, Volume 40, Issue 1, pp 117–123 | Cite as

Leptin cut-off values for determination of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007)

  • Alireza Esteghamati
  • Ali Zandieh
  • Basira Zandieh
  • Omid Khalilzadeh
  • Alipasha Meysamie
  • Manouchehr Nakhjavani
  • Mohammad Mehdi Gouya
Original Article


Leptin is strongly contributed to the clustering of metabolic syndrome (MetS) components and potentially can be regarded as a single predictor of MetS. This population-based study, for the first time, reports the diagnostic accuracy of different leptin cut-points for determining MetS. Further, the current study compares the predictive ability of the appropriate threshold of leptin with insulin resistance. Data of the individuals without history of known diabetes mellitus, aged 25–64 years, from the third national surveillance of risk factors of non-communicable diseases (SuRFNCD-2007) were analyzed. MetS was defined due to either adult treatment panel III (ATPIII) or the modified international diabetes federation (IDF) criteria. Receiver-operating characteristic (ROC) curves were depicted to define cut-off of serum leptin, using the maximum Youden index and the shortest distance methods. Further, the values of leptin cut-offs in prediction of MetS were compared with those of insulin resistance (defined as homeostasis model assessment of insulin resistance >1.775). In men, the optimal cut-offs of leptin for IDF- and ATPIII-defined MetS were 3.6 ng/ml (positive predictive value, PPV: 56.5%; negative predictive value, NPV: 72.7%) and 4.1 ng/ml (PPV: 49.6%; NPV: 78.1%), respectively. In women, the optimal threshold was equal to 11.0 ng/ml (PPV: 53.8%; NPV: 73.0% for IDF criteria and PPV: 60.1%; NPV: 64.9% for ATPIII criteria). The diagnostic accuracy of these values in identifying MetS was similar to that of insulin resistance. Therefore, leptin is comparable to insulin resistance in identifying MetS and can be used as single predictor of MetS.


Leptin Insulin resistance Metabolic syndrome Receiver operating characteristic curve 



Adult treatment panel III


Area under the ROC curve


Center for disease control


High-density lipoprotein cholesterol


Homeostasis model assessment of insulin resistance


International diabetes federation


Metabolic syndrome


Negative likelihood ratio


Negative predictive value


Positive likelihood ratio


Positive predictive value

ROC curve

Receiver operating characteristics curve


Surveillance of risk factors of non-communicable diseases




Conflicts of interest

The authors declare no conflicts of interests.


