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.

  • Review Article
  • Published:

Epidemic T2DM, early development and epigenetics: implications of the Chinese Famine

Nature Reviews Endocrinology volume 14, pages 738–746 (2018)Cite this article

Subjects

An Author Correction to this article was published on 01 April 2019

This article has been updated

Abstract

The gene–environment interactions resulting from famine and the subsequent increased intergenerational risk of type 2 diabetes mellitus (T2DM) have contributed to the current epidemic of T2DM in China, which poses major social, health and economic challenges. The epidemic of T2DM could threaten national development in China through premature morbidity and mortality from T2DM and associated non-communicable diseases. The Chinese Famine (1959–1961), as a contributor to the nation’s current national T2DM epidemic, provides an important and urgent public health warning. The effects of the famine give a strong message that research and actions that address the prevention of T2DM cannot be confined to lifestyle measures, as used in the landmark Da Qing study and the lifestyle prevention programmes and pharmaceutical interventions used in Western nations. To stem the T2DM epidemic, a new paradigm for prevention of T2DM must be developed. This paradigm should include a very strong emphasis on pregnancy planning and maternal and child health during and after the pregnancy. Without action, intergenerational cycles initiated by epigenetic modifications resulting from adverse environmental stimuli during the critical window of early development in utero might continue to fuel the T2DM epidemic in future generations.

Key points

  • The People’s Republic of China is now the epicentre of a global type 2 diabetes mellitus (T2DM) epidemic.

  • Early-life (in utero) exposure to poor nutrition during the Chinese Famine (1959–1961) probably contributed to this modern-day epidemic.

  • The epigenetic modifications resulting from malnutrition during the famine might convey an intergenerational risk of T2DM that continues to fuel the T2DM epidemic in China.

  • Research and actions that address prevention of T2DM cannot be confined to lifestyle measures and must consider the early developmental effect of in utero events.

  • The long-term and intergenerational consequences of famines and other man-made and natural disasters provide an urgent public health message for other nations currently experiencing or at future risk of such catastrophes.

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

Fig. 1: The association between overweight and obesity and T2DM among adults in various regions in China.
Fig. 2: The association between overweight and obesity and hyperglycaemia among woman planning pregnancy in different provinces of China.

Similar content being viewed by others

Change history

  • 01 April 2019

    In the version of this article published online and in print, there was a mistake in the legend of Fig. 2 regarding the descriptions of the red and blue colours in the Figure. The text should have read ‘The blue and red colours represent regions (provinces) with wheat and rice as the staple food, respectively.’ This has now been corrected in the HTML and PDF version of the article.

References

  1. Zimmet, P. Z., Magliano, D. J., Herman, W. H. & Shaw, J. E. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol. 2, 56–64 (2014).

    PubMed  Google Scholar 

  2. International Diabetes Federation. IDF Diabetes Atlas — 8th edition. Diabetes Atlas http://diabetesatlas.org/resources/2017-atlas.html (2017).

  3. Zimmet, P., Alberti, K. G., Magliano, D. J. & Bennett, P. H. Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. Nat. Rev. Endocrinol. 12, 616–622 (2016).

    PubMed  Google Scholar 

  4. Shanghai Diabetes Research Cooperative Group. Diabetes mellitus survey in Shanghai. Chin. Med. J. 93, 663–672 (1980).

    Google Scholar 

  5. Zhang, N., Du, S. M. & Ma, G. S. Current lifestyle factors that increase risk of T2DM in China. Eur. J. Clin. Nutr. 71, 832–838 (2017).

    CAS  PubMed  Google Scholar 

  6. Li, Y. et al. Time trends of dietary and lifestyle factors and their potential impact on diabetes burden in China. Diabetes Care 40, 1685–1694 (2017).

    PubMed  PubMed Central  Google Scholar 

  7. Lv, J. et al. Adherence to a healthy lifestyle and the risk of type 2 diabetes in Chinese adults. Int. J. Epidemiol. 46, 1410–1420 (2017).

