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Review Article
Diabetes, obesity and metabolism
Young-Onset Diabetes in East Asians: From Epidemiology to Precision Medicine
Juliana C.N. Chan, Chun-Kwan O, Andrea O.Y. Luk
Endocrinol Metab. 2024;39(2):239-254.   Published online April 16, 2024
DOI: https://doi.org/10.3803/EnM.2024.1968
  • 380 View
  • 15 Download
AbstractAbstract PDFPubReader   ePub   
Precision diagnosis is the keystone of clinical medicine. In East Asians, classical type 1 diabetes is uncommon in patients with youngonset diabetes diagnosed before age of 40, in whom a family history, obesity, and beta-cell and kidney dysfunction are key features. Young-onset diabetes affects one in five Asian adults with diabetes in clinic settings; however, it is often misclassified, resulting in delayed or non-targeted treatment. Complex aetiologies, long disease duration, aggressive clinical course, and a lack of evidence-based guidelines have contributed to variable care standards and premature death in these young patients. The high burden of comorbidities, notably mental illness, highlights the numerous knowledge gaps related to this silent killer. The majority of adult patients with youngonset diabetes are managed as part of a heterogeneous population of patients with various ages of diagnosis. A multidisciplinary care team led by physicians with special interest in young-onset diabetes will help improve the precision of diagnosis and address their physical, mental, and behavioral health. To this end, payors, planners, and providers need to align and re-design the practice environment to gather data systematically during routine practice to elucidate the multicausality of young-onset diabetes, treat to multiple targets, and improve outcomes in these vulnerable individuals.
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Original Articles
Calcium & Bone Metabolism
Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study
Ye An Kim, Ji Won Yoon, Young Lee, Hyuk Jin Choi, Jae Won Yun, Eunsin Bae, Seung-Hyun Kwon, So Eun Ahn, Ah-Ra Do, Heejin Jin, Sungho Won, Do Joon Park, Chan Soo Shin, Je Hyun Seo
Endocrinol Metab. 2021;36(6):1189-1200.   Published online December 2, 2021
DOI: https://doi.org/10.3803/EnM.2021.1241
  • 6,049 View
  • 193 Download
  • 11 Web of Science
  • 10 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods
We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results
rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion
The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Citations

Citations to this article as recorded by  
  • Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization
    Caroline De Souza Silverio , Carolina Bonilla
    Biomédica.2024; 44(1): 45.     CrossRef
  • Implications of vitamin D deficiency in systemic inflammation and cardiovascular health
    Sanjay Kumar Dey, Shashank Kumar, Diksha Rani, Shashank Kumar Maurya, Pratibha Banerjee, Madhur Verma, Sabyasachi Senapati
    Critical Reviews in Food Science and Nutrition.2023; : 1.     CrossRef
  • Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study
    Ji Hyun Lee, Ye An Kim, Young Sik Kim, Young Lee, Je Hyun Seo
    Nutrients.2023; 15(13): 3043.     CrossRef
  • Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait
    Abdur Rahman, Mohamed Abu-Farha, Arshad Channanath, Maha M. Hammad, Emil Anoop, Betty Chandy, Motasem Melhem, Fahd Al-Mulla, Thangavel Alphonse Thanaraj, Jehad Abubaker
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Recent Information on Vitamin D Deficiency in an Adult Korean Population Visiting Local Clinics and Hospitals
    Rihwa Choi, Sung-Eun Cho, Sang Gon Lee, Eun Hee Lee
    Nutrients.2022; 14(9): 1978.     CrossRef
  • The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
    Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
    Antioxidants.2022; 11(6): 1090.     CrossRef
  • A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts
    Young Lee, Ji Won Yoon, Ye An Kim, Hyuk Jin Choi, Byung Woo Yoon, Je Hyun Seo
    Genes.2022; 13(9): 1553.     CrossRef
  • Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health
    Elina Hyppönen, Karani S. Vimaleswaran, Ang Zhou
    Nutrients.2022; 14(20): 4408.     CrossRef
  • On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
    Leonidas H. Duntas, Krystallenia I. Alexandraki
    Nutrients.2022; 14(23): 5032.     CrossRef
  • The genetic and epigenetic contributions to the development of nutritional rickets
    Innocent Ogunmwonyi, Adewale Adebajo, Jeremy Mark Wilkinson
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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Diabetes, Obesity and Metabolism
Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat
Sun Ok Song, You-Cheol Hwang, Han Uk Ryu, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko
Endocrinol Metab. 2021;36(4):835-844.   Published online August 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.1130
  • 4,381 View
  • 120 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.
Methods
All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.
Results
A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.
Conclusion
These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Citations

Citations to this article as recorded by  
  • Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels
    Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
    Metabolism.2022; 137: 155327.     CrossRef
  • The associations between lipid profiles and visceral obesity among gastrointestinal cancer patients: a cross-sectional study
    Bo Gao, Xiangrui Li, Wenqing Chen, Shu’an Wang, Jian He, Yu Liu, Chao Ding, Xiaotian Chen
    Lipids in Health and Disease.2022;[Epub]     CrossRef
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Review Articles
Obesity and Metabolism
Genetic and Environmental Factors Contributing to Visceral Adiposity in Asian Populations
Rachel Williams, Muthu Periasamy
Endocrinol Metab. 2020;35(4):681-695.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.772
  • 8,776 View
  • 204 Download
  • 27 Web of Science
  • 29 Crossref
AbstractAbstract PDFPubReader   ePub   
Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity—the “skinny-fat” Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors—most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress—contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.

