vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-442Research ArticleГеронтологияGerontologyНЕПОЛНОЦЕННОЕ ПИТАНИЕ В РАННЕЙ ЖИЗНИ И РИСК РАЗВИТИЯ ДИАБЕТА 2-ГО ТИПА: ТЕОРЕТИЧЕСКИЙ БАЗИС И ЭПИДЕМИОЛОГИЧЕСКИЕ ДОКАЗАТЕЛЬСТВАMALNUTRITION IN EARLY LIFE AND RISK OF TYPE 2 DIABETES: THEORETICAL BASIS AND EPIDEMIOLOGICAL EVIDENCEЗабугаО. Г.ZabugaO. G.

Украина, 04114, г. Киев, ул. Вышгородская, д. 67

канд. биол. наук, мл. науч. сотр. лаборатории эпигенетики ГУ “Институт геронтологии им. Д.Ф. Чеботарева НАМН Украины”, Киев. Тел.: + 38 (044) 431-05-58

Vyshgorodskaya ul., 67, Kiev 04114, Ukraine

narelem12@gmail.comВайсерманА. М.VaisermanA. M.

Украина, 04114, г. Киев, ул. Вышгородская, д. 67

докт. мед. наук, зав. лабораторией эпигенетики ГУ “Институт геронтологии им. Д.Ф. Чеботарева НАМН Украины”, Киев. Тел.: + 38 (044) 431-05-58

Vyshgorodskaya ul., 67, Kiev 04114, Ukraine

vaiserman@geront.kiev.uaГУ “Институт геронтологии им. Д.Ф. Чеботарёва” НАМНУУкраинаD.F. Chebotarev State Institute of Gerontology NAMS of UkraineUkraine2017240420177224757Copyright © Забуга О.Г., Вайсерман А.М., 20172017Забуга О.Г., Вайсерман А.М.Zabuga O.G., Vaiserman A.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/442

Получены многочисленные экспериментальные и эпидемиологические доказательства того, что недостаточное питание во время раннего развития может влиять на риск развития метаболических патологий во взрослой жизни, включая сахарный диабет 2-го типа (СД2Т). Большая часть эпидемиологических доказательств подобной связи получена в квазиэкспериментальных исследованиях (“естественных экспериментах”), реализованных в популяциях разных стран мира. В этих исследованиях показано, что воздействие голода в течение пренатального и/или раннего постнатального развития связано с повышенным риском развития СД2Т во взрослой жизни. В качестве основного механизма, за счёт которого реализуется связь между воздействием голода в ранней жизни и повышенным риском СД2Т у взрослых людей, рассматривается эпигенетическая регуляция активности генов. Предполагается, что пренатальное воздействие голода может вызывать устойчивые эпигенетические изменения, которые имеют адаптивное значение на протяжении раннего постнатального развития, но предрасполагают к метаболическим нарушениям, включая СД2Т, в дальнейшей жизни. В представленном обзоре обобщены и обсуждены данные квазиэкспериментальных исследований, свидетельствующие о возможности раннего программирования риска СД2Т.

There is both animal and human evidence that inadequate nutrition during early development may affect risk for developing metabolic pathologies in adult life including type 2 diabetes (T2D). In populations of different countries, most findings indicating a causative relationship between undernutrition early in life and subsequent risk for T2D have been obtained from quasiexperimental investigations (“natural experiments”). Exposure to famine throughout prenatal and/or early postnatal development was shown to be associated with higher risk of T2D in many populations around the world. The epigenetic regulation of gene activity has been highlighted as a major mechanism linking early-life famine exposure and adult T2D. Prenatal exposure to the famine can induce persistent epigenetic alterations that have adaptive significance in early post-natal development but may predispose to metabolic dysfunctions including T2D in later life. In this review, findings from quasi-experimental studies on the developmental programming of T2D are summarized and discussed.

