Methods to Assess In Vivo Insulin Sensitivity and Insulin Secretion

  • Riccardo C. BonadonnaEmail author
  • Linda Boselli
  • Alessandra Dei Cas
  • Maddalena Trombetta
Reference work entry
Part of the Endocrinology book series (ENDOCR)


The assessments of insulin sensitivity/resistance and of insulin secretion/beta cell function in humans are still significant challenges. The interest for these traits stems from their proved, or presumed, implications in a great number of pathological conditions, such as obesity, type 2 diabetes, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), Alzheimer’s disease. A wide number of tests and surrogate indexes have been developed and applied in many experimental and observational settings to gauge exact values for each of these two traits. In this chapter, the general principles underlying the assessments of insulin sensitivity and of beta cell function are reviewed, and the most popular tests are described with their pros and cons.


Beta cell function Insulin secretion Insulin sensitivity/resistance Diabetes Mellitus Clinical physiology 



We thank prof. Stefano Del Prato, prof. Anna Solini, prof. Enzo Bonora and prof. Ivana Zavaroni for useful discussions about the topics of this chapter. This work was supported in part with funds of the Italian Ministry of Education, University and Research (MIUR) PRIN 2015 2015373Z39_004 and with University of Parma research funds, both to RCB, and with University of Verona research funds to MT, and with University of Parma research funds to ADC.


  1. Ahren B, Pacini G. Impaired adaptation of first-phase insulin secretion in postmenopausal women with glucose intolerance. Am J Phys. 1997;273(4 Pt 1):E701–7.Google Scholar
  2. Alzaid AA, Dinneen SF, Turk DJ, Caumo A, Cobelli C, Rizza RA. Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans. J Clin Invest. 1994;94(6):2341–8.CrossRefGoogle Scholar
  3. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Suppl 1):S11–24.CrossRefGoogle Scholar
  4. Basu R, Breda E, Oberg AL, Powell CC, Dalla Man C, Basu A, et al. Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes. 2003;52(7):1738–48.CrossRefGoogle Scholar
  5. Beard JC, Bergman RN, Ward WK, Porte D Jr. The insulin sensitivity index in nondiabetic man. Correlation between clamp-derived and IVGTT-derived values. Diabetes. 1986;35(3):362–9.CrossRefGoogle Scholar
  6. Bergman RN, Iyer MS. Indirect regulation of endogenous glucose production by insulin: the single gateway hypothesis revisited. Diabetes. 2017;66(7):1742–7.CrossRefGoogle Scholar
  7. Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest. 1981;68(6):1456–67.CrossRefGoogle Scholar
  8. Bergman RN, Stefanovski D, Kim SP. Systems analysis and the prediction and prevention of Type 2 diabetes mellitus. Curr Opin Biotechnol. 2014;28:165–70.CrossRefGoogle Scholar
  9. Bock G, Dalla Man C, Campioni M, Chittilapilly E, Basu R, Toffolo G, et al. Effects of nonglucose nutrients on insulin secretion and action in people with pre-diabetes. Diabetes. 2007;56(4):1113–9.CrossRefGoogle Scholar
  10. Bonadonna RC, Groop LC, Zych K, Shank M, DeFronzo RA. Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans. Am J Phys. 1990a;259(5 Pt 1):E736–50.Google Scholar
  11. Bonadonna RC, Groop L, Kraemer N, Ferrannini E, Del Prato S, DeFronzo RA. Obesity and insulin resistance in humans: a dose-response study. Metabolism. 1990b;39(5):452–9.CrossRefGoogle Scholar
  12. Bonadonna RC, Saccomani MP, Seely L, Zych KS, Ferrannini E, Cobelli C, et al. Glucose transport in human skeletal muscle. The in vivo response to insulin. Diabetes. 1993a;42(1):191–8.CrossRefGoogle Scholar
