Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Matsuda–DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno–Sobetsu study

Journal of Human Hypertension volume 26, pages 325–333 (2012)Cite this article

Abstract

Here we examined whether the Matsuda–DeFronzo insulin sensitivity index (ISI-M) is more efficient than the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing risk of hypertension. Cross-sectional and longitudinal analyses were conducted using normotensive subjects who were selected among 1399 subjects in the Tanno–Sobetsu cohort. In the cross-sectional analysis (n=740), blood pressure (BP) level was correlated with HOMA-IR and with ISI-M, but correlation coefficients indicate a tighter correlation with ISI-M. Multiple linear regression analysis adjusted by age, sex, body mass index (BMI) and serum triglyceride level (TG) showed contribution of ISI-M and fasting plasma glucose, but not of HOMA-IR. In the longitudinal analysis (n=607), 241 subjects (39.7%) developed hypertension during a 10-year follow-up period, and multiple logistic regression indicated that age, TG, systolic BP and ISI-M, but not HOMA-IR, were associated with development of hypertension. In subjects <60 years old, odds ratio of new-onset hypertension was higher in the low ISI-M group (ISI-M, less than the median) than in the high ISI-M group for any tertile of BMI. In conclusion, ISI-M is a better predictor of hypertension than is HOMA-IR. Non-hepatic IR may be a determinant, which is independent of TG, BP level and BMI, of the development of hypertension.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. O’Seaghdha CM, Perkovic V, Lam TH, McGinn S, Barzi F, Gu DF et al. Blood pressure is a major risk factor for renal death: an analysis of 560 352 participants from the Asia-Pacific region. Hypertension 2009; 54: 509–515.

    Article  Google Scholar 

  2. Zheng Y, Stein R, Kwan T, Yu C, Kwan J, Chen SL et al. Evolving cardiovascular disease prevalence, mortality, risk factors, and the metabolic syndrome in China. Clin Cardiol 2009; 32: 491–497.

    Article  Google Scholar 

  3. Agyemang C, Addo J, Bhopal R, de Graft Aikins A, Stronks K . Cardiovascular disease, diabetes and established risk factors among populations of sub-Saharan African descent in Europe: a literature review. Global Health 2009; 5: 7.

    Article  Google Scholar 

  4. Lavie CJ, Milani RV, Ventura HO . Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol 2009; 53: 1925–1932.

    Article  Google Scholar 

  5. Redon J, Cifkova R, Laurent S, Nilsson P, Narkiewicz K, Erdine S et al. Mechanisms of hypertension in the cardiometabolic syndrome. J Hypertens 2009; 27: 441–451.

    Article  CAS  Google Scholar 

  6. Savage DB, Petersen KF, Shulman GI . Mechanisms of insulin resistance in humans and possible links with inflammation. Hypertension 2005; 45: 828–833.

    Article  CAS  Google Scholar 

  7. Chapman MJ, Sposito AC . Hypertension and dyslipidaemia in obesity and insulin resistance: pathophysiology, impact on atherosclerotic disease and pharmacotherapy. Pharmacol Ther 2008; 117: 354–373.

    Article  CAS  Google Scholar 

  8. Razani B, Chakravarthy MV, Semenkovich CF . Insulin resistance and atherosclerosis. Endocrinol Metab Clin North Am 2008; 37: 603–621, viii.

    Article  CAS  Google Scholar 

  9. Tsuchihashi K, Hikita N, Hase M, Agata J, Saitoh S, Nakata T et al. Role of hyperinsulinemia in atherosclerotic coronary arterial disease: studies of semi-quantitative coronary angiography. Intern Med 1999; 38: 691–697.

    Article  CAS  Google Scholar 

  10. Wassink AM, van der Graaf Y, Olijhoek JK, Visseren FL . Metabolic syndrome and the risk of new vascular events and all-cause mortality in patients with coronary artery disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Eur Heart J 2008; 29: 213–223.

    Article  CAS  Google Scholar 

  11. Pierdomenico SD, Lapenna D, Di Tommaso R, Di Carlo S, Caldarella MP, Neri M et al. Prognostic relevance of metabolic syndrome in hypertensive patients at low-to-medium risk. Am J Hypertens 2007; 20: 1291–1296.