сахарный диабет 2-го типаголоднатуральные экспериментыквазиэкспериментальные исследованияэпигенетикаобзорtype 2 diabetesfaminenatural experimentquasi-experimental designepigeneticsreviewReferencesWilmot E., Idris I. Early onset type 2 diabetes: risk factors, clinical impact and management // Ther. Adv. Chronic. Dis. 2014. Vol. 5. N 6. P. 234–244.Wilmot E., Idris I. Early onset type 2 diabetes: risk factors, clinical impact and management // Ther. Adv. Chronic. Dis. 2014. Vol. 5. N 6. P. 234–244.Jaacks L.M., Siegel K.R., Gujral U.P., Narayan K.M. Type 2 diabetes: A 21st century epidemic // Best Pract. Res. Clin. Endocrinol. Metab. 2016. Vol. 30. N 3. P. 331–343.Jaacks L.M., Siegel K.R., Gujral U.P., Narayan K.M. Type 2 diabetes: A 21st century epidemic // Best Pract. Res. Clin. Endocrinol. Metab. 2016. Vol. 30. N 3. P. 331–343.Nielsen J.H., Haase T.N., Jaksch C., et al. Impact of fetal and neonatal environment on beta cell function and development of diabetes // Acta Obstet. Gynecol. Scand. 2014. Vol. 93. N 11. P. 1109–1122.Nielsen J.H., Haase T.N., Jaksch C., et al. Impact of fetal and neonatal environment on beta cell function and development of diabetes // Acta Obstet. Gynecol. Scand. 2014. Vol. 93. N 11. P. 1109–1122.Dabelea D., Hanson R.L., Lindsay R.S., Pettitt D.J., Imperatore G., Gabir M.M., Roumain J., Bennett P.H., Knowler W.C. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships // Diabetes. 2000. Vol. 49. N 12. P. 2208–2211.Dabelea D., Hanson R.L., Lindsay R.S., Pettitt D.J., Imperatore G., Gabir M.M., Roumain J., Bennett P.H., Knowler W.C. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships // Diabetes. 2000. Vol. 49. N 12. P. 2208–2211.Eriksson J.G. Developmental origins of health and disease – from a small body size at birth to epigenetics // Ann. Med. 2016. Vol. 48. N 6. P. 456–467.Eriksson J.G. Developmental origins of health and disease – from a small body size at birth to epigenetics // Ann. Med. 2016. Vol. 48. N 6. P. 456–467.Kim J.B. Dynamic cross talk between metabolic organs in obesity and metabolic diseases // Exp. Mol. Med. 2016. Vol. 48. N 3. e214.Kim J.B. Dynamic cross talk between metabolic organs in obesity and metabolic diseases // Exp. Mol. Med. 2016. Vol. 48. N 3. e214.Nettle D., Bateson M. Adaptive developmental plasticity: what is it, how can we recognize it and when can it evolve? // Proc. Biol. Sci. 2015. Vol. 282. N 1812. Article ID 20151005.Nettle D., Bateson M. Adaptive developmental plasticity: what is it, how can we recognize it and when can it evolve? // Proc. Biol. Sci. 2015. Vol. 282. N 1812. Article ID 20151005.Hales C.N., Barker D.J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. 1992 // Int. J. Epidemiol. 2013. Vol. 42. N 5. P. 1215–1222.Hales C.N., Barker D.J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. 1992 // Int. J. Epidemiol. 2013. Vol. 42. N 5. P. 1215–1222.Thorn S.R., Rozance P.J., Brown L.D., Hay W.W. Jr. The intrauterine growth restriction phenotype: fetal adaptations and potential implications for later life insulin resistance and diabetes // Semin. Reprod. Med. 2011. Vol. 29. N 3. P. 225–236.Thorn S.R., Rozance P.J., Brown L.D., Hay W.W. Jr. The intrauterine growth restriction phenotype: fetal adaptations and potential implications for later life insulin resistance and diabetes // Semin. Reprod. Med. 2011. Vol. 29. N 3. P. 225–236.Carolan-Olah M., Duarte-Gardea M., Lechuga J. A critical review: early life nutrition and prenatal programming for adult disease // J. Clin. Nurs. 2015. Vol. 24. N 23–24. P. 3716–3729.Carolan-Olah M., Duarte-Gardea M., Lechuga J. A critical review: early life nutrition and prenatal programming for adult disease // J. Clin. Nurs. 2015. Vol. 24. N 23–24. P. 3716–3729.Tarry-Adkins J.L., Ozanne S.E. Nutrition in early life and age-associated diseases // Ageing Res. Rev. 2016. pii: S1568-1637(16)30179-9.Tarry-Adkins J.L., Ozanne S.E. Nutrition in early life and age-associated diseases // Ageing Res. Rev. 2016. pii: S1568-1637(16)30179-9.Whincup P.H., Kaye S.J., Owen C.G., et al. Birth weight and risk of type 2 diabetes: a systematic review // J. Am. Med. Assoc. 2008. Vol. 300. N 24. P. 2886–2897.Whincup P.H., Kaye S.J., Owen C.G., et al. Birth weight and risk of type 2 diabetes: a systematic review // J. Am. Med. Assoc. 