Diabetes & Metabolism Journal

Original Articles

Metabolic Risk/Epidemiology
Birth Weight, Adult Fat Distribution, and Type 2 Diabetes Mellitus Risk: Sex-Specific Study in a Large Prospective Cohort: Ding Ding, Xiaoyi Luo, Shuhao Chen, Zhilin Liu, Xiaojing Kuang, Tianrui Zhuang, Gaoli She, Hailan Huang, Xingfen Yang, Jie Li, Ran An; Received June 29, 2025 Accepted October 23, 2025 Published online January 29, 2026; DOI: https://doi.org/10.4093/dmj.2025.0569 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Regional fat distribution is a key determinant of metabolic risk, independent of total adiposity. However, the developmental origins of fat depot-specific accumulation and its contribution to type 2 diabetes mellitus (T2DM) remain unclear. We aimed to investigate whether adult fat distribution mediates the association between birth weight (BW) and T2DM risk.
Methods
We analyzed 30,718 diabetes-free UK Biobank participants with magnetic resonance imaging/dual-energy X-ray absorptiometry derived measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and gynoid adipose tissue (GAT), liver fat fraction (LFF), pancreatic fat fraction (PFF), and muscle fat infiltration (MFI). Fat depots were adjusted for body mass index (BMI) using sex-specific residuals. Cox regression assessed associations of BW and fat depots with T2DM risk. Mediation analysis assessed indirect effects of fat distribution.
Results
Lower BW was associated with a higher risk of T2DM (hazard ratio per 1 kg increase, 0.71; 95% confidence interval, 0.64 to 0.79), with stronger effects in women. Lower BW was linked to greater VAT, LFF, and PFF, and lower GAT, independent of BMI. Higher levels of VAT, LFF, and PFF were associated with increased T2DM risk, while GAT was protective. Mediation analysis revealed that fat distribution partially mediated the BW-T2DM relationship, with LFF showing the strongest mediation effect (11%). Mediation patterns differed by sex: LFF and VAT were the predominant mediators in women, while LFF and GAT contributed substantially in men.
Conclusion
Fat distribution—particularly liver and visceral fat—partially mediates the BW-T2DM relationship, independent of BMI. These findings highlight the clinical importance of fat depot profiling in understanding the developmental origins of diabetes and guiding early risk stratification.

Genetics
Evaluation of Sex-Stratified Polygenic Risk Scores for Type 2 Diabetes Mellitus and Glycemic Traits in the Framingham Heart Study: Ningyuan Wang, Yixin Zhang, Philip Schroeder, Alicia Huerta-Chagoya, Ravi Mandla, James B. Meigs, Alisa K. Manning, Ching-Ti Liu, Josée Dupuis, Josep M. Mercader; Received June 25, 2025 Accepted October 14, 2025 Published online December 9, 2025; DOI: https://doi.org/10.4093/dmj.2025.0557 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetes is a multifactorial disease with significant genetic predisposition. Polygenic risk scores (PRS) have been developed to estimate an individual’s genetic risk of a disease. Traditionally, PRS utilize sex-combined genome-wide association studies (GWAS) due to the limited availability of sex-stratified summary statistics. This study explores sex-dimorphic genetic effects and evaluates the potential benefits of incorporating sex-stratified effects in PRS for type 2 diabetes mellitus (T2DM) and glycemic traits by comparing PRS performance derived from sex-combined versus sex-stratified GWAS.
Methods
We performed a sex-heterogeneity test across sex-specific GWAS and identified nine signals with sex-dimorphic effects for T2DM. PRS[sex-combined] and PRS[sex-stratified] were developed using sex-combined and sex-stratified GWAS results for T2DM (41,444 cases and 354,539 controls), fasting glucose (n=120,595) and fasting insulin (n=98,210). We evaluated these PRS models in 8,379 participants (1,303 cases and 7,076 controls) from the Framingham Heart Study not included in the PRS derivation.
Results
Our findings suggest that sex-combined PRS currently offer better predictive performance for T2DM and glycemic traits.
Conclusion
These results highlight the need for larger sex-stratified studies and the optimization of sex-stratified risk models for clinical practice.

