What is insulin resistance and what causes it?

Insulin resistance is a condition where the body's cells become less responsive to insulin, resulting in elevated blood sugar levels. It is often caused by a combination of genetic factors, poor diet, lack of exercise, and obesity. Insulin resistance can lead to type 2 diabetes if left untreated.

Understanding Insulin Resistance: The Cardio IQ Insulin Resistance Score

The Cardio IQ® Insulin Resistance Score (IR), which uses fasting insulin and C-peptide measurements to estimate a person's likelihood of having insulin resistance. It eliminates the need for multiple samples and reduces the chance of errors that can occur with some other tests.

Having a high score (indicating a greater probability of insulin resistance) was linked to an increased risk of developing type 2 diabetes, even after accounting for other risk factors. 

An IR score of <33 suggests that an individual has normal insulin sensitivity.

A score of 33 to 66 suggests that an individual has >4-fold greater odds of having IR compared with an individual with a score <33 .

A score >66 suggests that an individual has >15-fold greater odds of having IR compared to an individual with a score

Fasting Required for 10-12 hours. Water only.

What is insulin resistance and what causes it?

Insulin resistance is a condition where the body's cells become less responsive to insulin, resulting in elevated blood sugar levels. It is often caused by a combination of genetic factors, poor diet, lack of exercise, and obesity. Insulin resistance can lead to type 2 diabetes if left untreated.

What is the Cardio IQ® Insulin Resistance Panel with Score?

In people with insulin resistance (IR), their cells don't respond well to insulin and don't absorb enough glucose from the blood. This can lead to conditions like prediabetes and type 2 diabetes, along with others like high blood pressure, heart disease, stroke, non-alcoholic fatty liver disease, polycystic ovary syndrome (PCOS), and certain types of cancer. Insulin resistance is also associated with slightly higher levels of inflammation throughout the body, including kidney disease. Spotting and addressing insulin resistance early can help prevent or slow down these health conditions, including disease control. Obesity (defined as having a certain body mass index, or BMI) is a major cause of insulin resistance. It is important to note that a high-calorie, high-sugar diet, lack of physical activity, and other factors can also contribute to insulin resistance.

Insulin Resistance, Glucose and Prediabetes

Insulin resistance can start slowly and be hard to identify. In the early stages, the pancreas may produce extra insulin to make up for the reduced sensitivity. This can keep blood sugar and HbA1c (a measure of long-term blood sugar control) at normal levels. Monitoring only blood sugar won't catch the start of insulin resistance. If you have a family history of diabetes or conditions that can cause insulin resistance, talk to your healthcare provider about your risk of developing insulin resistance. If insulin sensitivity keeps dropping, the extra insulin produced won't be able to keep blood sugar levels normal, leading to higher blood sugar levels, prediabetes, and eventually type 2 diabetes. It is important to note that losing excess weight by just 7 percent can help lower your risk of developing diabetes and improve your body weight. Around 1 in 3 people in the United States have prediabetes, according to figures from the Centers for Disease Control and Prevention (CDC).

What Other Tests Can be Used for Insulin Resistance?

There are research methods to detect insulin resistance even in people with normal fasting plasma glucose levels, but they are time-consuming and complicated, so they're not practical for routine use. Simpler methods have shown promise for assessing the risk of diabetes. For instance, combining HbA1c and the HOMA-IR score, which uses fasting insulin and glucose levels, improved risk assessment for type 2 diabetes compared to using HbA1c alone.

C-peptide, a molecule released with insulin, can be an indirect marker of insulin resistance. Compared to insulin, C-peptide lasts longer in the blood, is present at higher levels, and fluctuates less. But measuring C-peptide is not commonly done due to the cost and inconvenience of collecting more samples and doing an additional test.

The Cardio IQ® Insulin Resistance Score uses fasting insulin and C-peptide measurements to estimate a person's likelihood of having insulin resistance. It eliminates the need for multiple samples and reduces the chance of errors that can occur with some other tests.

This score was developed in a study and used to estimate the odds of having insulin resistance in the United States. It showed that having a high score (indicating a greater probability of insulin resistance) was linked to an increased risk of developing type 2 diabetes in a group of older Europeans, even after accounting for other risk factors. Additionally, it has been observed that certain ethnicities, such as African Americans, have a higher susceptibility to diabetes. Therefore, understanding the impact of insulin resistance on different populations, including the United States, is crucial in managing and preventing diabetes.

Frequently Asked Questions

What is insulin resistance (IR)? 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. As long as your pancreas can make enough insulin production to overcome your cells’ weak response to insulin, your blood glucose levels will stay in the healthy range.

