Acta Diabetologica

, Volume 49, Supplement 1, pp 195–204 | Cite as

Index of glucose effectiveness derived from oral glucose tolerance test

  • Shoichiro Nagasaka
  • Ikuyo Kusaka
  • Koh Yamashita
  • Yoshiko Funase
  • Keishi Yamauchi
  • Masafumi Katakura
  • Shun Ishibashi
  • Toru AizawaEmail author
Original Article


Aim of this study was to formulate an index for glucose effectiveness (Sg), SgIo, based on 3-point (0, 30 and 120 min) 75 g oral glucose tolerance test (OGTT). The equation for SgIO was developed in the Chikuma cohort (n = 502). Firstly, post-loading plasma glucose without insulin action and Sg (PPG-without insulin and Sg) was calculated as follows: fasting plasma glucose (mg/dl) + [0.75 × 75,000]/[0.19 × BW(kg) × 10]. Secondly, ‘PPG-without insulin/with Sg’ was obtained from inverse correlation between log10DIO and 2-h post-glucose plasma glucose at OGTT (2hPG) in each glucose tolerance category: DIO denotes oral disposition index, a product of the Matsuda Index and δIRI0–30/δPG0–30. Thirdly, expected 2hPG (2hPGE) of a given subject was obtained from the regression, and the ratio of 2hPG to 2hPGE (2hPG/2hPGE) was determined as an adjustment factor. Lastly, SgIO ([mg/dl]/min) was calculated as \( \frac{{[{\text{PPG}} \hbox{-} {\text{without}}\;{\text{insulin}}\;{\text{and}}\;{\text{Sg}}] - [{\text{PPG}} \hbox{-} {\text{without}}\;{\text{insulin}}/{\text{with}}\;{\text{Sg}}] \times [(2{\text{hPG}})/(2{\text{hPG}}_{\text{E}})]}}{120} \). SgIO was validated against Sg obtained by frequently sampled intravenous glucose tolerance test in the Jichi cohort (n = 205). Also, the accuracy of prediction of Sg by SgIo was tested by the Bland–Altman plot. SgIO was 3.61 ± 0.73, 3.17 ± 0.74 and 2.15 ± 0.60 in subjects with normal glucose tolerance (NGT), non-diabetic hyperglycemia and diabetes, respectively, in the Chikuma cohort. In the Jichi cohort, SgIO was significantly correlated with Sg in the entire group (r = 0.322, P < 0.001) and in subjects with NGT (r = 0.286, P < 0.001), and SgIo accurately predicted Sg. In conclusion, SgIO could be a simple, quantitative index for Sg.


Glucose effectiveness Insulin Diabetes 



Body mass index


Normal glucose tolerance


Non-diabetic hyperglycemia


Impaired fasting glucose


Impaired glucose tolerance


Diabetes mellitus


Type 2 diabetes


Frequently sampled intravenous glucose tolerance test


Oral glucose tolerance test


Immunoreactive insulin


Post-loading plasma glucose


Fasting plasma glucose


2-h post-glucose PG


Expected 2hPG


Glucose effectiveness


Oral Sg index


Sg determined by FSIVGTT or the clamp method


Insulin sensitivity index


Disposition index


Oral disposition index


Insulin sensitivity determined by Matsuda Index


Standardized major axis


Standard deviation



The study was in part supported by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (Shoichiro Nagasaka). We thank Masayuki Yamada, Kissei Pharmaceuticals, for invaluable advice regarding statistics.