Metabolic Risk/Epidemiology
Temporal Changes in Resting Heart Rate and Risk of Diabetes Mellitus: Mi Kyoung Son, Kyoungho Lee, Hyun-Young Park; Diabetes Metab J. 2024;48(4):752-762. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0305

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Background
To investigate the association between the time-varying resting heart rate (RHR) and change in RHR (∆RHR) over time and the risk of diabetes mellitus (DM) by sex.
Methods
We assessed 8,392 participants without DM or atrial fibrillation/flutter from the Korean Genome and Epidemiology Study, a community-based prospective cohort study that was initiated in 2001 to 2002. The participants were followed up until December 31, 2018. Updating RHR with biennial in-study re-examinations, the time-varying ∆RHR was calculated by assessing the ∆RHR at the next follow-up visit.
Results
Over a median follow-up of 12.3 years, 1,345 participants (16.2%) had DM. As compared with RHR of 60 to 69 bpm, for RHR of ≥80 bpm, the incidence of DM was significantly increased for both male and female. A drop of ≥5 bpm in ∆RHR when compared with the stable ∆RHR group (–5< ∆RHR <5 bpm) was associated significantly with lower risk of DM in both male and female. However, an increase of ≥5 bpm in ∆RHR was significantly associated with higher risk of DM only in female, not in male (hazard ratio for male, 1.057 [95% confidence interval, 0.869 to 1.285]; and for female, 1.218 [95% confidence interval, 1.008 to 1.471]).
Conclusion
In this community-based longitudinal cohort study, a reduction in ∆RHR was associated with a decreased risk of DM, while an increase in ∆RHR was associated with an increased risk of DM only in female.

Citations

Citations to this article as recorded by

Unstable resting heart rate trajectory patterns are associated with an increase in incident risk of type 2 diabetes mellitus: the China-PAR project
Yuying Wu, Yang Zhao, Yanyan Zhang, Xueru Fu, Liuding Wen, Weifeng Huo, Jianxin Li, Xiangfeng Lu, Fulan Hu, Dongsheng Hu, Ming Zhang
Journal of Epidemiology and Community Health.2025; 79(10): 758. CrossRef

Metabolic Risk/Epidemiology
Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study: He Gao, Jinying Yang, Wenfei Pan, Min Yang; Diabetes Metab J. 2022;46(2):307-318. Published online March 7, 2022; DOI: https://doi.org/10.4093/dmj.2020.0287

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Background
Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference.
Methods
Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes.
Results
According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes.
Conclusion
IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