2008. Vol. 300. N 24. P. 2886–2897.Kensara O.A., Wootton S.A., Phillips D.I., Patel M., Jackson A.A., Elia M. Hertfordshire Study Group. Fetal programming of body composition: Relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older Englishmen // Am. J. Clin. Nutr. 2005. Vol. 82. N 5. P. 980–987.Kensara O.A., Wootton S.A., Phillips D.I., Patel M., Jackson A.A., Elia M. Hertfordshire Study Group. Fetal programming of body composition: Relation between birth weight and body composition measured with dual-energy X-ray absorptiometry and anthropometric methods in older Englishmen // Am. J. Clin. Nutr. 2005. Vol. 82. N 5. P. 980–987.Morrison K.M., Ramsingh L., Gunn E., Streiner D., Van Lieshout R., Boyle M., Gerstein H., Schmidt L., Saigal S. Cardiometabolic health in adults born premature with extremely low birth weight // Pediatrics. 2016. Vol. 138. N 4. e20160515.Morrison K.M., Ramsingh L., Gunn E., Streiner D., Van Lieshout R., Boyle M., Gerstein H., Schmidt L., Saigal S. Cardiometabolic health in adults born premature with extremely low birth weight // Pediatrics. 2016. Vol. 138. N 4. e20160515.Stirrat L.I., Reynolds R.M. The effect of fetal growth and nutrient stresses on steroid pathways // J. Steroid. Biochem. Mol. Biol. 2016. Vol. 160. P. 214–220.Stirrat L.I., Reynolds R.M. The effect of fetal growth and nutrient stresses on steroid pathways // J. Steroid. Biochem. Mol. Biol. 2016. Vol. 160. P. 214–220.Frankel S., Elwood P., Sweetnam P., Yarnell J., Smith G.D. Birthweight, body-mass index in middle age, and incident coronary heart disease // Lancet. 1996. Vol. 348. N 9040. P. 1478–1480.Frankel S., Elwood P., Sweetnam P., Yarnell J., Smith G.D. Birthweight, body-mass index in middle age, and incident coronary heart disease // Lancet. 1996. Vol. 348. N 9040. P. 1478–1480.Harder T., Rodekamp E., Schellong K., Dudenhau -sen J.W., Plagemann A. Birth weight and subsequent risk of type 2 diabetes:a meta-analysis // Am. J. Epidemiol. 2007. Vol. 165. N 8. P. 849–857.Harder T., Rodekamp E., Schellong K., Dudenhau -sen J.W., Plagemann A. Birth weight and subsequent risk of type 2 diabetes:a meta-analysis // Am. J. Epidemiol. 2007. Vol. 165. N 8. P. 849–857.Dulloo A.G. Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance // Best Pract. Res. Clin. Endocrinol. Metab. 2008. Vol. 22. N 1. P. 155–171.Dulloo A.G. Thrifty energy metabolism in catch-up growth trajectories to insulin and leptin resistance // Best Pract. Res. Clin. Endocrinol. Metab. 2008. Vol. 22. N 1. P. 155–171.Cho W.K., Suh B.K. Catch-up growth and catch-up fat in children born small for gestational age // Korean J. Pediatr. 2016. Vol. 59. N 1. P. 1–7.Cho W.K., Suh B.K. Catch-up growth and catch-up fat in children born small for gestational age // Korean J. Pediatr. 2016. Vol. 59. N 1. P. 1–7.Ong T.P., Ozanne S.E. Developmental programming of type 2 diabetes: early nutrition and epigenetic mechanisms // Curr. Opin. Clin. Nutr. Metab. Care. 2015. Vol. 18. N 4. P. 354– 360.Ong T.P., Ozanne S.E. Developmental programming of type 2 diabetes: early nutrition and epigenetic mechanisms // Curr. Opin. Clin. Nutr. Metab. Care. 2015. Vol. 18. N 4. P. 354– 360.Paluch B.E., Naqash A.R., Brumberger Z., Nemeth M.J., Griffiths E.A. Epigenetics: A primer for clinicians // Blood Rev. 2016. Vol. 30. N 4. P. 285–295.Paluch B.E., Naqash A.R., Brumberger Z., Nemeth M.J., Griffiths E.A. Epigenetics: A primer for clinicians // Blood Rev. 2016. Vol. 30. N 4. P. 285–295.van Dijk S.J., Tellam R.L., Morrison J.L., Muhlhausler B.S., Molloy P.L. Recent developments on the role of epigenetics in obesity and metabolic disease // Clin. Epigenetics. 2015. Vol. 7. P. 66.van Dijk S.J., Tellam R.L., Morrison J.L., Muhlhausler B.S., Molloy P.L. Recent developments on the role of epigenetics in obesity and metabolic disease // Clin. Epigenetics. 2015. Vol. 7. P. 66.Vaiserman A. Epidemiologic evidence for association between adverse environmental exposures in early life and epigenetic variation: a potential link to disease susceptibility? // Clin. Epigenetics. 2015. Vol. 7. P. 96.Vaiserman A. Epidemiologic evidence for association between adverse environmental exposures in early life and epigenetic variation: a potential link to disease susceptibility? // Clin. Epigenetics. 