Diabetes Metab J.  2021 Sep;45(5):641-654. 10.4093/dmj.2021.0220.

Assessment of Insulin Secretion and Insulin Resistance in Human

Affiliations
  • 1Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea
  • 2Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, University Paris-Diderot, Paris, France
  • 3Faculty of Medicine, University Paris-Diderot, Paris, France
  • 4Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea

Abstract

The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

Keyword

Diabetes mellitus; Insulin resistance; Insulin secretion

Figure

  • Fig. 1. Hyperinsulinemic-euglycemic glucose clamp technique.


Cited by  1 articles

Insulin Resistance and Impaired Insulin Secretion Predict Incident Diabetes: A Statistical Matching Application to the Two Korean Nationwide, Population-Representative Cohorts
Hyemin Jo, Soyeon Ahn, Jung Hun Ohn, Cheol Min Shin, Eunjeong Ji, Donggil Kim, Sung Jae Jung, Joongyub Lee
Endocrinol Metab. 2024;39(5):711-721.    doi: 10.3803/EnM.2024.1986.


Reference

1. Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus: present and future perspectives. Nat Rev Endocrinol. 2011; 8:228–36.
2. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004; 88:787–835.
Article
3. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837–53.
4. Viberti G, Kahn SE, Greene DA, Herman WH, Zinman B, Holman RR, et al. A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care. 2002; 25:1737–43.
Article
5. Moller DE, Flier JS. Insulin resistance: mechanisms, syndromes, and implications. N Engl J Med. 1991; 325:938–48.
6. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008; 294:E15–26.
Article
7. Reaven G. The metabolic syndrome or the insulin resistance syndrome?: different names, different concepts, and different goals. Endocrinol Metab Clin North Am. 2004; 33:283–303.
Article
8. Nielsen JH, Galsgaard ED, Moldrup A, Friedrichsen BN, Billestrup N, Hansen JA, et al. Regulation of beta-cell mass by hormones and growth factors. Diabetes. 2001; 50 Suppl 1:S25–9.
Article
9. Newsholme P, Krause M. Nutritional regulation of insulin secretion: implications for diabetes. Clin Biochem Rev. 2012; 33:35–47.
10. Koeppen BM, Stanton BA. Berne & Levy physiology. 7th ed. Philadelphia: Elsevier;2018.
11. Rorsman P, Renstrom E. Insulin granule dynamics in pancreatic beta cells. Diabetologia. 2003; 46:1029–45.
Article
12. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018; 98:2133–223.
Article
13. Faerch K, Vistisen D, Pacini G, Torekov SS, Johansen NB, Witte DR, et al. Insulin resistance is accompanied by increased fasting glucagon and delayed glucagon suppression in individuals with normal and impaired glucose regulation. Diabetes. 2016; 65:3473–81.
Article
14. Chon S, Gautier JF. An update on the effect of incretin-based therapies on β-cell function and mass. Diabetes Metab J. 2016; 40:99–114.
Article
15. Luzi L, DeFronzo RA. Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. Am J Physiol. 1989; 257(2 Pt 1):E241–6.
Article
16. Steiner KE, Mouton SM, Bowles CR, Williams PE, Cherrington AD. The relative importance of first- and second-phase insulin secretion in countering the action of glucagon on glucose turnover in the conscious dog. Diabetes. 1982; 31:964–72.
Article
17. Hansen BC, Vinik A, Jen KL, Schielke GP. Fluctuations in basal levels and effects of altered nutrition on plasma somatostatin. Am J Physiol. 1982; 243:R289–95.
Article
18. Ferrannini E, Cobelli C. The kinetics of insulin in man. II. Role of the liver. Diabetes Metab Rev. 1987; 3:365–97.
Article
19. Ferrannini E, Cobelli C. The kinetics of insulin in man. I. General aspects. Diabetes Metab Rev. 1987; 3:335–63.
Article
20. Hansen BC, Striffler JS, Bodkin NL. Decreased hepatic insulin extraction precedes overt noninsulin dependent (type II) diabetes in obese monkeys. Obes Res. 1993; 1:252–60.
Article
21. Hovorka R, Jones RH. How to measure insulin secretion. Diabetes Metab Rev. 1994; 10:91–117.
Article
22. Hovorka R, Soons PA, Young MA. ISEC: a program to calculate insulin secretion. Comput Methods Programs Biomed. 1996; 50:253–64.
Article
23. DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009; 32(Suppl 2):S157–63.
Article
24. Pacini G, Finegood DT, Bergman RN. A minimal-model-based glucose clamp yielding insulin sensitivity independent of glycemia. Diabetes. 1982; 31(5 Pt 1):432–41.
Article
25. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000; 85:2402–10.
Article
26. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999; 22:1462–70.
Article
27. 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; 28:412–9.
