The Oral Disposition Index: A Valuable Estimate of β-Cell Function in Obese Youth

Abstract

See related article, p 51The physiological regulation of glucose homeostasis requires that pancreatic β-cells compensate for changes in whole-body insulin sensitivity through a proportionate and reciprocal change in insulin secretion.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google Scholar The resultant negative feedback loop has been characterized mathematically as a rectangular hyperbolic function between insulin secretion and insulin sensitivity, as originally postulated by Bergman et al.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar Kahn et al4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar subsequently confirmed the existence of this hyperbolic relationship in humans, using acute insulin response and the insulin sensitivity index, obtained during the frequently sampled intravenous glucose tolerance test (FSIVGTT).4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar Two key concepts arose from these earlier studies. First, for the appropriate assessment of β-cell compensation, insulin secretion must be evaluated in the context of ambient insulin sensitivity.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar Second, the hyperbolic relationship between the acute insulin response and the insulin sensitivity index implies that the product of these 2 indices, termed the disposition index measured with oral glucose tolerance test (oDI), should yield a constant for a given degree of glucose tolerance and thereby provide a measure of β-cell function.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google Scholar Indeed, the oDI has since emerged as a valuable tool in clinical research by providing an integrated measure of β-cell compensation, whereby insulin secretion is appropriately assessed in relation to prevailing insulin sensitivity. A lower oDI is clearly present in subjects with prediabetes.5Abdul-Ghani M.A. Tripathy D. De Fronzo R.A. Contribution of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fastin glucose.Diabetes Care. 2006; 29: 1130-1139Crossref PubMed Scopus (612) Google Scholar, 6Faerch K. Borch-Johnsen K. Holst J.J. Vaag A. Pathophysiology and aetiology of impaired fasting glycemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?.Diabetologia. 2009; 52: 1714-1723Crossref PubMed Scopus (159) Google Scholar, 7Cali A.M.G. Dalla Man C. Cobelli C. Dziura J. Seyal A. Shaw M. et al.Primary defects in β-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents.Diabetes Care. 2009; 32: 456-461Crossref PubMed Scopus (92) Google Scholar, 8Weis R. Caprio Trombetta M. Taksali S. Tamborlane W. Bonadonna R. β-cell function across the spectrum of glucose tolerance in obese youth.Diabetes. 2005; 54: 1735-1743Crossref PubMed Scopus (136) Google Scholar The oDI has ∼70% heritability and may be a useful trait for identifying genetic predisposition to type 2 diabetes mellitus.9Elbein S.C. Hasstedt S.J. Wegner K. Kahn S.E. Heritability of pancreatic β-cell function among nondiabetic members of Caucasian familial type 2 diabetes kindreds.J Clin Endocrinol Metab. 1999; 84: 1398-1403Crossref PubMed Google ScholarCalculating the oDIMeasures of both insulin sensitivity and acute first-phase insulin secretion during the FSIVGTT were originally used to determine the oDI.2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar In addition to the FSIVGTT, the oDI has been widely estimated from measures of insulin sensitivity and insulin secretion derived from the euglycemic–hyperinsulinemic clamp technique in combination with the intravenous glucose tolerance test.5Abdul-Ghani M.A. Tripathy D. De Fronzo R.A. Contribution of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fastin glucose.Diabetes Care. 2006; 29: 1130-1139Crossref PubMed Scopus (612) Google Scholar, 6Faerch K. Borch-Johnsen K. Holst J.J. Vaag A. Pathophysiology and aetiology of impaired fasting glycemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?.Diabetologia. 2009; 52: 1714-1723Crossref PubMed Scopus (159) Google Scholar, 8Weis R. Caprio Trombetta M. Taksali S. Tamborlane W. Bonadonna R. β-cell function across the spectrum of glucose tolerance in obese youth.Diabetes. 2005; 54: 1735-1743Crossref PubMed Scopus (136) Google Scholar It should be noted, however, that the high supraphysiological insulin infusion dose used during the clamping (80 mU/m2·min) provides mainly a measure of peripheral skeletal muscle insulin sensitivity, not of hepatic insulin sensitivity, because hepatic glucose production is almost completely suppressed at these high insulin doses.10DeFronzo R.A. Tobin J.D. Andre R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.Am J Physiol Endcrinol Metab. 