- Clinical Study
- Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults
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Sung Hye Kong, Ji Won Yoon, Jung Hee Kim, JooYong Park, Jiyeob Choi, Ji Hyun Lee, A Ram Hong, Nam H. Cho, Chan Soo Shin
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Endocrinol Metab. 2020;35(4):801-810. Published online November 24, 2020
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DOI: https://doi.org/10.3803/EnM.2020.735
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Abstract
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- Background
As the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS).
Methods TBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers.
Results In the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=–0.0281, β=–0.0465, respectively).
Conclusion In this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.
- Clinical Study
- Low Predictive Value of FRAX Adjusted by Trabecular Bone Score for Osteoporotic Fractures in Korean Women: A Community-Based Cohort Study
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Hana Kim, Jung Hee Kim, Min Joo Kim, A Ram Hong, HyungJin Choi, EuJeong Ku, Ji Hyun Lee, Chan Soo Shin, Nam H. Cho
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Endocrinol Metab. 2020;35(2):359-366. Published online June 24, 2020
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DOI: https://doi.org/10.3803/EnM.2020.35.2.359
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Abstract
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- Background
The value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women.
Methods After screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS.
Results During the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell’s C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively.
Conclusion FRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.
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Citations
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- Comparison of predictive value of FRAX, trabecular bone score, and bone mineral density for vertebral fractures in systemic sclerosis: A cross-sectional study
Kyung-Ann Lee, Hyun-Joo Kim, Hyun-Sook Kim Medicine.2023; 102(2): e32580. CrossRef - Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools
Michelle Gates, Jennifer Pillay, Megan Nuspl, Aireen Wingert, Ben Vandermeer, Lisa Hartling Systematic Reviews.2023;[Epub] CrossRef - Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study
Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim Frontiers in Endocrinology.2023;[Epub] CrossRef - Comparison of HU histogram analysis and BMD for proximal femoral fragility fracture assessment: a retrospective single-center case–control study
Sun-Young Park, Hong Il Ha, Injae Lee, Hyun Kyung Lim European Radiology.2022; 32(3): 1448. CrossRef - Association of Trabecular Bone Score-Adjusted Fracture Risk Assessment Tool with Coronary Artery Calcification in Women
Tzyy-Ling Chuang, Yuh-Feng Wang, Malcolm Koo, Mei-Hua Chuang Diagnostics.2022; 12(1): 178. CrossRef - Risk of osteoporotic fracture in women using the FRAX tool with and without bone mineral density score in patients followed at a tertiary outpatient clinic ‒ An observational study
Maria Helena Sampaio Favarato, Maria Flora de Almeida, Arnaldo Lichtenstein, Milton de Arruda Martins, Mario Ferreira Junior Clinics.2022; 77: 100015. CrossRef - Comparison of Trabecular Bone Score–Adjusted Fracture Risk Assessment (TBS-FRAX) and FRAX Tools for Identification of High Fracture Risk among Taiwanese Adults Aged 50 to 90 Years with or without Prediabetes and Diabetes
Tzyy-Ling Chuang, Mei-Hua Chuang, Yuh-Feng Wang, Malcolm Koo Medicina.2022; 58(12): 1766. CrossRef - Application of the Trabecular Bone Score in Clinical Practice
Sung Hye Kong, Namki Hong, Jin-Woo Kim, Deog Yoon Kim, Jung Hee Kim Journal of Bone Metabolism.2021; 28(2): 101. CrossRef
- Clinical Study
- Association of Body Mass Index with the Risk of Incident Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality: A Community-Based Prospective Study
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Ji Cheol Bae, Nam H. Cho, Jae Hyeon Kim, Kyu Yeon Hur, Sang-Man Jin, Moon-Kyu Lee
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Endocrinol Metab. 2020;35(2):416-424. Published online June 24, 2020
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DOI: https://doi.org/10.3803/EnM.2020.35.2.416
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6,694
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Abstract
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- Background
Type 2 diabetes and cardiovascular disease (CVD) are the most important sequelae of obesity and the leading cause of death. We evaluated the association between body mass index (BMI) and the risk of incident type 2 diabetes, CVD, and all-cause mortality in a prospective study of a Korean population.
Methods The shapes of the associations were modeled by restricted cubic splines regression analysis. After categorizing all subjects (n=8,900) into octiles based on their BMI levels, we estimated the hazard ratio (HR) for the association of categorized BMI levels with the risk of incident CVD and type 2 diabetes using a Cox’s proportional hazard analysis.
Results The mean age of participants was 52 years and 48% were men. Of the subjects at baseline, 39.0% of men and 45.6% of women were classified as obese (BMI ≥25 kg/m2). Over a mean follow-up of 8.1 years, CVD events occurred in 509 participants; 436 died; and 1,258 subjects developed type 2 diabetes. The increased risk of incident diabetes began to be significant at BMI 23 to 24 kg/m2 in both sexes (HR, 1.8). For CVD events, the risk began to increase significantly at BMI 26 to 28 kg/m2 (HR, 1.6). We found a reverse J-shaped relationship between BMI and all-cause mortality, with an increased risk among individuals with BMI values in lower range (BMI <21 kg/m2).
