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CardioIQ® Insulin Resistance Panel with ScoreTest code(s) 36509
Question 1. What is insulin resistance? Why does it matter?
Insulin resistance (IR) is a metabolic condition that occurs when cells become less sensitive to insulin’s stimulation to absorb glucose from the bloodstream. When cells become insulin resistant, pancreatic β-cells increase the production of insulin to overcome IR and maintain normoglycemia.1,2 Over time, IR may continue to increase and/or pancreatic function may decline,2 allowing blood glucose and HbA1c levels to elevate. This can be a gradual process and makes early identification of IR difficult.
If IR is left untreated, it can lead to development of prediabetes and type 2 diabetes mellitus (T2DM). It is also associated with other clinical conditions including hypertension, cardiovascular disease, stroke, nonalcoholic fatty liver disease, polycystic ovary syndrome, and certain forms of cancer.1 Therefore, early identification of IR and intervention can halt or reverse progression of clinical conditions.
The CardioIQ Insulin Resistance Panel with Score estimates the probability that an individual currently has IR. It is based on laboratory test measurements of insulin and C-peptide, which are used in a calculation to provide a score that indicates the probability of the individual having IR.3
Although insulin and C-peptide are co-secreted from pancreatic β-cells at the same rate, their stability and clearance vary: C-peptide has much longer half-life in circulation (20-30 minutes for C-peptide compared to 3-5 minutes for insulin), and insulin is primarily cleared by the liver, whereas C-peptide is cleared through the kidneys.4 Together, insulin and C-peptide measurements provide a better indicator of IR than either alone.3
The score calculation using insulin (pmol/L) and C-peptide (pmol/L) via LC/MS/MS is3:
Question 3. How does the CardioIQ® Insulin Resistance Panel with Score compare to other methods of assessing IR?
The insulin suppression test5 and euglycemic clamp6 are standards for assessing IR. However, these methods are not well-suited for primary care clinics: they are time-consuming and labor-intensive, and require intravenous infusion. Fasting insulin and the homeostatic model assessment of IR (HOMA-IR), a score of IR based on fasting glucose and insulin measurements, are simple methods that can indicate IR.
In a study of apparently healthy individuals who were assessed for IR by the insulin suppression test, the insulin and C-peptide score outperformed insulin and the HOMA-IR. The OR comparing the top quartile of those with IR vs no IR was 6.9 for the insulin and C-peptide score, compared to 1.6 for insulin and 1.5 for the HOMA-IR.3
Question 4. Can I order insulin and C-peptide separately and calculate the score myself?
No. The insulin and C-peptide values used in the calculation are measured simultaneously by LC/MS/MS methodology from a single sample7. C-peptide cannot be ordered separately using this methodology, and C-peptide (test code 372) by immunoassay is not an equivalent test and cannot be used in the calculation of the score. The panel component Insulin, Intact, LC/MS/MS (test code 93103) can be ordered separately.
Question 5. Who is the test appropriate for?
The CardioIQ® Insulin Resistance Panel with Score will aid in early identification of IR. Testing is appropriate for those:
- At risk for IR, prediabetes, or T2DM
- Who are overweight/obese
- Who have a family history of T2DM
- Who have a history of gestational diabetes mellitus
- Who meet the criteria for metabolic syndrome
Who have clinical features of IR including:
- Central obesity
- Acanthosis nigricans (dark patches of thick, velvety skin on the back of the neck, armpits and groin)
Question 6. How do I interpret results?
The CardioIQ® Insulin Resistance Panel with Score provides a calculated score based on the insulin and C-peptide values (see Question 2). Each score is associated with a probability of IR based on population tertiles.3
A score less than 33 is optimal and indicates normal insulin sensitivity.
A score of 33-66 indicates an individual has >4-fold greater probability of having IR relative to someone with a score less than 33.
A score of greater than 66 indicates an individual has >15-fold greater probability of having IR relative to someone with a score less than 33.
Question 7. What’s the difference between the Insulin Resistance Panel with Score and the Diabetes Risk Panel with Score?
While both these tests identify metabolic risk, they differ in other clinical aspects: the disease state identified, timing of risk, and panel components. The Insulin Resistance Panel with Score provides a value that indicates the likelihood an individual currently has IR using insulin and C-peptide, whereas the Diabetes Risk Panel with Score assesses an individual’s probability of developing diabetes in the next 8 years.
Question 8. What conditions might affect this test?
C-peptide is renally cleared; therefore, those with reduced kidney function may have an increased amount of C-peptide, which may affect the Insulin Resistance Score. While kidney function has been associated with risk of IR,3,8 this test has not been validated for use in individuals with reduced kidney function; results in this population should be interpreted with caution.
- Reaven GM. The insulin resistance syndrome. Curr Atheroscler Rep. 2003;5:364-371.
- Saisho Y. β-cell dysfunction: Its critical role in prevention and management of type 2 diabetes. World J Diabetes. 2015;6:109-124.
- Abassi F, Shiffman D, Tong CH, et al. Insulin resistance probability scores for apparently healthy individuals. J Endocr Soc. In press.
- Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017;8:475-487.
- Pei D, Jones CN, Bhargava R, et al. Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test. Diabetologica. 1994;37:843-845.
- DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214-223.
- Taylor SW, Clarke NJ, Chen Z, et al. A high-throughput mass spectrometry assay to simultaneously measure intact insulin and C-peptide. Clin Chim Acta. 2016;455:202-208.
- De Cosmo S, Menzaghi C, Prudente S, et al. Role of insulin resistance in kidney dysfunction: insights into the mechanism and epidemiological evidence. Nephrol Dial Transplant. 2013;28:29-36.