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Review Article
Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia
Joonyub Leeorcid, Kun-Ho Yoonorcid

DOI: https://doi.org/10.3803/EnM.2024.2193
Published online: January 15, 2025

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

Corresponding author: Kun‐Ho Yoon Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82‐2‐2258‐3589, Fax: +82‐2‐595‐2534, E-mail: yoonk@catholic.ac.kr
• Received: October 7, 2024   • Revised: October 15, 2024   • Accepted: October 29, 2024

Copyright © 2025 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.
Type 2 diabetes mellitus (T2DM) is a complex disorder that arises from an imbalance between insulin resistance and pancreatic β-cell dysfunction. When individuals develop insulin resistance, β-cells initially respond by increasing insulin production. However, if β-cells cannot sustain the heightened insulin demand, blood glucose levels rise, leading to T2DM [1,2]. The relative contributions of insulin resistance and β-cell dysfunction to the development of T2DM vary among individuals and regions. East Asian patients with T2DM, who represent a significant portion of the global diabetes burden, exhibit distinct characteristics [3,4]. Previous research, including our own, has shown that East Asian patients with T2DM typically present with a lower body mass index (BMI), reduced insulin secretion, and earlier onset of the disease [4-7]. Recently, the prevalence of T2DM in East Asia has surged. For example, the prevalence of diabetes in Korea increased from 1.5% in 1971 to 16.7% in 2022 [8,9], and in China, it rose from 1% in 1980 to 12.4% in 2018 [10,11]. This increase in diabetes prevalence in East Asia has occurred concurrently with a rise in obesity rates [12]. In Korea, the prevalence of obesity increased by 10.7% over the last 24 years [13,14], accompanied by a 16.6% increase in the prevalence of obesity in patients with T2DM [9,15]. Consequently, insulin sensitivity in Korean patients with T2DM has gradually decreased [16]. Despite the steady increase in the prevalence of obesity in Korea, the steep rise in T2DM incidence appears to have slowed recently [8,9]. This shift in the epidemiological landscape prompts a reevaluation of whether the characteristics of T2DM in East Asians are changing. In this paper, we explore the current evidence and perspectives on the evolving characteristics of T2DM in East Asia.
Cumulative evidence suggests that East Asian patients with T2DM exhibit compensatory defects in insulin secretion. The Botnia study, which conducted oral glucose tolerance tests (OGTT) on 5,396 individuals across various glucose spectra, revealed increased insulin secretory function during the prediabetes stage in Caucasians [17]. In contrast, our research has shown that insulin secretion in response to oral glucose challenges is impaired in the Korean prediabetes population, indicating a compensatory defect in β-cell function [18,19]. Similarly, cross-sectional OGTT studies in Japan and China have demonstrated that the prediabetic population does not exhibit a compensatory increase in insulin secretion [20,21]. These findings are supported by a prospective cohort study in Korea, which showed a progressive decline in the disposition index during the transition from normal glucose tolerance to diabetes [22]. The frequently sampled intravenous glucose tolerance test (FSIGT) is a useful and accurate method for evaluating early insulin secretory responses. When performed in the Korean population, FSIGT indicated that the acute insulin response decreased even at the prediabetic stage [23]. The Japanese population also showed a decreased acute insulin response compared to Caucasians [24,25]. A comprehensive meta-analysis of FSIGT studies demonstrated that East Asians have a lower acute insulin response than Caucasians or Africans, regardless of their glucose spectra [26]. Direct quantitative comparisons of β-cell mass between East Asians and Westerners are lacking. However, indirect histological evidence supports a compensatory defect in insulin secretory capacity in East Asians. The Japanese population exhibits limited changes in β-cell mass and Ki67+ replicative β-cells in response to obesity, regardless of the presence of diabetes [27,28], which contrasts with findings in Western populations [29,30]. These findings indicate that compensatory defects in insulin secretion are common in East Asian populations.