    PubMed  PubMed Central  Google Scholar 

  8. Yang, W. et al. Prevalence of diabetes among men and women in China. N. Engl. J. Med. 362, 1090–1101 (2010).

    CAS  PubMed  Google Scholar 

  9. Zuo, H., Shi, Z. & Hussain, A. Prevalence, trends and risk factors for the diabetes epidemic in China: a systematic review and meta-analysis. Diabetes Res. Clin. Pract. 104, 63–72 (2014).

    PubMed  Google Scholar 

  10. Wang, L. et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA 317, 2515–2523 (2017).

    PubMed  PubMed Central  Google Scholar 

  11. Zimmet, P. Z., El-Osta, A. & Shi, Z. The diabetes epidemic in China is a public health emergency: the potential role of prenatal exposure. J. Public Health Emerg. 1, 80 (2017).

    Google Scholar 

  12. Chen, L., Magliano, D. J. & Zimmet, P. Z. The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives. Nat. Rev. Endocrinol. 8, 228–236 (2011).

    PubMed  Google Scholar 

  13. Keating, S. T., Plutzky, J. & El-Osta, A. Epigenetic changes in diabetes and cardiovascular risk. Circ. Res. 118, 1706–1722 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Fajans, S. S. & Bell, G. I. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 34, 1878–1884 (2011).

    PubMed  PubMed Central  Google Scholar 

  15. Carroll, R. W. & Murphy, R. Monogenic diabetes: a diagnostic algorithm for clinicians. Genes 4, 522–535 (2013).

    PubMed  PubMed Central  Google Scholar 

  16. Block, T. & El-Osta, A. Epigenetic programming, early life nutrition and the risk of metabolic disease. Atherosclerosis 266, 31–40 (2017).

    CAS  PubMed  Google Scholar 

  17. Gluckman, P. D., Hanson, M. A., Cooper, C. & Thornburg, K. L. Effect of in utero and early-life conditions on adult health and disease. N. Engl. J. Med. 359, 61–73 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Rodriguez, H., Rafehi, H., Bhave, M. & El-Osta, A. Metabolism and chromatin dynamics in health and disease. Mol. Aspects Med. 54, 1–15 (2017).

    CAS  PubMed  Google Scholar 

  19. Tobi, E. W. et al. DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood. Sci. Adv. 4, eaao4364 (2018).

    PubMed  PubMed Central  Google Scholar 

  20. Portela, A. & Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol. 28, 1057–1068 (2010).

    CAS  PubMed  Google Scholar 

  21. Heijmans, B. T. et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl Acad. Sci. USA 105, 17046–17049 (2008).

    CAS  PubMed  Google Scholar 

  22. Anway, M. D., Cupp, A. S., Uzumcu, M. & Skinner, M. K. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308, 1466–1469 (2005).

    CAS  PubMed  Google Scholar 

  23. Keating, S. T. & El-Osta, A. Epigenetics and metabolism. Circ. Res. 116, 715–736 (2015).

    CAS  PubMed  Google Scholar 

  24. Ravelli, A. C. et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet 351, 173–177 (1998).

    CAS  PubMed  Google Scholar 

  25. van Abeelen, A. F. et al. Cardiovascular consequences of famine in the young. Eur. Heart J. 33, 538–545 (2012).

    PubMed  Google Scholar 

  26. Lussana, F. et al. Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile. Am. J. Clin. Nutr. 88, 1648–1652 (2008).

    CAS  PubMed  Google Scholar 

  27. Lumey, L. H., Stein, A. D. & Susser, E. Prenatal famine and adult health. Annu. Rev. Public Health 32, 237–262 (2011).

    CAS  PubMed  Google Scholar 

  28. Yajnik, C. S. Early life origins of insulin resistance and type 2 diabetes in India and other Asian countries. J. Nutr. 134, 205–210 (2004).

    CAS  PubMed  Google Scholar 

  29. Li, R. et al. Increasing prevalence of type 2 diabetes in Chinese adults in Shanghai. Diabetes Care 35, 1028–1030 (2012).

    PubMed  PubMed Central  Google Scholar 

  30. Ning, F. et al. Risk factors associated with the dramatic increase in the prevalence of diabetes in the adult Chinese population in Qingdao, China. Diabet. Med. 26, 855–863 (2009).