  13. Bonadonna RC, del Prato S, Bonora E, Gulli G, Solini A, DeFronzo RA. Effects of physiological hyperinsulinemia on the intracellular metabolic partition of plasma glucose. Am J Phys. 1993b;265(6 Pt 1):E943–53.Google Scholar
  14. Bonadonna RC, Saccomani MP, Del Prato S, Bonora E, DeFronzo RA, Cobelli C. Role of tissue-specific blood flow and tissue recruitment in insulin-mediated glucose uptake of human skeletal muscle. Circulation. 1998;98(3):234–41.CrossRefGoogle Scholar
  15. Bonadonna RC, Stumvoll M, Fritsche A, Muggeo M, Haring H, Bonora E, et al. Altered homeostatic adaptation of first- and second-phase beta-cell secretion in the offspring of patients with Type 2 diabetes: studies with a minimal model to assess beta-cell function. Diabetes. 2003;52(2):470–80.CrossRefGoogle Scholar
  16. Bonora E, Moghetti P, Zancanaro C, Cigolini M, Querena M, Cacciatori V, et al. Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies. J Clin Endocrinol Metab. 1989;68(2):374–8.CrossRefGoogle Scholar
  17. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23(1):57–63.CrossRefGoogle Scholar
  18. Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes. 2001;50(1):150–8.CrossRefGoogle Scholar
  19. Castellino P, Luzi L, Simonson DC, Haymond M, DeFronzo RA. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Role of substrate availability on estimates of whole body protein synthesis. J Clin Invest. 1987;80(6):1784–93.CrossRefGoogle Scholar
  20. Caumo A, Bergman RN, Cobelli C. Insulin sensitivity from meal tolerance tests in normal subjects: a minimal model index. J Clin Endocrinol Metab. 2000;85(11):4396–402.CrossRefGoogle Scholar
  21. Cobb J, Gall W, Adam KP, Nakhle P, Button E, Hathorn J, et al. A novel fasting blood test for insulin resistance and prediabetes. J Diabetes Sci Technol. 2013;7(1):100–10.CrossRefGoogle Scholar
  22. Cretti A, Lehtovirta M, Bonora E, Brunato B, Zenti MG, Tosi F, et al. Assessment of beta-cell function during the oral glucose tolerance test by a minimal model of insulin secretion. Eur J Clin Investig. 2001;31(5):405–16.CrossRefGoogle Scholar
  23. Dalla Man C, Caumo A, Cobelli C. The oral glucose minimal model: estimation of insulin sensitivity from a meal test. IEEE Trans Biomed Eng. 2002;49(5):419–29.CrossRefGoogle Scholar
  24. Dalla Man C, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C. Minimal model estimation of glucose absorption and insulin sensitivity from oral test: validation with a tracer method. Am J Physiol Endocrinol Metab. 2004;287(4):E637–43.CrossRefGoogle Scholar
  25. Dalla Man C, Campioni M, Polonsky KS, Basu R, Rizza RA, Toffolo G, et al. Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of beta-cell responsivity and insulin sensitivity in nondiabetic individuals. Diabetes. 2005a;54(11):3265–73.CrossRefGoogle Scholar
  26. Dalla Man C, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C. Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model. Am J Physiol Endocrinol Metab. 2005b;289(5):E909–14.CrossRefGoogle Scholar
  27. Dalla Man C, Yarasheski KE, Caumo A, Robertson H, Toffolo G, Polonsky KS, et al. Insulin sensitivity by oral glucose minimal models: validation against clamp. Am J Physiol Endocrinol Metab. 2005c;289(6):E954–9.CrossRefGoogle Scholar
  28. DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988;37(6):667–87.CrossRefGoogle Scholar
  29. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Phys. 1979;237(3):E214–23.Google Scholar
  30. Del Prato S, Bonadonna RC, Bonora E, Gulli G, Solini A, Shank M, et al. Characterization of cellular defects of insulin action in Type 2 (non-insulin-dependent) diabetes mellitus. J Clin Invest. 1993;91(2):484–94.CrossRefGoogle Scholar
  31. Del Prato S, Matsuda M, Simonson DC, Groop LC, Sheehan P, Leonetti F, et al. Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance. Diabetologia. 1997;40(6):687–97.CrossRefGoogle Scholar
