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Authors: Ranganath, MD, PhD; Ritu Madan, MBBS, MD, and Ron T. Varghese, MBBS.
Location: Diabetes, Endocrinology, and Obesity Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
Last Updated: October 16, 2024.
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This section covers different techniques for assessing insulin sensitivity/resistance, ranging from complex procedures to simple tests. The gold standard is the glucose clamp method for directly measuring insulin sensitivity. Other validated and easy-to-use surrogates include QUICKI and Log (HOMA). Dynamic tests can evaluate both insulin secretion and activity.
It is important to consider both insulin sensitivity and resistance when evaluating metabolic health. Monitoring insulin levels and assessing insulin sensitivity can help in the early detection and management of conditions such as diabetes.
For additional information on Endocrinology, please visit our web-text at WWW.ENDOTEXT.ORG.
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Insulin resistance plays a significant role in type 2 diabetes and associated conditions like obesity, high blood pressure, and heart issues.
This resistance is strongly connected to the occurrence of type 2 diabetes and its complications. Symptoms such as abdominal fat accumulation, glucose intolerance, and high blood pressure are common in individuals with insulin resistance.
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Insulin’s functions include regulating blood sugar levels and enhancing glucose utilization in various body organs. Insulin resistance is characterized by reduced responsiveness to insulin’s effects on glucose metabolism.
The ability of insulin to stimulate glucose intake determines responsiveness, while sensitivity refers to the concentration required for a reaction. Insulin resistance was identified in 1936 in diabetic patients who needed large insulin doses.
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An illustration demonstrating the impact of insulin sensitivity on whole-body glucose disposal. Different curves show variations in sensitivity and responsiveness to insulin.
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Method
The gold standard method for measuring insulin sensitivity directly in humans is the glucose clamp technique. Insulin is continuously administered to maintain high insulin levels, allowing monitoring of glucose disposal. The rate of glucose infusion matches the rate of glucose disposal under stable conditions.
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A state of equilibrium must be reached during a glucose clamp study. Tracers or stable isotopes can be employed to estimate hepatic glucose production and evaluate hepatic insulin sensitivity.
Advantages and Limitations
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Method
The insulin-suppression test directly evaluates metabolic insulin sensitivity/resistance. Somatostatin is used to suppress insulin and glucagon secretion. Insulin and glucose are administered to measure SSPI and SSPG levels. SSPG values are inversely related to insulin sensitivity. This test provides a direct measurement of exogenous insulin disposal under steady-state conditions.
Advantages and Limitations
The minimal model offers an indirect assessment of insulin sensitivity based on glucose and insulin data during an FSIVGTT. Glucose and insulin are infused, and blood samples are collected over time. SI is calculated using minimal model analysis. The model can also estimate glucose effectiveness and FFA insulin sensitivity.
Schematic equations and parameters for the minimal model of glucose metabolism are displayed. The minimal model comprises two interconnected differential equations. SI is computed from model parameters that fit glucose disappearance during FSIVGTT. SG reflects glucose effectiveness in promoting its own disposal.
Advantages and Limitations
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For more detailed information on HOMA, please visit our website.
QUICKI is a reliable mathematical tool that combines fasting blood glucose and plasma insulin levels to accurately measure insulin sensitivity. Log transformation of fasting insulin levels improves its correlation with SIclamp, but this correlation can be affected in diabetic individuals with high fasting glucose levels and impaired β-cell function. To address this, adding log (fasting glucose) to log (fasting insulin) helps maintain a linear correlation with SIclamp in both diabetic and non-diabetic subjects. The reciprocal of this sum further transforms the data to generate an insulin sensitivity index with a positive correlation with SIclamp. Thus, the formula for QUICKI is 1/Log (Fasting Insulin, μU/ml) + Log (Fasting Glucose, mg/dl). QUICKI shows better correlation with SIclamp compared to other indexes like SI from the minimal model or HOMA-IR across different insulin sensitivity and resistance levels. Adipo-IR, a measure derived from FFA and insulin levels, has shown potential in larger population studies but more detailed techniques may be needed for mechanistic studies of adipose tissue insulin action.
### PROCEDURE
Surrogate indexes like Matsuda index, Stumvoll index, Gutt index, and others that use data from dynamic tests such as OGTT or IVGTT provide valuable insights into insulin sensitivity/resistance. These indexes take into account both fasting levels and post-glucose load plasma glucose and insulin levels. By studying glucose disposal and hormonal actions post-glucose challenge, these indexes help assess insulin sensitivity in different tissues. Using oral tracers in conjunction with OGTT can further improve the accuracy of these measures. While OGTT is simpler than procedures like FSIVGTT, dynamic testing may require more effort and resources.
#### ADVANTAGES AND LIMITATIONS
Dynamic surrogates from tests like OGTT offer valuable information about insulin secretion and action, correlating well with glucose clamp estimates of insulin sensitivity. While these tests are more physiological than intravenous methods, their reproducibility may be a concern. Metabolomics, which analyze small-molecule metabolites, have identified new markers for insulin resistance, showing promise in predicting future diabetes risk.
## Ethnic Differences in Insulin Sensitivity
Certain ethnic groups like Hispanics, African Americans, and South Asians are at a higher risk for diabetes due to differences in insulin sensitivity and response. Studies have shown that some traditional measures like HOMA-IR and QUICKI may not accurately reflect insulin sensitivity in these populations, emphasizing the need for more specific and validated markers. Metabolomics, which study small-molecule metabolites, have identified new markers correlated with insulin sensitivity, offering potential for predicting resistance and guiding future research.
| Method | Insulin Sensitivity Measure |
|---|---|
| Direct Assessment | |
| Hyperinsulinemic Euglycemic Glucose Clamp | Glucose infusion rate (GIR) in a steady state = glucose disposal rate (M). SI Clamp = M/(G x ΔI), where M is adjusted for G (steady-state blood glucose level) and ΔI (difference between fasting and steady-state plasma insulin levels) |
| Insulin-suppression Test (IST) | Steady-state plasma glucose (SSPG) levels during continuous infusions of insulin and glucose with suppressed natural insulin release |
| Indirect Assessment | |
| Minimal Model Analysis of Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) | Minimal model defines parameters for glucose clearance during the test. SI: fractional glucose clearance per insulin unit; SG: glucose effectiveness. |
| Simple Proxy Indexes | |
| Calculated from Fasting Stats | |
| Homeostasis Model Assessment (HOMA) | HOMA-IR = (Fasting Insulin x Fasting Glucose) / 22.5 |
| Quantitative Insulin Sensitivity Check Index (QUICKI) | QUICKI = 1/[Log (Fasting Insulin) + Log (Fasting Glucose)] |
| Derived from Dynamic Tests (OGTT) | |
| Matsuda Index | ISI(Matsuda) = 10000/√[(Gfasting x Ifasting x Gmean x Imean)] |
| Gutt Index – ISI (0, 120) (mg. l2.mmol-1.mIU-1.min-1) | ISI (0, 120) = 75000 + (G0-G120) x 0.19 x BW / 120 x Gmean (0, 120min) x Log [Imean (0, 120min)] |
SUMMARY
In this section, we explore different approaches to assess insulin sensitivity or resistance. From intricate techniques to straightforward examinations using blood samples after fasting, a range of methods is available. It is crucial to grasp the physiological principles underpinning each method to accurately analyze the results. While the glucose clamp method is considered the gold standard for precise measurements, QUICKI and Log (HOMA) have been validated as effective alternatives. Dynamic tests offer insights into both insulin secretion and function.