    CAS  PubMed  Google Scholar 

  31. Ma, R. C. W., Tsoi, K. Y., Tam, W. H. & Wong, C. K. C. Developmental origins of type 2 diabetes: a perspective from China. Eur. J. Clin. Nutr. 71, 870–880 (2017).

    CAS  PubMed  Google Scholar 

  32. Chan, J. C. Diabetes and noncommunicable disease: prevent the preventables. JAMA 310, 916–917 (2013).

    CAS  PubMed  Google Scholar 

  33. Li, Y. et al. Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood. Diabetes 59, 2400–2406 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Lumey, L. H., Khalangot, M. D. & Vaiserman, A. M. Association between type 2 diabetes and prenatal exposure to the Ukraine famine of 1932-33: a retrospective cohort study. Lancet Diabetes Endocrinol. 3, 787–794 (2015).

    CAS  PubMed  Google Scholar 

  35. King, H. et al. Diabetes and associated disorders in Cambodia: two epidemiological surveys. Lancet 366, 1633–1639 (2005).

    PubMed  Google Scholar 

  36. Kiernan, B. The Pol Pot Regime: Race, Power, and Genocide in Cambodia Under the Khmer Rouge, 1975–79 3rd edn (Yale Univ. Press, 2008).

  37. Zimmet, P., Taft, P., Guinea, A., Guthrie, W. & Thoma, K. The high prevalence of diabetes mellitus on a Central Pacific Island. Diabetologia 13, 111–115 (1977).

    CAS  PubMed  Google Scholar 

  38. Garrett, J. Island Exiles (ABC Books, 1996).

  39. Tan, K. H. X. et al. Diabetes mellitus prevalence is increasing in South Asians but is stable in Chinese living in Singapore and Mauritius. J. Diabetes 9, 855–864 (2017).

    PubMed  Google Scholar 

  40. Phan, T. P. et al. Forecasting the burden of type 2 diabetes in Singapore using a demographic epidemiological model of Singapore. BMJ Open Diabetes Res. Care 2, e000012 (2014).

    PubMed  PubMed Central  Google Scholar 

  41. Smil, V. China’s great famine: 40 years later. BMJ 319, 1619–1621 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Dennis Tao, Y. China’s agricultural crisis and famine of 1959–1961: a survey and comparison to Soviet famines. Comp. Econom. Studies 50, 1–29 (2008).

    Google Scholar 

  43. Li, J. et al. Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a population-based cohort study of families in Suihua, China. Am. J. Clin. Nutr. 105, 221–227 (2017).

    CAS  PubMed  Google Scholar 

  44. Gluckman, P. D., Hanson, M. A., Buklijas, T., Low, F. M. & Beedle, A. S. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat. Rev. Endocrinol. 5, 401–408 (2009).

    CAS  PubMed  Google Scholar 

  45. Li, Y. et al. Exposure to the Chinese famine in early life and the risk of hypertension in adulthood. J. Hypertens. 29, 1085–1092 (2011).

    CAS  PubMed  Google Scholar 

  46. Wang, J. et al. Exposure to the Chinese famine in childhood increases type 2 diabetes risk in adults. J. Nutr. 146, 2289–2295 (2016).

    CAS  PubMed  Google Scholar 

  47. Wang, N. et al. Is exposure to famine in childhood and economic development in adulthood associated with diabetes? J. Clin. Endocrinol. Metab. 100, 4514–4523 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Meng, R. et al. Prenatal famine exposure, adulthood obesity patterns and risk of type 2 diabetes. Int. J. Epidemiol. 47, 399–408 (2018).

    PubMed  Google Scholar 

  49. Sun, Y., Zhang, L., Duan, W., Meng, X. & Jia, C. Association between famine exposure in early life and type 2 diabetes mellitus and hyperglycemia in adulthood: results from the China Health And Retirement Longitudinal Study (CHARLS). J. Diabetes 10, 724–733 (2018).

    CAS  PubMed  Google Scholar 

  50. Liu, L. et al. Increase in the prevalence of hypertension among adults exposed to the Great Chinese Famine during early life. Environ. Health Prev. Med. 22, 64 (2017).