Despite clear evidence of insulin secretory defects, the mechanisms underlying the limited insulin secretory capacity in East Asia remain unclear. The systemic threshold for β-cell compensatory capacity is influenced by the insulin secretion demand placed on β-cells, which in turn depends on the number and function of these cells, collectively referred to as functional β-cell mass. This leads to the question of what determines the peak functional β-cell mass in individuals. Previous studies indicate that β-cell mass is established early, as non-obese patients with T2DM exhibit lower β-cell mass regardless of the duration of diabetes or glycemic levels [4]. In human adults, β-cell regeneration primarily occurs in scattered islets, potentially originating from pancreatic duct cells [31]. However, although these scattered islets are commonly observed in adults, they contribute minimally to the overall β-cell mass [32]. The relative area of these scattered islets adjacent to the pancreatic duct accounts for only 0.1% in healthy controls and 0.2% in patients with T2DM, supporting the idea that peak functional β-cell mass is determined early in life. Therefore, environmental factors encountered early in life, along with genetic predispositions, may play a role in the reduced functional β-cell mass observed in East Asians [33].
Several genetic studies have identified East Asian-specific diabetes-related single nucleotide polymorphisms (SNPs) that may contribute to insulin secretory defects in this population [22,34,35]. A genome-wide association study (GWAS) involving 4,106 participants from the Korean Genome and Epidemiology Study found that genetic variants in glucokinase (GCK; rs4607517 G>A) were associated with a decreased disposition index and progression to diabetes [22]. Previously, GCK was shown to be a key regulator of glucose-induced β-cell replication in vivo [36]. Whole-exome sequencing of 917 Korean participants, including 619 with T2DM and 298 controls, suggested that genetic variants of paired box 4 (PAX4; rs2233580 C>T) are associated with the development of T2DM. PAX4 is a transcription factor that plays a crucial role in cell development [37]. Currently, the correlation between the SNP in PAX4 (rs2233580 C>T) and the development of T2DM is under investigation. An integrative meta-analysis of eight GWAS across East Asian countries, involving 6,952 patients with T2DM and 11,865 controls from Korea, Japan, China, Taiwan, Singapore, and the Philippines, identified several East Asian-specific genetic variants [38]. These include SNPs that potentially affect β-cells, such as GLI-similar family zinc finger 3 (GLIS3; rs7041847 G>A), FITM2-R3HDML-HNF4A (rs6017317 T>G), KCNK16 (rs1535500 G>T), and GCC1-PAX4 (rs6467136 A>G). However, the relationship between these genetic variants, compensatory insulin secretion defects, and the onset of T2DM remains unclear. Additionally, the epigenetic variance of β-cells with respect to ethnicity has been poorly characterized. Recently, the epigenetic landscape of human islets has been described at single-cell resolution [39]. Understanding how the epigenetic landscape of East Asian islets differs from that of other ethnicities, and how chromatin accessibility is associated with genetic variance in East Asians, are important topics for future research.
Environmental factors may contribute to the low functional β-cell mass in East Asians. During the developmental period, insulin-positive cells emerge as small clusters at 5 to 7 weeks postconceptional, with numbers increasing significantly by 11 weeks postconception [40]. Post-birth, β-cells are dispersed in small clusters and exhibit a high replication rate during the postnatal period. After 10 weeks, β-cells organize into islets and increase in size. Although the replication rate of β-cells gradually declines, the expansion of pancreatic volume allows for an increase in total β-cell mass until approximately 20 years of age [41]. Therefore, environmental exposure during this period can substantially impact the level of functional β-cell mass. The fetal period is crucial, as intrauterine environmental factors can significantly impact fetal β-cell mass [42,43]. Birth weight is associated with the risk and clinical characteristics of T2DM in humans [44,45]. Intrauterine growth retardation has been shown to alter DNA methylation of the Pdx1 promoter in the fetus [46]. Maternal protein restriction during pregnancy can alter the epigenetic landscape of the Hnf4α enhancer region or decrease miRNA-375 expression in fetal pancreatic β-cells, which reduces β-cell proliferation and insulin secretion after birth [43,47]. Dietary intake during the postnatal period can influence β-cell proliferation and maturation [48,49]. The pubertal stage is a critical period during which baseline β-cell mass can be established. After reaching adulthood, β-cell mass remains plastic, making puberty the last period in which one can significantly increase β-cell mass under physiological conditions, aside from pregnancy [50-53]. A histological study based on human samples demonstrated that individuals with a history of childhood obesity tended to have an increased β-cell area and larger islet size [54]. East Asian countries, including Korea, Japan, and China, experienced extreme poverty and famine after World War II. These environmental influences could have contributed to the low functional β-cell mass in this region.