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 (NAFLD), polycystic ovary syndrome, and certain forms of cancer.¹ Therefore, early identification of IR and intervention can halt or reverse progression of clinical conditions.

What is the CardioIQ^® Insulin Resistance Panel With Score?

The CardioIQ^® Insulin Resistance Panel With Score estimates the probability that an individual currently has insulin resistance (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

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 insulin resistance (IR) and glucose tolerance. 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 and glucose tolerance. Additionally, a fasting blood sugar test and a blood test can also be used to diagnose insulin resistance and glucose tolerance. You will often be required to fast (avoid eating or drinking anything except water) 8 hours before the test. The blood sample will be sent to a lab for testing, and anything more than 100 milligrams per deciliter (mg/dL) is an indication of insulin resistance and glucose tolerance.

In a study of apparently healthy individuals assessed for IR by the insulin suppression test, the insulin and C-peptide score outperformed insulin and the HOMA-IR. The odds ratio (OR) comparing the top quartile of those with IR vs no IR was 6.9 for the IR score, 1.6 for insulin alone, and 1.5 for the HOMA-IR.³

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 mass spectrometry (LC/MS/MS) methodology from a single sample.⁷ 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.

Who is the test appropriate for?

The CardioIQ^® Insulin Resistance Panel with Score will aid in early identification of insulin resistance (IR). Testing is appropriate for individuals:

• 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:
  • Hypertension
  • Central obesity
  • Acanthosis nigricans (dark patches of thick, velvety skin on the back of the neck, armpits and groin)
• Hypertension
• Central obesity
• Acanthosis nigricans (dark patches of thick, velvety skin on the back of the neck, armpits and groin)

How do I interpret results of the CardioIQ Insulin Resistance test?

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.

A score less than 33 is optimal and indicates normal insulin sensitivity.

A score of 33 to 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.  

For patients without known diabetes, a fasting insulin level >10 µU/mL is consistent with the presence of hepatic steatosis.⁸ Consider further evaluation to assess the presence and stage of nonalcoholic fatty liver disease (NAFLD). 

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.

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,^3,9 this test has not been validated for use in individuals with reduced kidney function; results in this population should be interpreted with caution. 

Insulin analogs lispro and glargine interfere with insulin quantitation, while insulin analogs aspart and degludec do not. The presence of insulin antibodies may cause an artificially low result.

How can nutrition decrease or prevent insulin resistance?

Nutrition can play a crucial role in reducing insulin resistance, a condition that occurs when the body becomes less responsive to insulin. One way to combat insulin resistance is by consuming a diet that is rich in fiber and low in refined carbohydrates and sugars. Foods such as fruits, vegetables, whole grains, and lean proteins can help regulate blood sugar levels and improve insulin sensitivity. Additionally, incorporating healthy fats like omega-3 fatty acids found in fish or nuts can also be beneficial for reducing inflammation and improving insulin sensitivity. Lastly, staying hydrated and limiting alcohol consumption can also support healthy insulin levels.

What complications can be caused by insulin resistance?

Insulin resistance occurs when the body's cells become resistant to insulin, a hormone produced by the pancreas that regulates blood sugar levels. This condition can lead to several complications such as type 2 diabetes, cardiovascular disease, hypertension, and non-alcoholic fatty liver disease. Insulin resistance can also increase the risk of developing certain cancers, including breast and colon cancer. Additionally, it can contribute to obesity and metabolic syndrome, a cluster of conditions that includes high blood pressure, high blood sugar levels, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. Managing insulin resistance through lifestyle modifications like exercise and a healthy diet is crucial in preventing these complications.

References

You can include the links in your thesis references by following the citation schema below:

1. Reaven GM. The insulin resistance syndrome. Curr Atheroscler Rep. 2003;5(5):364-371¹
2. Saisho Y. β-cell dysfunction: its critical role in prevention and management of type 2 diabetes. World J Diabetes. 2015;6(1):109-124²
3. Abbasi F, Shiffman D, Tong CH, et al. Insulin resistance probability scores for apparently healthy individuals. J Endocr Soc. 2018;2(9):1050-1057³
4. Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017;8(3):475-487⁴
5. 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(8):843-845⁵
6. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214-223⁶
7. 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.
8. Bril F, McPhaul MJ, Kalavalapalli S, et al. Intact fasting insulin identifies nonalcoholic fatty liver disease in patients without diabetes. J Clin Endocrinol Metab. 2021;106(11):e4360-e4371.
9. 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(1):29-36.