1979; 237: 773-795Google Scholar Thus, when using insulin sensitivity derived from euglycemic-hyperinsulinemic clamping in the calculation of the disposition index, it may be relevant to also calculate a disposition index based on hepatic insulin sensitivity, an important regulator of pancreatic insulin secretion.3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google ScholarAlthough both the euglycemic-hyperinsulinemic clamp and the FSIVGTT are considered ideal tests for quantifying insulin sensitivity and secretion in vivo and thus for calculating the oDI, they are both difficult to perform, particularly in children. To avoid using the FSIVGTT or clamping required for calculation of the oDI, large clinical and epidemiologic studies generally use the oral glucose tolerance test (OGTT). As such, several simple indices have been derived to allow the use of measurements obtained during the OGTT for estimating insulin secretion as well as insulin sensitivity. Utzschneider et al11Utzschneider K.M. Prigeon R.L. Faulenbach M.V. Tong J. Carr D.B. Boyko E.J. et al.Oral Disposition Index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.Diabetes Care. 2009; 32: 776-778Crossref Scopus (8) Google Scholar recently found that the oDI predicts the development of future diabetes above and beyond the 2-hour glucose level in adults.The study reported by Sjaarda et al12Sjaarda A.L. Bacha F. Lee S.J. Tfayli H. Andreatta E. Arslanian S. Oral Disposition Index in obese youth from normal to prediabetes to diabetes: relationship to the Clamp Disposition Index.J Pediatr. 2012; 161: 51-57Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar in this issue of The Journal provides strong evidence that the oDI provides a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose levels. The strength of the study is the fact that the authors used 2 robust clamp techniques to assess insulin sensitivity and secretion in a large group of obese adolescents across the spectrum of glucose tolerance. Calculating the various indexes from the OGTT, they were then able to compare the relationships among these indices. Moreover, they found that the oDI is predictive of the 2-hour glucose level. Although the correlation between the 2 different disposition indices was only modest, the oDI estimates had a similar ability to detect group differences in β-cell function as the calculated disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI), had analogous predictive power to the cDI for the 2-hour glucose concentration from the OGTT, and identified comparable decrements in β-cell function across the glucose-intolerant groups as the cDI. These findings justify the use of the oDI, which should be considered a key biomarker for predicting the development of type 2 diabetes mellitus and for longitudinal assessment of β-cell function relative to insulin sensitivity in large-scale prevention/intervention studies. See related article, p 51The physiological regulation of glucose homeostasis requires that pancreatic β-cells compensate for changes in whole-body insulin sensitivity through a proportionate and reciprocal change in insulin secretion.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google Scholar The resultant negative feedback loop has been characterized mathematically as a rectangular hyperbolic function between insulin secretion and insulin sensitivity, as originally postulated by Bergman et al.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar Kahn et al4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar subsequently confirmed the existence of this hyperbolic relationship in humans, using acute insulin response and the insulin sensitivity index, obtained during the frequently sampled intravenous glucose tolerance test (FSIVGTT).4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar Two key concepts arose from these earlier studies. First, for the appropriate assessment of β-cell compensation, insulin secretion must be evaluated in the context of ambient insulin sensitivity.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar Second, the hyperbolic relationship between the acute insulin response and the insulin sensitivity index implies that the product of these 2 indices, termed the disposition index measured with oral glucose tolerance test (oDI), should yield a constant for a given degree of glucose tolerance and thereby provide a measure of β-cell function.1Bergman R.N. Philips L.S. Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurements of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose.J Clin Invest. 1981; 68: 1456-1467Crossref PubMed Scopus (1334) Google Scholar, 2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google Scholar Indeed, the oDI has since emerged as a valuable tool in clinical research by providing an integrated measure of β-cell compensation, whereby insulin secretion is appropriately assessed in relation to prevailing insulin sensitivity. A lower oDI is clearly present in subjects with prediabetes.5Abdul-Ghani M.A. Tripathy D. De Fronzo R.A. Contribution of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fastin glucose.Diabetes Care. 2006; 29: 1130-1139Crossref PubMed Scopus (612) Google Scholar, 6Faerch K. Borch-Johnsen K. Holst J.J. Vaag A. Pathophysiology and aetiology of impaired fasting glycemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?.Diabetologia. 2009; 52: 1714-1723Crossref PubMed Scopus (159) Google Scholar, 7Cali A.M.G. Dalla Man C. Cobelli C. Dziura J. Seyal A. Shaw M. et al.Primary defects in β-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents.Diabetes Care. 2009; 32: 456-461Crossref PubMed Scopus (92) Google Scholar, 8Weis R. Caprio Trombetta M. Taksali S. Tamborlane W. Bonadonna R. β-cell function across the spectrum of glucose tolerance in obese youth.Diabetes. 2005; 54: 1735-1743Crossref PubMed Scopus (136) Google Scholar The oDI has ∼70% heritability and may be a useful trait for identifying genetic predisposition to type 2 diabetes mellitus.9Elbein S.C. Hasstedt S.J. Wegner K. Kahn S.E. Heritability of pancreatic β-cell function among nondiabetic members of Caucasian familial type 2 diabetes kindreds.J Clin Endocrinol Metab. 