Despite clear evidence of low functional β-cell mass in East Asians, recent studies suggest that the characteristics of patients with T2DM in this region may be changing. Rapid economic development and westernization have significantly increased the prevalence of obesity in East Asian countries. In Korea, for instance, the obesity rate is projected to rise from 27.7% in 1998 to 38.4% in 2021. Concurrently, the prevalence of obesity among patients with T2DM has risen from 37.8% in 1998 to 54.4% in 2020 [9,55]. According to the Shiga Diabetes Clinical Survey, the prevalence of obesity in Japanese patients with diabetes increased from 32.1% in 2000 to 40.9% in 2012 [56]. Similarly, in China, the prevalence of obesity rose from 4.2% in 1993 to 15.7% in 2015 [57]. This trend has led to decreased insulin sensitivity among patients with T2DM. Interestingly, although obesity rates continue to climb in Korea, the rapid increase in T2DM cases has recently shown signs of slowing. Specifically, the annual incidence of diabetes in Korea has decreased by 0.1% annually. In China, despite a 170% increase in the prevalence of diabetes from 1990 to 2019, the age-adjusted incidence rate of diabetes remains lower than the global rate, attributed to the aging of the Chinese population rather than to newly developed T2DM [58]. This changing epidemiological landscape raises the question of whether the functional β-cell mass in this region is adapting.
Currently, there is no direct evidence to suggest a recent increase in functional β-cell mass in East Asian countries. However, the environmental changes experienced by individuals in this region during their early life indirectly support this hypothesis (Fig. 1). Rapid economic development has enhanced nutrient availability and improved socioeconomic and health conditions across many East Asian countries [4,59]. Alongside this, there have been significant advancements in pre- and perinatal care and nutrition. Notably, maternal protein supplementation has increased, which may have contributed to better intrauterine health and, consequently, an increase in fetal functional β-cell mass [60]. Environmental changes during adolescence may also have played a role in increasing functional β-cell mass in East Asia. In Korea, for instance, the prevalence of adolescent obesity has risen sharply from 9.7% in 2012 to 19.3% in 2021 [13]. This increase in BMI among adolescents could have contributed to an increase in functional β-cell mass in Korea, potentially influencing the decreased incidence of T2DM. However, these relationships should be interpreted with caution, as there are conflicting reports regarding the link between adolescent obesity and T2DM [61-63].
Previously, we suggested that changes in insulin resistance, rather than insulin secretory capacity, occurred among Koreans between 1990 and 2000 [16]. In this study, we analyzed OGTT results from a Korean population across various glucose tolerance categories—normal glucose tolerance, prediabetes, and T2DM—from the 1990s and 2000s. The mean age of participants ranged from the early 40s to early 50s across these subgroups, suggesting that their adolescent years likely occurred between the 1950s and 1970s, a period that may not accurately reflect recent environmental changes during adolescence. Additionally, epigenetic changes resulting from the intrauterine environment may persist across several generations [64]. Therefore, the metabolic impacts of enhanced pre- and perinatal care might not have become apparent until more recently. Future research should focus on trends in functional β-cell mass, utilizing OGTT, FSIGT, and histological examinations to further substantiate this perspective.
The number of foreign residents in East Asian countries is rapidly increasing. For instance, in Korea, the proportion of foreign residents has risen to 4.89%, marking a gradual transition from an ethnically homogeneous to a multiracial society [65]. While the genetic traits of East Asian patients with T2DM discussed in this article are likely to remain consistent, it is crucial to understand how these shifts in genetic background, along with environmental factors, affect the characteristics of patients with T2DM. This understanding is an important area for future research (Fig. 1).