    Article  Google Scholar 

  12. Takeuchi H, Saitoh S, Takagi S, Ohnishi H, Ohhata J, Isobe T et al. Metabolic syndrome and cardiac disease in Japanese men: applicability of the concept of metabolic syndrome defined by the National Cholesterol Education Program-Adult Treatment Panel III to Japanese men—the Tanno and Sobetsu Study. Hypertens Res 2005; 28: 203–208.

    Article  Google Scholar 

  13. Rooney DP, Edgar JD, Sheridan B, Atkinson AB, Bell PM . The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man. Eur J Clin Invest 1991; 21: 430–435.

    Article  CAS  Google Scholar 

  14. Shimamoto K, Hirata A, Fukuoka M, Higashiura K, Miyazaki Y, Shiiki M et al. Insulin sensitivity and the effects of insulin on renal sodium handling and pressor systems in essential hypertensive patients. Hypertension 1994; 23: I29–I33.

    Article  CAS  Google Scholar 

  15. Miyazaki Y, Murakami H, Hirata A, Fukuoka M, Masuda A, Ura N et al. Effects of the angiotensin converting enzyme inhibitor temocapril on insulin sensitivity and its effects on renal sodium handling and the pressor system in essential hypertensive patients. Am J Hypertens 1998; 11: 962–970.

    Article  CAS  Google Scholar 

  16. Garrison RJ, Kannel WB, Stokes III J, Castelli WP . Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med 1987; 16: 235–251.

    Article  CAS  Google Scholar 

  17. Shetterly SM, Rewers M, Hamman RF, Marshall JA . Patterns and predictors of hypertension incidence among Hispanics and non-Hispanic whites: the San Luis Valley Diabetes Study. J Hypertens 1994; 12: 1095–1102.

    Article  CAS  Google Scholar 

  18. Ohmori S, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K et al. Hyperinsulinaemia and blood pressure in a general Japanese population: the Hisayama Study. J Hypertens 1994; 12: 1191–1197.

    Article  CAS  Google Scholar 

  19. Feskens EJ, Tuomilehto J, Stengard JH, Pekkanen J, Nissinen A, Kromhout D . Hypertension and overweight associated with hyperinsulinaemia and glucose tolerance: a longitudinal study of the Finnish and Dutch cohorts of the Seven Countries Study. Diabetologia 1995; 38: 839–847.

    Article  CAS  Google Scholar 

  20. Haffner SM, Miettinen H, Gaskill SP, Stern MP . Metabolic precursors of hypertension. The San Antonio Heart Study. Arch Intern Med 1996; 156: 1994–2001.

    Article  CAS  Google Scholar 

  21. Tsuruta M, Hashimoto R, Adachi H, Imaizumi T, Nomura G . Hyperinsulinaemia as a predictor of hypertension: an 11-year follow-up study in Japan. J Hypertens 1996; 14: 483–488.

    Article  CAS  Google Scholar 

  22. Imazu M, Yamamoto H, Toyofuku M, Sumii K, Okubo M, Egusa G et al. Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study. Hypertens Res 2001; 24: 531–536.

    Article  CAS  Google Scholar 

  23. Hirose H, Saito I, Kawabe H, Saruta T . Insulin resistance and hypertension: seven-year follow-up study in middle-aged Japanese men (the KEIO study). Hypertens Res 2003; 26: 795–800.

    Article  Google Scholar 

  24. Ferrannini E, Balkau B, Coppack SW, Dekker JM, Mari A, Nolan J et al. Insulin resistance, insulin response, and obesity as indicators of metabolic risk. J Clin Endocrinol Metab 2007; 92: 2885–2892.

    Article  CAS  Google Scholar 

  25. Bonora E, Capaldo B, Perin PC, Del Prato S, De Mattia G, Frittitta L et al. Hyperinsulinemia and insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in non-diabetic subjects. The GISIR database. Nutr Metab Cardiovasc Dis 2008; 18: 624–631.

