Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice

2008 ◽  
Vol 294 (2) ◽  
pp. E261-E270 ◽  
Author(s):  
Sihoon Lee ◽  
Ranganath Muniyappa ◽  
Xu Yan ◽  
Hui Chen ◽  
Lilly Q. Yue ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Predictive Accuracy ◽  
Cardiovascular Complications ◽  
Glucose Clamp ◽  
Calibration Model ◽  
Model Assessment ◽  
Insulin Sensitivity And Resistance ◽  
Wide Range ◽  
Linear Correlations

Insulin resistance contributes to the pathophysiology of diabetes, obesity, and their cardiovascular complications. Mouse models of these human diseases are useful for gaining insight into pathophysiological mechanisms. The reference standard for measuring insulin sensitivity in both humans and animals is the euglycemic glucose clamp. Many studies have compared surrogate indexes of insulin sensitivity and resistance with glucose clamp estimates in humans. However, regulation of metabolic physiology in humans and rodents differs and comparisons between surrogate indexes and the glucose clamp have not been directly evaluated in rodents previously. Therefore, in the present study, we compared glucose clamp-derived measures of insulin sensitivity (GIR and SIClamp) with surrogate indexes, including quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment (HOMA), 1/HOMA, log(HOMA), and 1/fasting insulin, using data from 87 mice with a wide range of insulin sensitivities. We evaluated simple linear correlations and performed calibration model analyses to evaluate the predictive accuracy of each surrogate. All surrogate indexes tested were modestly correlated with both GIR and SIClamp. However, a stronger correlation between body weight per se and both GIR and SIClamp was noted. Calibration analyses of surrogate indexes adjusted for body weight demonstrated improved predictive accuracy for GIR [e.g., R = 0.68, for QUICKI and log(HOMA)]. We conclude that linear correlations of surrogate indexes with clamp data and predictive accuracy of surrogate indexes in mice are not as substantial as in humans. This may reflect intrinsic differences between human and rodent physiology as well as increased technical difficulties in performing glucose clamps in mice.

scholarly journals Comparison between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic Euglycemic Glucose Clamps in Rhesus Monkeys

Endocrinology ◽  
2011 ◽  
Vol 152 (2) ◽  
pp. 414-423 ◽  
Author(s):  
Ho-Won Lee ◽  
Ranganath Muniyappa ◽  
Xu Yan ◽  
Lilly Q. Yue ◽  
Ellen H. Linden ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Receiver Operating Characteristic ◽  
Rhesus Monkeys ◽  
Operating Characteristic ◽  
Predictive Accuracy ◽  
Glucose Clamp ◽  
Calibration Model ◽  
Model Assessment ◽  
Characteristic Analysis ◽  
Receiver Operating

Abstract The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SIClamp (r ≈ 0.4–0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies.

scholarly journals SAT-624 Predictive Ability of Lipoprotein Insulin Resistance (LPIR) Score in South Asians: A Comparison of Surrogate Indices of Insulin Sensitivity/Resistance

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Andin Fosam ◽  
Shivraj Grewal ◽  
Abdul-Latif Armiyaw ◽  
Camila Sarcone ◽  
Antoinette Rabel ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Mean Squared Error ◽  
Predictive Accuracy ◽  
South Asians ◽  
Model Analysis ◽  
Calibration Model ◽  
Model Assessment ◽  
Intravenous Glucose ◽  
Insulin Resistant

Abstract South Asians (SA) are at higher risk for developing insulin resistance (IR) and type 2 diabetes. Consequently, identifying IR in this population is important. Lack of standardization and harmonization of insulin assays limit the clinical use of insulin-based surrogate indexes of insulin resistance. The lipoprotein insulin resistance (LPIR) score, a metabolomic marker, reflects the lipoprotein abnormalities observed in insulin-resistant states. The reliability of the LPIR score to predict IR in South Asians is currently unknown. In this study, we aimed to evaluate the predictive accuracy of LPIR compared to other fasting-based surrogate indices in SA. In a cross-sectional study of 59 non-diabetic SA subjects (age 36 ± 8 years, BMI 26.5 ± 5.2 kg/m2), we used calibration model analysis to assess the ability of the LPIR score and other simple surrogate indices [homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and Adipose tissue insulin sensitivity (Adipo-SI)] to predict insulin sensitivity derived from the reference frequently sampled intravenous glucose tolerance test (FSIVGTT) and Minimal Model analysis (SiMM). LPIR scores were calculated using six lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance (NMR) spectroscopy. Further, quantitative predictive accuracy and index comparisons were determined by root mean squared error (RMSE) of prediction and leave-one-out cross-validation-type RMSE of prediction (CVPE). Receiver operating characteristic (ROC) curve analysis was performed to determine how well LPIR distinguished insulin resistant individuals, categorized as an SiMM < 3. As determined by calibration model analysis, Adipo-SI, HOMA-IR, and QUICKI showed moderate correlations with for SiMM (Adipo-SI: r = 0.66; HOMA-IR: r = 0.60; QUICKI: r = 0.57, p = <0.0001). No significant differences were noted among CVPE or RMSE from any of the routinely used surrogate indices when compared with LPIR. The ROC area under the curve was 0.76 (95% CI 0.64–0.87) suggesting that LPIR performed well in identifying insulin resistant subjects. The optimal cut-off in IR individuals was LPIR >46 (sensitivity: 75.9 %, specificity: 70.0%). We conclude that NMR-derived LPIR may be an appropriate index to assess insulin resistance in South Asians.

scholarly journals Limited predictive ability of surrogate indices of insulin sensitivity/resistance in Asian-Indian men