Low functional β-cell mass is a significant trait in East Asian patients with T2DM, likely resulting from a complex interplay of genetic and environmental factors. Epidemiological evidence indicates a potential adaptation of β-cells in this demographic. The rapid changes in environmental conditions, especially concerning maternal nutrition and adolescent obesity in East Asian countries, might have influenced this adaptation. The characteristics of T2DM in this region seem to evolve dynamically rather than remaining static. Given the genetic predispositions, the insulin secretion defect in East Asians might persist; however, the relative impact of this defect on the development of T2DM appears to be in flux. Further research is needed to thoroughly explore and document the alterations in insulin secretion and sensitivity among East Asians.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Acknowledgements
This work was supported by the Research Foundation of Internal Medicine, The Catholic University of Korea. The authors also wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year 2024.
This work was supported by the Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korean government (MSIT) (No. 2022-000965, development of diabetes patients’ healthcare digital twin technology based on continuous lifelog variables) and Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HC19C0341) to Kun-Ho Yoon; and National Research Foundation of Korea (2022R1I1A1A01068401) and the Korea Health Industry Development Institute (RS-2024-00408915, RS-2024-00404132) to Joonyub Lee.
Fig. 1.
Evolving characteristics of type 2 diabetes mellitus (T2DM) in East Asia. East Asian patients with T2DM have traditionally been characterized by low functional β-cell mass. However, over the past few decades, environmental changes early in life may have mitigated the rising incidence of T2DM in this population, likely by increasing their peak β-cell mass. In addition to these early-life environmental changes, the growing proportion of foreign residents is expected to reshape the epidemiological landscape of T2DM in East Asia.
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  • 1. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 2004;88:787–835.ArticlePubMed
  • 2. Lyssenko V, Almgren P, Anevski D, Perfekt R, Lahti K, Nissen M, et al. Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes 2005;54:166–74.ArticlePubMedPDF
  • 3. International Diabetes Federation. IDF diabetes atlas; 10th ed. Brussels: IDF; 2021.
  • 4. Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006;368:1681–8.ArticlePubMed
  • 5. Ma RC, Chan JC. Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States. Ann N Y Acad Sci 2013;1281:64–91.ArticlePubMedPMCPDF
  • 6. Rhee EJ. Diabetes in Asians. Endocrinol Metab (Seoul) 2015;30:263–9.ArticlePubMedPMC
  • 7. Yabe D, Seino Y, Fukushima M, Seino S. β Cell dysfunction versus insulin resistance in the pathogenesis of type 2 diabetes in East Asians. Curr Diab Rep 2015;15:602.ArticlePubMedPDF
  • 8. Kim DJ. The epidemiology of diabetes in Korea. Diabetes Metab J 2011;35:303–8.ArticlePubMedPMC
  • 9. Bae JH, Han KD, Ko SH, Yang YS, Choi JH, Choi KM, et al. Diabetes fact sheet in Korea 2021. Diabetes Metab J 2022;46:417–26.ArticlePubMedPMCPDF
  • 10. A mass survey of diabetes mellitus in a population of 300,000 in 14 provinces and municipalities in China (author’s transl). Zhonghua Nei Ke Za Zhi 1981;20:678–83.PubMed
  • 11. Wang L, Peng W, Zhao Z, Zhang M, Shi Z, Song Z, et al. Prevalence and treatment of diabetes in China, 2013-2018. JAMA 2021;326:2498–506.ArticlePubMedPMC
  • 12. Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 2009;301:2129–40.ArticlePubMed