  32. DesCartes R. Principia philosophiae. Frankfurt am Main: Knoch, F. & Sons; 1644a. p. 1722.Google Scholar
  33. Descartes R. Principles of phylosophy. 1644b. Available from:
  34. Dodd GT, Tiganis T. Insulin action in the brain: roles in energy and glucose homeostasis. J Neuroendocrinol. 2017;29e:12513.Google Scholar
  35. Dube S, Errazuriz I, Cobelli C, Basu R, Basu A. Assessment of insulin action on carbohydrate metabolism: physiological and non-physiological methods. Diabet Med. 2013;30(6):664–70.CrossRefGoogle Scholar
  36. Engin A. The definition and prevalence of obesity and metabolic syndrome. Adv Exp Med Biol. 2017;960:1–17.CrossRefGoogle Scholar
  37. Eriksson O, Laughlin M, Brom M, Nuutila P, Roden M, Hwa A, et al. In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use. Diabetologia. 2016;59(7):1340–9.CrossRefGoogle Scholar
  38. Faber OK, Binder C. C-peptide response to glucagon. A test for the residual beta-cell function in diabetes mellitus. Diabetes. 1977;26(7):605–10.CrossRefGoogle Scholar
  39. Ferrannini E, Santoro D, Bonadonna R, Natali A, Parodi O, Camici PG. Metabolic and hemodynamic effects of insulin on human hearts. Am J Phys. 1993;264(2 Pt 1):E308–15.Google Scholar
  40. Finegood DT, Pacini G, Bergman RN. The insulin sensitivity index. Correlation in dogs between values determined from the intravenous glucose tolerance test and the euglycemic glucose clamp. Diabetes. 1984;33(4):362–8.CrossRefGoogle Scholar
  41. Fritsche A, Stefan N, Hardt E, Schutzenauer S, Haring H, Stumvoll M. A novel hyperglycaemic clamp for characterization of islet function in humans: assessment of three different secretagogues, maximal insulin response and reproducibility. Eur J Clin Investig. 2000;30(5):411–8.CrossRefGoogle Scholar
  42. Fujita Y, Kozawa J, Iwahashi H, Yoneda S, Uno S, Yoshikawa A, et al. Increment of serum C-peptide measured by glucagon test closely correlates with human relative beta-cell area. Endocr J. 2015;62(4):329–37.CrossRefGoogle Scholar
  43. Graci S, Baratta R, Degano C, Luppa A, Vigneri R, Frittitta L, et al. The intravenous insulin tolerance test is an accurate method for screening a general population for insulin resistance and related abnormalities. J Endocrinol Investig. 1999;22(6):472–5.CrossRefGoogle Scholar
  44. Greenbaum CJ, Beam CA, Boulware D, Gitelman SE, Gottlieb PA, Herold KC, et al. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite type 1 diabetes TrialNet data. Diabetes. 2012;61(8):2066–73.CrossRefGoogle Scholar
  45. Greenfield MS, Doberne L, Kraemer F, Tobey T, Reaven G. Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes. 1981;30(5):387–92.CrossRefGoogle Scholar
  46. Groop LC, Saloranta C, Shank M, Bonadonna RC, Ferrannini E, DeFronzo RA. The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1991;72(1):96–107.CrossRefGoogle Scholar
  47. Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab. 2015;19(1):160–4.CrossRefGoogle Scholar
  48. Hannon TS, Kahn SE, Utzschneider KM, Buchanan TA, Nadeau KJ, Zeitler PS, et al. Review of methods for measuring beta-cell function: design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab. 2017;20(1):14–24.CrossRefGoogle Scholar
  49. Hill NR, Levy JC, Matthews DR. Expansion of the homeostasis model assessment of beta-cell function and insulin resistance to enable clinical trial outcome modeling through the interactive adjustment of physiology and treatment effects: iHOMA2. Diabetes Care. 2013;36(8):2324–30.CrossRefGoogle Scholar
  50. Himsworth HP. Insulin deficiency and insulin inefficiency. Br Med J. 1940;1(4139):719–22.CrossRefGoogle Scholar