1999; 84: 1398-1403Crossref PubMed Google Scholar See related article, p 51 See related article, p 51 Calculating the oDIMeasures of both insulin sensitivity and acute first-phase insulin secretion during the FSIVGTT were originally used to determine the oDI.2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar In addition to the FSIVGTT, the oDI has been widely estimated from measures of insulin sensitivity and insulin secretion derived from the euglycemic–hyperinsulinemic clamp technique in combination with the intravenous glucose tolerance test.5Abdul-Ghani M.A. Tripathy D. De Fronzo R.A. Contribution of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fastin glucose.Diabetes Care. 2006; 29: 1130-1139Crossref PubMed Scopus (612) Google Scholar, 6Faerch K. Borch-Johnsen K. Holst J.J. Vaag A. Pathophysiology and aetiology of impaired fasting glycemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?.Diabetologia. 2009; 52: 1714-1723Crossref PubMed Scopus (159) Google Scholar, 8Weis R. Caprio Trombetta M. Taksali S. Tamborlane W. Bonadonna R. β-cell function across the spectrum of glucose tolerance in obese youth.Diabetes. 2005; 54: 1735-1743Crossref PubMed Scopus (136) Google Scholar It should be noted, however, that the high supraphysiological insulin infusion dose used during the clamping (80 mU/m2·min) provides mainly a measure of peripheral skeletal muscle insulin sensitivity, not of hepatic insulin sensitivity, because hepatic glucose production is almost completely suppressed at these high insulin doses.10DeFronzo R.A. Tobin J.D. Andre R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.Am J Physiol Endcrinol Metab. 1979; 237: 773-795Google Scholar Thus, when using insulin sensitivity derived from euglycemic-hyperinsulinemic clamping in the calculation of the disposition index, it may be relevant to also calculate a disposition index based on hepatic insulin sensitivity, an important regulator of pancreatic insulin secretion.3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google ScholarAlthough both the euglycemic-hyperinsulinemic clamp and the FSIVGTT are considered ideal tests for quantifying insulin sensitivity and secretion in vivo and thus for calculating the oDI, they are both difficult to perform, particularly in children. To avoid using the FSIVGTT or clamping required for calculation of the oDI, large clinical and epidemiologic studies generally use the oral glucose tolerance test (OGTT). As such, several simple indices have been derived to allow the use of measurements obtained during the OGTT for estimating insulin secretion as well as insulin sensitivity. Utzschneider et al11Utzschneider K.M. Prigeon R.L. Faulenbach M.V. Tong J. Carr D.B. Boyko E.J. et al.Oral Disposition Index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.Diabetes Care. 2009; 32: 776-778Crossref Scopus (8) Google Scholar recently found that the oDI predicts the development of future diabetes above and beyond the 2-hour glucose level in adults.The study reported by Sjaarda et al12Sjaarda A.L. Bacha F. Lee S.J. Tfayli H. Andreatta E. Arslanian S. Oral Disposition Index in obese youth from normal to prediabetes to diabetes: relationship to the Clamp Disposition Index.J Pediatr. 2012; 161: 51-57Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar in this issue of The Journal provides strong evidence that the oDI provides a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose levels. The strength of the study is the fact that the authors used 2 robust clamp techniques to assess insulin sensitivity and secretion in a large group of obese adolescents across the spectrum of glucose tolerance. Calculating the various indexes from the OGTT, they were then able to compare the relationships among these indices. Moreover, they found that the oDI is predictive of the 2-hour glucose level. Although the correlation between the 2 different disposition indices was only modest, the oDI estimates had a similar ability to detect group differences in β-cell function as the calculated disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI), had analogous predictive power to the cDI for the 2-hour glucose concentration from the OGTT, and identified comparable decrements in β-cell function across the glucose-intolerant groups as the cDI. These findings justify the use of the oDI, which should be considered a key biomarker for predicting the development of type 2 diabetes mellitus and for longitudinal assessment of β-cell function relative to insulin sensitivity in large-scale prevention/intervention studies. Measures of both insulin sensitivity and acute first-phase insulin secretion during the FSIVGTT were originally used to determine the oDI.2Bergman R.N. Ader M. Huecking K. Van Citters G. Accurate assessment of β-cell function: the hyperbolic correction.Diabetes. 2002; 51: S212-S220Crossref PubMed Google Scholar, 4Kahn S.E. Prigeon R.I. McCullough D.K. Boyko E.J. Bergman R.N. Schwartz M.V. et al.Quantification of the relationship between insulin sensitivity and β-cell function in human subjects: evidence for an hyperbolic function.Diabetes. 