  • 13. Jeong SM, Jung JH, Yang YS, Kim W, Cho IY, Lee YB, et al. 2023 Obesity fact sheet: prevalence of obesity and abdominal obesity in adults, adolescents, and children in Korea from 2012 to 2021. J Obes Metab Syndr 2024;33:27–35.ArticlePubMedPMC
  • 14. Oh SW. Obesity and metabolic syndrome in Korea. Diabetes Metab J 2011;35:561–6.ArticlePubMedPMC
  • 15. Won JC, Lee JH, Kim JH, Kang ES, Won KC, Kim DJ, et al. Diabetes fact sheet in Korea, 2016: an appraisal of current status. Diabetes Metab J 2018;42:415–24.ArticlePubMedPMCPDF
  • 16. Yang HK, Lee JH, Choi IY, Kwon HS, Shin JA, Jeong SH, et al. The insulin resistance but not the insulin secretion parameters have changed in the Korean population during the last decade. Diabetes Metab J 2015;39:117–25.ArticlePubMedPMC
  • 17. Tripathy D, Carlsson M, Almgren P, Isomaa B, Taskinen MR, Tuomi T, et al. Insulin secretion and insulin sensitivity in relation to glucose tolerance: lessons from the Botnia Study. Diabetes 2000;49:975–80.ArticlePubMedPDF
  • 18. Choi YH, Ahn YB, Yoon KH, Kang MI, Cha BY, Lee KW, et al. New ADA criteria in the Korean population: fasting blood glucose is not enough for diagnosis of mild diabetes especially in the elderly. Korean J Intern Med 2000;15:211–7.ArticlePubMedPMC
  • 19. Kim DJ, Lee MS, Kim KW, Lee MK. Insulin secretory dysfunction and insulin resistance in the pathogenesis of Korean type 2 diabetes mellitus. Metabolism 2001;50:590–3.ArticlePubMed
  • 20. Fukushima M, Suzuki H, Seino Y. Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes. Diabetes Res Clin Pract 2004;66 Suppl 1:S37–43.ArticlePubMed
  • 21. Qian L, Xu L, Wang X, Fu X, Gu Y, Lin F, et al. Early insulin secretion failure leads to diabetes in Chinese subjects with impaired glucose regulation. Diabetes Metab Res Rev 2009;25:144–9.ArticlePubMed
  • 22. Ohn JH, Kwak SH, Cho YM, Lim S, Jang HC, Park KS, et al. 10-Year trajectory of β-cell function and insulin sensitivity in the development of type 2 diabetes: a community-based prospective cohort study. Lancet Diabetes Endocrinol 2016;4:27–34.ArticlePubMed
  • 23. Kim SH, Kim DJ, Lee BW, Seo IA, Chung JH, Min YK, et al. Insulin secretory dysfunction in the pathogenesis of type 2 diabetes in Koreans: a minimal model analysis. J Korean Diabetes Assoc 2003;27:414–9.
  • 24. Taniguchi A, Nakai Y, Fukushima M, Kawamura H, Imura H, Nagata I, et al. Pathogenic factors responsible for glucose intolerance in patients with NIDDM. Diabetes 1992;41:1540–6.ArticlePubMed
  • 25. Welch S, Gebhart SS, Bergman RN, Phillips LS. Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. J Clin Endocrinol Metab 1990;71:1508–18.ArticlePubMed
  • 26. Kodama K, Tojjar D, Yamada S, Toda K, Patel CJ, Butte AJ. Ethnic differences in the relationship between insulin sensitivity and insulin response: a systematic review and meta-analysis. Diabetes Care 2013;36:1789–96.PubMedPMC
  • 27. Kou K, Saisho Y, Satoh S, Yamada T, Itoh H. Change in β-cell mass in Japanese nondiabetic obese individuals. J Clin Endocrinol Metab 2013;98:3724–30.ArticlePubMed
  • 28. Inaishi J, Saisho Y, Sato S, Kou K, Murakami R, Watanabe Y, et al. Effects of obesity and diabetes on α- and β-cell mass in surgically resected human pancreas. J Clin Endocrinol Metab 2016;101:2874–82.ArticlePubMedPMC
  • 29. Saisho Y, Butler AE, Manesso E, Elashoff D, Rizza RA, Butler PC. β-Cell mass and turnover in humans: effects of obesity and aging. Diabetes Care 2013;36:111–7.PubMed
  • 30. Hanley SC, Austin E, Assouline-Thomas B, Kapeluto J, Blaichman J, Moosavi M, et al. β-Cell mass dynamics and islet cell plasticity in human type 2 diabetes. Endocrinology 2010;151:1462–72.ArticlePubMed
  • 31. Sasaki H, Saisho Y, Inaishi J, Watanabe Y, Tsuchiya T, Makio M, et al. Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes. Diabetologia 2021;64:1816–21.ArticlePubMedPMCPDF
  • 32. Cho JH, Kim JW, Shin JA, Shin J, Yoon KH. β-Cell mass in people with type 2 diabetes. J Diabetes Investig 2011;2:6–17.ArticlePubMedPMC
  • 33. Inaishi J, Saisho Y. Beta-cell mass in obesity and type 2 diabetes, and its relation to pancreas fat: a mini-review. Nutrients 2020;12:3846.ArticlePubMedPMC
  • 34. Kwak SH, Chae J, Lee S, Choi S, Koo BK, Yoon JW, et al. Nonsynonymous variants in PAX4 and GLP1R are associated with type 2 diabetes in an East Asian population. Diabetes 2018;67:1892–902.ArticlePubMedPDF
  • 35. Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, et al. The genetic architecture of type 2 diabetes. Nature 2016;536:41–7.PubMedPMC
  • 36. Porat S, Weinberg-Corem N, Tornovsky-Babaey S, Schyr-Ben-Haroush R, Hija A, Stolovich-Rain M, et al. Control of pancreatic β cell regeneration by glucose metabolism. Cell Metab 2011;13:440–9.ArticlePubMed
  • 37. Lau HH, Krentz NA, Abaitua F, Perez-Alcantara M, Chan JW, Ajeian J, et al. PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development. Nat Commun 2023;14:6119.ArticlePubMedPMCPDF
  • 38. Cho YS, Chen CH, Hu C, Long J, Ong RT, Sim X, et al. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nat Genet 2011;44:67–72.PubMedPMC
  • 39. Chiou J, Zeng C, Cheng Z, Han JY, Schlichting M, Miller M, et al. Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk. Nat Genet 2021;53:455–66.ArticlePubMedPMCPDF
  • 40. Villalba A, Gitton Y, Inoue M, Aiello V, Blain R, Toupin M, et al. A 3D atlas of the human developing pancreas to explore progenitor proliferation and differentiation. Diabetologia 2024;67:1066–78.ArticlePubMedPMCPDF
  • 41. Meier JJ, Butler AE, Saisho Y, Monchamp T, Galasso R, Bhushan A, et al. Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans. Diabetes 2008;57:1584–94.PubMed
  • 42. Barker DJ. The fetal origins of type 2 diabetes mellitus. Ann Intern Med 1999;130(4 Pt 1):322–4.ArticlePubMed
  • 43. Sandovici I, Smith NH, Nitert MD, Ackers-Johnson M, UribeLewis S, Ito Y, et al. Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc Natl Acad Sci U S A 2011;108:5449–54.ArticlePubMedPMC
  • 44. McCance DR, Pettitt DJ, Hanson RL, Jacobsson LT, Knowler WC, Bennett PH. Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype? BMJ 1994;308:942–5.ArticlePubMedPMC
  • 45. Hansen AL, Thomsen RW, Brons C, Svane HM, Jensen RT, Andersen MK, et al. Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes. Diabetologia 2023;66:1680–92.ArticlePubMedPMCPDF
  • 46. Park JH, Stoffers DA, Nicholls RD, Simmons RA. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 2008;118:2316–24.ArticlePubMedPMC
  • 47. Dumortier O, Hinault C, Gautier N, Patouraux S, Casamento V, Van Obberghen E. Maternal protein restriction leads to pancreatic failure in offspring: role of misexpressed microRNA-375. Diabetes 2014;63:3416–27.ArticlePubMedPDF
  • 48. Stolovich-Rain M, Enk J, Vikesa J, Nielsen FC, Saada A, Glaser B, et al. Weaning triggers a maturation step of pancreatic β cells. Dev Cell 2015;32:535–45.ArticlePubMed
  • 49. Srinivasan M, Patel MS. Metabolic programming in the immediate postnatal period. Trends Endocrinol Metab 2008;19:146–52.ArticlePubMed
  • 50. Gregg BE, Moore PC, Demozay D, Hall BA, Li M, Husain A, et al. Formation of a human β-cell population within pancreatic islets is set early in life. J Clin Endocrinol Metab 2012;97:3197–206.ArticlePubMedPMC
  • 51. Lam CJ, Cox AR, Jacobson DR, Rankin MM, Kushner JA. Highly proliferative α-cell-related islet endocrine cells in human pancreata. Diabetes 2018;67:674–86.ArticlePubMedPMCPDF
