Insulin sensitivity and insulin sensitivity score -
Furthermore, QUICKI provides a reproducible and robust estimate of insulin sensitivity, because equally strong correlations with SI Clamp were obtained when fasting data from either the glucose clamp or FSIVGTT studies were used to calculate QUICKI.
In addition, QUICKI derived from the average results of two fasting blood samples over 10 min was similar to QUICKI calculated from a single sample. Finally, the good correlation between QUICKI and SI Clamp obtained from a completely independent dataset acquired at a different institution provides further validation of the reliability of QUICKI.
However, the correlation coefficient for the nonobese subgroup was 0. There are several potential explanations for the lower correlation we observed within the nonobese subgroup. The most likely explanation for this finding is that variability in insulin determinations due to limitations in assay sensitivity causes larger percentage of errors in QUICKI when insulin levels are lowest typical of the most insulin-sensitive subjects.
Alternatively, periodic oscillations in insulin secretion both ultradian and to min periods have been reported in healthy subjects and may also contribute to the weaker correlation in this subgroup 21 , Interestingly, these oscillations diminish with impaired glucose tolerance and diabetes 23 , Therefore, in our nonobese subjects there may be a sampling error that results in aliasing of the data.
However, this effect is unlikely to be occurring in our studies, because fasting samples were obtained at the same time in the morning for each subject, and calculating QUICKI from the average of several blood samples instead of a single sample did not significantly affect our correlations.
Another possible explanation for the lower correlation between QUICKI and SI Clamp in the nonobese subgroup is that the insulin infusion rate used in our glucose clamp studies was inappropriately high for individuals who are very insulin sensitive.
Nevertheless, as discussed above, the good correlation between SI Clamp derived from high and low insulin infusion rates suggests that our choice of high insulin infusion rate did not introduce significant error into SI Clamp estimates in nonobese subjects.
However, it is possible that comparison of QUICKI with clamp data obtained with low insulin infusion rates has additional variability, because hepatic glucose production may not be completely suppressed under these conditions. Previous studies have suggested that fasting insulin per se may provide a reasonable index of insulin sensitivity that has positive predictive power with respect to the development of diseases associated with insulin resistance, such as obesity, hypertension, and diabetes 25 — However, in diabetes, where fasting hyperglycemia is accompanied by inadequate insulin secretion, this relationship may not be maintained.
To account for this, the so-called HOMA approach uses a mathematical model to obtain an insulin sensitivity index that is defined as the product of the fasting plasma insulin and blood glucose values divided by a constant Several recent studies have demonstrated that the HOMA approach to estimating insulin sensitivity is useful in large epidemiological studies 28 , Interestingly, our novel index, QUICKI, is similar to HOMA, except that QUICKI also transforms the data by taking both the logarithm and the reciprocal of the glucose-insulin product.
One rational for these transformations is the fact that the distribution of fasting insulin values is skewed. Thus, transformation of these data might be predicted to generate a better fit to glucose clamp measurements of insulin sensitivity.
As expected, given the similarities between QUICKI and HOMA, the two methods correlate well. Nevertheless, the correlation between QUICKI and SI Clamp is significantly better than the correlation between HOMA and SI Clamp.
Furthermore, it is clear that HOMA is not linear over wide ranges of insulin sensitivity, because the slopes of the linear regression lines for each subgroup change and generally correlate with the insulin sensitivity of each subgroup.
From inspection of Fig. Indeed, log [HOMA] correlates very highly with QUICKI. This suggests that transformation of the data is beneficial for estimating insulin sensitivity and that QUICKI may be a more accurate index of insulin sensitivity than HOMA across a broad range of insulin sensitivities.
Of the three alternatives to the glucose clamp method for estimating insulin sensitivity in vivo that we examined in this study, QUICKI had the best overall linear correlation with the gold standard clamp measurement.
In contrast to the multiple frequent blood samples and the lengthy time course required for both the glucose clamp and the minimal model approach, QUICKI can be obtained from a fasting blood sample. In addition, the ability to calculate QUICKI does not depend on a robust insulin secretory capacity, and we were able to use this method to estimate insulin sensitivity for all of our diabetic subjects as opposed to the minimal model approach.
