• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Dec 1981; 68(6): 1456–1467.
PMCID: PMC370948

Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose.


The quantitative contributions of pancreatic responsiveness and insulin sensitivity to glucose tolerance were measured using the "minimal modeling technique" in 18 lean and obese subjects (88-206% ideal body wt). The individual contributions of insulin secretion and action were measured by interpreting the dynamics of plasma glucose and insulin during the intravenous glucose tolerance test in terms of two mathematical models. One, the insulin kinetics model, yields parameters of first-phase (phi 1) and second-phase (phi 2) responsivity of the beta-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameters, SI. Lean and obese subjects were subdivided into good (KG greater than 1.5) and lower (KG less than 1.5) glucose tolerance groups. The etiology of lower glucose tolerance was entirely different in lean and obese subjects. Lean, lower tolerance was related to pancreatic insufficiency (phi 2 77% lower than in good tolerance controls [P less than 0.03]), but insulin sensitivity was normal (P greater than 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P less than 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (phi 1: P greater than 0.06; phi 2: P greater than 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of second-phase beta-cell responsivity and insulin sensitivity (phi 2 . SI). Thus, these two factors were primarily responsible for overall determination of glucose tolerance. The effect of phi 1 was to modulate the KG value within those groups whose overall tolerance was determined by phi 2 . SI. This phi 1 modulating influence was more pronounced among insulin sensitive (phi 1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; phi 1 vs. KG, r = 0.91) subjects. This study demonstrates the feasibility of the minimal model technique to determine the etiology of impaired glucose tolerance.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • KARAM JH, GRODSKY GM, FORSHAM PH. Excessive insulin response to glucose in obese subjects as measured by immunochemical assay. Diabetes. 1963 May-Jun;12:197–204. [PubMed]
  • RABINOWITZ D, ZIERLER KL. Forearm metabolism in obesity and its response to intra-arterial insulin. Characterization of insulin resistance and evidence for adaptive hyperinsulinism. J Clin Invest. 1962 Dec;41:2173–2181. [PMC free article] [PubMed]
  • Ginsberg H, Olefsky JM, Reaven GM. Further evidence that insulin resistance exists in patients with chemical diabetes. Diabetes. 1974 Aug;23(8):674–678. [PubMed]
  • Reaven GM, Olefsky JM. Relationship between heterogeneity of insulin responses and insulin resistance in normal subjects and patients with chemical diabetes. Diabetologia. 1977 May;13(3):201–206. [PubMed]
  • Cerasi E, Luft R. "What is inherited--what is added" hypothesis for the pathogenesis of diabetes mellitus. Diabetes. 1967 Sep;16(9):615–627. [PubMed]
  • Lerner RL, Porte D., Jr Acute and steady-state insulin responses to glucose in nonobese diabetic subjects. J Clin Invest. 1972 Jul;51(7):1624–1631. [PMC free article] [PubMed]
  • Reaven GM. Insulin-independent diabetes mellitus: metabolic characteristics. Metabolism. 1980 May;29(5):445–454. [PubMed]
  • Bergman RN, Cobelli C. Minimal modeling, partition analysis, and the estimation of insulin sensitivity. Fed Proc. 1980 Jan;39(1):110–115. [PubMed]
  • 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 Dec;49(12):2151–2160. [PMC free article] [PubMed]
  • Insel PA, Liljenquist JE, Tobin JD, Sherwin RS, Watkins P, Andres R, Berman M. Insulin control of glucose metabolism in man: a new kinetic analysis. J Clin Invest. 1975 May;55(5):1057–1066. [PMC free article] [PubMed]
  • Toffolo G, Bergman RN, Finegood DT, Bowden CR, Cobelli C. Quantitative estimation of beta cell sensitivity to glucose in the intact organism: a minimal model of insulin kinetics in the dog. Diabetes. 1980 Dec;29(12):979–990. [PubMed]
  • Bergman RN, Ider YZ, Bowden CR, Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol. 1979 Jun;236(6):E667–E677. [PubMed]
  • Bergman RN, Urquhart J. The pilot gland approach to the study of insulin secretory dynamics. Recent Prog Horm Res. 1971;27:583–passim. [PubMed]
  • Grodsky GM. A threshold distribution hypothesis for packet storage of insulin and its mathematical modeling. J Clin Invest. 1972 Aug;51(8):2047–2059. [PMC free article] [PubMed]
  • Bucolo RJ, Bergman RN, Marsh DJ, Yates FE. Dynamics of glucose autoregulation in the isolated, blood-perfused canine liver. Am J Physiol. 1974 Jul;227(1):209–217. [PubMed]
  • Cherrington AD, Williams PE, Harris MS. Relationship between the plasma glucose level and glucose uptake in the conscious dog. Metabolism. 1978 Jul;27(7):787–791. [PubMed]
  • Turner RC, Holman RR, Matthews D, Hockaday TD, Peto J. Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism. 1979 Nov;28(11):1086–1096. [PubMed]
  • Olefsky JM. The insulin receptor: its role in insulin resistance of obesity and diabetes. Diabetes. 1976 Dec;25(12):1154–1162. [PubMed]
  • Kolterman OG, Reaven GM, Olefsky JM. Relationship between in vivo insulin resistance and decreased insulin receptors in obese man. J Clin Endocrinol Metab. 1979 Mar;48(3):487–494. [PubMed]
  • Lerner RL, Porte D., Jr Relationship between intravenous glucose loads, insulin responses and glucose disappearance rate. J Clin Endocrinol Metab. 1971 Sep;33(3):409–417. [PubMed]
  • Olefsky J, Farquhar JW, Reaven G. Relationship between fasting plasma insulin level and resistance to insulin-mediated glucose uptake in normal and diabetic subjects. Diabetes. 1973 Jul;22(7):507–513. [PubMed]
  • Olefsky JM, Saekow M. The effects of dietary carbohydrate content on insulin binding and glucose metabolism by isolated rat adipocytes. Endocrinology. 1978 Dec;103(6):2252–2263. [PubMed]
  • Sherwin RS, Kramer KJ, Tobin JD, Insel PA, Liljenquist JE, Berman M, Andres R. A model of the kinetics of insulin in man. J Clin Invest. 1974 May;53(5):1481–1492. [PMC free article] [PubMed]
  • Porte D, Jr, Smith PH, Ensinck JW. Neurohumoral regulation of the pancreatic islet A and B cells. Metabolism. 1976 Nov;25(11 Suppl 1):1453–1456. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...