2015. Vol. 7. P. 96.Geraghty A.A., Lindsay K.L., Alberdi G., McAuliffe F.M., Gibney E.R. Nutrition during pregnancy impacts offspring’s epigenetic status – evidence from human and animal studies // Nutr. Metab. Insights. 2016. Vol. 8. N 1. P. 41–47.Geraghty A.A., Lindsay K.L., Alberdi G., McAuliffe F.M., Gibney E.R. Nutrition during pregnancy impacts offspring’s epigenetic status – evidence from human and animal studies // Nutr. Metab. Insights. 2016. Vol. 8. N 1. P. 41–47.Alam F., Islam M.A., Gan S.H., Mohamed M., Sasongko T.H. DNA methylation: an epigenetic insight into type 2 diabetes mellitus // Curr. Pharm. Des. 2016. Vol. 22. N 28. P. 4398–4419.Alam F., Islam M.A., Gan S.H., Mohamed M., Sasongko T.H. DNA methylation: an epigenetic insight into type 2 diabetes mellitus // Curr. Pharm. Des. 2016. Vol. 22. N 28. P. 4398–4419.Kwak S.H., Park K.S. Recent progress in genetic and epigenetic research on type 2 diabetes // Exp. Mol. Med. 2016. Vol. 48. N 3. e220.Kwak S.H., Park K.S. Recent progress in genetic and epigenetic research on type 2 diabetes // Exp. Mol. Med. 2016. Vol. 48. N 3. e220.Porta M., ed. A dictionary of epidemiology (5th Edition). NY: Oxford Univ. Press, 2008. 320 p.Porta M., ed. A dictionary of epidemiology (5th Edition). NY: Oxford Univ. Press, 2008. 320 p.Heijmans B.T., Tobi E.W., Lumey L.H., Slagboom P.E. The epigenome: archive of the prenatal environment // Epigenetics. 2009. Vol. 4. N 8. P. 526–531.Heijmans B.T., Tobi E.W., Lumey L.H., Slagboom P.E. The epigenome: archive of the prenatal environment // Epigenetics. 2009. Vol. 4. N 8. P. 526–531.Lumey L.H., Stein A.D., Susser E. Prenatal famine and adult health // Annu. Rev. Public Health. 2011. Vol. 32. P. 237–262.Lumey L.H., Stein A.D., Susser E. Prenatal famine and adult health // Annu. Rev. Public Health. 2011. Vol. 32. P. 237–262.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. 2011. Vol. 70. N 2. P. 141–145.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. 2011. Vol. 70. N 2. P. 141–145.Heijmans B.T., Tobi E.W., Stein A.D., Putter H., Blauw G.J., Susser E.S., Slagboom, P.E., Lumey L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans // Proc. Natl Acad. Sci. U. S. A. 2008. Vol. 105. N 44. P. 17046–17049.Heijmans B.T., Tobi E.W., Stein A.D., Putter H., Blauw G.J., Susser E.S., Slagboom, P.E., Lumey L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans // Proc. Natl Acad. Sci. U. S. A. 2008. Vol. 105. N 44. P. 17046–17049.van Abeelen A.F., Elias S.G., Bossuyt P.M., Grobbee D.E., van der Schouw Y.T., Roseboom T.J., Uiterwaal C.S. Famine exposure in the young and the risk of type 2 diabetes in adulthood // Diabetes. 2012. Vol. 61. N 9. P. 2255–2260.van Abeelen A.F., Elias S.G., Bossuyt P.M., Grobbee D.E., van der Schouw Y.T., Roseboom T.J., Uiterwaal C.S. Famine exposure in the young and the risk of type 2 diabetes in adulthood // Diabetes. 2012. Vol. 61. N 9. P. 2255–2260.Portrait F., Teeuwiszen E., Deeg D. Early life undernutrition and chronic diseases at older ages: the effects of the Dutch famine on cardiovascular diseases and diabetes // Soc. Sci. Med. 2011. Vol. 73. N 5. P. 711–718.Portrait F., Teeuwiszen E., Deeg D. Early life undernutrition and chronic diseases at older ages: the effects of the Dutch famine on cardiovascular diseases and diabetes // Soc. Sci. Med. 2011. Vol. 73. N 5. P. 711–718.Lumey L.H., Terry M.B., Delgado-Cruzata L., Liao Y., Wang Q., Susser E., McKeague I., Santella R.M. Adult global DNA methylation in relation to pre-natal nutrition // Int. J. Epidemiol. 2012. Vol. 41. N 1. P. 116–123.Lumey L.H., Terry M.B., Delgado-Cruzata L., Liao Y., Wang Q., Susser E., McKeague I., Santella R.M. Adult global DNA methylation in relation to pre-natal nutrition // Int. J. Epidemiol. 2012. Vol. 41. N 1. P. 116–123.Tobi E.W., Lumey L.H., Talens R.P., Kremer D., Putter H., Stein A.D., Slagboom P.E., Heijmans B.T. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific // Hum. Mol. Genet. 2009. Vol. 18. N 21. P. 4046–4053.Tobi E.W., Lumey L.H., Talens R.P., Kremer D., Putter H., Stein A.D., Slagboom P.E., Heijmans B.T. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific // Hum. Mol. Genet. 