  1. 1.
    Bergman RN, Finegood DT, Ader M (1985) Assessment of insulin sensitivity in vivo. Endocr Rev 6:45–86PubMedCrossRefGoogle Scholar
  2. 2.
    Welch S, Gebhart SS, Bergman RN, Phillips LS (1990) Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. J Clin Endocrinol Metab 71:1508–1518PubMedCrossRefGoogle Scholar
  3. 3.
    Taniguchi A, Nakai Y, Fukushima M, Kawamura H, Imura H, Nagata I et al (1992) Pathogenic factors responsible for glucose intolerance in patients with NIDDM. Diabetes 41:1540–1546PubMedCrossRefGoogle Scholar
  4. 4.
    Taniguchi A, Nakai Y, Fukushima M, Imura H, Kawamura H, Nagata I et al (1994) Insulin sensitivity, insulin secretion, and glucose effectiveness in subjects with impaired glucose tolerance: a minimal model analysis. Metabolism 43:714–718PubMedCrossRefGoogle Scholar
  5. 5.
    Best JD, Kahn SE, Ader M, Watanabe RM, Ni TC, Bergman RN (1996) Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care 19:1018–1030PubMedGoogle Scholar
  6. 6.
    Basu A, Caumo A, Bettini F, Gelisio A, Alzaid A, Cobelli C et al (1997) Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol. Diabetes 46:421–432PubMedCrossRefGoogle Scholar
  7. 7.
    Nagasaka S, Tokuyama K, Kusaka I, Hayashi H, Rokkaku K, Nakamura T et al (1999) Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach. Diabetes 48:1054–1060PubMedCrossRefGoogle Scholar
  8. 8.
    Taniguchi A, Fukushima M, Sakai M, Nagata I, Doi K, Nagasaka S et al (2000) Insulin secretion, insulin sensitivity, and glucose effectiveness in nonobese individuals with varying degrees of glucose tolerance. Diabetes Care 23:127–128PubMedCrossRefGoogle Scholar
  9. 9.
    Tokuyama Y, Sakurai K, Yagui K, Hashimoto N, Saito Y, Kanatsuka A (2001) Pathophysiologic phenotypes of Japanese subjects with varying degrees of glucose tolerance: using the combination of C-peptide secretion rate and minimal model analysis. Metabolism 50:812–818PubMedCrossRefGoogle Scholar
  10. 10.
    Tonelli J, Kishore P, Lee DE, Hawkins M (2005) The regulation of glucose effectiveness: how glucose modulates its own production. Curr Opin Clin Nutr Metab Care 8:450–456PubMedCrossRefGoogle Scholar
  11. 11.
    Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR (1992) Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 340:925–929PubMedCrossRefGoogle Scholar
  12. 12.
    Osei K, Rhinesmith S, Gaillard T, Schuster D (2004) Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. Diabetes Care 27:1439–1446PubMedCrossRefGoogle Scholar
  13. 13.
    Lorenzo C, Wagenknecht LE, Karter AJ, Hanley AJ, Rewers MJ, Haffner SM (2011) Cross-sectional and longitudinal changes of glucose effectiveness in relation to glucose tolerance: the insulin resistance atherosclerosis study. Diabetes Care 34:1959–1964PubMedCrossRefGoogle Scholar
  14. 14.
    Sakamaki H, Yamasaki H, Matsumoto K, Izumino K, Kondo H, Sera Y et al (1998) No deterioration in insulin sensitivity, but impairment of both pancreatic beta-cell function and glucose sensitivity, in Japanese women with former gestational diabetes mellitus. Diabet Med 15:1039–1044PubMedCrossRefGoogle Scholar
  15. 15.
    Nishida Y, Tokuyama K, Nagasaka S, Higaki Y, Shirai Y, Kiyonaga A et al (2004) Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model. Diabetes 53:315–320PubMedCrossRefGoogle Scholar
  16. 16.
    Hayashi Y, Nagasaka S, Takahashi N, Kusaka I, Ishibashi S, Numao S et al (2005) A single bout of exercise at higher intensity enhances glucose effectiveness in sedentary men. J Clin Endocrinol Metab 90:4035–4040PubMedCrossRefGoogle Scholar
  17. 17.
    Page R, Boolell M, Kalfas A, Sawyer S, Pestell R, Ward G et al (1991) Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in Cushing’s disease: a minimal model analysis. Clin Endocrinol 35:509–517CrossRefGoogle Scholar