2010 ◽  
Vol 299 (6) ◽  
pp. E1106-E1112 ◽  
Author(s):  
Ranganath Muniyappa ◽  
Brian A. Irving ◽  
Uma S. Unni ◽  
William M. Briggs ◽  
K. Sreekumaran Nair ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Asian Indian ◽  
Clinical Studies ◽  
Asian Indians ◽  
Glucose Clamp ◽  
Secondary Outcome ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Indian Men

Insulin resistance is highly prevalent in Asian Indians and contributes to worldwide public health problems, including diabetes and related disorders. Surrogate measurements of insulin sensitivity/resistance are used frequently to study Asian Indians, but these are not formally validated in this population. In this study, we compared the ability of simple surrogate indices to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In this cross-sectional study of Asian-Indian men ( n = 70), we used a calibration model to assess the ability of simple surrogate indices for insulin sensitivity [quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment (HOMA2-IR), fasting insulin-to-glucose ratio (FIGR), and fasting insulin (FI)] to predict an insulin sensitivity index derived from the reference glucose clamp method (SIClamp). Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction as well as leave-one-out cross-validation-type RMSE of prediction (CVPE). QUICKI, FIGR, and FI, but not HOMA2-IR, had modest linear correlations with SIClamp (QUICKI: r = 0.36; FIGR: r = −0.36; FI: r = −0.27; P < 0.05). No significant differences were noted among CVPE or RMSE from any of the surrogate indices when compared with QUICKI. Surrogate measurements of insulin sensitivity/resistance such as QUICKI, FIGR, and FI are easily obtainable in large clinical studies, but these may only be useful as secondary outcome measurements in assessing insulin sensitivity/resistance in clinical studies of Asian Indians.

Acute Overfeeding Does Not Alter Liver or Adipose Tissue-Derived Cytokines in Healthy Humans

2016 ◽  
Vol 69 (3-4) ◽  
pp. 165-170 ◽  
Author(s):  
Miaoxin Chen ◽  
Bo Liu ◽  
Campbell H. Thompson ◽  
Gary A. Wittert ◽  
Leonie K. Heilbronn
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
The Body ◽  
Hepatic Insulin Resistance ◽  
Model Assessment ◽  
Healthy Individuals ◽  
Monocyte Chemoattractant Protein 1 ◽  
Healthy Humans ◽  
Balanced Diet

Background/Aims: The secretions of liver-derived cytokines angiopoietin-like 6, insulin-like growth factor 1, selenoprotein-P and C-reactive protein and adipokines, adiponectin and monocyte chemoattractant protein-1 are altered in obese individuals, and they directly induce insulin resistance in both cellular and animal models. This study is aimed at examining the effects of acute overnutrition on these cytokines in healthy individuals, and identifying association with markers of insulin resistance. Methods: Thirty-one young healthy individuals (10 men, body mass index (BMI) 22.4 ± 2.7; 21 women, BMI 23.3 ± 4.9) were enrolled for the study. Metabolic assessments were done 3 days after an energy balanced diet (30% fat) and 3 days of a high-fat overfeeding diet (+1,250 kcal/day, 45% fat), and the assessments included the fasting body weight and blood samples to analyze the selected cytokines and evaluate the insulin sensitivity by a hyperinsulinemic euglycemic clamp (80 mU/m2/min). Results: Three days of overfeeding increased the body weight, fasting glucose and insulin, and thus the homeostasis model assessment of insulin resistance. However, there were no changes in peripheral insulin sensitivity, or in the circulating cytokines assessed. Conclusions: The hepatokines and adipokines assessed were not acutely sensitive to overnutrition in healthy individuals, despite increases in markers of hepatic insulin resistance.

Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats

2008 ◽  
Vol 295 (5) ◽  
pp. E1269-E1276 ◽  
Author(s):  
J. Cacho ◽  
J. Sevillano ◽  
J. de Castro ◽  
E. Herrera ◽  
M. P. Ramos
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fasting Glucose ◽  
Roc Curves ◽  
Glucose Clamp ◽  
Model Assessment ◽  
Sprague Dawley ◽  
Insulin Levels ◽  
Sprague Dawley Rats

Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose clamp. However, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in nonpregnant and 20-day-pregnant Wistar and Sprague-Dawley rats. We have analyzed the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and the fasting glucose-to-insulin ratio (FGIR) by comparing them with the insulin sensitivity (SIClamp) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague-Dawley rats. We found that HOMA-IR, QUICKI, and FGIR correlated significantly with SIClamp, exhibited good sensitivity and specificity, accurately predicted SIClamp, and yielded lower insulin sensitivity in pregnant than in nonpregnant rats. Together, our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.

scholarly journals Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

2009 ◽  
Vol 297 (5) ◽  
pp. E1023-E1029 ◽  
Author(s):  
Ranganath Muniyappa ◽  
Hui Chen ◽  
Radhika H. Muzumdar ◽  
Francine H. Einstein ◽  
Xu Yan ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Predictive Accuracy ◽  
Glucose Clamp ◽  
Secondary Outcome ◽  
The Metabolic Syndrome ◽  
Metabolic Physiology ◽  
Using Data ◽  
Rat Study ◽  
Mouse Study

Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR ( r = 0.34–0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome.

scholarly journals No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Tong-yan Han ◽  
Xin-li Wang ◽  
Yun-pu Cui ◽  
Hong-mao Ye ◽  
Xiao-mei Tong ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Postnatal Period ◽  
The Body ◽  
Model Assessment ◽  
Z Score ◽  
Inclusion Criteria ◽  
Impaired Insulin ◽  
Catch Up ◽  
The Relationship

Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA) infants.Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI) levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA).Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG) and catch-up growth (CUG). By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months.Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

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