Furthermore, in our study population, QUICKI was more accurate than either SI MM or HOMA and displayed excellent reproducibility. Potential limitations to QUICKI include difficulty in applying it to subjects with type 1 diabetes who lack endogenous insulin secretion.
In addition, we were unable to determine whether QUICKI is applicable to subjects with severe diabetes who could not be safely taken off of their antidiabetic medications. Nevertheless, it is also problematic to determine insulin sensitivity in subjects with type 1 diabetes and uncontrolled type 2 diabetes using other methods.
Furthermore, the determination of relative insulin sensitivity and resistance in these types of subjects may be of less interest in large epidemiological studies. However, in analyzing an independent dataset, we observed very similar correlations between QUICKI and SI Clamp , strongly suggesting that QUICKI is a robust index of insulin sensitivity.
We conclude that fasting glucose and insulin levels contain sufficient information to accurately assess insulin sensitivity in vivo over a wide range in a diverse population.
QUICKI is a novel, simple, accurate, and reproducible method for determining insulin sensitivity in humans that may be a useful tool in large epidemiological investigations that study the role of insulin resistance in the pathophysiology of important public health problems such as obesity, cardiovascular diseases, and diabetes.
We thank Dr. Anne E. Sumner for technical assistance with some of the studies and Dr. Paul Albert for help with some of the statistical analyses. We also thank Drs. Simeon I. Taylor and Derek LeRoith for critical reading of the manuscript and helpful suggestions.
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Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Subjects and Methods. Journal Article. Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans.
Arie Katz , Arie Katz. Oxford Academic. Sridhar S. Kieren Mather. Alain D. Dean A. Gail Sullivan. Michael J. Revision received:. PDF Split View Views. Cite Cite Arie Katz, Sridhar S. Select Format Select format.
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FSIVGTT method. Open in new tab. Table 2. Clinical characteristics of study subjects. Age yr. Figure 1. Open in new tab Download slide. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Table 3. SI clamp. SI MM. SI Clamp 1 SI MM 0. Lilly lecture Search ADS. Google Scholar Crossref. Insulin as a vascular and sympathoexcitatory hormone: implications for blood pressure regulation, insulin sensitivity, and cardiovascular morbidity.
Hypertension and associated metabolic abnormalities—the role of insulin resistance and the sympathoadrenal system. Do non-insulin-dependent diabetes mellitus and cardiovascular disease share common antecedents? Glucose clamp technique: a method for quantifying insulin secretion and resistance.
Google Scholar PubMed. OpenURL Placeholder Text. Manual feedback technique for the control of blood glucose concentration. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. Differences between the tolbutamide-boosted and the insulin-modified minimal model protocols.
A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Non-insulin-mediated glucose disappearance in subjects with IDDM. Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling.
Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal-model method. The concept of insulin resistance is relatively easy to understand, but determining precisely who is insulin resistant is more complicated. The relationship between glucose and insulin is quite complex and involves the interaction of many metabolic and regulatory factors.
Normal insulin sensitivity varies widely and is influenced by age, ethnicity, and obesity. Simply put, not all people with impaired insulin sensitivity are necessarily suffering from a disorder, and pregnancy is a perfect example of this.
A World Health Organization consensus group recently concluded that the insulin sensitivity index SI of the lowest 25 percent of a general population can be considered insulin resistant. The European Group for the Study of Insulin Resistance took a more restricted view, defining insulin resistance as the SI of the lowest 10 percent of a non-obese, nondiabetic, normotensive Caucasian population.
Richard Legro and his associates also used the SI of the lowest 10 percent of an obese, non-PCOS population to define insulin resistance. Ideally, we should be deriving the normal SI range from a population of women who are not obese, have regular menstrual cycles, are not suffering from hirsutism, and have normal circulating androgen levels.
The hyperinsulinemic-euglycemic clamp technique is the most scientifically sound technique for measuring insulin sensitivity, and it's against this standard that all other tests are usually compared.