Citations

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  • Differences in the levels of inflammatory markers between metabolically healthy obese and other obesity phenotypes in adults: A systematic review and meta-analysis
    Zhouli Su, Ljupcho Efremov, Rafael Mikolajczyk
    Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(2): 251.     CrossRef
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    Yoo-Bin Seo, Sung-Goo Kang, Sang-Wook Song
    Obesity Research & Clinical Practice.2024; 18(1): 28.     CrossRef
  • Visceral Adipose Tissue: The Hidden Culprit for Type 2 Diabetes
    Sneha Dhokte, Krzysztof Czaja
    Nutrients.2024; 16(7): 1015.     CrossRef
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    S. V. Bulgakova, D. P. Kurmaev, E. V. Treneva
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    Niki Katsiki, Manfredi Rizzo, Dimitri P. Mikhailidis
    Journal of Diabetes and its Complications.2023; 37(4): 108419.     CrossRef
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    Radhika Aditya Jadhav, G. Arun Maiya, Shashikiran Umakanth, K.N. Shivashankara
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    Arshdeep Singh, Vandana Midha, Ramit Mahajan, Shruti Verma, Chandan Kakkar, Jasmine Grover, Dharmatma Singh, Ramandeep Kaur, Abhishek Masih, Namita Bansal, Catherine Wall, Ajit Sood
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    Padmini Sekar, Eduard Flores Ventura, Anto Cordelia T. A. Dhanapal, Eddy Seong Guan Cheah, Annaletchumy Loganathan, Phoon Lee Quen, Mahenderan Appukutty, Nurpudji Astuti Taslim, Hardinsyah Hardinsyah, Mohd Fairulnizal Md Noh, Julie A Lovegrove, Ian Givens
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    Journal of Diabetes Investigation.2022; 13(5): 756.     CrossRef
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    Sunmin Park
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    Saptarshi Bhattacharya, Sanjay Kalra, Nitin Kapoor, Rajiv Singla, Deep Dutta, Sameer Aggarwal, Deepak Khandelwal, Vineet Surana, Atul Dhingra, Viny Kantroo, Sachin Chittawar, Nilakshi Deka, Vivek Bindal, Puja Dutta
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    Kyung-Wook Kim
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Obesity and Metabolism
Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
Jong-Dai Kim, Won-Young Lee
Endocrinol Metab. 2016;31(3):354-360.   Published online August 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.3.354
  • 4,461 View
  • 42 Download
  • 16 Web of Science
  • 16 Crossref
AbstractAbstract PDFPubReader   

It is well known that many Korean patients with type 2 diabetes mellitus (T2DM) were non-obese and had decreased insulin secretion in past. However, during the past three decades, lifestyles in Korea have been westernized. As a result, the prevalence of obesity, the main cause of diabetes has increased. Thus, there is still a question as to whether the main pathophysiology of current Korean T2DM is insulin resistance or an insulin secretion defect. Because various anti-diabetes medications having different mechanisms of action are currently used as therapeutics, it is important to understand which of these factors is the main physiology in the development of diabetes in Koreans. In this review, we review changes in obesity prevalence, insulin resistance and insulin secretion defects in Korean T2DM during three decades.

Citations

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    Sunmin Park
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  • Triglyceride-Glucose Index Cutoff Point Is an Accurate Marker for Predicting the Prevalence of Metabolic Syndrome in Obese Caucasian Subjects
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Close layer
Obesity and Metabolism
Diabetes in Asians
Eun-Jung Rhee
Endocrinol Metab. 2015;30(3):263-269.   Published online September 22, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.263
  • 8,229 View
  • 155 Download
  • 117 Web of Science
  • 114 Crossref
AbstractAbstract PDFPubReader   

The prevalence of diabetes is increasing globally, particularly in Asia. According to the 2013 Diabetes Atlas, an estimated 366 million people are affected by diabetes worldwide; 36% of those affected live in the Western Pacific region, with a significant proportion in East Asia. The reasons for this marked increase in the prevalence of diabetes can be extrapolated from several distinct features of the Asian region. First, the two most populated countries, China and India, are located in Asia. Second, Asians have experienced extremely rapid economic growth, including rapid changes in dietary patterns, during the past decades. As a result, Asians tend to have more visceral fat within the same body mass index range compared with Westerners. In addition, increased insulin resistance relative to reduced insulin secretory function is another important feature of Asian individuals with diabetes. Young age of disease onset is also a distinctive characteristic of these patients. Moreover, changing dietary patterns, such as increased consumption of white rice and processed red meat, contributes to the deteriorated lifestyle of this region. Recent studies suggest a distinctive responsiveness to novel anti-diabetic agents in Asia; however, further research and efforts to reverse the increasing prevalence of diabetes are needed worldwide.

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