28. Tripathy D, Almgren P, Tuomi T, Groop L. Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity. Diabetes Care. 2004; 27:2204–10.
Article
29. Ferrannini E, Bjorkman O, Reichard GA Jr, Pilo A, Olsson M, Wahren J, et al. The disposal of an oral glucose load in healthy subjects: a quantitative study. Diabetes. 1985; 34:580–8.
Article
30. Finegood DT, Hramiak IM, Dupre J. A modified protocol for estimation of insulin sensitivity with the minimal model of glucose kinetics in patients with insulin-dependent diabetes. J Clin Endocrinol Metab. 1990; 70:1538–49.
Article
31. Quon MJ, Cochran C, Taylor SI, Eastman RC. Direct comparison of standard and insulin modified protocols for minimal model estimation of insulin sensitivity in normal subjects. Diabetes Res. 1994; 25:139–49.
32. Saad MF, Steil GM, Kades WW, Ayad MF, Elsewafy WA, Boyadjian R, et al. Differences between the tolbutamide-boosted and the insulin-modified minimal model protocols. Diabetes. 1997; 46:1167–71.
Article
33. Beard JC, Bergman RN, Ward WK, Porte D Jr. The insulin sensitivity index in nondiabetic man. Correlation between clampderived and IVGTT-derived values. Diabetes. 1986; 35:362–9.
Article
34. Bergman RN, Prager R, Volund A, Olefsky JM. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest. 1987; 79:790–800.
Article
35. Yang YJ, Youn JH, Bergman RN. Modified protocols improve insulin sensitivity estimation using the minimal model. Am J Physiol. 1987; 253(6 Pt 1):E595–602.
Article
36. Bergman RN, Ider YZ, Bowden CR, Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol. 1979; 236:E667–77.
Article
37. Cobelli C, Bettini F, Caumo A, Quon MJ. Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling. Am J Physiol. 1998; 275:E1031–6.
38. Cobelli C, Caumo A, Omenetto M. Minimal model SG overestimation and SI underestimation: improved accuracy by a Bayesian two-compartment model. Am J Physiol. 1999; 277:E481–8.
39. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–23.
Article
40. Choi CS, Kim C, Lee WJ, Park JY, Hong SK, Lee MG, et al. Association between birth weight and insulin sensitivity in healthy young men in Korea: role of visceral adiposity. Diabetes Res Clin Pract. 2000; 49:53–9.
Article
41. Larsson H, Ahren B. Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine. Diabetologia. 1998; 41:772–7.
Article
42. Choi CS, Kim MY, Han K, Lee MS. Assessment of β-cell function in human patients. Islets. 2012; 4:79–83.
Article
43. Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al. Endotext. South Dartmouth: MDText.com Inc;2021. Chapter, Assessing insulin sensitivity and resistance in humans [cited 2021 Sep 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278954.
44. Campbell PJ, Mandarino LJ, Gerich JE. Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus. Metabolism. 1988; 37:15–21.
Article
45. Rizza RA, Mandarino LJ, Gerich JE. Dose-response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol. 1981; 240:E630–9.
Article
46. Morris AD, Ueda S, Petrie JR, Connell JM, Elliott HL, Donnelly R. The euglycaemic hyperinsulinaemic clamp: an evaluation of current methodology. Clin Exp Pharmacol Physiol. 1997; 24:513–8.
Article
47. Gelfand RA, Barrett EJ. Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest. 1987; 80:1–6.
Article
48. 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; 30:387–92.
Article
49. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med. 2004; 350:664–71.
Article
50. Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, Barrett EJ. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes. 2006; 55:1436–42.
Article
51. 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:E2–10.
52. Eaton RP, Allen RC, Schade DS, Erickson KM, Standefer J. Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J Clin Endocrinol Metab . 1980; 51:520–8.
Article
53. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007; 30 Suppl 1:S42–7.
54. Yasuhara D, Naruo T, Nagai N, Tanaka M, Muranaga T, Nozoe S. Insulinogenic index at 15 min as a marker of nutritional rehabilitation in anorexia nervosa. Am J Clin Nutr. 2003; 77:292–9.
Article
55. 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. 2005; 54:3265–73.
56. 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; 49:2151–60.
Article
57. Harano Y, Hidaka H, Takatsuki K, Ohgaku S, Haneda M, Motoi S, et al. Glucose, insulin, and somatostatin infusion for the determination of insulin sensitivity in vivo. Metabolism. 1978; 27(9 Suppl 1):1449–52.
Article
58. Bergman RN, Ader M, Finegood DT, Pacini G. Extrapancreatic effect of somatostatin infusion to increase glucose clearance. Am J Physiol. 1984; 247(3 Pt 1):E370–9.
