The Impact of Malnutrition in Early Life on the Risk of Development of Type 2 Diabetes Mellitus

Year 2021, , 368 - 374, 30.12.2021

Ülger Kaçar Mutlutürk , Zeynep Caferoğlu , Nihal Hatipoğlu

https://doi.org/10.25048/tudod.929258

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that has a complex interaction of genetic, epigenetic and environmental
factors. Type 2 diabetes mellitus has significant effects on global health and economic burden, moreover the increase of its worldwide
incidence suggests that this disease may be affected not only by genetic or adult environmental conditions, but also by adverse conditions
in early life. In recent years, evidence from both animal experiments and natural experiments such as famine show that insufficient
nutrient intake in early life has been associated with the risk of T2DM in adult life. There is evidence that growth restriction caused
by intrauterine inadequate nutrient intake may impair fetal development, thus causing fetal adipose tissue and pancreatic beta cell
dysfunction. As a result, continuous adaptive changes, including reduced capacity for insulin secretion and insulin resistance; may
occur. These changes can lead to an improved ability to store fat, so the individual may be prone to the development of T2DM in later
life. In this regard, epigenetic mechanisms such as DNA methylation, histone modification and microRNA interactions play a key role.
In this review, basic mechanisms and research findings showing the role of developmental epigenetic variation in T2DM pathogenesis
are summarized.

Keywords

Type 2 diabetes mellitus, Malnutrition, Famine, Epigenetic

Erken Yaşamda Yetersiz Beslenmenin Tip 2 Diyabetes Mellitus Gelişim Riskine Etkisi

Abstract

Tip 2 diyabetes mellitus (T2DM) genetik, epigenetik ve çevresel faktörlerin karmaşık bir etkileşimi olan çok faktörlü bir hastalıktır. Tip 2
diyabetes mellitusun küresel sağlık ve ekonomik yük üzerinde önemli etkileri vardır. Biriken kanıtlar doğrultusunda bu hastalığın dünya
genelinde insidansındaki artışı sadece genetik veya yetişkin çevresel koşullardan değil aynı zamanda yaşamın erken dönemlerindeki
olumsuz durumlardan etkilenebileceğini düşündürmektedir. Son yıllarda, hem hayvan deneyleri hem de kıtlık gibi doğal durumlardan
elde edilen kanıtlar, erken yaşamda yetersiz besin alımını, yetişkin yaşamındaki T2DM riski ile ilişkilendirmiştir. İntrauterin yetersiz
besin alımı ile ortaya çıkan büyüme kısıtlamasının, fetal gelişimi bozabileceği ve böylece fetal yağ dokusu ve pankreatik beta hücre
disfonksiyonuna neden olabileceğine dair kanıtlar vardır. Bunun sonucunda insülin sekresyon kapasitesinde azalma ve insülin direnci
de dâhil olmak üzere, glukoz-insülin metabolizmasında kalıcı adaptif değişiklikler meydana gelebilir. Bu değişiklikler artan bir yağ
depolama kabiliyetine yol açabilir, böylece birey daha sonraki yaşamda T2DM gelişimine yatkın hâle gelebilir. Bu ilişkide DNA
metilasyonu, histon modifikasyonu ve mikroRNA etkileşimleri gibi epigenetik mekanizmalar temel rol oynamaktadır. Bu derlemede,
T2DM patogenezinde gelişimsel epigenetik varyasyonun rolünü gösteren temel mekanizmalar ve araştırma bulguları özetlenmiştir

