Diabetes & Metabolism Journal

Original Article

Genetics
Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population: Heejin Jin, Soo Heon Kwak, Ji Won Yoon, Sanghun Lee, Kyong Soo Park, Sungho Won, Nam H. Cho; Diabetes Metab J. 2023;47(2):255-266. Published online January 19, 2023; DOI: https://doi.org/10.4093/dmj.2021.0375

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Background
Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time.
Methods
We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project.
Results
A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic β-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level.
Conclusion
We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.

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Corrigendum

Clinical Significance of Body Fat Distribution in Coronary Artery Calcification Progression in Korean Population: Heesun Lee, Hyo Eun Park, Ji Won Yoon, Su-Yeon Choi; Diabetes Metab J. 2021;45(6):974-974. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0304; Corrects: Diabetes Metab J 2021;45(2):219

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Original Article

Cardiovascular Risk/Epidemiology
Clinical Significance of Body Fat Distribution in Coronary Artery Calcification Progression in Korean Population: Heesun Lee, Hyo Eun Park, Ji Won Yoon, Su-Yeon Choi; Diabetes Metab J. 2021;45(2):219-230. Published online October 28, 2020; DOI: https://doi.org/10.4093/dmj.2019.0161; Correction in: Diabetes Metab J 2021;45(6):974

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Background
Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression.
Methods
This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units.
Results
During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m², increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P<0.001) and remained of prognostic value regardless of BMI or WC status. Further, it provided improved risk stratification of CAC progression beyond known prognosticators.
Conclusion
Predominant VAT area on CT is the strongest predictor of CAC progression regardless of BMI or WC in apparently healthy Korean population. Assessment of body fat distribution may be helpful to identify subjects at higher risk.

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Response

Response: Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging (Diabetes Metab J 2016;40:140-6): Ji Won Yoon, Hak Chul Jang; Diabetes Metab J. 2016;40(3):250-251. Published online June 20, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.250

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Original Articles

Clinical Care/Education
Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging: Ji Won Yoon, Yong-Chan Ha, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Soo Lim, Young Joo Park, Jae Young Lim, Ki Woong Kim, Kyong Soo Park, Hak Chul Jang; Diabetes Metab J. 2016;40(2):140-146. Published online March 31, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.2.140

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Background

The study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes.

Methods

This was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (n=30) and uncertainty about the diagnosis of diabetes (n=27). Body composition was measured using dual-energy X-ray absorptiometry and computed tomography. Muscle strength for knee extension was measured using an isokinetic dynamometer. Muscle quality was assessed from the ratio of leg strength to the entire corresponding leg muscle mass.

Results

The muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c) level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510; P=0.045) after adjustment for age, body mass index, smoking amount, alcohol consumption, physical activity, and duration of diabetes. Physical performance status was also impaired in subjects with an HbA1c of ≥8.5%.

Conclusion

Poor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.

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Prevalence and Clinical Characteristics of Aspirin Resistance in the Patients with Type 2 Diabetes Mellitus.: Mi Yeon Kang, Young Min Cho, Hyun Kyung Kim, Jee Hyun An, Hwa Young Ahn, Ji Won Yoon, Hoon Sung Choi, Jie Seon Lee, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2008;32(1):53-59. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.53

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BACKGROUND
We examined the prevalence and clinical characteristics of aspirin resistance in the Korean patients with type 2 diabetes mellitus. METHODS: We studied 181 Korean patients with type 2 diabetes mellitus who were taking aspirin (100 mg/day for > or = 3 months) and no other antiplatelet agents. The VerifyNow System was used to determine aspirin responsiveness. Aspirin resistance was defined as an aspirin reaction unit (ARU) > or = 550. We measured the cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) to evaluate arteriosclerosis. The anthropometric parameters, electrocardiogram, blood pressure, fasting plasma glucose, lipid profiles, hemoglobin A1c, highly sensitive C-reactive protein (hsCRP), homocysteine, and microalbuminuria were measured in each patient. RESULTS: The prevalence of aspirin resistance in type 2 diabetic patients was 9.4% (17 of 181). Those who had aspirin resistance were older than those without aspirin resistance (64.6 +/- 10.6 vs. 59.8 +/- 8.1, P = 0.024). Aspirin resistance was not associated with fasting plasma glucose, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, hemoglobin A1c, hsCRP, homocysteine, microalbuminuria, ABI, CAVI, and body mass index. CONCLUSION: Prevalence of aspirin resistance in the Korean patients with type 2 diabetes mellitus was 9.4%. Although aspirin resistance was associated with old age, we could not find any good clinical parameter to predict it. Therefore, aspirin resistance should be evaluated in diabetic patients taking aspirin for prevention of cardiovascular complications.

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Jue Wang, Bin Cao, Yan Gao, Dong Han, Haiping Zhao, Yuhua Chen, Yumin Luo, Juan Feng, Yanxia Guo
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