  1. 1.
    D.A. de Luis, M.G. Sagrado, R. Conde, R. Aller, O. Izaola, Relation of visfatin to cardiovascular risk factors and adipocytokines in patients with impaired fasting glucose. Nutrition (2009) [Epub ahead of print]Google Scholar
  2. 2.
    P.J. Havel, Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. Proc. Nutr. Soc. 59, 359–371 (2000)PubMedCrossRefGoogle Scholar
  3. 3.
    M.L. Correia, K. Rahmouni, Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes Obes. Metab. 8, 603–610 (2006)PubMedCrossRefGoogle Scholar
  4. 4.
    F. Leyva, I.F. Godsland, M. Ghatei, A.J. Proudler, S. Aldis, C. Walton, S. Bloom, J.C. Stevenson, Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. Arterioscler. Thromb. Vasc. Biol. 18, 928–933 (1998)PubMedCrossRefGoogle Scholar
  5. 5.
    P.Z. Zimmet, V.R. Collins, M.P. de Courten, A.M. Hodge, G.R. Collier, G.K. Dowse, K.G. Alberti, J. Tuomilehto, F. Hemraj, H. Gareeboo, P. Chitson, D. Fareed, Is there a relationship between leptin and insulin sensitivity independent of obesity? A population-based study in the Indian Ocean nation of Mauritius Mauritius NCD Study Group. Int. J. Obes. Relat. Metab. Disord. 22, 171–177 (1998)PubMedCrossRefGoogle Scholar
  6. 6.
    A. Esteghamati, O. Khalilzadeh, M. Anvari, A. Rashidi, M. Mokhtari, M. Nakhjavani, Association of serum leptin levels with homeostasis model assessment-estimated insulin resistance and metabolic syndrome: the key role of central obesity. Metab. Syndr. Relat. Disord. 7, 447–452 (2009)PubMedCrossRefGoogle Scholar
  7. 7.
    P. Welsh, H.M. Murray, B.M. Buckley, A.J. de Craen, I. Ford, J.W. Jukema, P.W. Macfarlane, C.J. Packard, D.J. Stott, R.G. Westendorp, J. Shepherd, N. Sattar, Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population. Diabetes Care 32, 308–310 (2009)PubMedCrossRefGoogle Scholar
  8. 8.
    S. Soderberg, P. Zimmet, J. Tuomilehto, P. Chitson, H. Gareeboo, K.G. Alberti, J.E. Shaw, Leptin predicts the development of diabetes in Mauritian men, but not women: a population-based study. Int. J. Obes. (Lond) 31, 1126–1133 (2007)CrossRefGoogle Scholar
  9. 9.
    A.M. Wallace, A.D. McMahon, C.J. Packard, A. Kelly, J. Shepherd, A. Gaw, N. Sattar, Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation 104, 3052–3056 (2001)PubMedCrossRefGoogle Scholar
  10. 10.
    S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J. Gordon, R.M. Krauss, P.J. Savage, S.C. Smith Jr., J.A. Spertus, F. Costa, Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112, 2735–2752 (2005)PubMedCrossRefGoogle Scholar
  11. 11.
    J.B. Meigs, Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am. J. Epidemiol. 152, 908–911 (2000)PubMedCrossRefGoogle Scholar
  12. 12.
    J.E. Yun, H. Kimm, J. Jo, S.H. Jee, Serum leptin is associated with metabolic syndrome in obese and nonobese Korean populations. Metabolism 59, 424–429 (2010)PubMedCrossRefGoogle Scholar
  13. 13.
    M. Pladevall, B. Singal, L.K. Williams, C. Brotons, H. Guyer, J. Sadurni, C. Falces, M. Serrano-Rios, R. Gabriel, J.E. Shaw, P.Z. Zimmet, S. Haffner, A single factor underlies the metabolic syndrome: a confirmatory factor analysis. Diabetes Care 29, 113–122 (2006)PubMedCrossRefGoogle Scholar
  14. 14.
    A.M. Hodge, E.J. Boyko, M. de Courten, P.Z. Zimmet, P. Chitson, J. Tuomilehto, K.G. Alberti, Leptin and other components of the Metabolic Syndrome in Mauritius—a factor analysis. Int. J. Obes. Relat. Metab. Disord. 25, 126–131 (2001)PubMedCrossRefGoogle Scholar
  15. 15.
    M. Zitzmann, J. Gromoll, A. von Eckardstein, E. Nieschlag, The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia 46, 31–39 (2003)PubMedGoogle Scholar
  16. 16.
    A. Esteghamati, A. Zandieh, O. Khalilzadeh, A. Morteza, A. Meysamie, M. Nakhjavani, M.M. Gouya, Clustering of leptin and physical activity with components of metabolic syndrome in Iranian population: an exploratory factor analysis. Endocrine 38, 206–213 (2010)PubMedCrossRefGoogle Scholar
  17. 17.
    P. Zimmet, E.J. Boyko, G.R. Collier, M. de Courten, Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. Ann. N. Y. Acad. Sci. 892, 25–44 (1999)PubMedCrossRefGoogle Scholar
  18. 18.