Citations

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Sex-specific associations between exposure to metal mixtures and mitochondrial DNA copy number: A repeated-measures study
Junxiu He, Xiaoting Ge, Sencai Lin, Yu Bao, Hong Cheng, Sihan Hu, Xiuming Feng, Qinghua Fan, Ying Yang, Xiaobo Yang
Journal of Environmental Sciences.2026; 161: 761. CrossRef
A genetic association study of iron absorption in adults of East Asian or Northern European ancestry from the Iron Genes in East Asian and Northern European Adults Study (FeGenes)
Alexa Barad, Huifang Xu, Andrew G Clark, Zhenglong Gu, Eva K Pressman, Kaixiong Ye, Kimberly O O’Brien
The American Journal of Clinical Nutrition.2026; 123(6): 101298. CrossRef
Iron Overload: Pathophysiology, Diagnosis and Monitoring
Elena Chatzikalil, Polyxeni Delaporta, Konstantinos Bistas, Antonis Kattamis
International Journal of Laboratory Hematology.2026;[Epub] CrossRef
Effect of Lifestyle Intervention on the Mobilization of Fat Depots and Organ Iron Deposition in Individuals with Obesity: A Prospective Study
Hong Liu, Junhong Duan, Gaopeng Guan, Pengfei Rong, Ping Jin
Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 4113. CrossRef
Role of nutrition in diabetes mellitus and infections
Xue-Lu Yu, Li-Yun Zhou, Xiao Huang, Xin-Yue Li, Ming-Ke Wang, Ji-Shun Yang
World Journal of Clinical Cases.2025;[Epub] CrossRef
Characterization of iron status biomarkers and hematological indices among young adults of East Asian or Northern European ancestry: A cross-sectional analysis from the Iron Genes in East Asian and Northern European Adults Study (FeGenes)
Alexa Barad, Yaqin Xu, Erica Bender, Wanhui Kang, Ruihan Xu, Zhenglong Gu, Eva K Pressman, Kimberly O O’Brien
The American Journal of Clinical Nutrition.2025; 121(2): 394. CrossRef
Associations between iron status and diabetic kidney disease: A nationwide study
Liya Gong, Yanpei Mai, Ziqi Wu, Jingwen Luo, Ge Wen
Nutrition, Metabolism and Cardiovascular Diseases.2025; 35(8): 103907. CrossRef
Differences in nonheme iron absorption between healthy adults of East Asian or Northern European ancestry from the Iron Genes in East Asian and Northern European Adults Study (FeGenes): A cross-sectional stable iron isotope study
Alexa Barad, Yaqin Xu, Erica Bender, Eva K Pressman, Zhenglong Gu, Kimberly O O’Brien
The American Journal of Clinical Nutrition.2025; 121(2): 417. CrossRef
Research on the Relationship Between Ectopic Fat and Iron Deposition in the Liver and Pancreas, with Glucose Metabolism in Elderly Obese Patients
Hao Nie, Min Liu, Junhong Duan, Hong Liu
Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 2331. CrossRef
Associations Between Dietary Iron, SNP rs2794720, and Metabolic Syndrome Risk in Chinese Males and Females: A Community-Based Study in a Chinese Metropolis
Zihan Hu, Hongwei Liu, Zhengyuan Wang, Jiajie Zang, Fan Wu, Zhenni Zhu
Nutrients.2025; 17(20): 3185. CrossRef
The nomenclature of fatty liver disease and its impact on obesity traits, insulin resistance, and hepatic fibrosis
Liangguang Xiang, Xiaoyun Li, Jiamin Gong, Long He, Wanxin Li, Jun Chen, Ruimei Feng, Shanshan Du, Weimin Ye
Lipids in Health and Disease.2025;[Epub] CrossRef
Ferroptosis in diabetes mellitus and its complications: overview of clinical and preclinical research
Xiaoya Li, Meirong Fang, Xingyu Liu, Jingyi Jiang, Shengchen Wang, Xiaoshuang Mao, Zhongmei Zou, Wen Jin
Cell Death Discovery.2025;[Epub] CrossRef
Micronutrient Patterns and Low Intake of Vitamin A, Vitamin D, Folate, Magnesium, and Potassium Among Prediabetes and Type 2 Diabetes Patients
Oana C Iatcu, Andrei Lobiuc, Mihai Covasa
Cureus.2024;[Epub] CrossRef
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Burhan Basaran, Hulya Turk
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Quantitative susceptibility mapping for iron monitoring of multiple subcortical nuclei in type 2 diabetes mellitus: a systematic review and meta-analysis
Sana Mohammadi, Sadegh Ghaderi, Fatemeh Sayehmiri, Mobina Fathi
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The Association Between Dietary Iron, the SNP of the JAZF1 rs864745, and Glucose Metabolism in a Chinese Population
Zihan Hu, Hongwei Liu, Baozhang Luo, Chunfeng Wu, Changyi Guo, Zhengyuan Wang, Jiajie Zang, Fan Wu, Zhenni Zhu
Nutrients.2024; 16(22): 3831. CrossRef
Plasma Ferritin Concentrations in the General Population: A Cross-Sectional Analysis of Anthropometric, Metabolic, and Dietary Correlates
Cara Övermöhle, Sabina Waniek, Gerald Rimbach, Katharina Susanne Weber, Wolfgang Lieb
The Journal of Nutrition.2023; 153(5): 1524. CrossRef
Association of Body Iron Metabolism with Type 2 Diabetes Mellitus in Chinese Women of Childbearing Age: Results from the China Adult Chronic Disease and Nutrition Surveillance (2015)
Jie Feng, Xiaoyun Shan, Lijuan Wang, Jiaxi Lu, Yang Cao, Lichen Yang
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Iron overload induces islet β cell ferroptosis by activating ASK1/P-P38/CHOP signaling pathway
Ling Deng, Man-Qiu Mo, Jinling Zhong, Zhengming Li, Guoqiao Li, Yuzhen Liang
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The role of ferroptosis in metabolic diseases
Ling Xie, Bin Fang, Chun Zhang
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2023; 1870(6): 119480. CrossRef
Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes
Xuekui Liu, Xiu Hong, Shiqiang Jiang, Rui Li, Qian Lv, Jie Wang, Xiuli Wang, Manqing Yang, Houfa Geng, Yang Li
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Association between serum iron and liver transaminases based on a large adult women population
Andong He, Zhuoping Zhou, Lili Huang, Ka Cheuk Yip, Jing Chen, Ruiling Yan, Ruiman Li
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Association between serum ferritin and uric acid levels and nonalcoholic fatty liver disease in the Chinese population
Fangli Zhou, Xiaoli He, Dan Liu, Yan Ye, Haoming Tian, Li Tian
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The Role of Iron Overload in Diabetic Cognitive Impairment: A Review
Ji-Ren An, Qing-Feng Wang, Gui-Yan Sun, Jia-Nan Su, Jun-Tong Liu, Chi Zhang, Li Wang, Dan Teng, Yu-Feng Yang, Yan Shi
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 3235. CrossRef
The Association Between METS-IR and Serum Ferritin Level in United States Female: A Cross-Sectional Study Based on NHANES
Han Hao, Yan Chen, Ji Xiaojuan, Zhang Siqi, Chu Hailiang, Sun Xiaoxing, Wang Qikai, Xing Mingquan, Feng Jiangzhou, Ge Hongfeng
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Iron deficiency in cardiac surgical patients
L Hof, O Old, A.U. Steinbicker, P Meybohm, S Choorapoikayil, K Zacharowski
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Metabolic Risk/Epidemiology
Sex Differences in the Effects of CDKAL1 Variants on Glycemic Control in Diabetic Patients: Findings from the Korean Genome and Epidemiology Study: Hye Ah Lee, Hyesook Park, Young Sun Hong; Diabetes Metab J. 2022;46(6):879-889. Published online February 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0265