2009. Vol. 18. N 21. P. 4046–4053.Thurner S., Klimek P., Szell M., Duftschmid G., Endel G., Kautzky-Willer A., Kasper D.C. Quantification of excess risk for diabetes for those born in times of hunger, in an entire population of a nation, across a century // Proc. Natl. Acad. Sci. U.S.A. 2013. Vol. 110. N 12. P. 4703–4707.Thurner S., Klimek P., Szell M., Duftschmid G., Endel G., Kautzky-Willer A., Kasper D.C. Quantification of excess risk for diabetes for those born in times of hunger, in an entire population of a nation, across a century // Proc. Natl. Acad. Sci. U.S.A. 2013. Vol. 110. N 12. P. 4703–4707.Klitz W., Niklasson B. Viral underpinning to the Austrian record of type 2 diabetes? // Proc. Natl. Acad. Sci. U.S.A. 2013. Vol. 110. N 30. P. E2750–E2750.Klitz W., Niklasson B. Viral underpinning to the Austrian record of type 2 diabetes? // Proc. Natl. Acad. Sci. U.S.A. 2013. Vol. 110. N 30. P. E2750–E2750.Thurner S., Klimek P., Szell M., Duftschmid G., Endel G., Kautzky-Willer A., Kasper D.C. Reply to Klitz and Niklasson: Can viral infections explain the cross-sectional Austrian diabetes data? // Proc. Natl. Acad. Sci. U.S.A. 2013. Vol. 110. N 30. E2751.Thurner S., Klimek P., Szell M., Duftschmid G., Endel G., Kautzky-Willer A., Kasper D.C. Reply to Klitz and Niklasson: Can viral infections explain the cross-sectional Austrian diabetes data? // Proc. Natl. Acad. Sci. U.S.A. 2013. Vol. 110. N 30. E2751.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. 2015. Vol. 3. N 10. P. 787–794.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. 2015. Vol. 3. N 10. P. 787–794.Sparén P., Vågerö D., Shestov D.B., Plavinskaja S., Parfenova N., Hoptiar V., Paturot D., Galanti M.R. Long term mortality after severe starvation during the siege of Leningrad: prospective cohort study // Brit. Med. J. 2004. Vol. 328. N 7430. P. 11.Sparén P., Vågerö D., Shestov D.B., Plavinskaja S., Parfenova N., Hoptiar V., Paturot D., Galanti M.R. Long term mortality after severe starvation during the siege of Leningrad: prospective cohort study // Brit. Med. J. 2004. Vol. 328. N 7430. P. 11.Stanner S.A., Bulmer K., Andrès C., Lantseva O.E., Borodina V., Poteen V.V., Yudkin J.S. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study // Brit. Med. J. 1997. Vol. 315. N 7119. P. 1342–1348.Stanner S.A., Bulmer K., Andrès C., Lantseva O.E., Borodina V., Poteen V.V., Yudkin J.S. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study // Brit. Med. J. 1997. Vol. 315. N 7119. P. 1342–1348.Stanner S.A., Yudkin J.S. Fetal programming and the Leningrad Siege study // Twin Res. 2001. Vol. 4. N 5. P. 287–292.Stanner S.A., Yudkin J.S. Fetal programming and the Leningrad Siege study // Twin Res. 2001. Vol. 4. N 5. P. 287–292.Bateson P. Fetal experience and good adult design // Int. J. Epidemiol. 2001. Vol. 30. N 5. P. 928–934.Bateson P. Fetal experience and good adult design // Int. J. Epidemiol. 2001. Vol. 30. N 5. P. 928–934.Khoroshinina L.P., Zhavoronkova N.V. Starving in childhood and diabetes mellitus in elderly age // Adv. Gerontol. 2008. Vol. 21. N 4. P. 684–687.Khoroshinina L.P., Zhavoronkova N.V. Starving in childhood and diabetes mellitus in elderly age // Adv. Gerontol. 2008. Vol. 21. N 4. P. 684–687.Khoroshinina L.P. Peculiarities of somatic diseases in people of middle and old age survived Leningrad siege at childhood // Adv. Gerontol. 2004. Vol. 14. P. 55–65.Khoroshinina L.P. Peculiarities of somatic diseases in people of middle and old age survived Leningrad siege at childhood // Adv. Gerontol. 2004. Vol. 14. P. 55–65.Koupil I., Shestov D.B., Sparén P., Plavinskaja S., Parfenova N., Vågerö D. Blood pressure, hypertension and mortality from circulatory disease in men and women who survived the siege of Leningrad // Eur. J. Epidemiol. 2007. Vol. 22. N 4. P. 223–234.Koupil I., Shestov D.B., Sparén P., Plavinskaja S., Parfenova N., Vågerö D. Blood pressure, hypertension and mortality from circulatory disease in men and women who survived the siege of Leningrad // Eur. J. Epidemiol. 2007. Vol. 22. N 4. P. 223–234.Jowett A.J. The demographic responses to famine: the case of China 1958-61 // GeoJournal. 1991. Vol. 23. N 2. P. 135–146.Jowett A.J. The demographic responses to famine: the case of China 1958-61 // GeoJournal. 