, Volume 61, Issue 2, pp 258–266 | Cite as

Gender-specific differences of interaction between cadmium exposure and obesity on prediabetes in the NHANES 2007–2012 population

  • Fei Jiang
  • Xueyuan Zhi
  • Miao Xu
  • Bingyan Li
  • Zengli Zhang
Original Article



Data from National Health and Nutrition Examination Survey (NHANES) for the years 2007–2012 were used to evaluate the interactions of cadmium (Cd) exposure with being overweight/obesity on the risk of prediabetes among adults 20 years older.


A total of 3552 subjects were included in the analysis. Urinary cadmium levels (UCd) was used as a biomarker for long-term exposure to Cd. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S).


Following covariates adjustments, we found significant associations of UCd with higher prediabetes prevalence, and this association was more apparent in males (Q4 vs Q1: OR = 1.95, 95%CI: 1.34–2.84); while overweight/obesity was associated with prediabetes both in males and in females. Additionally, there was a significant interaction between Cd exposure and being overweight/obesity on prediabetes risk among males (RERI = 1.18, 95% CI: 0.42–1.93; AP = 0.35, 95% CI: 0.12–0.58; S = 2.00, 95% CI: 0.92–4.34).


Our results suggest that being overweight/obesity may substantially amplify the adverse effects of long-term cadmium exposure on prediabetes risk, and this interaction is more severe in male adults. Further studies are needed to confirm these findings.