1993; 42: 1663-1667Crossref PubMed Scopus (1268) Google Scholar In addition to the FSIVGTT, the oDI has been widely estimated from measures of insulin sensitivity and insulin secretion derived from the euglycemic–hyperinsulinemic clamp technique in combination with the intravenous glucose tolerance test.5Abdul-Ghani M.A. Tripathy D. De Fronzo R.A. Contribution of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fastin glucose.Diabetes Care. 2006; 29: 1130-1139Crossref PubMed Scopus (612) Google Scholar, 6Faerch K. Borch-Johnsen K. Holst J.J. Vaag A. Pathophysiology and aetiology of impaired fasting glycemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?.Diabetologia. 2009; 52: 1714-1723Crossref PubMed Scopus (159) Google Scholar, 8Weis R. Caprio Trombetta M. Taksali S. Tamborlane W. Bonadonna R. β-cell function across the spectrum of glucose tolerance in obese youth.Diabetes. 2005; 54: 1735-1743Crossref PubMed Scopus (136) Google Scholar It should be noted, however, that the high supraphysiological insulin infusion dose used during the clamping (80 mU/m2·min) provides mainly a measure of peripheral skeletal muscle insulin sensitivity, not of hepatic insulin sensitivity, because hepatic glucose production is almost completely suppressed at these high insulin doses.10DeFronzo R.A. Tobin J.D. Andre R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.Am J Physiol Endcrinol Metab. 1979; 237: 773-795Google Scholar Thus, when using insulin sensitivity derived from euglycemic-hyperinsulinemic clamping in the calculation of the disposition index, it may be relevant to also calculate a disposition index based on hepatic insulin sensitivity, an important regulator of pancreatic insulin secretion.3Cobelli C. Toffolo G.M. Man C.D. Campioni M. Denti P. Caumo A. et al.Assessment of β cell function in humans, simultaneous with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests.Am J Physiol Endocrinol Metab. 2007; 293: E1-15Crossref PubMed Scopus (254) Google Scholar Although both the euglycemic-hyperinsulinemic clamp and the FSIVGTT are considered ideal tests for quantifying insulin sensitivity and secretion in vivo and thus for calculating the oDI, they are both difficult to perform, particularly in children. To avoid using the FSIVGTT or clamping required for calculation of the oDI, large clinical and epidemiologic studies generally use the oral glucose tolerance test (OGTT). As such, several simple indices have been derived to allow the use of measurements obtained during the OGTT for estimating insulin secretion as well as insulin sensitivity. Utzschneider et al11Utzschneider K.M. Prigeon R.L. Faulenbach M.V. Tong J. Carr D.B. Boyko E.J. et al.Oral Disposition Index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.Diabetes Care. 2009; 32: 776-778Crossref Scopus (8) Google Scholar recently found that the oDI predicts the development of future diabetes above and beyond the 2-hour glucose level in adults. The study reported by Sjaarda et al12Sjaarda A.L. Bacha F. Lee S.J. Tfayli H. Andreatta E. Arslanian S. Oral Disposition Index in obese youth from normal to prediabetes to diabetes: relationship to the Clamp Disposition Index.J Pediatr. 2012; 161: 51-57Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar in this issue of The Journal provides strong evidence that the oDI provides a simple surrogate estimate of β-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose levels. The strength of the study is the fact that the authors used 2 robust clamp techniques to assess insulin sensitivity and secretion in a large group of obese adolescents across the spectrum of glucose tolerance. Calculating the various indexes from the OGTT, they were then able to compare the relationships among these indices. Moreover, they found that the oDI is predictive of the 2-hour glucose level. Although the correlation between the 2 different disposition indices was only modest, the oDI estimates had a similar ability to detect group differences in β-cell function as the calculated disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI), had analogous predictive power to the cDI for the 2-hour glucose concentration from the OGTT, and identified comparable decrements in β-cell function across the glucose-intolerant groups as the cDI. These findings justify the use of the oDI, which should be considered a key biomarker for predicting the development of type 2 diabetes mellitus and for longitudinal assessment of β-cell function relative to insulin sensitivity in large-scale prevention/intervention studies. Oral Disposition Index in Obese Youth from Normal to Prediabetes to Diabetes: Relationship to Clamp Disposition IndexThe Journal of PediatricsVol. 161Issue 1PreviewWe sought to assess the glucose disposition index using an oral glucose tolerance test (OGTT; oDI) compared with the glucose disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI) in obese pediatric subjects spanning the range of glucose tolerance. Full-Text PDF CorrectionThe Journal of PediatricsVol. 161Issue 4PreviewIn the editorial, “The Oral Disposition Index: A Valuable Estimate of ß-Cell Function in Obese Youth,” by Caprio, J Pediatr 2012;161:3-4, the authors inadvertently included the incorrect pages for reference 11. The correct reference should be: Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ, et al. Oral Disposition Index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 2009;32:335-41. Full-Text PDF