  18. 18.
    Matsumoto K, Yamasaki H, Akazawa S, Sakamaki H, Ishibashi M, Abiru N et al (1996) High-dose but not low-dose dexamethasone impairs glucose tolerance by inducing compensatory failure of pancreatic beta-cells in normal men. J Clin Endocrinol Metab 81:2621–2626PubMedCrossRefGoogle Scholar
  19. 19.
    Nielsen MF, Caumo A, Chandramouli V, Schumann WC, Cobelli C, Landau BR et al (2004) Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects. Am J Physiol Endocrinol Metab 286:E102–E110PubMedCrossRefGoogle Scholar
  20. 20.
    Doi K, Taniguchi A, Nakai Y, Kawamura H, Higaki Y, Yokoi H et al (1997) Decreased glucose effectiveness but not insulin resistance in glucose-tolerant offspring of Japanese non-insulin-dependent diabetic patients: a minimal-model analysis. Metabolism 46:880–883PubMedCrossRefGoogle Scholar
  21. 21.
    Ader M, Pacini G, Yang YJ, Bergman RN (1985) Importance of glucose per se to intravenous glucose tolerance. Comparison of the minimal-model prediction with direct measurements. Diabetes 34:1092–1103PubMedCrossRefGoogle Scholar
  22. 22.
    Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW et al (1994) The contribution of insulin-dependent and insulin-independent glucose uptake to intravenous glucose tolerance in healthy human subjects. Diabetes 43:587–592PubMedCrossRefGoogle Scholar
  23. 23.
    Sato Y, Komatsu M, Katakura M, Ohfusa H, Yamada S, Yamauchi K et al (2002) Diminution of early insulin response to glucose in subjects with normal but minimally elevated fasting plasma glucose. Evidence for early beta-cell dysfunction. Diabet Med 19:566–571PubMedCrossRefGoogle Scholar
  24. 24.
    Katakura M, Komatsu M, Sato Y, Hashizume K, Aizawa T (2004) Primacy of beta-cell dysfunction in the development of hyperglycemia: a study in the Japanese general population. Metabolism 53:949–953PubMedCrossRefGoogle Scholar
  25. 25.
    Aizawa T, Yamada M, Katakura M, Funase Y, Yamashita K, Yamauchi K (2012) Hyperbolic correlation between insulin sensitivity and insulin secretion fades away in lean subjects with superb glucose regulation. Endocr J 59:127–136PubMedCrossRefGoogle Scholar
  26. 26.
    Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. Accessed at
  27. 27.
    Cederholm J, Wibell L (1985) Evaluation of insulin release and relative peripheral resistance with use of the oral glucose tolerance test: a study in subjects with normoglycaemia, glucose intolerance and non-insulin-dependent diabetes mellitus. Scand J Clin Lab Invest 45:741–751PubMedCrossRefGoogle Scholar
  28. 28.
    Soonthornpun S, Setasuban W, Thamprasit A, Chayanunnukul W, Rattarasarn C, Geater A (2003) Novel insulin sensitivity index derived from oral glucose tolerance test. J Clin Endocrinol Metab 88:1019–1023PubMedCrossRefGoogle Scholar
  29. 29.
    Giannini C, Weiss R, Cali A, Bonadonna R, Santoro N, Pierpont B, Shaw M, Caprio S (2012) Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. Diabetes 61:606–614PubMedCrossRefGoogle Scholar
  30. 30.
    Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470PubMedCrossRefGoogle Scholar
  31. 31.
    DeFronzo RA, Matsuda M (2010) Reduced time points to calculate the composite index. Diabetes Care 33:e93PubMedCrossRefGoogle Scholar
  32. 32.
    Kosaka K, Hagura R, Kuzuya T, Kuzuya N (1974) Insulin secretory response of diabetics during the period of improvement of glucose tolerance to normal range. Diabetologia 10:775–782PubMedCrossRefGoogle Scholar
  33. 33.
    Kosaka K, Kuzuya T, Hagura R, Yoshinaga H (1996) Insulin response to oral glucose load is consistently decreased in established non-insulin-dependent diabetes mellitus: the usefulness of decreased early insulin response as a predictor of non-insulin-dependent diabetes mellitus. Diabet Med 13(9 Suppl 6):S109–S119PubMedGoogle Scholar