  51. James HA, O’Neill BT, Nair KS. Insulin regulation of proteostasis and clinical implications. Cell Metab. 2017;26(2):310–23.CrossRefGoogle Scholar
  52. Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993;42(11):1663–72.CrossRefGoogle Scholar
  53. Kahn SE, Lachin JM, Zinman B, Haffner SM, Aftring RP, Paul G, et al. Effects of rosiglitazone, glyburide, and metformin on beta-cell function and insulin sensitivity in ADOPT. Diabetes. 2011;60(5):1552–60.CrossRefGoogle Scholar
  54. Lassen NA, Perl W. Tracer kinetic methods in medical physiology. New York: Raven Press; 1979.Google Scholar
  55. Laxminarayan S, Reifman J, Steil GM. Use of a food and drug administration-approved type 1 diabetes mellitus simulator to evaluate and optimize a proportional-integral-derivative controller. J Diabetes Sci Technol. 2012;6(6):1401–12.CrossRefGoogle Scholar
  56. Lehtovirta M, Kaprio J, Groop L, Trombetta M, Bonadonna RC. Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins. Diabetologia. 2005;48(8):1604–13.CrossRefGoogle Scholar
  57. Lencioni C, Volpe L, Miccoli R, Cuccuru I, Chatzianagnostou K, Ghio A, et al. Early impairment of beta-cell function and insulin sensitivity characterizes normotolerant Caucasian women with previous gestational diabetes. Nutr Metab Cardiovasc Dis. 2006;16(7):485–93.CrossRefGoogle Scholar
  58. Madsbad S, Krarup T, McNair P, Christiansen C, Faber OK, Transbol I, et al. Practical clinical value of the C-peptide response to glucagon stimulation in the choice of treatment in diabetes mellitus. Acta Med Scand. 1981;210(3):153–6.PubMedGoogle Scholar
  59. Mandarino L, Bonadonna RC, McGuinness OP, Halseth AE, Wassermann DH. Regulation of muscle glucose uptake in vivo. In: Jefferson LS, Cherrington AD, editors. Handbook of physiology. Vol. II: The endocrine pancreas and regulaiton of metabolism. American Physiological Society, Oxford University Press, Oxford, UK; 2001. p. 803–45.Google Scholar
  60. Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care. 2001a;24(3):539–48.CrossRefGoogle Scholar
  61. Mari A, Camastra S, Toschi E, Giancaterini A, Gastaldelli A, Mingrone G, et al. A model for glucose control of insulin secretion during 24 h of free living. Diabetes. 2001b;50(Suppl 1):S164–8.CrossRefGoogle Scholar
  62. Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Ferrannini E. Meal and oral glucose tests for assessment of beta -cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab. 2002;283(6):E1159–66.CrossRefGoogle Scholar
  63. Mari A, Pacini G, Brazzale AR, Ahren B. Comparative evaluation of simple insulin sensitivity methods based on the oral glucose tolerance test. Diabetologia. 2005;48(4):748–51.CrossRefGoogle Scholar
  64. Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A, et al. Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab. 2001;86(11):5457–64.CrossRefGoogle Scholar
  65. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–70.CrossRefGoogle Scholar
  66. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.CrossRefGoogle Scholar
  67. Meier JJ, Menge BA, Breuer TG, Muller CA, Tannapfel A, Uhl W, et al. Functional assessment of pancreatic beta-cell area in humans. Diabetes. 2009;58(7):1595–603.CrossRefGoogle Scholar
  68. Muscelli E, Mari A, Casolaro A, Camastra S, Seghieri G, Gastaldelli A, et al. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and Type 2 diabetic patients. Diabetes. 2008;57(5):1340–8.CrossRefGoogle Scholar
  69. Navalesi R, Pilo A, Ferrannini E. Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin. J Clin Invest. 1978;61(1):197–208.CrossRefGoogle Scholar
  70. Oram RA, Jones AG, Besser RE, Knight BA, Shields BM, Brown RJ, et al. The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia. 2014;57(1):187–91.CrossRefGoogle Scholar