Keywords

tip 2 diyabet, yetersiz beslenme, kıtlık, epigenetik

References

• 1. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW et al. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018; 138:271-281.
• 2. Wu Y, Ding Y, Tanaka Y, ZhangW. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int. J. Med. Sci. 2014; 11: 1185–1200.
• 3. Estampador AC, FranksPW. Precision medicine in obesity and type 2 diabetes: the relevance of early-life exposures. Clin Chem 61. 2018;130–141.
• 4. Liu L, Wang Y, Sun J, Pang Z. Association of famine exposure during early life with the risk of type 2 diabetes in adulthood: a meta-analysis. Eur J Nutr. 2018; 57: 741–749.
• 5. Bansal A, Simmons RA. Epigenetics and developmental origins of diabetes: correlation or causation? Am J Physiol Endocrinol Metab. 2018; 315: 15–28.
• 6. Cheng Z, Zheng L, Almeida FA. Epigenetic reprogramming in metabolic disorders: nutritional factors and beyond. J Nutr Biochem. 2018; 54: 1–10.
• 7. Pinney SE. Intrauterine growth retardation–A developmental model of type 2 diabetes. Drug Discov Today Dis. Models. 2013; 10: 71–77.
• 8. Wang N, Cheng J, Han B, Li Q, Chen Y, Xia F et al. Exposureto severe famine in the prenatal or post natal period and the development of diabetes in adulthood: An observational study. Diabetologia. 2017; 60: 262–269.
• 9. Mandy M, Nyirenda M. Developmental Origins of Health and Disease: the relevance to developing nations. Int Health 10. 2018; 66–70.
• 10. Nielsen JH, Haase TN, Jaksch C, Nalla A, Søstrup B, Nalla AA et al. Impact of fetal and neonatal environment on beta cell function and development of diabetes. ActaObstet Gynecol Scand.2014; 93: 1109–1122.
• 11. Vaiserman A and Lushchak O. Developmental origins of type 2 diabetes: Focus on epigenetics. Ageing Research Reviews 55. 2019; 100957.
• 12. Stöger R. The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes? Bioessays. 2008; 30: 156–166.
• 13. Briana DD and Malamitsi-Puchner A. Intrauterine growth restriction and adult disease: the role of adipocytokines. Eur J Endocrinol. 2009; 160: 337-347.
• 14. Siddiqui K, Joy SS, Nawaz SS. Impact of Early Life or Intrauterine Factors and Socio-Economic Interaction on Diabetes - An Evidence on Thrifty Hypothesis. J Lifestyle Med. 2019 Jul;9(2):92-101.
• 15. Whincup PH, Kaye SJ, Owen CG, Huxley R, Cook DG, Anazawa S et al. Birth weight and risk of type 2 diabetes: a systematic review. JAMA. 2008; 300: 2886–2897.
• 16. Martin A, Connelly A, Bland RM, Reilly JJ. Health impact of catch-up growth in low-birth weight infants: systematic review, evidence appraisal, and meta-analysis. Matern Child Nutr 2017;13. doi:10.1111/mcn.12297
• 17. Sutton EF, Gilmore LA, Dunger DB, Heijmans BT, Hivert MF, Ling C et al. Developmental programming: state-of-the-science and future directions̶ Summary from a Pennington Biomedical symposium. Obesity 24. 2016; 1018–1026.
• 18. Cho, WK, Suh BK. Catch-up growth and catch-up fat in children born small for gestational age. Korean J Pediatr. 2016; 59: 1–7.
• 19. Fernandez-Twinn DS, Hjort L, Novakovic B, Ozanne SE, Saffery R. Intrauterine programming of obesity and type 2 diabetes. Diabetologia. 2019; 62: 1789–1801.
• 20. Tarry-Adkins JL, Ozanne SE. Mechanisms of early life programming: current knowledge and future directions. Am J Clin Nutr 94. 2011; 1765–1771.
• 21. Dumortier O, Blondeau B, Duvillie B, Reusens B, Breant B, Remacle C. Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet. Diabetologia. 2007; 50, 2495–2503.
• 22. Harder T, Rodekamp E, Schellong K, Dudenhausen JW, Plagemann A. Birth weight and subsequent risk of type 2 diabetes: A meta-analysis. Am J Epidemiol. 2007; 165, 849–857.
• 23. Vaiserman MA. Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence. Nutrients. 2017; 9,236. doi: 10.3390/nu9030236.