    PubMed  PubMed Central  Google Scholar 

  51. Wu, L. et al. Prenatal exposure to the Great Chinese Famine and mid-age hypertension. PLOS ONE 12, e0176413 (2017).

    PubMed  PubMed Central  Google Scholar 

  52. Zheng, X. et al. The Great Chinese Famine exposure in early life and the risk of nonalcoholic fatty liver disease in adult women. Ann. Hepatol. 16, 901–908 (2017).

    CAS  PubMed  Google Scholar 

  53. Wang, Y., Wang, X., Kong, Y., Zhang, J. H. & Zeng, Q. The Great Chinese Famine leads to shorter and overweight females in Chongqing Chinese population after 50 years. Obesity 18, 588–592 (2010).

    CAS  PubMed  Google Scholar 

  54. Kang, Y. et al. Nutritional deficiency in early life facilitates aging-associated cognitive decline. Curr. Alzheimer Res. 14, 841–849 (2017).

    CAS  PubMed  Google Scholar 

  55. Li, Y. et al. Exposure to the chinese famine in early life and the risk of metabolic syndrome in adulthood. Diabetes Care 34, 1014–1018 (2011).

    PubMed  PubMed Central  Google Scholar 

  56. Zheng, X. et al. Risk of metabolic syndrome in adults exposed to the great Chinese famine during the fetal life and early childhood. Eur. J. Clin. Nutr. 66, 231–236 (2012).

    CAS  PubMed  Google Scholar 

  57. Godfrey, K. M. & Barker, D. J. Fetal nutrition and adult disease. Am. J. Clin. Nutr. 71, 1344S–1352S (2000).

    CAS  PubMed  Google Scholar 

  58. Hales, C. N. & Barker, D. J. The thrifty phenotype hypothesis. Br. Med. Bull. 60, 5–20 (2001).

    CAS  PubMed  Google Scholar 

  59. Roseboom, T. J., Painter, R. C., van Abeelen, A. F., Veenendaal, M. V. & de Rooij, S. R. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas 70, 141–145 (2011).

    PubMed  Google Scholar 

  60. Keating, S. T., van Diepen, J. A., Riksen, N. P. & El-Osta, A. Epigenetics in diabetic nephropathy, immunity and metabolism. Diabetologia 61, 6–20 (2018).

    CAS  PubMed  Google Scholar 

  61. Shi, Z. et al. Early life exposure to Chinese famine modifies the association between hypertension and cardiovascular disease. J. Hypertens. 36, 54–60 (2018).

    CAS  PubMed  Google Scholar 

  62. Pettitt, D. J., Nelson, R. G., Saad, M. F., Bennett, P. H. & Knowler, W. C. Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care 16, 310–314 (1993).

    CAS  PubMed  Google Scholar 

  63. Zhou, M. et al. Geographical variation in diabetes prevalence and detection in china: multilevel spatial analysis of 98,058 adults. Diabetes Care 38, 72–81 (2015).

    PubMed  Google Scholar 

  64. Zhou, Q. et al. Prevalence of diabetes and regional differences in chinese women planning pregnancy: a nationwide population-based cross-sectional study. Diabetes Care 40, e16–e18 (2017).

    PubMed  Google Scholar 

  65. Shi, Z., Taylor, A. W., Hu, G., Gill, T. & Wittert, G. A. Rice intake, weight change and risk of the metabolic syndrome development among Chinese adults: the Jiangsu Nutrition Study (JIN). Asia Pac. J. Clin. Nutr. 21, 35–43 (2012).

    CAS  PubMed  Google Scholar 

  66. Fransen, H. P. et al. Exposure to famine at a young age and unhealthy lifestyle behaviour later in life. PLOS ONE 11, e0156609 (2016).

    PubMed  PubMed Central  Google Scholar 

  67. Chen, C. M. Overview of obesity in Mainland China. Obes. Rev. 9 (Suppl. 1), 14–21 (2008).

    PubMed  Google Scholar 

  68. Chan, J. C. et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 301, 2129–2140 (2009).

    CAS  PubMed  Google Scholar 

  69. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363, 157–163 (2004).

    Google Scholar 

  70. Nanditha, A. et al. Diabetes in Asia and the Pacific: implications for the global epidemic. Diabetes Care 39, 472–485 (2016).