Cadmium Obesity Prediabetes Interaction 



This study was supported by the National Natural Science Foundation of China (No.81703209, No.81773414, and No.81673151), Postdoctoral Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation (No.2017M621823), and A Project Funded by the Priority Academic Program Development to Jiangsu Higher Education Institutions (PAPD).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. 1.
    International Diabetes Federation, IDF Diabetes Atlas, (2018) Accessed 9 April 2018
  2. 2.
    C.M. Edwards, K. Cusi, Prediabetes: a worldwide epidemic. Endocrinol. Metab. Clin. North. Am. 45, 751–764 (2016)CrossRefPubMedGoogle Scholar
  3. 3.
    B. Brannick, S. Dagogo-Jack, Prediabetes and cardiovascular disease: pathophysiology and interventions for prevention and risk reduction. Endocrinol. Metab. Clin. North. Am. 47, 33–50 (2018)CrossRefPubMedGoogle Scholar
  4. 4.
    A.G. Tabak, C. Herder, W. Rathmann, E.J. Brunner, M. Kivimaki, Prediabetes: a high-risk state for diabetes development. Lancet 379, 2279–2290 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    K.A. Thayer, J.J. Heindel, J.R. Bucher, M.A. Gallo, Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ. Health Perspect. 120, 779–789 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    I. Iavicoli, L. Fontana, A. Bergamaschi, The effects of metals as endocrine disruptors. J. Toxicol. Environ. Health B. Crit. Rev. 12, 206–223 (2009)CrossRefPubMedGoogle Scholar
  7. 7.
    S. Satarug, S.H. Garrett, M.A. Sens, D.A. Sens, Cadmium, environmental exposure, and health outcomes. Environ. Health Perspect. 118, 182–190 (2010)CrossRefPubMedGoogle Scholar
  8. 8.
    S. Satarug, Long-term exposure to cadmium in food and cigarette smoke, liver effects and hepatocellular carcinoma. Curr. Drug. Metab. 13, 257–271 (2012)CrossRefPubMedGoogle Scholar
  9. 9.
    A.A. Tinkov, T. Filippini, O.P. Ajsuvakova, J. Aaseth, Y.G. Gluhcheva, J.M. Ivanova, G. Bjorklund, M.G. Skalnaya, E.R. Gatiatulina, E.V. Popova, O.N. Nemereshina, M. Vinceti, A.V. Skalny, The role of cadmium in obesity and diabetes. Sci. Total Environ. 601-602, 741–755 (2017)CrossRefPubMedGoogle Scholar
  10. 10.
    J.C. Erie, J.A. Good, J.A. Butz, D.O. Hodge, J.S. Pulido, Urinary cadmium and age-related macular degeneration. Am. J. Ophthalmol. 144, 414–418 (2007)CrossRefPubMedGoogle Scholar
  11. 11.
    G.L. Ginsberg, Cadmium risk assessment in relation to background risk of chronic kidney disease. J. Toxicol. Environ. Health A 75, 374–390 (2012)CrossRefPubMedGoogle Scholar
  12. 12.
    J.M. Lavado-Garcia, L.M. Puerto-Parejo, R. Roncero-Martin, J.M. Moran, J.D. Pedrera-Zamorano, I.J. Aliaga, O. Leal-Hernandez, M.L. Canal-Macias, Dietary intake of cadmium, lead and mercury and its association with bone health in healthy premenopausal women. Int. J. Environ. Res. Public. Health 14, 1437 (2017).Google Scholar
  13. 13.
    S.C. Larsson, N. Orsini, A. Wolk, Urinary cadmium concentration and risk of breast cancer: a systematic review and dose-response meta-analysis. Am. J. Epidemiol. 182, 375–380 (2015)CrossRefPubMedGoogle Scholar
  14. 14.
    J.C. Han, S.Y. Park, B.G. Hah, G.H. Choi, Y.K. Kim, T.H. Kwon, E.K. Kim, M. Lachaal, C.Y. Jung, W. Lee, Cadmium induces impaired glucose tolerance in rat by down-regulating GLUT4 expression in adipocytes. Arch. Biochem. Biophys. 413, 213–220 (2003)CrossRefPubMedGoogle Scholar
  15. 15.
    M.M. El, M.R. Raja, X. Zhang, K.W. MacRenaris, S. Bhatt, X. Chen, M. Urbanek, T.V. O’Halloran, W.J. Lowe, Accumulation of cadmium in insulin-producing beta cells. Islets 4, 405–416 (2012)CrossRefGoogle Scholar
  16. 16.
    K.D. Chapatwala, M. Hobson, D. Desaiah, B. Rajanna, Effect of cadmium on hepatic and renal gluconeogenic enzymes in female rats. Toxicol. Lett. 12, 27–34 (1982)CrossRefPubMedGoogle Scholar
  17. 17.
    S. Mohammad, J. Ahmad, Management of obesity in patients with type 2 diabetes mellitus in primary care. Diabetes Metab. Syndr. 10, 171–181 (2016)CrossRefPubMedGoogle Scholar
  18. 18.
    L. Khaodhiar, S. Cummings, C.M. Apovian, Treating diabetes and prediabetes by focusing on obesity management. Curr. Diab. Rep. 9, 348–354 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    E.J. Henriksen, M.K. Diamond-Stanic, E.M. Marchionne, Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic. Biol. Med. 51, 993–999 (2011)CrossRefPubMedGoogle Scholar
  20. 20.
    N. Esser, S. Legrand-Poels, J. Piette, A.J. Scheen, N. Paquot, Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Clin. Pract. 105, 141–150 (2014)CrossRefPubMedGoogle Scholar
  21. 21.
    J.A. Colacino, A.E. Arthur, K.K. Ferguson, L.S. Rozek, Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress. Environ. Res. 131, 6–12 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    X. Nie, N. Wang, Y. Chen, C. Chen, B. Han, C. Zhu, Y. Chen, F. Xia, Z. Cang, M. Lu, Y. Meng, B. Jiang, J.M. D, Y. Lu, Blood cadmium in Chinese adults and its relationships with diabetes and obesity. Environ. Sci. Pollut. Res. Int. 23, 18714–18723 (2016)CrossRefPubMedGoogle Scholar
  23. 23.
    G.G. Schwartz, D. Il’Yasova, A. Ivanova, Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III. Diabetes Care 26, 468–470 (2003)CrossRefPubMedGoogle Scholar
  24. 24.
    A. Wallia, N.B. Allen, S. Badon, M.M. El, Association between urinary cadmium levels and prediabetes in the NHANES 2005-2010 population. Int. J. Hyg. Environ. Health 217, 854–860 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    H.S. Son, S.G. Kim, B.S. Suh, D.U. Park, D.S. Kim, S.D. Yu, Y.S. Hong, J.D. Park, B.K. Lee, J.D. Moon, J. Sakong, Association of cadmium with diabetes in middle-aged residents of abandoned metal mines: the first health effect surveillance for residents in abandoned metal mines. Ann. Occup. Environ. Med. 27, 20 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Z.A. Shaikh, T.T. Vu, K. Zaman, Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants. Toxicol. Appl. Pharmacol. 154, 256–263 (1999)CrossRefPubMedGoogle Scholar