• 24. Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA, Greally JM. Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreaticislets of rats. J BiolChem. 2010; 285, 15111–1518.
• 25. Zheng J, Xiao X, Zhang Q, Yu M. DNA methylation: the pivotal interaction between early-life nutrition and glucose metabolism in later life. British Journal of Nutrition. 2014; 112, 1850–1857.
• 26. Gong L, Pan YX, Chen H. Gestational low protein diet in therat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation. Epigenetics. 2010; 5, 619–626.
• 27. Altmann S, Murani E, Schwerin M, Metges CC, Wimmers K,Ponsuksili S. Dietary protein restriction and excess of pregnant German Landrace Sows Induce changes in hepatic gene expression and promoter methylation of key metabolic genes in the offspring. J Nutr Biochem. 2013; 24, 484–495.
• 28. Zheng J, Xiao X, Zhang Q, Yu M, Xu J, Wang Z. Maternal protein restriction inducesearly-onset glucose intolerance and alters hepatic genes expression in the peroxisome proliferator-activated receptor pathway in offspring. J Diabetes Investig. 2015; 6, 269–279.
• 29. Lumey LH, Stein AD, Susser E. Prenatal famine and adult health. Annu Rev Public Health.2011; 32: 237–262.
• 30. Fall CHD and Kumaran K. Metabolic programming in early life in humans. Phil Trans R Soc B. 2019; 374.
• 31. Liu H, Chen X, Shi T, Qu G, Zhao T, Xuan K et al. Association of famine exposure with the risk of type 2 diabetes: A meta-analysis. Clinical Nutrition 39. 2020; 1717-1723.
• 32. Li C, Lumey LH. Exposure totheChinesefamine of 1959–61 in early life and current health conditions: A systematic review and meta-analysis. Lancet. 2016; 388: 363.
• 33. Wang N, Wang X, Han B, LiQ, Chen Y, Zhu C et al. Is exposure to famine in childhood and economic development in adulthood associated with diabetes? J Clin Endocrinol Metab.2015; 100, 4514–4523.
• 34. Sun Y, Zhang L, Duan W, Meng X, Jıa 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) Journal of Diabetes 10. 2018; 724–733.
• 35. Lumey LH, Khalangot MD, Vaiserman AM. Association between type 2 diabetes and prenatal exposureto the Ukraine famine of 1932-33: a retrospective cohort study. Lancet Diabetes Endocrinol. 2015; 3(10): 787–794.
• 36. HultM, Tornhammar P, Ueda P, Chima C, Bonamy AE, Ozumba B et al. Hypertension, diabetes and overweight: looming legacies of the Biafran famine. PloSOne. 2010; 5:e13582.
• 37. Ravelli AC, Meulen JH, Osmond J, Barker DJ, Bleker OP. Obesity at theage of 50 y in men and women exposed to famine prenatally. Am J ClinNutr.1999; 70(5): 811–816.
• 38. Lumey LH, Terry MB, Delgado-Cruzata L, Liao Y, Wang Q, Susser E et al. Adultglobal DNA methylation in relation to pre-natalnutrition. Int J Epidemiol. 2012; 41, 116–123.
• 39. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES et al. Persistent epigenetic difference sassociated with prenatal exposure to famine in humans. Proc Natl Acad Sci. 2008; 105, 17046–17049.
• 40. Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009; 18, 4046–4053.
• 41. Finer S, Iqbal MS, Lowe R, Ogunkolade BW, Pervin S, Mathews C et al. Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study. BMJ Open. 2016; 6: e011768.
• 42. Li J, Liu S, Li S, Feng R, Na L, Chu X 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. 2016; 105, 221–227.
• 43. Vaiserman AM. Early-life origin of adult disease: evidence from natural experiments. Exp. Gerontol. 2011; 46, 189–192.
• 44. Si1 J, Yu1 C, Guo Y, Bian Z, Li1 X, Yang L et al. Season of birth and the risk of type 2 diabetes in adulthood: a prospective cohortstudy of 0.5million Chinese adults. Diabetologia. 2017; 60: 836–842.
• 45. Vaiserman AM, Khalangot MD, Carstensen B, Tronko MD, Kravchenko VI, Voitenko VP et al. Seasonality of birth in adult type 2 diabetic patients in three Ukrainian regions. Diabetologia. 2009; 52: 2665–2667.