  71. Oram RA, McDonald TJ, Shields BM, Hudson MM, Shepherd MH, Hammersley S, et al. Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors. Diabetes Care. 2015;38(2):323–8.CrossRefGoogle Scholar
  72. Oxford DTU-Uo. HOMA calculator. 2017. Available from:
  73. Polonsky K, Jaspan J, Pugh W, Cohen D, Schneider M, Schwartz T, et al. Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction. J Clin Invest. 1983;72(3):1114–23.CrossRefGoogle Scholar
  74. Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, et al. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest. 1986a;77(1):98–105.CrossRefGoogle Scholar
  75. Polonsky KS, Given BD, Pugh W, Licinio-Paixao J, Thompson JE, Karrison T, et al. Calculation of the systemic delivery rate of insulin in normal man. J Clin Endocrinol Metab. 1986b;63(1):113–8.CrossRefGoogle Scholar
  76. Pye S, Watarai T, Davies G, Radziuk J. Comparison of the continuously calculated fractional splanchnic extraction of insulin with its fractional disappearance using a new double-tracer technique. Metabolism. 1993;42(2):145–53.CrossRefGoogle Scholar
  77. Quon MJ. QUICKI is a useful and accurate index of insulin sensitivity. J Clin Endocrinol Metab. 2002;87(2):949–51.CrossRefGoogle Scholar
  78. Radziuk J. Insulin sensitivity and its measurement: structural commonalities among the methods. J Clin Endocrinol Metab. 2000;85(12):4426–33.PubMedGoogle Scholar
  79. Rickels MR, Naji A, Teff KL. Acute insulin responses to glucose and arginine as predictors of beta-cell secretory capacity in human islet transplantation. Transplantation. 2007;84(10):1357–60.CrossRefGoogle Scholar
  80. Rubenstein AH, Clark JL, Melani F, Steiner DF. Secretion of pro-insulin C-peptide by pancreatic beta cells and its circulation in blood. Nature. 1969;224:697–9.CrossRefGoogle Scholar
  81. Rutter GA, Pullen TJ, Hodson DJ, Martinez-Sanchez A. Pancreatic beta-cell identity, glucose sensing and the control of insulin secretion. Biochem J. 2015;466(2):203–18.CrossRefGoogle Scholar
  82. Salinari S, Bertuzzi A, Mingrone G. Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test. Am J Physiol Endocrinol Metab. 2011;300(6):E955–65.CrossRefGoogle Scholar
  83. Santilli F, Simeone PG, Guagnano MT, Leo M, Maccarone MT, Di Castelnuovo A, et al. Effects of liraglutide on weight loss, fat distribution, and beta-cell function in obese subjects with prediabetes or early Type 2 diabetes. Diabetes Care. 2017;40(11):1556–64.CrossRefGoogle Scholar
  84. Seltzer HS, Allen EW, Herron AL Jr, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967;46(3):323–35.CrossRefGoogle Scholar
  85. Seufert J. Incretins and their endocrine and metabolic functions. Endocr Dev. 2017;32:38–48.CrossRefGoogle Scholar
  86. Shankar SS, Vella A, Raymond RH, Staten MA, Calle RA, Bergman RN, et al. Standardized mixed-meal tolerance and arginine stimulation tests provide reproducible and complementary measures of beta-cell function: results from the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series. Diabetes Care. 2016;39(9):1602–13.CrossRefGoogle Scholar
  87. Sharma A, Laurenti MC, Dalla Man C, Varghese RT, Cobelli C, Rizza RA, et al. Glucose metabolism during rotational shift-work in healthcare workers. Diabetologia. 2017;60(8):1483–90.CrossRefGoogle Scholar
  88. Shen SW, Reaven GM, Farquhar JW. Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest. 1970;49(12):2151–60.CrossRefGoogle Scholar
  89. Sluiter WJ, Erkelens DW, Reitsma WD, Doorenbos H. Glucose tolerance and insulin release, a mathematical approach I. Assay of the beta-cell response after oral glucose loading. Diabetes. 1976;25(4):241–4.CrossRefGoogle Scholar