Article
59. Faber OK, Binder C. C-peptide response to glucagon: a test for the residual beta-cell function in diabetes mellitus. Diabetes. 1977; 26:605–10.
Article
60. Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia. 2001; 44:929–45.
Article
61. Pfeifer MA, Graf RJ, Halter JB, Porte D Jr. The regulation of glucose-induced insulin secretion by pre-stimulus glucose level and tolbutamide in normal man. Diabetologia. 1981; 21:198–205.
Article
62. Leighton E, Sainsbury CA, Jones GC. A practical review of cpeptide testing in diabetes. Diabetes Ther. 2017; 8:475–87.
Article
63. Yosten GL, Maric-Bilkan C, Luppi P, Wahren J. Physiological effects and therapeutic potential of proinsulin C-peptide. Am J Physiol Endocrinol Metab. 2014; 307:E955–68.
Article
64. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013; 30:803–17.
Article
65. 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; 41:368–77.
Article
66. Saisho Y. Postprandial C-peptide to glucose ratio as a marker of β cell function: implication for the management of type 2 diabetes. Int J Mol Sci. 2016; 17:744.
Article
67. Rijkelijkhuizen JM, Girman CJ, Mari A, Alssema M, Rhodes T, Nijpels G, et al. Classical and model-based estimates of betacell function during a mixed meal vs. an OGTT in a population-based cohort. Diabetes Res Clin Pract. 2009; 83:280–8.
Article
68. Bergman RN, Ader M, Huecking K, Van Citters G. Accurate assessment of beta-cell function: the hyperbolic correction. Diabetes. 2002; 51 Suppl 1:S212–20.
69. Bonadonna RC, Groop L, Kraemer N, Ferrannini E, Del Prato S, DeFronzo RA. Obesity and insulin resistance in humans: a dose-response study. Metabolism. 1990; 39:452–9.
Article
70. Chen H, Sullivan G, Yue LQ, Katz A, Quon MJ. QUICKI is a useful index of insulin sensitivity in subjects with hypertension. Am J Physiol Endocrinol Metab. 2003; 284:E804–12.
71. Bergman RN. Orchestration of glucose homeostasis: from a small acorn to the California oak. Diabetes. 2007; 56:1489–501.
Article
72. Haffner SM, Howard G, Mayer E, Bergman RN, Savage PJ, Rewers M, et al. Insulin sensitivity and acute insulin response in African-Americans, non-Hispanic whites, and Hispanics with NIDDM: the Insulin Resistance Atherosclerosis Study. Diabetes. 1997; 46:63–9.
Article
73. Laakso M. How good a marker is insulin level for insulin resistance? Am J Epidemiol. 1993; 137:959–65.
Article
74. Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1998; 83:2694–8.
Article
75. Silfen ME, Manibo AM, McMahon DJ, Levine LS, Murphy AR, Oberfield SE. Comparison of simple measures of insulin sensitivity in young girls with premature adrenarche: the fasting glucose to insulin ratio may be a simple and useful measure. J Clin Endocrinol Metab. 2001; 86:2863–8.
Article
76. Vuguin P, Saenger P, Dimartino-Nardi J. Fasting glucose insulin ratio: a useful measure of insulin resistance in girls with premature adrenarche. J Clin Endocrinol Metab. 2001; 86:4618–21.
Article
77. Quon MJ. Limitations of the fasting glucose to insulin ratio as an index of insulin sensitivity. J Clin Endocrinol Metab. 2001; 86:4615–7.
Article
78. Radziuk J. Insulin sensitivity and its measurement: structural commonalities among the methods. J Clin Endocrinol Metab. 2000; 85:4426–33.
Article
79. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27:1487–95.
Article
80. Chen H, Sullivan G, Quon MJ. Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes. 2005; 54:1914–25.
Article
81. 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; 86:5457–64.
82. Hanley AJ, Williams K, Gonzalez C, D’Agostino RB Jr, Wagenknecht LE, Stern MP, et al. Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study. Diabetes. 2003; 52:463–9.
Article
83. McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA, et al. Diagnosing insulin resistance in the general population. Diabetes Care. 2001; 24:460–4.
Article
84. 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; 23:295–301.
Article
85. Avignon A, Boegner C, Mariano-Goulart D, Colette C, Monnier L. Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state. Int J Obes Relat Metab Disord. 1999; 23:512–7.
Article
86. Gutt M, Davis CL, Spitzer SB, Llabre MM, Kumar M, Czarnecki EM, et al. Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures. Diabetes Res Clin Pract. 2000; 47:177–84.
Article
87. Belfiore F, Iannello S, Volpicelli G. Insulin sensitivity indices calculated from basal and OGTT-induced insulin, glucose, and FFA levels. Mol Genet Metab. 1998; 63:134–41.
Article
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