1991. Vol. 23. N 2. P. 135–146.Li C., Lumey L.H. Exposure to the Chinese famine of 1959-61 in early life and current health conditions: a systematic review and meta-analysis // Lancet. 2016. Vol. 388. N 1. P. S63.Li C., Lumey L.H. Exposure to the Chinese famine of 1959-61 in early life and current health conditions: a systematic review and meta-analysis // Lancet. 2016. Vol. 388. N 1. P. S63.Li Y., He Y., Qi L., Jaddoe V.W., Feskens E.J., Yang X., Ma G., Hu F.B. Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood // Diabetes. 2010. Vol. 59. N 10. P. 2400–2406.Li Y., He Y., Qi L., Jaddoe V.W., Feskens E.J., Yang X., Ma G., Hu F.B. Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood // Diabetes. 2010. Vol. 59. N 10. P. 2400–2406.Wang N., Wang X., Han B., Li Q., Chen Y., Zhu C., Chen Y., Xia F., Cang Z., Zhu C., et al. Is exposure to famine in childhood and economic development in adulthood associated with diabetes? // J. Clin. Endocrinol. Metab. 2015. Vol. 100. N 12. P. 4514–4523.Wang N., Wang X., Han B., Li Q., Chen Y., Zhu C., Chen Y., Xia F., Cang Z., Zhu C., et al. Is exposure to famine in childhood and economic development in adulthood associated with diabetes? // J. Clin. Endocrinol. Metab. 2015. Vol. 100. N 12. P. 4514–4523.Wang N., Cheng J., Han B., Li Q., Chen Y., Xia F., Jiang B., Jensen M.D., Lu Y. Exposure to severe famine in the prenatal or postnatal period and the development of diabetes in adulthood: an observational study // Diabetologia. 2017. Vol. 60. N 2. P. 262–269.Wang N., Cheng J., Han B., Li Q., Chen Y., Xia F., Jiang B., Jensen M.D., Lu Y. Exposure to severe famine in the prenatal or postnatal period and the development of diabetes in adulthood: an observational study // Diabetologia. 2017. Vol. 60. N 2. P. 262–269.Wang J., Li Y., Han X., et al. Exposure to the Chinese Famine in childhood increases type 2 diabetes risk in adults // J. Nutr. 2016. Vol. 146. N 11. P. 2289–2295.Wang J., Li Y., Han X., et al. Exposure to the Chinese Famine in childhood increases type 2 diabetes risk in adults // J. Nutr. 2016. Vol. 146. N 11. P. 2289–2295.Li J., Liu S., Li S., et al. Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a populationbased cohort study of families in Suihua, China // Am. J. Clin. Nutr. 2017. Vol. 105. N 1. P. 221–227.Li J., Liu S., Li S., et al. Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a populationbased cohort study of families in Suihua, China // Am. J. Clin. Nutr. 2017. Vol. 105. N 1. P. 221–227.Miller J.P. Medical relief in the Nigerian civil war // Lancet. 1970. Vol. 760. N 1. P. 1330–1334.Miller J.P. Medical relief in the Nigerian civil war // Lancet. 1970. Vol. 760. N 1. P. 1330–1334.Hult M., Tornhammar P., Ueda P., Chima C., Bonamy A.K., Ozumba B., Norman M. Hypertension, diabetes and overweight: looming legacies of the Biafran famine // PLoS One. 2010. Vol. 5. N 10. e13582.Hult M., Tornhammar P., Ueda P., Chima C., Bonamy A.K., Ozumba B., Norman M. Hypertension, diabetes and overweight: looming legacies of the Biafran famine // PLoS One. 2010. Vol. 5. N 10. e13582.Bercovich E., Keinan-Boker L., Shasha S.M. Longterm health effects in adults born during the Holocaust // Isr. Med. Assoc. J. 2014. Vol. 16. N 4. P. 203–207.Bercovich E., Keinan-Boker L., Shasha S.M. Longterm health effects in adults born during the Holocaust // Isr. Med. Assoc. J. 2014. Vol. 16. N 4. P. 203–207.Keinan-Boker L., Shasha-Lavsky H., Eilat-Zanani S., Edri-Shur A., Shasha S.M. Chronic health conditions in Jewish Holocaust survivors born during World War II // Isr. Med. Assoc. J. 2015. Vol. 17. N 4. P. 206–212.Keinan-Boker L., Shasha-Lavsky H., Eilat-Zanani S., Edri-Shur A., Shasha S.M. Chronic health conditions in Jewish Holocaust survivors born during World War II // Isr. Med. Assoc. J. 2015. Vol. 17. N 4. P. 206–212.Watson P.E., McDonald B.W. Seasonal variation of nutrient intake in pregnancy: effects on infant measures and possible influence on diseases related to season of birth // Eur. J. Clin Nutr. 2007. Vol. 61. N 11. P. 1271–1280.Watson P.E., McDonald B.W. Seasonal variation of nutrient intake in pregnancy: effects on infant measures and possible influence on diseases related to season of birth // Eur. J. Clin Nutr. 2007. Vol. 61. N 11. P. 1271–1280.Flouris A.D., Spiropoulos Y., Sakellariou G.J., Koutedakis Y. Effect of seasonal programming on fetal development and longevity: links with environmental temperature // Am. J. Hum. Biol. 2009. Vol. 21. N 2. P. 214–216.Flouris A.D., Spiropoulos Y., Sakellariou G.J., Koutedakis Y. Effect of seasonal programming on fetal development and longevity: links with environmental temperature // Am. J. Hum. Biol. 2009. Vol. 21. N 2. P. 214–216.Finch C.E., Crimmins E.M. Inflammatory exposure and historical changes in human life- spans // Science. 2004. Vol. 305. N 5691. P. 1736–1739.Finch C.E., Crimmins E.M. Inflammatory exposure and historical changes in human life- spans // Science. 2004. Vol. 305. N 5691. P. 1736–1739.Lowell W.E., Davis G.E. Jr. The light of life: evidence that the sun modulates human lifespan // Med. Hypotheses. 2008. Vol. 70. N 3. P. 501–507.Lowell W.E., Davis G.E. Jr. The light of life: evidence that the sun modulates human lifespan // Med. Hypotheses. 2008. Vol. 70. N 3. P. 501–507.Smith A.D., Crippa A., Woodcoc, J., Brage S. Physical activity and incident type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of prospective cohort studies // Diabetologia. 2016. Vol. 59. N 12. P. 2527–2545.Smith A.D., Crippa A., Woodcoc, J., Brage S. Physical activity and incident type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of prospective cohort studies // Diabetologia. 2016. Vol. 59. N 12. P. 2527–2545.Vaiserman A.M. Early-life exposure to substance abuse and risk of type 2 diabetes in adulthood // Curr. Diab. Rep. 2015. Vol. 15. N 8. Article 48.Vaiserman A.M. Early-life exposure to substance abuse and risk of type 2 diabetes in adulthood // Curr. Diab. Rep. 2015. Vol. 15. N 8. Article 48.Chodick G., Flash S., Deoitch Y., Shalev V. Seasonality in birth weight: review of global patterns and potential causes // Hum. Biol. 2009. Vol. 81. N 4. P. 463–477.Chodick G., Flash S., Deoitch Y., Shalev V. Seasonality in birth weight: review of global patterns and potential causes // Hum. Biol. 2009. Vol. 81. N 4. P. 463–477.Banegas J.R., Rodríguez-Artalejo F., de la Cruz J.J., Graciani A., Villar F., del Rey-Calero J. Adult men born in spring have lower blood pressure // J. Hypertens. 2000. Vol. 18. N 12. P. 1763–1766.Banegas J.R., Rodríguez-Artalejo F., de la Cruz J.J., Graciani A., Villar F., del Rey-Calero J. Adult men born in spring have lower blood pressure // J. Hypertens. 2000. Vol. 18. N 12. P. 1763–1766.Phillips D.I., Young J.B. Birth weight, climate at birth and the risk of obesity in adult life // Int. J. Obes. Relat. Metab. Disord. 2000. Vol. 24. N 3. P. 281–287.Phillips D.I., Young J.B. Birth weight, climate at birth and the risk of obesity in adult life // Int. J. Obes. Relat. Metab. Disord. 2000. Vol. 24. N 3. P. 281–287.Wattie N., Ardern C.I., Baker J. Season of birth and prevalence of overweight and obesity in Canada // Early Hum. Dev. 2008. Vol. 84. N 8. P. 539–547.Wattie N., Ardern C.I., Baker J. Season of birth and prevalence of overweight and obesity in Canada // Early Hum. Dev. 2008. Vol. 84. N 8. P. 539–547.Lawlor D.A., Davey-Smith G., Mitchell R., Ebrahim S. Temperature at birth, coronary heart disease, and insulin resistance: cross sectional analyses of the British women’s heart and health study // Heart. 2004. Vol. 90. N 4. P. 381–388.Lawlor D.A., Davey-Smith G., Mitchell R., Ebrahim S. Temperature at birth, coronary heart disease, and insulin resistance: cross sectional analyses of the British women’s heart and health study // Heart. 2004. Vol. 90. N 4. P. 381–388.Laron Z., Lewy H., Wilderman I., Casu A., Willis J., Redondo M.J., Libman I., White N., Craig M. Seasonality of month of birth of children and adolescents with type 1 diabetes mellitus in homogenous and heterogeneous populations // Isr. Med. Assoc. J. 2005. Vol. 7. N 6. P. 381–384.Laron Z., Lewy H., Wilderman I., Casu A., Willis J., Redondo M.J., Libman I., White N., Craig M. Seasonality of month of birth of children and adolescents with type 1 diabetes mellitus in homogenous and heterogeneous populations // Isr. Med. Assoc. J. 2005. Vol. 7. N 6. P. 381–384.Grover V., Lipton R.B., Sclove S.L. Seasonality of month of birth among African American children with diabetes mellitus in the City of Chicago // J. Pediatr. Endocrinol. Metab. 