    CAS  PubMed  Google Scholar 

  71. Bragg, F. et al. Associations of general and central adiposity with incident diabetes in Chinese men and women. Diabetes Care 41, 494–502 (2018).

    PubMed  Google Scholar 

  72. Li, M. & Shi, Z. Dietary pattern during 1991–2011 and its association with cardio metabolic risks in Chinese adults: the China health and nutrition survey. Nutrients 9, 1218 (2017).

    PubMed Central  Google Scholar 

  73. Shi, Z. et al. Vegetable-rich food pattern is related to obesity in China. Int. J. Obes. 32, 975–984 (2008).

    CAS  Google Scholar 

  74. Villegas, R. et al. Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai Women’s Health Study. Am. J. Clin. Nutr. 87, 162–167 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Villegas, R. et al. Dietary calcium and magnesium intakes and the risk of type 2 diabetes: the Shanghai Women’s Health Study. Am. J. Clin. Nutr. 89, 1059–1067 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Villegas, R. et al. Dietary patterns are associated with lower incidence of type 2 diabetes in middle-aged women: the Shanghai Women’s Health Study. Int. J. Epidemiol. 39, 889–899 (2010).

    PubMed  PubMed Central  Google Scholar 

  77. Shi, Z. et al. Iron intake and body iron stores, anaemia and risk of hyperglycaemia among Chinese adults: the prospective Jiangsu Nutrition Study (JIN). Public Health Nutr. 13, 1319–1327 (2010).

    PubMed  Google Scholar 

  78. Shi, Z., Riley, M., Taylor, A. & Noakes, M. Meal-specific food patterns and the incidence of hyperglycemia in a Chinese adult population. Br. J. Nutr. 118, 53–59 (2017).

    CAS  PubMed  Google Scholar 

  79. Ng, S. W., Howard, A. G., Wang, H. J., Su, C. & Zhang, B. The physical activity transition among adults in China: 1991–2011. Obes. Rev. 15 (Suppl. 1), 27–36 (2014).

    PubMed  Google Scholar 

  80. Tian, Y. et al. BMI, leisure-time physical activity, and physical fitness in adults in China: results from a series of national surveys, 2000–2014. Lancet Diabetes Endocrinol. 4, 487–497 (2016).

    PubMed  Google Scholar 

  81. Pan, X. R. et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and diabetes Study. Diabetes Care 20, 537–544 (1997).

    CAS  PubMed  Google Scholar 

  82. Shi, Z. et al. Association of impaired fasting glucose, diabetes and dietary patterns with mortality: a 10-year follow-up cohort in Eastern China. Acta Diabetol. 53, 799–806 (2016).

    CAS  PubMed  Google Scholar 

  83. Tucker, P. & Gilliland, J. The effect of season and weather on physical activity: a systematic review. Public Health 121, 909–922 (2007).

    CAS  PubMed  Google Scholar 

  84. Diabetes Prevention Program Research, G. The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 25, 2165–2171 (2002).

    Google Scholar 

  85. American Diabetes, A. Diagnosis and classification of diabetes mellitus. Diabetes Care 33 (Suppl. 1), 62–69 (2010).

    Google Scholar 

  86. Tobi, E. W. et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum. Mol. Genet. 18, 4046–4053 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Paul Zimmet, Zumin Shi.

Authors and Affiliations

  1. Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia

    Paul Zimmet & Assam El-Osta

  2. Human Nutrition Department, Qatar University, Doha, Qatar

    Zumin Shi

  3. Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

    Assam El-Osta

  4. Peking University Diabetes Center, Director of Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

    Linong Ji

Authors
  1. Paul Zimmet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zumin Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Assam El-Osta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Linong Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.Z. and Z.S. contributed to all aspects of this manuscript. A.E.-O. and L.J. provided substantial contribution to discussion of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Paul Zimmet.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zimmet, P., Shi, Z., El-Osta, A. et al. Epidemic T2DM, early development and epigenetics: implications of the Chinese Famine. Nat Rev Endocrinol 14, 738–746 (2018). https://doi.org/10.1038/s41574-018-0106-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-018-0106-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing