Total economic cost of diabetes care in the United States in 2017: $327 billion. 

A diagnosis of diabetes is based on one of four abnormalities, one of which is an abnormal oral glucose tolerance test that measures IGT. This test assesses an individual’s response to glucose and the rate which it clears from the blood, and it is used to diagnose diabetes, risk for prediabetes, or gestational diabetes. A set amount of glucose (usually 75 g) is ingested by the patient after a 9-hour fast, and a venipuncture is done 2 hours (± 15 minutes) after ingestion (CDC, 2007). Then the glucose concentration is checked. A reading of 140 mg/dL to 199 mg/dL is considered “prediabetes”, and > 200 mg/dL is considered diagnostic for diabetes. 

However, other tests exist for assessment of IGT. For example, Quantose IGT uses a proprietary algorithm to produce an “IGT score.” This algorithm combines glucose and seven biomarkers, which are as follows: α-hydroxybutyric acid (AHB), 4-methyl-2-oxopentanoic acid (4MOP), oleic acid, linoleoylglycerophosphocholine (LGPC), β-hydroxybutyric acid (BHBA), serine, and pantothenic acid (vitamin B5). 

Cobb et al. used the data from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study to generate and validate the Quantose test. 1,277 subjects from the RISC study were divided into a training set and a test set for algorithm development and validation. A total of 26 metabolites from this study were collated and investigated for potential inclusion into an insulin resistance algorithm along with body mass index (BMI) and insulin, and three metabolites (α-HB, L-GPC, and oleate) were incorporated into the algorithm. The test was validated with a 383-item sample, finding areas under the curve of 0.79 for insulin resistance and 0.70 for IGT progression. The investigators concluded that the Quantose test had clinical utility in the prediction of progression from normal glucose tolerance to impaired glucose tolerance and is superior to other simple baseline measures (fasting insulin, BMI, fasting glucose, HOMA-IR) in this regard. They further stated that the test may have value as an earlier predictor of prediabetes or Type 2 diabetes mellitus risk when compared with these traditional glycemic markers. The authors declared their potential conflicts of interest with respect to the research, authorship and/or publication of this article. The study was funded by Metabolon Inc. and 10 of the 13 authors of the study were full-time employees of Metabolon Inc. 

Tripathy et al. evaluated the utility of Quantose IGT. The authors monitored changes in insulin sensitivity after pioglitazone therapy. 428 of the patients from the “ACT NOW” IGT study were placed on therapy and followed them for 2.4 years. The investigators found treatment lowered IGT progression to diabetes (hazard ratio: 0.25), and Quantose score was found to correlate with the Matsuda index of insulin sensitivity. Quantose score was also found to be progressively as higher across “closeout” glucose tolerance status (diabetes, IGT, normal glucose tolerance). The authors concluded that “Quantose MQ [score] may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.” 

There are no established guidelines or recommendations regarding the Quantose IGT test from any professional association and regulatory agencies. The USPSTF, AAFP, AACE, and ADA all recommend the OGTT as the primary evaluation of IGT. 

References

1. AAFP. (2017). Summary of Recommendations for Clinical Preventive Services. Retrieved from https://www.aafp.org/patient-care/clinical-recommendations/all/diabetes-screening.html
2. ADA. (2021). Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021.
3. CDC. (2007). Oral Glucose Tolerance Test (OGTT) Procedures Manual Retrieved from https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_ogtt.pdf
4. CDC. (2020). National Diabetes Statistics Report 2020. Retrieved from https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
5. Cobb, J., Gall, W., Adam, K. P., Nakhle, P., Button, E., Hathorn, J., . . . Ferrannini, E. (2013). A novel fasting blood test for insulin resistance and prediabetes. J Diabetes Sci Technol, 7(1), 100-110. doi:10.1177/193229681300700112
6. Labtech_Diagnostics. (2018). Technical Information Guide. Retrieved from https://labtechdiagnostics.net/wp-content/uploads/2018/10/quantose.pdf
7. Mechanick, J. I., Garber, A. J., Grunberger, G., Handelsman, Y., & Garvey, W. T. (2018). DYSGLYCEMIA-BASED CHRONIC DISEASE: AN AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS POSITION STATEMENT. Endocr Pract, 24(11), 995-1011. doi:10.4158/ps-2018-0139
8. Siu, A. L. (2015). Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med, 163(11), 861-868. doi:10.7326/m15-2345
9. Tripathy, D., Cobb, J. E., Gall, W., Adam, K. P., George, T., Schwenke, D. C., . . . DeFronzo, R. A. (2015). A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study. J Clin Endocrinol Metab, 100(5), 1855-1862. doi:10.1210/jc.2014-3824

Coding Section 

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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