Conclusion These results suggest that the BMI cut-off points for observed risk were varied depending on the diseases and that the BMI classification of obesity need to be revised to reflect differential risk of obesity-related diseases.
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Zhipeng Huang, Donghong Wei, Xueping Yu, Zicheng Huang, Yijie Lin, Wenji Lin, Zhijun Su, Jianjia Jiang Medicine.2023; 102(6): e32922. CrossRef - Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality
Yoon-Jong Bae, Sang-Jun Shin, Hee-Taik Kang BMC Endocrine Disorders.2022;[Epub] CrossRef - Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults
Chul Woo Ahn, Sungjae Shin, Seunghyun Lee, Hye-Sun Park, Namki Hong, Yumie Rhee Endocrinology and Metabolism.2022; 37(5): 781. CrossRef - The Prognostic Value of Combined Status of Body Mass Index and Psychological Well-Being for the Estimation of All-Cause and CVD Mortality Risk: Results from a Long-Term Cohort Study in Lithuania
Dalia Lukšienė, Abdonas Tamosiunas, Ricardas Radisauskas, Martin Bobak Medicina.2022; 58(11): 1591. CrossRef - The Relationship between Body Mass Index and Incident Diabetes Mellitus in Chinese Aged Population: A Cohort Study
M. L. Tang, Y. Q. Zhou, A. Q. Song, J. L. Wang, Y. P. Wan, R. Y. Xu, Carol Forsblom Journal of Diabetes Research.2021; 2021: 1. CrossRef - Correlation between adiponectin level and the degree of fibrosis in patients with non-alcoholic fatty liver disease
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- Clinical Study
- Glucose-Dependent Insulinotropic Peptide Level Is Associated with the Development of Type 2 Diabetes Mellitus
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Sunghwan Suh, Mi Yeon Kim, Soo Kyoung Kim, Kyu Yeon Hur, Mi Kyoung Park, Duk Kyu Kim, Nam H. Cho, Moon-Kyu Lee
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Endocrinol Metab. 2016;31(1):134-141. Published online March 16, 2016
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DOI: https://doi.org/10.3803/EnM.2016.31.1.134
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2,932
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Abstract
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- Background
Incretin hormone levels as a predictor of type 2 diabetes mellitus have not been fully investigated. Therefore, we measured incretin hormone levels to examine the relationship between circulating incretin hormones, diabetes, and future diabetes development in this study. MethodsA nested case-control study was conducted in a Korean cohort. The study included the following two groups: the control group (n=149), the incident diabetes group (n=65). Fasting total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic peptide (GIP) levels were measured and compared between these groups. ResultsFasting total GIP levels were higher in the incident diabetes group than in the control group (32.64±22.68 pmol/L vs. 25.54±18.37 pmol/L, P=0.034). There was no statistically significant difference in fasting total GLP-1 levels between groups (1.14±1.43 pmol/L vs. 1.39±2.13 pmol/L, P=0.199). In multivariate analysis, fasting total GIP levels were associated with an increased risk of diabetes (odds ratio, 1.005; P=0.012) independent of other risk factors. ConclusionFasting total GIP levels may be a risk factor for the development of type 2 diabetes mellitus. This association persisted even after adjusting for other metabolic parameters such as elevated fasting glucose, hemoglobin A1c, and obesity in the pre-diabetic period.
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Jenna E. Hunt, Jens J. Holst, Sara L. Jepsen Frontiers in Endocrinology.2022;[Epub] CrossRef - Combined treatment with a gastric inhibitory polypeptide receptor antagonist and a peptidyl peptidase-4 inhibitor improves metabolic abnormalities in diabetic mice
Fei Yang, Shan Dang, Hongjun LV, Bingyin Shi Journal of International Medical Research.2021; 49(1): 030006052098566. CrossRef - Elevated levels of fasting serum GIP may be protective factors for diabetic retinopathy in type 2 diabetes mellitus
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- Sex Factors in the Metabolic Syndrome as a Predictor of Cardiovascular Disease
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Sunghwan Suh, Jongha Baek, Ji Cheol Bae, Kyoung-Nyoun Kim, Mi Kyoung Park, Duk Kyu Kim, Nam H. Cho, Moon-Kyu Lee
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Endocrinol Metab. 2014;29(4):522-529. Published online December 29, 2014
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DOI: https://doi.org/10.3803/EnM.2014.29.4.522
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- Background
Metabolic syndrome (MetS) is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD. MethodsA total of 8,898 subjects (4,241 males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up). ResultsThe prevalence of MetS at baseline was 22.0% (932/4,241) and 29.7% (1,383/4,657) in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95% confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females) and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females). Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192). Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk. ConclusionMetS is a significant risk factor for the development of CVD although its impact varies between sexes.
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