  • 52. Moon JH, Lee J, Kim KH, Kim HJ, Kim H, Cha HN, et al. Multiparity increases the risk of diabetes by impairing the proliferative capacity of pancreatic β cells. Exp Mol Med 2023;55:2269–80.ArticlePubMedPMCPDF
  • 53. Kim H, Toyofuku Y, Lynn FC, Chak E, Uchida T, Mizukami H, et al. Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med 2010;16:804–8.ArticlePubMedPMCPDF
  • 54. Sasaki H, Saisho Y, Inaishi J, Watanabe Y, Tsuchiya T, Makio M, et al. Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults. Diabetologia 2020;63:1199–210.ArticlePubMedPMCPDF
  • 55. Kim CS, Ko SH, Kwon HS, Kim NH, Kim JH, Lim S, et al. Prevalence, awareness, and management of obesity in Korea: data from the Korea national health and nutrition examination survey (1998-2011). Diabetes Metab J 2014;38:35–43.ArticlePubMedPMC
  • 56. Miyazawa I, Kadota A, Miura K, Okamoto M, Nakamura T, Ikai T, et al. Twelve-year trends of increasing overweight and obesity in patients with diabetes: the Shiga Diabetes Clinical Survey. Endocr J 2018;65:527–36.ArticlePubMed
  • 57. Ma S, Xi B, Yang L, Sun J, Zhao M, Bovet P. Trends in the prevalence of overweight, obesity, and abdominal obesity among Chinese adults between 1993 and 2015. Int J Obes (Lond) 2021;45:427–37.ArticlePubMedPDF
  • 58. Liu J, Shen M, Zhuang G, Zhang L. Investigating the temporal trends of diabetes disease burden in China during 1990-2019 from a global perspective. Front Endocrinol (Lausanne) 2024;15:1324318.ArticlePubMedPMC
  • 59. Pingali P, Abraham M. Food systems transformation in Asia: a brief economic history. Agric Econ 2022;53:895–910.ArticlePDF
  • 60. Ota E, Hori H, Mori R, Tobe-Gai R, Farrar D. Antenatal dietary education and supplementation to increase energy and protein intake. Cochrane Database Syst Rev 2015;6:CD000032.Article
  • 61. Karin A, Jon E, Martin A, Lena B, Martin L, Naveed S, et al. Body mass index in adolescence, risk of type 2 diabetes and associated complications: a nationwide cohort study of men. EClinicalMedicine 2022;46:101356.ArticlePubMedPMC
  • 62. Katanoda K, Noda M, Goto A, Mizunuma H, Lee JS, Hayashi K. Being underweight in adolescence is independently associated with adult-onset diabetes among women: the Japan Nurses’ Health Study. J Diabetes Investig 2019;10:827–36.ArticlePubMedPDF
  • 63. Tirosh A, Shai I, Afek A, Dubnov-Raz G, Ayalon N, Gordon B, et al. Adolescent BMI trajectory and risk of diabetes versus coronary disease. N Engl J Med 2011;364:1315–25.ArticlePubMedPMC
  • 64. Martinez D, Pentinat T, Ribo S, Daviaud C, Bloks VW, Cebria J, et al. In utero undernutrition in male mice programs liver lipid metabolism in the second-generation offspring involving altered Lxra DNA methylation. Cell Metab 2014;19:941–51.ArticlePubMed
  • 65. Park HR. Multicultural era nears as foreign population exceeds 2.5M [Internet]. Sejong: Koreanet; 2024 [cited 2024 Dec 13]. Available from: https://www.korea.net/NewsFocus/Society/view?articleId=245554.

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      Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia
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      Fig. 1. Evolving characteristics of type 2 diabetes mellitus (T2DM) in East Asia. East Asian patients with T2DM have traditionally been characterized by low functional β-cell mass. However, over the past few decades, environmental changes early in life may have mitigated the rising incidence of T2DM in this population, likely by increasing their peak β-cell mass. In addition to these early-life environmental changes, the growing proportion of foreign residents is expected to reshape the epidemiological landscape of T2DM in East Asia.
      Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia

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