  27. 27.
    J. Liu, W. Qu, M.B. Kadiiska, Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol. Appl. Pharmacol. 238, 209–214 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    D.H. Lee, J.S. Lim, K. Song, Y. Boo, D.J. Jacobs, Graded associations of blood lead and urinary cadmium concentrations with oxidative-stress-related markers in the U.S. population: results from the third National Health and Nutrition Examination Survey. Environ. Health Perspect. 114, 350–354 (2006)CrossRefPubMedGoogle Scholar
  29. 29.
    G. Pizzino, N. Irrera, A. Bitto, G. Pallio, F. Mannino, V. Arcoraci, F. Aliquo, L. Minutoli, C. De Ponte, P. D’Andrea, F. Squadrito, D. Altavilla, Cadmium-induced oxidative stress impairs glycemic control in adolescents. Oxid. Med. Cell Longev. 2017, 6341671 (2017)PubMedPubMedCentralGoogle Scholar
  30. 30.
    I. Abdelaziz, M.I. Elhabiby, A.A. Ashour, Toxicity of cadmium and protective effect of bee honey, vitamins C and B complex. Hum. Exp. Toxicol. 32, 362–370 (2013)CrossRefPubMedGoogle Scholar
  31. 31.
    J. Mladenovic, B. Ognjanovic, N. Dordevic, M. Matic, V. Knezevic, A. Stajn, Z. Saicic, Protective effects of oestradiol against cadmium-induced changes in blood parameters and oxidative damage in rats. Arh. Hig. Rada Toksikol. 65, 37–46 (2014)CrossRefPubMedGoogle Scholar
  32. 32.
    S. Furukawa, T. Fujita, M. Shimabukuro, M. Iwaki, Y. Yamada, Y. Nakajima, O. Nakayama, M. Makishima, M. Matsuda, I. Shimomura, Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114, 1752–1761 (2004)CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    I. Savini, M.V. Catani, D. Evangelista, V. Gasperi, L. Avigliano, Obesity-associated oxidative stress: strategies finalized to improve redox state. Int. J. Mol. Sci. 14, 10497–10538 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    G.S. Hotamisligil, P. Arner, J.F. Caro, R.L. Atkinson, B.M. Spiegelman, Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J. Clin. Invest. 95, 2409–2415 (1995)CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    C. Phosat, P. Panprathip, N. Chumpathat, P. Prangthip, N. Chantratita, N. Soonthornworasiri, S. Puduang, K. Kwanbunjan, Elevated C-reactive protein, interleukin 6, tumor necrosis factor alpha and glycemic load associated with type 2 diabetes mellitus in rural Thais: a cross-sectional study. BMC Endocr. Disord. 17, 44 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    H.P. Kopp, C.W. Kopp, A. Festa, K. Krzyzanowska, S. Kriwanek, E. Minar, R. Roka, G. Schernthaner, Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler. Thromb. Vasc. Biol. 23, 1042–1047 (2003)CrossRefPubMedGoogle Scholar
  37. 37.
    C. Holdstock, L. Lind, B.E. Engstrom, M. Ohrvall, M. Sundbom, A. Larsson, F.A. Karlsson, CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects. Int. J. Obes. (Lond.). 29, 1275–1280 (2005)CrossRefGoogle Scholar
  38. 38.
    E.S. Abd, A.M. Saiem, Impact of weight loss on oxidative stress and inflammatory cytokines in obese type 2 diabetic patients. Afr. Health Sci. 16, 725–733 (2016)CrossRefGoogle Scholar
  39. 39.
    A. Navas-Acien, E. Selvin, A.R. Sharrett, E. Calderon-Aranda, E. Silbergeld, E. Guallar, Lead, cadmium, smoking, and increased risk of peripheral arterial disease. Circulation 109, 3196–3201 (2004)CrossRefPubMedGoogle Scholar
  40. 40.
    Y.S. Lin, D. Rathod, W.C. Ho, J.J. Caffrey, Cadmium exposure is associated with elevated blood C-reactive protein and fibrinogen in the U. S. population: the third national health and nutrition examination survey (NHANES III, 1988-1994). Ann. Epidemiol. 19, 592–596 (2009)CrossRefPubMedGoogle Scholar
  41. 41.
    B.M. Cheung, K.L. Ong, L.Y. Wong, Elevated serum alkaline phosphatase and peripheral arterial disease in the United States National Health and Nutrition Examination Survey 1999-2004. Int. J. Cardiol. 135, 156–161 (2009)CrossRefPubMedGoogle Scholar
  42. 42.
    M. Kippler, K. Engstrom, S.J. Mlakar, M. Bottai, S. Ahmed, M.B. Hossain, R. Raqib, M. Vahter, K. Broberg, Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth weight. Epigenetics 8, 494–503 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Q. Ba, M. Li, P. Chen, C. Huang, X. Duan, L. Lu, J. Li, R. Chu, D. Xie, H. Song, Y. Wu, H. Ying, X. Jia, H. Wang, Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ. Health Perspect. 125, 437–446 (2017)PubMedCrossRefGoogle Scholar
  44. 44.
    C. Nagata, Y. Nagao, C. Shibuya, Y. Kashiki, H. Shimizu, Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiol. Biomark. Prev. 14, 705–708 (2005)CrossRefGoogle Scholar
  45. 45.
    S. De Craemer, K. Croes, N. van Larebeke, S. De Henauw, G. Schoeters, E. Govarts, I. Loots, T. Nawrot, V. Nelen, E. Den Hond, L. Bruckers, Y. Gao, W. Baeyens, Metals, hormones and sexual maturation in Flemish adolescents in three cross-sectional studies (2002-2015). Environ. Int. 102, 190–199 (2017)CrossRefPubMedGoogle Scholar
  46. 46.
    K. Esposito, G. Bellastella, M.I. Maiorino, D. Giugliano, Particulate matter air pollution: individual choices for improving cardiometabolic well-being. Endocrine 59, 495–498 (2018)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fei Jiang
    • 1
  • Xueyuan Zhi
    • 1
  • Miao Xu
    • 1
  • Bingyan Li
    • 2
  • Zengli Zhang
    • 1
  1. 1.Department of Occupational and Environmental Health, School of Public HealthMedical College of Soochow UniversitySuzhouChina
  2. 2.Department of Nutrition and Food Hygiene, School of Public HealthMedical College of Soochow UniversitySuzhouChina

Personalised recommendations