2004. Vol. 17. N 3. P. 289–296.Grover V., Lipton R.B., Sclove S.L. Seasonality of month of birth among African American children with diabetes mellitus in the City of Chicago // J. Pediatr. Endocrinol. Metab. 2004. Vol. 17. N 3. P. 289–296.Jongbloet P.H., van Soestbergen M., van der Veen E.A. Month-of-birth distribution of diabetics and ovopathy: a new aetiological view // Diabetes Res. 1988. Vol. 9. N 2. P. 51–58.Jongbloet P.H., van Soestbergen M., van der Veen E.A. Month-of-birth distribution of diabetics and ovopathy: a new aetiological view // Diabetes Res. 1988. Vol. 9. N 2. P. 51–58.Vaiserman A.M., Khalangot M.D., Carstensen B., Tronko M.D., Kravchenko V.I., Voitenko V.P., Mechova L.V., Koshel N.M., Grigoriev P.E. Seasonality of birth in adult type 2 diabetic patients in three Ukrainian regions // Diabetologia. 2009. Vol. 52. N 12. P. 2665–2667.Vaiserman A.M., Khalangot M.D., Carstensen B., Tronko M.D., Kravchenko V.I., Voitenko V.P., Mechova L.V., Koshel N.M., Grigoriev P.E. Seasonality of birth in adult type 2 diabetic patients in three Ukrainian regions // Diabetologia. 2009. Vol. 52. N 12. P. 2665–2667.Vaiserman A.M., Khalangot M.D. Similar seasonality of birth in type 1 and type 2 diabetes patients: A sign for common etiology? // Med. Hypotheses. 2008. Vol. 71. N 4. P. 604–605.Vaiserman A.M., Khalangot M.D. Similar seasonality of birth in type 1 and type 2 diabetes patients: A sign for common etiology? // Med. Hypotheses. 2008. Vol. 71. N 4. P. 604–605.Jensen C.B., Zimmermann E., Gamborg M., Heitmann B.L., Baker J.L., Vaag A., S rensen T.I. No evidence of seasonality of birth in adult type 2 diabetes in Denmark // Diabetologia. 2015. Vol. 58. N 9. P. 2045–2050.Jensen C.B., Zimmermann E., Gamborg M., Heitmann B.L., Baker J.L., Vaag A., S rensen T.I. No evidence of seasonality of birth in adult type 2 diabetes in Denmark // Diabetologia. 2015. Vol. 58. N 9. P. 2045–2050.Lockett G.A., Soto-Ram rez N., Ray M.A., Everson T.M., Xu C.J., Patil V.K., Terry, W., Kaushal A., Rezwan F.I., Ewart S.L., et al. Association of season of birth with DNA methylation and allergic disease // Allergy. 2016. Vol. 71. N 9. P. 1314–1324.Lockett G.A., Soto-Ram rez N., Ray M.A., Everson T.M., Xu C.J., Patil V.K., Terry, W., Kaushal A., Rezwan F.I., Ewart S.L., et al. Association of season of birth with DNA methylation and allergic disease // Allergy. 2016. Vol. 71. N 9. P. 1314–1324.Dugué P.A., Geurts Y.M., Milne R.L., Lockett G.A., Zhang H., Karmaus W., Holloway J.W. Is there an association between season of birth and blood DNA methylation in adulthood? // Allergy. 2016. Vol. 71. N 10. P. 1501–1504.Dugué P.A., Geurts Y.M., Milne R.L., Lockett G.A., Zhang H., Karmaus W., Holloway J.W. Is there an association between season of birth and blood DNA methylation in adulthood? // Allergy. 2016. Vol. 71. N 10. P. 1501–1504.Desiderio A., Spinelli R., Ciccarelli M., Nigro C., Miele C., Beguinot F., Raciti G.A. Epigenetics: spotlight on type 2 diabetes and obesity // J. Endocrinol. Invest. 2016. Vol. 39. N 10. P. 1095–1103.Desiderio A., Spinelli R., Ciccarelli M., Nigro C., Miele C., Beguinot F., Raciti G.A. Epigenetics: spotlight on type 2 diabetes and obesity // J. Endocrinol. Invest. 2016. Vol. 39. N 10. P. 1095–1103.Sterns J.D., Smith C.B., Steele J.R., Stevenson K.L., Gallicano G.I. Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition // Front. Cell Dev. Biol. 2014. Vol. 2. P. 15.Sterns J.D., Smith C.B., Steele J.R., Stevenson K.L., Gallicano G.I. Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition // Front. Cell Dev. Biol. 2014. Vol. 2. P. 15.Gillman M.W. Prenatal famine and developmental origins of type 2 diabetes // Lancet Diabetes Endocrinol. 2015. Vol. 3. N 10. P. 751–752.Gillman M.W. Prenatal famine and developmental origins of type 2 diabetes // Lancet Diabetes Endocrinol. 2015. Vol. 3. N 10. P. 751–752.Vaiserman A.M., Pasyukova E.G. Epigenetic drugs: a novel anti-aging strategy? // Front. Genet. 2012. Vol. 3. P. 224.Vaiserman A.M., Pasyukova E.G. Epigenetic drugs: a novel anti-aging strategy? // Front. Genet. 2012. Vol. 3. P. 224.

The authors declare that there are no conflicts of interest present.