    S.B. Patel, G.P. Reams, R.M. Spear, R.H. Freeman, D. Villarreal, Villarreal, Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease. Curr. Hypertens. Rep. 10, 131–137 (2008)PubMedCrossRefGoogle Scholar
  19. 19.
    S.P. Kalra, Disruption in the leptin-NPY link underlies the pandemic of diabetes and metabolic syndrome: new therapeutic approaches. Nutrition 24, 820–826 (2008)PubMedCrossRefGoogle Scholar
  20. 20.
    A. Katsuki, Y. Sumida, E.C. Gabazza, S. Murashima, M. Furuta, R. Araki-Sasaki, Y. Hori, Y. Yano, Y. Adachi, Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes Care 24, 362–365 (2001)PubMedCrossRefGoogle Scholar
  21. 21.
    T.M. Wallace, D.R. Matthews, The assessment of insulin resistance in man. Diabet. Med. 19, 527–534 (2002)PubMedCrossRefGoogle Scholar
  22. 22.
    T.M. Wallace, J.C. Levy, D.R. Matthews, Use and abuse of HOMA modeling. Diabetes Care 27, 1487–1495 (2004)PubMedCrossRefGoogle Scholar
  23. 23.
    A. Esteghamati, A. Meysamie, O. Khalilzadeh, A. Rashidi, M. Haghazali, F. Asgari, M. Kamgar, M.M. Gouya, M. Abbasi, Third national Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2007) in Iran: methods and results on prevalence of diabetes, hypertension, obesity, central obesity, and dyslipidemia. BMC Public Health 9, 167 (2009)PubMedCrossRefGoogle Scholar
  24. 24.
    D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985)PubMedCrossRefGoogle Scholar
  25. 25.
    S. Genuth, K.G. Alberti, P. Bennett, J. Buse, R. Defronzo, R. Kahn, J. Kitzmiller, W.C. Knowler, H. Lebovitz, A. Lernmark, D. Nathan, J. Palmer, R. Rizza, C. Saudek, J. Shaw, M. Steffes, M. Stern, J. Tuomilehto, P. Zimmet, Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26, 3160–3167 (2003)PubMedCrossRefGoogle Scholar
  26. 26.
    A. Esteghamati, M. Abbasi, A. Rashidi, A. Meysamie, O. Khalilzadeh, M. Haghazali, F. Asgari, M. Nakhjavani, Optimal waist circumference cut-offs for the diagnosis of metabolic syndrome in Iranian adults: results of the third national survey of risk factors of non-communicable diseases (SuRFNCD-2007). Diabet. Med. 26, 745–746 (2009)PubMedCrossRefGoogle Scholar
  27. 27.
    International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome [article online]. 2006. Accessed 10 August 2010
  28. 28.
    A. Esteghamati, H. Ashraf, O. Khalilzadeh, A. Zandieh, M. Nakhjavani, A. Rashidi, M. Haghazali, F. Asgari, Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007). Nutr. Metab. (Lond.) 7, 26 (2010)CrossRefGoogle Scholar
  29. 29.
    P. Quehenberger, M. Exner, R. Sunder-Plassmann, K. Ruzicka, C. Bieglmayer, G. Endler, C. Muellner, W. Speiser, O. Wagner, Leptin induces endothelin-1 in endothelial cells in vitro. Circ. Res. 90, 711–718 (2002)PubMedCrossRefGoogle Scholar
  30. 30.
    M. Carlyle, O.B. Jones, J.J. Kuo, J.E. Hall, Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension 39, 496–501 (2002)PubMedCrossRefGoogle Scholar
  31. 31.
    W.G. Haynes, D.A. Morgan, S.A. Walsh, A.L. Mark, W.I. Sivitz, Receptor-mediated regional sympathetic nerve activation by leptin. J. Clin. Invest. 100, 270–278 (1997)PubMedCrossRefGoogle Scholar
  32. 32.
    O. Ukkola, Y.A. Kesaniemi, Leptin and high-sensitivity C-reactive protein and their interaction in the metabolic syndrome in middle-aged subjects. Metabolism 56, 1221–1227 (2007)PubMedCrossRefGoogle Scholar
  33. 33.
    Y. Ikeda, T. Suehiro, T. Nakamura, Y. Kumon, K. Hashimoto, Clinical significance of the insulin resistance index as assessed by homeostasis model assessment. Endocr. J. 48, 81–86 (2001)PubMedCrossRefGoogle Scholar
  34. 34.
    M.J. Kelly, F.D. Dunstan, K. Lloyd, D.L. Fone, Evaluating cutpoints for the MHI-5 and MCS using the GHQ-12: a comparison of five different methods. BMC Psychiatry 8, 10 (2008)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Alireza Esteghamati
    • 1
  • Ali Zandieh
    • 1
  • Basira Zandieh
    • 1
  • Omid Khalilzadeh
    • 1
  • Alipasha Meysamie
    • 2
  • Manouchehr Nakhjavani
    • 1
  • Mohammad Mehdi Gouya
    • 3
  1. 1.Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of Preventive Medicine, School of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Center for Disease ControlMinistry of Health and Medical EducationTehranIran

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