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Background
Using long-term data from the Korean Genome and Epidemiology Study, we defined poor glycemic control and investigated possible risk factors, including variants related to type 2 diabetes mellitus (T2DM). In addition, we evaluated interaction effects among risk factors for poor glycemic control.
Methods
Among 436 subjects with newly diagnosed diabetes, poor glycemic control was defined based on glycosylated hemoglobin trajectory patterns by group-based trajectory modeling. For the variants related to T2DM, genetic risk scores (GRSs) were calculated and divided into quartiles. Risk factors for poor glycemic control were assessed using a logistic regression model.
Results
Of the subjects, 43% were in the poor-glycemic-control group. Body mass index (BMI) and triglyceride (TG) were associated with poor glycemic control. The risk for poor glycemic control increased by 11.0% per 1 kg/m² increase in BMI and by 3.0% per 10 mg/dL increase in TG. The risk for GRS with poor glycemic control was sex-dependent (P_interaction=0.07), and a relationship by GRS quartiles was found in females but not in males. Moreover, the interaction effect was found to be significant on both additive and multiplicative scales. The interaction effect was evident in the variants of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1).
Conclusion
Females with risk alleles of variants in CDKAL1 associated with T2DM had a higher risk for poor glycemic control than males.

Citations

Citations to this article as recorded by

Sex‐ and age‐specific determinants of diabetes: Insights from BKMR and cox modelling of metabolic and lifestyle risk factors in a Korean cohort
Hye Ah Lee
Diabetes, Obesity and Metabolism.2025; 27(9): 5247. CrossRef
Hepatic Cdkal1 deletion regulates HDL catabolism and promotes reverse cholesterol transport
Dan Bi An, Soo-jin Ann, Seungmin Seok, Yura Kang, Sang-Hak Lee
Atherosclerosis.2023; 375: 21. CrossRef

Metabolic Risk/Epidemiology
Longitudinal Change in Myocardial Function and Clinical Parameters in Middle-Aged Subjects: A 3-Year Follow-up Study: Dong-Hyuk Cho, Hyung Joon Joo, Mi-Na Kim, Hee-Dong Kim, Do-Sun Lim, Seong-Mi Park; Diabetes Metab J. 2021;45(5):719-729. Published online June 15, 2021; DOI: https://doi.org/10.4093/dmj.2020.0132

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Background
Metabolic syndrome (MetS) is closely associated with the aging process. However, changes in metabolic conditions and cardiac function that occur in middle aged population remain unclear. We evaluated longitudinal changes in metabolic parameters and cardiac function during a 3-year period in subjects with suspected MetS.
Methods
We studied 191 participants with suspected MetS at baseline and after 3 years. Anthropometric parameters, including waist circumference (WC), and metabolic parameters, including fasting blood glucose and lipid profile were measured. Conventional echocardiography with two-dimensional speckle tracking was performed.
Results
Mean age was 56.2±4.4 years, and there were 97 women (50.8%). Men had increased WC and triglycerides (TG) (WC 91.2±6.8 cm vs. 84.0±8.0 cm, P<0.001; TG 184.4±116.3 mg/dL vs. 128.2±53.6 mg/dL, P<0.001), and reduced global longitudinal strain (GLS) (–15.4%±2.1% vs. –17.1%±2.0%, P<0.001) compared to women. After 3.4 years, values of WC and TG did not change in men but increased in women (all P<0.05). The absolute value of left ventricular (LV) GLS did not change in men but was reduced in women (P=0.011). Change in TG was independently associated with worsening of LV GLS only in women (standardized β, –0.309; 95% confidence interval, –0.130 to –0.009; P=0.025).
Conclusion
In middle aged population, a vulnerable period for metabolic disturbance, cardiac remodeling tended to progress, which was prominent in women. Progression of adiposity and dyslipidemia after menopause may accelerate subclinical cardiac remodeling in middle-aged women. Lifestyle modification and medical interventions may help prevent further cardiac dysfunction in these subjects.