  34. 34.
    Sokal RR, Rohlf FJ (2011) Biometry, 4th edn. WH Freeman, New YorkGoogle Scholar
  35. 35.
    Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 327:307–310CrossRefGoogle Scholar
  36. 36.
    Islam MM, Horibe H, Kobayashi F (1999) Current trend in prevalence of diabetes mellitus in Japan, 1964–1992. J Epidemiol 9:155–162PubMedCrossRefGoogle Scholar
  37. 37.
    Caumo A, Bergman RN, Cobelli C (2000) Insulin sensitivity from meal tolerance tests in normal subjects: a minimal model index. J Clin Endocrinol Metab 85:4396–4402PubMedCrossRefGoogle Scholar
  38. 38.
    Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C (2001) Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes 50:150–158PubMedCrossRefGoogle Scholar
  39. 39.
    Kanat M, Norton L, Winnier D, Jenkinson C, DeFronzo RA, Abdul-Ghani MA (2011) Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose. Acta Diabetol 48:209–217PubMedCrossRefGoogle Scholar
  40. 40.
    Gallwitz B, Kazda C, Kraus P, Nicolay C, Schernthaner G (2011) Contribution of insulin deficiency and insulin resistance to the development of type 2 diabetes: nature of early stage diabetes. Acta Diabetol Aug 23 [Epub ahead of print]Google Scholar
  41. 41.
    Aloulou I, Brun JF, Mercier J (2006) Evaluation of insulin sensitivity and glucose effectiveness during a standardized breakfast test: comparison with the minimal model analysis of an intravenous glucose tolerance test. Metabolism 55:676–690PubMedCrossRefGoogle Scholar
  42. 42.
    Brun JF, Ghanassia E, Fédou C, Bordenave S, Raynaud de Mauverger E, Mercier J (2010) Assessment of insulin sensitivity (SI) and glucose effectiveness (SG) from a standardized hyperglucidic breakfast test in type 2 diabetics exhibiting various levels of insulin resistance. Acta Diabetol Oct 28 [Epub ahead of print]Google Scholar
  43. 43.
    Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K et al (1996) Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J Clin Invest 98:1195–1209PubMedCrossRefGoogle Scholar
  44. 44.
    Escalante-Pulido M, Escalante-Herrera A, Milke-Najar ME, Alpizar-Salazar M (2003) Effects of weight loss on insulin secretion and in vivo insulin sensitivity in obese diabetic and non-diabetic subjects. Diabetes Nutr Metab 16:277–283PubMedGoogle Scholar
  45. 45.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRefGoogle Scholar
  46. 46.
    Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G et al (2000) Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410PubMedCrossRefGoogle Scholar
  47. 47.
    Tokuyama K, Nagasaka S, Mori S, Takahashi N, Kusaka I, Kiyonaga A et al (2009) Hepatic insulin sensitivity assessed by integrated model of hepatic and peripheral glucose regulation. Diabetes Technol Ther 11:487–492PubMedCrossRefGoogle Scholar
  48. 48.
    Livesey G, Wilson PD, Dainty JR, Brown JC, Faulks RM, Roe MA et al (1998) Simultaneous time-varying systemic appearance of oral and hepatic glucose in adults monitored with stable isotopes. Am J Physiol 275:E717–E728PubMedGoogle Scholar
  49. 49.
    Cobelli C, Caumo A, Omenetto M (1999) Minimal model SG overestimation and SI underestimation: improved accuracy by a Bayesian two-compartment model. Am J Physiol 277:E481–E488PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Shoichiro Nagasaka
    • 1
  • Ikuyo Kusaka
    • 1
  • Koh Yamashita
    • 2
  • Yoshiko Funase
    • 2
  • Keishi Yamauchi
    • 2
  • Masafumi Katakura
    • 3
  • Shun Ishibashi
    • 1
  • Toru Aizawa
    • 2
    Email author
  1. 1.Division of Endocrinology and Metabolism, Diabetes Center, Department of MedicineJichi Medical UniversityShimotsukeJapan
  2. 2.Aizawa Hospital Diabetes CenterMatsumotoJapan
  3. 3.Department of MedicineChikuma Central HospitalChikumaJapan

Personalised recommendations