Original articleMeasuring insulin sensitivity in youth: How do the different indices compare with the gold-standard method?Comparaison entre différents indices permettant d’estimer la sensibilité à l’insuline chez l’enfant et la méthode de référence du clamp hyperinsulinémique euglycémique
Introduction
Insulin resistance is the central component of several conditions that are now seen more frequently in young people, including obesity, polycystic ovarian syndrome and diabetes [1], [2]. Furthermore, the results of several large population-based studies suggest that the clustering of CVD risk factors is highest in children and adolescents with the highest degree of insulin resistance [3], [4], [5], making this group most at risk for developing CVD, type 2 diabetes, and premature mortality. These findings provide a rationale for the measurement of IS in youth to identify this high-risk group, to ascertain its associated features and to evaluate interventions aimed at decreasing insulin resistance.
The measurement of IS remains a challenge. The current gold-standard test, the HEC, involves a constant-rate insulin infusion with concomitant, variable glucose infusion to maintain euglycaemia. The HEC is an invasive time- and labour-intensive approach that is not suitable for epidemiological and diagnostic studies [6]. The modified minimal-model FSIVGTT uses a computer-based mathematical model to measure IS after bolus injection of intravenous glucose, followed 20-min later by a bolus intravenous dose of either insulin or tolbutamide [7]. This method, while validated in young people [8], has the same limitations as the HEC in terms of feasibility for epidemiological and clinical purposes. Surrogate measures of IS derived from the OGTT have also been developed, and appear to be well correlated with estimations derived from clamp studies in adults [9], [10], [11], [12], [13], [14], [15], [16], [17]. Little work, however, has so far been done to evaluate the performance of these surrogate measures in youth. Surrogate estimates of IS from fasting values of glucose and insulin have been developed, and are well validated in adult populations [18], [19]. These fasting indices are more readily acceptable to the patient, more cost-effective and easier to use, however validation studies of such surrogate measures in children remain scarce [7], [20].
The objective of the present study was to examine the degree to which three different approaches to measuring IS correlate with the gold-standard HEC in healthy children–namely, the FSIVGTT, indices derived from the OGTT and selected fasting indices (HOMA, QUICKI and fasting insulin]. To our knowledge, this is the first study to examine the criterion validity of each of these three methods against the gold-standard HEC in a healthy paediatric population.
Section snippets
Study population
Children between 6 and 18 years of age, with heights and weights between the 5th and 95th percentiles for age and gender (thus, including normal weight and overweight/obese youth), were eligible for the present study. Children who were known to be pregnant, to have a chronic illness or to have diabetes were excluded. Participants were recruited as a convenience sample. Written informed consent was obtained from all participants and their parents. The study also received ethical approval from
Results
Twenty healthy children were recruited for the present study. The participants’ baseline characteristics are presented in Table 1. The complete spectrum of stages of sexual maturity was represented in this sample. By design, no participant had impaired fasting glucose, impaired glucose tolerance or diabetes. Age, gender and Tanner stage did not appear to predict IS in this small sample. However, children who had higher BMI Z scores had lower IS, as measured by metabolized glucose, after
Conclusion
In a group of children aged 6–13 years, measurement of IS using the FSIVGTT, OGTT and fasting measures were moderately to highly correlated to the gold-standard HEC test. In particular, three indices derived from the OGTT showed the strongest correlations to clamp results–namely, the ISI Matsuda, SIisOGTT and Log sum insulin. Similar findings have been observed in adults, with these indices all correlating strongly (r = 0.57–0.65) to clamp results [16]. While studies in youth have correlated
Conflict of interest statement
No potential conflicts of interest relevant to this article were reported.
Acknowledgements
The present study was funded by the Garrod Association. The authors also wish to thank the participants and their families for their time and involvement in the present research. In addition, we wish to recognize the invaluable participation of Isabelle Vignault (RN) and Annie Tardif (technician) in the clamp studies.
References (38)
- et al.
Validation of the insulin sensitivity index (ISI[0,120]): comparison with other measures
Diabetes Res Clin Pract
(2000) - et al.
Insulin release and peripheral sensitivity at the oral glucose tolerance test
Diabetes Res Clin Pract
(1990) - et al.
Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels
Mol Genet Metab
(1998) - et al.
Relationship between the hyperinsulinemic-euglycaemic clamp and a new simple index assessing insulin sensitivity in overweight and obese postmenopausal women
Diabetes Metab
(2007) - et al.
Correlation of oral glucose tolerance test–derived estimates of insulin sensitivity with insulin clamp measurements in an African-American Cohort
Metabolism
(2004) - et al.
Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents
J Pediatr
(2004) - et al.
Comparison between B-cell function and insulin resistance indexes in prepubertal and pubertal obese children
Metabolism
(2002) - et al.
Pathophysiology of type 2 diabetes mellitus in children and adolescents
Treat Endocrinol
(2002) - et al.
Polycystic ovary syndrome in adolescents: is there an epidemic?
Curr Opin Endocrinol Diabetes
(2002) - et al.
Cardiovascular risk factors clustering features of insulin resistance syndrome (Syndrome X) in a biracial (Black-White) population of children, adolescents and young adults: the Bogalusa Heart Study
Am J Epidemiol
(1999)
Insulin resistance syndrome in a representative sample of children and adolescents from Quebec, Canada
Int J Obes Relat Metab Disord
The role of insulin in clustering of serum lipids and blood pressure in children and adolescents. The cardiovascular risk in Young Finns Study
Diabetologia
Glucose clamp technique: a method for quantifying insulin secretion and resistance
Am J Physiol
Indexes of insulin resistance and secretion in obese children and adolescents. A validation study
Diabetes Care
The modified minimal model: application to measurement of insulin sensitivity in children
J Clin Endocrinol Metab
Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp
Diabetes Care
Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity
Diabetes Care
A model-based method for assessing insulin sensitivity from the oral glucose tolerance test
Diabetes Care
Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state
Int J Obes Relat Metab Disord
Cited by (69)
Body Mass Index Z Score vs Weight-for-Length Z Score in Infancy and Cardiometabolic Outcomes at Age 8-10 Years
2021, Journal of PediatricsCitation Excerpt :Plasma insulin was measured using an ultrasensitive Access immunoassay system (Beckman Coulter Inc). Insulin sensitivity was measured with the Matsuda insulin sensitivity index.25,26 Insulin secretion was measured by the ratio of the area under the curve of insulin to glucose over the first 30 minutes (AUC I/G30 min) and 120 minutes (AUC I/G120 min) of the oral glucose tolerance test.27
Lifestyle Habits, Dietary Factors, and the Metabolically Unhealthy Obese Phenotype in Youth
2019, Journal of PediatricsCitation Excerpt :The glucose oxidase method was used to compute the plasma glucose concentrations on the Beckman Coulter Synchron LX20 automat. Insulin sensitivity was measured with the Matsuda insulin sensitivity index.32 Insulin secretion was measured by the ratio of the area under the curve of insulin to glucose over the first 30 minutes and 120 minutes.33
Insulin resistance and cognitive test performance in elderly adults: National health and nutrition examination survey (NHANES)
2018, Journal of the Neurological SciencesCitation Excerpt :HOMA-IR was calculated as follows: ([FPG (mmol/L) × FIS (μU/ml)]/22.5) [57]. While the validity of HOMA-IR as a surrogate measure of peripheral insulin sensitivity has been questioned recently given its failure to correlate with diet-induced insulin sensitivity in dogs [58] and its erroneous prediction of differences in insulin sensitivity between non-diabetic African and European Americans [59], virtually all clinical studies report a significant correlation of HOMA-IR (or the similarly derived QUICKI index) with insulin sensitivity directly measured with the euglycemic - hyperinsulinemic clamp technique in normal, pre-diabetic, and diabetic cases of various ethnicities [60–63]. As noted above, the DSS subtest of the Wechsler Adult Intelligence Scale, 3rd edition was used to measure cognitive test performance [64].
Optimal Anthropometric Indicators and Cut Points for Predicting Metabolic Syndrome in Chinese Patients with Type 2 Diabetes Mellitus by Gender
2023, Diabetes, Metabolic Syndrome and Obesity