Citations

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Positive additive interaction effects of age, sex, obesity, and metabolic syndrome on left ventricular dysfunction
Dan Zhou, Zhongwen Ye, Zhiqiang Nie, Chaolei Chen, Songyuan Luo, Mengqi Yan, Jiabin Wang, Yingqing Feng
Journal of Diabetes.2024;[Epub] CrossRef
Epicardial Adipose Tissue and Heart Failure, Friend or Foe?
Dong-Hyuk Cho, Seong-Mi Park
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Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients
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Obesity and Metabolic Syndrome
The Relationship between Thyroid Function and Different Obesity Phenotypes in Korean Euthyroid Adults: Jeong Mi Kim, Bo Hyun Kim, Hyungi Lee, Eun Heui Kim, Mijin Kim, Jong Ho Kim, Yun Kyung Jeon, Sang Soo Kim, In Joo Kim, Yong Ki Kim; Diabetes Metab J. 2019;43(6):867-878. Published online April 3, 2019; DOI: https://doi.org/10.4093/dmj.2018.0130

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Background

Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete.

Methods

This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health.

Results

At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P<0.001) in total study population. However, this significant association no longer remained after adjustment for age, urine iodine concentration, and smoking (P=0.085). After adjustment for confounders, statistically significant association was observed between lower thyroid stimulating hormone (TSH) and MHNO phenotype (P=0.044). In men participants (not women), higher fT4 values were significantly associated with MHNO phenotype (P<0.001). However, no significant association was observed between thyroid function (TSH or fT4) and obesity phenotypes in groups classified by age (cutoff age of 55 years).

Conclusion

Although there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.

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Min-Hee Kim, Jeongmin Lee, Dong-Jun Lim, Kyle Masato Ishikawa, James Davis, Eunjung Lim, Hyeong Jun Ahn
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Yingkun Qiu, Qinyu Liu, Yinghua Luo, Jiadi Chen, Qingzhu Zheng, Yuping Xie, Yingping Cao
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Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population: Min Jin Go, Joo-Yeon Hwang, Tae-Joon Park, Young Jin Kim, Ji Hee Oh, Yeon-Jung Kim, Bok-Ghee Han, Bong-Jo Kim; Diabetes Metab J. 2014;38(5):375-387. Published online October 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.5.375

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Background

Until recently, genome-wide association study (GWAS)-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM) or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration of potential confounding factors will be very valuable for clinical applicability. To identify novel susceptibility loci for T2DM and glycemic traits, we performed a two-stage genetic association study in a Korean population.

Methods

We performed a logistic analysis for T2DM, and the first discovery GWAS was analyzed for 1,042 cases and 2,943 controls recruited from a population-based cohort (KARE, n=8,842). The second stage, de novo replication analysis, was performed in 1,216 cases and 1,352 controls selected from an independent population-based cohort (Health 2, n=8,500). A multiple linear regression analysis for glycemic traits was further performed in a total of 14,232 nondiabetic individuals consisting of 7,696 GWAS and 6,536 replication study participants. A meta-analysis was performed on the combined results using effect size and standard errors estimated for stage 1 and 2, respectively.

Results

A combined meta-analysis for T2DM identified two new (rs11065756 and rs2074356) loci reaching genome-wide significance in CCDC63 and C12orf51 on the 12q24 region. In addition, these variants were significantly associated with fasting plasma glucose and homeostasis model assessment of β-cell function. Interestingly, two independent single nucleotide polymorphisms were associated with sex-specific stratification in this study.

Conclusion

Our study showed a strong association between T2DM and glycemic traits. We further observed that two novel loci with multiple diverse effects were highly specific to males. Taken together, these findings may provide additional insights into the clinical assessment or subclassification of disease risk in a Korean population.