  90. Steil GM, Grodsky GM. The artificial pancreas: is it important to understand how the beta cell controls blood glucose? J Diabetes Sci Technol. 2013;7(5):1359–69.CrossRefGoogle Scholar
  91. Steil GM, Hwu CM, Janowski R, Hariri F, Jinagouda S, Darwin C, et al. Evaluation of insulin sensitivity and beta-cell function indexes obtained from minimal model analysis of a meal tolerance test. Diabetes. 2004;53(5):1201–7.CrossRefGoogle Scholar
  92. Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T, et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care. 2000;23(3):295–301.CrossRefGoogle Scholar
  93. Stumvoll M, Haring H, Fritsche A. For debate: starling’s curve of the pancreas--overuse of a concept? Horm Metab Res. 2003;35(7):391–5.CrossRefGoogle Scholar
  94. Toffolo G, Breda E, Cavaghan MK, Ehrmann DA, Polonsky KS, Cobelli C. Quantitative indexes of beta-cell function during graded up&down glucose infusion from C-peptide minimal models. Am J Physiol Endocrinol Metab. 2001;280(1):E2–10.CrossRefGoogle Scholar
  95. Toschi E, Camastra S, Mari A, Gastaldelli A, Baldi S, Masoni A, et al. A model for assessing insulin secretion and its control under free-living conditions. Diabetes. 2001;50(Suppl 1):S178–9.CrossRefGoogle Scholar
  96. Trombetta M, Boselli L, Cretti A, Cali A, Vettore M, Caruso B, et al. Type 2 diabetes mellitus: a disease of the governance of the glucose-insulin system: an experimental metabolic control analysis study. Nutr Metab Cardiovasc Dis. 2013;23(1):23–30.CrossRefGoogle Scholar
  97. Van Cauter E, Mestrez F, Sturis J, Polonsky KS. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes. 1992;41(3):368–77.CrossRefGoogle Scholar
  98. Varghese RT, Dalla Man C, Laurenti MC, Piccinini F, Sharma A, Shah M, et al. Performance of individually-measured vs population-based C-peptide kinetics to assess beta-cell function in presence and absence of acute insulin resistance. Diabetes Obes Metab. 2017;20:549–555.CrossRefGoogle Scholar
  99. Vella A, Reed AS, Charkoudian N, Shah P, Basu R, Basu A, et al. Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles. Am J Physiol Endocrinol Metab. 2003;285(1):E25–30.CrossRefGoogle Scholar
  100. Vicini P, Caumo A, Cobelli C. The hot IVGTT two-compartment minimal model: indexes of glucose effectiveness and insulin sensitivity. Am J Phys. 1997;273(5 Pt 1):E1024–32.Google Scholar
  101. Visentin R, Dalla Man C, Basu R, Basu A, Rizza RA, Cobelli C. Hepatic insulin sensitivity in healthy and prediabetic subjects: from a dual- to a single-tracer oral minimal model. Am J Physiol Endocrinol Metab. 2015;309(2):E161–7.CrossRefGoogle Scholar
  102. Weiss R, Caprio S, Trombetta M, Taksali SE, Tamborlane WV, Bonadonna R. Beta-cell function across the spectrum of glucose tolerance in obese youth. Diabetes. 2005;54(6):1735–43.CrossRefGoogle Scholar
  103. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of Type 2 diabetes mellitus. J Clin Invest. 1999;104(6):787–94.CrossRefGoogle Scholar
  104. Yoneda H, Ikegami H, Yamamoto Y, Yamato E, Cha T, Kawaguchi Y, et al. Analysis of early-phase insulin responses in nonobese subjects with mild glucose intolerance. Diabetes Care. 1992;15(11):1517–21.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Riccardo C. Bonadonna
    • 1
    • 2
    Email author
  • Linda Boselli
    • 3
  • Alessandra Dei Cas
    • 1
    • 2
  • Maddalena Trombetta
    • 3
    • 4
  1. 1.Department of Medicine and SurgeryUniversity of ParmaParmaItaly
  2. 2.Division of Endocrinology and Metabolic DiseasesAzienda Ospedaliera Universitaria of ParmaParmaItaly
  3. 3.Department of MedicineUniversity of VeronaVeronaItaly
  4. 4.Division of Endocrinology, Diabetes and Metabolic DiseasesAzienda Ospedaliero-Universitaria Integrata of VeronaVeronaItaly

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