Because this and similar "clamp" techniques are expensive, time consuming, and labor intensive, they are not very practical in an office setting. To overcome these obstacles, alternative tests have been developed, including the frequently sampled IV glucose tolerance test FSIVGTT , insulin tolerance test ITT , insulin sensitivity test IST , and continuous infusion of glucose with model assessment CIGMA.
Unfortunately, all of these methods require IV access and multiple venipunctures, making them relatively impractical for office assessment. The oral glucose tolerance test OGTT does not require IV access but does involve several venipunctures and 2 to 4 hours of patient and technician time.
Each of these tests has been shown to correlate reasonably well with dynamic clamp techniques. Hyperinsulinemic-euglycemic clamp : The gold standard for evaluating insulin sensitivity, this "clamp" technique requires a steady IV infusion of insulin to be administered in one arm.
The serum glucose level is "clamped" at a normal fasting concentration by administering a variable IV glucose infusion in the other arm.
Numerous blood samplings are then taken to monitor serum glucose so that a steady "fasting" level can be maintained. In theory, the IV insulin infusion should completely suppress hepatic glucose production and not interfere with the test's ability to determine how sensitive target tissues are to the hormone.
The degree of insulin resistance should be inversely proportional to the glucose uptake by target tissues during the procedure. In other words, the less glucose that's taken up by tissues during the procedure, the more insulin resistant a patient is. A variation of this technique, the hyperinsulinemic-hyperglycemic clamp provides a better measurement of pancreatic beta cell function but is less physiologic than the euglycemic technique.
Insulin sensitivity test IST : IST involves IV infusion of a defined glucose load and a fixed-rate infusion of insulin over approximately 3 hours.
Somatostatin may be infused simultaneously to prevent insulin secretion, inhibit hepatic gluconeogenesis, and delay secretion of counter-regulatory hormones— particularly glucagon, growth hormone, cortisol, and catecholamines.
Fewer blood samples are required for this test, compared to clamp techniques. The mean plasma glucose concentration over the last 30 minutes of the test reflects insulin sensitivity. Although lengthy, IST is less labor intensive than clamp techniques and the FSIVGTT.
Insulin tolerance test ITT : A simplified version of IST, ITT measures the decline in serum glucose after an IV bolus of regular insulin 0. Several insulin and glucose levels are sampled over the following 15 minutes depending on the protocol used.
The ITT primarily measures insulin-stimulated uptake of glucose into skeletal muscle. Because this test is so brief, there's very little danger of counter-regulatory hormones interfering with its results.
IV access should be established for insulin injection, blood sampling, and for rapid administration of D50W should severe hypoglycemia occur. These values reflect the rate of decline of log transformed glucose values.
Frequently sampled IV glucose tolerance tests FSIVGTT. This method is less labor intensive than clamp techniques yet still requires as many as 25 blood samples over a 3-hour period, and a computer-assisted mathematical analysis.
Several variations of the FSIVGTT have been published. One recently published study infused 0. The SI was calculated by a computer-based program. Tolbutamide administration can also be used during FSIVGTT to augment endogenous insulin secretion and is particularly useful in women with diabetes.
Continuous infusion of glucose with model assessment CIGMA : Like ITT, CIGMA requires fewer venipunctures and is less laborious than clamp techniques.
A constant IV glucose infusion is administered, and samples for glucose and insulin are drawn at 50, 55, and 60 minutes.
A mathematical model is then used to calculate SI. The results are reasonably compatible with clamp techniques; however, few laboratories have used CIGMA for insulin sensitivity testing in diabetic patients and there is no substantive data using the CIGMA technique in women with PCOS.
Oral glucose tolerance test OGTT : OGTT, a mainstay in the diagnosis of impaired glucose tolerance IGT and diabetes mellitus in pregnant and nonpregnant women, may be used to assess insulin sensitivity as well.
Arie Katz, Sridhar S. Nambi, Red pepper sushi Mather, Sensitivith D. Baron, Dean Innsulin. Follmann, Gail Sullivan, Oxidative stress causes J. Insulin Sxore plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 non-obese, 13 obese, and 15 type 2 diabetic subjects.
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