Citations

Citations to this article as recorded by

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Letter: Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population (Diabetes Metab J2014;38:375-87)
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Response: Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population (Diabetes Metab J2014;38:375-87)
Min Jin Go, Bong-Jo Kim
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Sex Hormone Binding Globulin, Body Fat Distribution and Insulin Resistance in Premenopausal Women.: Young Sook Lee, Hye Jin Lee, Jee Young Oh, Young Sun Hong, Yeon Ah Sung; Korean Diabetes J. 2003;27(1):63-72. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Low levels of sex-hormone binding globulin (SHBG), an indirect index of androgenicity, have been reported to be associated with obesity, especially central obesity. In women, increased androgenicity is related to hyperinsulinemia, impaired glucose tolerance and the development of type 2 diabetes mellitus. Recent studies have suggested that the relationship between SHBG and insulin resistance was mediated by the change in total or visceral adiposity, and that ethnical differences in the relationship between sex hormone and body fat distribution might exist. METHODS: We examined the associations of SHBG to the body fat distribution and insulin resistance in Korean premenopausal women. The fasting serum level of SHBG was measured by RIA, and the insulin sensitivity by the minimal model derived sensitivity index (SI), using the insulin modified intravenous glucose tolerance test. The amount of body fat, and its distribution, were assessed by anthropometric measurement, bioelectric impedance analyses, and computed tomography at the level of the umbilicus. RESULTS: 1. SHBG was significantly inversely correlated with the body mass index (BMI), waist circumference, visceral fat area, and fasting insulin levels, and was significantly positively correlated to the SI. 2. SHBG was significantly lower in premenopausal women with an impaired glucose tolerance, compared to those with a normal glucose tolerance, and significantly lower in those with hypertension (systolic BP> or =140 mmHg or diastolic BP> or =90 mmHg), compared to those with normal blood pressure. SHBG was also significantly lower in persons with central obesity(waist circumference > or = 80 cm) compared to those without. 3. In a multiple linear regression analysis, the SI was significantly associated with SHBG, after adjustment for age, BMI, systolic blood pressure, triglycerides, HDL- cholesterol, and percentage body fat, but this association disappeared after additional adjustment for visceral fat area. 4. In a multiple linear regression analysis, the fasting plasma insulin, BMI and percentage body fat were significant independent factors associated with SHBG. CONCLUSION: Increased androgenicity as assessed by decreased serum SHBG concentrations, is strongly associated with an unfavorable body fat distribution, hypertension, glucose intolerance, hyperinsulinemia, and insulin resistance.

Free Testosterone and Sex Hormone-Binding Globulin Level in Type 2 Diabetic Men.: Ki Deuk Nam, Young Seol Kim, Cheol Young Park, Seung Joon Oh, Deog Yoon Kim, Jeong Taek Woo, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Kil Choi; Korean Diabetes J. 2000;24(6):699-707. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance is a risk factor for cardiovascular disease and type 2 diabetes mellitus. There are many previous studies indicating that insulin lowers serum sex hormone-binding globulin levels, and there is inverse correlation between insulin resistance and serum sex hormone-binding globulin levels in women. However, in men, a limited number of studies are available to explain the effect of sex hormone on age and insulin. Therefore, the present study was undertaken to investigate the relationship among free testosterone, hormone- binding globulin and age in type 2 diabetic men and control subjects. METHOD: Age, body mass index, total cholesterol, triglyceride, fasting blood sugar, and insulin concentrations were examined on 89 type 2 diabetic men and 47 control subjects. The free testosterone level was measured by commercially available double-antibody system (Radioimmunoassay). The sex hormone-binding globulin level was also measured by commercially available double-antibody system(Immunoradiometric assay). RESULTS: 1) Sex hormone-binding globulin level was significantly increased in patients with type 2 diabetes. However, there was no significant difference in free testosterone level between the two groups. 2) Sex hormone-binding globulin was positively correlated with age (r=0.4, p<0.001) in patients with type 2 diabetes. Sex hormone-binding globulin and free testos terone were not correlated with age in control sujects. 3) Free testosterone and sex hormone-binding globulin concentrations were not significantly related to serum insulin concentration after adjusting for age and body mass index. CONCLUSIONS: We observed increased sex hormone-binding globulin concentration in diabetes man, and was a positively related to age. Further studies are needed to understand the relationships between age, insulin resistance, testosterone, and sex hormone-binding globulin concentrations.

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