    Article  CAS  Google Scholar 

  26. Higashiura K, Ura N, Takada T, Agata J, Yoshida H, Miyazaki Y et al. Alteration of muscle fiber composition linking to insulin resistance and hypertension in fructose-fed rats. Am J Hypertens 1999; 12: 596–602.

    Article  CAS  Google Scholar 

  27. Higashiura K, Ura N, Takada T, Li Y, Torii T, Togashi N et al. The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats. Am J Hypertens 2000; 13: 290–297.

    Article  CAS  Google Scholar 

  28. Rizzoni D, Pasini E, Flati V, Rodella LF, Paiardi S, Assanelli D et al. Angiotensin receptor blockers improve insulin signaling and prevent microvascular rarefaction in the skeletal muscle of spontaneously hypertensive rats. J Hypertens 2008; 26: 1595–1601.

    Article  CAS  Google Scholar 

  29. Wei Y, Sowers JR, Clark SE, Li W, Ferrario CM, Stump CS . Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-kappaB activation via NADPH oxidase. Am J Physiol Endocrinol Metab 2008; 294: E345–E351.

    Article  CAS  Google Scholar 

  30. Kratochvilova S, Vyhnanovska P, Vlasakova Z, Hajek M, Skibova J, Pelikanova T . Metabolic characteristics of soleus muscle in relation to insulin action in the offspring of hypertensive parents. Metabolism 2006; 55: 1388–1396.

    Article  CAS  Google Scholar 

  31. Hernandez N, Torres SH, Vera O, De Sanctis JB, Flores E . Muscle fiber composition and capillarization in relation to metabolic alterations in hypertensive men. J Med 2001; 32: 67–82.

    CAS  PubMed  Google Scholar 

  32. Abdul-Ghani MA, Matsuda M, DeFronzo RA . Strong association between insulin resistance in liver and skeletal muscle in non-diabetic subjects. Diabet Med 2008; 25: 1289–1294.

    CAS  PubMed  Google Scholar 

  33. Matsuda M, DeFronzo RA . Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462–1470.

    Article  CAS  Google Scholar 

  34. Takagi S, Saitoh S, Nakano M, Hayashi Y, Obara F, Onishi H et al. Relationship between blood pressure level and mortality rate: an 18-year study conducted in two rural communities in Japan. J Hypertens 2000; 18: 139–144.

    Article  CAS  Google Scholar 

  35. Ohnishi H, Saitoh S, Ura N, Takagi S, Obara F, Akasaka H et al. Relationship between insulin resistance and accumulation of coronary risk factors. Diabetes Obes Metab 2002; 4: 388–393.

    Article  CAS  Google Scholar 

  36. Ohnishi H, Saitoh S, Takagi S, Ohata J, Takeuchi H, Isobe T et al. Incidence of insulin resistance in obese subjects in a rural Japanese population: the Tanno and Sobetsu study. Diabetes Obes Metab 2005; 7: 83–87.

    Article  CAS  Google Scholar 

  37. Ohnishi H, Saitoh S, Takagi S, Ohata J, Isobe T, Kikuchi Y et al. Relationship between insulin-resistance and remnant-like particle cholesterol. Atherosclerosis 2002; 164: 167–170.

    Article  CAS  Google Scholar 

  38. Matthews D HJ, Rudenski A, Naylor B, Treacher D, Turner R . Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  Google Scholar 

  39. Fukuyama N, Homma K, Wakana N, Kudo K, Suyama A, Ohazama H et al. Validation of the friedewald equation for evaluation of plasma LDL-cholesterol. J Clin Biochem Nutr 2008; 43: 1–5.

    Article  CAS  Google Scholar 

  40. Arima H, Tanizaki Y, Yonemoto K, Doi Y, Ninomiya T, Hata J et al. Impact of blood pressure levels on different types of stroke: the Hisayama study. J Hypertens 2009; 27: 2437–2443.

    Article  CAS  Google Scholar 

  41. Takashima N, Miura K, Hozawa A, Kadota A, Okamura T, Nakamura Y . Population attributable fraction of smoking and metabolic syndrome on cardiovascular disease mortality in Japan: a 15-year follow up of NIPPON DATA90. BMC Public Health 2010; 10: 306.

    Article  Google Scholar 

  42. Chu MC, Cosper P, Orio F, Carmina E, Lobo RA . Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin. Am J Obstet Gynecol 2006; 194: 100–104.

    Article  CAS  Google Scholar 

  43. 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: 134–141.

    Article  CAS  Google Scholar 

  44. Cederholm J, Wibell L . Insulin release and peripheral sensitivity at the oral glucose tolerance test. Diabetes Res Clin Pract 1990; 10: 167–175.

    Article  CAS  Google Scholar 

  45. Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab 2004; 89: 1096–1101.

    Article  CAS  Google Scholar 

  46. Abdul-Ghani MA, Balas B, Matsuda M, DeFronzo RA . Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 2007; 30: 89–94.

    Article  CAS  Google Scholar 

  47. McGill JB, Haffner S, Rees TJ, Sowers JR, Tershakovec AM, Weber M . Progress and controversies: treating obesity and insulin resistance in the context of hypertension. J Clin Hypertens (Greenwich) 2009; 11: 36–41.

    Article  Google Scholar 

  48. Cooper SA, Whaley-Connell A, Habibi J, Wei Y, Lastra G, Manrique C et al. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol Heart Circ Physiol 2007; 293: H2009–H2023.

    Article  CAS  Google Scholar 

  49. Zhao CX, Xu X, Cui Y, Wang P, Wei X, Yang S et al. Increased endothelial nitric-oxide synthase expression reduces hypertension and hyperinsulinemia in fructose-treated rats. J Pharmacol Exp Ther 2009; 328: 610–620.

    Article  CAS  Google Scholar 

  50. de Jongh RT, Serne EH, RG IJ, Stehouwer CD . Microvascular function: a potential link between salt sensitivity, insulin resistance and hypertension. J Hypertens 2007; 25: 1887–1893.

    Article  CAS  Google Scholar 

  51. Hall JE, Brands MW, Zappe DH, Dixon WN, Mizelle HL, Reinhart GA et al. Hemodynamic and renal responses to chronic hyperinsulinemia in obese, insulin-resistant dogs. Hypertension 1995; 25: 994–1002.

    Article  CAS  Google Scholar 

  52. Hall JE, Brands MW, Mizelle HL, Gaillard CA, Hildebrandt DA . Chronic intrarenal hyperinsulinemia does not cause hypertension. Am J Physiol 1991; 260: F663–F669.

    CAS  PubMed  Google Scholar 

  53. Iyer SN, Katovich MJ . Fructose feeding in rats is not associated with sodium retention. Am J Hypertens 1996; 9: 1018–1023.

    Article  CAS  Google Scholar 

  54. Tomiyama H, Kushiro T, Abeta H, Kurumatani H, Taguchi H, Kuga N et al. Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats. Hypertension 1992; 20: 596–600.

    Article  CAS  Google Scholar 

  55. Strazzullo P, Barbato A, Galletti F, Barba G, Siani A, Iacone R et al. Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study. J Hypertens 2006; 24: 1633–1639.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The present study was supported by a Program for Developing the Supporting System for Upgrading the Education and Research of the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan, a grant for scientific research from the Ministry of Health, Labor and Welfare, Tokyo Japan (H19-cardiovascular-common-021) and Japanese Society for the Promotion of Science Grants-in-Aid for Scientific Research (no. 19590639), Tokyo, Japan.

Author information

Authors and Affiliations

  1. Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan

    M Furugen, S Saitoh, H Ohnishi, H Akasaka, K Mitsumata, M Chiba, T Furukawa, Y Miyazaki, K Shimamoto & T Miura

Authors
  1. M Furugen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Saitoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Ohnishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Akasaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Mitsumata
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Chiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Miyazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Shimamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Miura.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Furugen, M., Saitoh, S., Ohnishi, H. et al. Matsuda–DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno–Sobetsu study. J Hum Hypertens 26, 325–333 (2012). https://doi.org/10.1038/jhh.2011.23

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2011.23

Keywords

This article is cited by

Search

Advanced search

Quick links