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1.  Utilizing Genetic Predisposition Score in Predicting Risk of Type 2 Diabetes Mellitus Incidence: A Community-based Cohort Study on Middle-aged Koreans 
Journal of Korean Medical Science  2015;30(8):1101-1109.
Contribution of genetic predisposition to risk prediction of type 2 diabetes mellitus (T2DM) was investigated using a prospective study in middle-aged adults in Korea. From a community cohort of 6,257 subjects with 8 yr' follow-up, genetic predisposition score with subsets of 3, 18, 36 selected single nucleotide polymorphisms (SNPs) (genetic predisposition score; GPS-3, GPS-18, GPS-36) in association with T2DM were determined, and their effect was evaluated using risk prediction models. Rs5215, rs10811661, and rs2237892 were in significant association with T2DM, and hazard ratios per risk allele score increase were 1.11 (95% confidence intervals: 1.06-1.17), 1.09 (1.01-1.05), 1.04 (1.02-1.07) with GPS-3, GPS-18, GPS-36, respectively. Changes in AUC upon addition of GPS were significant in simple and clinical models, but the significance disappeared in full clinical models with glycated hemoglobin (HbA1c). For net reclassification index (NRI), significant improvement observed in simple (range 5.1%-8.6%) and clinical (3.1%-4.4%) models were no longer significant in the full models. Influence of genetic predisposition in prediction ability of T2DM incidence was no longer significant when HbA1c was added in the models, confirming HbA1c as a strong predictor for T2DM risk. Also, the significant SNPs verified in our subjects warrant further research, e.g. gene-environmental interaction and epigenetic studies.
Graphical Abstract
PMCID: PMC4520941  PMID: 26240488
Diabetes Mellitus; Genetic Predisposition; Hemoglobin A, Glycosylated
2.  Diethylhexyl Phthalates Is Associated with Insulin Resistance via Oxidative Stress in the Elderly: A Panel Study 
PLoS ONE  2013;8(8):e71392.
Insulin resistance (IR) is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of IR. Therefore, we evaluated whether exposure to phthalates affects IR, and oxidative stress is involved in the phthalates-IR pathway.
We recruited 560 elderly participants, and obtained blood and urine samples during repeated medical examinations. For the determination of phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative stress biomarker, was also measured in urine samples. We measured serum levels of fasting glucose and insulin, and derived the homeostatic model assessment (HOMA) index to assess IR. A mixed-effect model and penalized regression spline were used to estimate the associations among phthalate metabolites, MDA, and IR.
The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.26, P = 0.040), and the association was apparent among participants with a history of DM (β = 0.88, P = 0.037) and among females (β = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not found. When we evaluated whether oxidative stress is involved in increases of HOMA by ∑DEHP, MDA levels were significantly associated with increases of ∑DEHP (β = 0.11, P<0.001) and HOMA (β = 0.49, P = 0.049).
Our study results suggest that exposure to DEHP in the elderly population increases IR, which is related with oxidative stress, and that participants with a history of DM and females are more susceptible to DEHP exposure.
PMCID: PMC3747269  PMID: 23977034
3.  PM10 Exposure and Non-accidental Mortality in Asian Populations: A Meta-analysis of Time-series and Case-crossover Studies 
We investigated the association between particulate matter less than 10 µm in aerodynamic diameter (PM10) exposure and non-accidental mortality in Asian populations by meta-analysis, using both time-series and case-crossover analysis.
Among the 819 published studies searched from PubMed and EMBASE using key words related to PM10 exposure and non-accidental mortality in Asian countries, 8 time-series and 4 case-crossover studies were selected for meta-analysis after exclusion by selection criteria. We obtained the relative risk (RR) and 95% confidence intervals (CI) of non-accidental mortality per 10 µg/m3 increase of daily PM10 from each study. We used Q statistics to test the heterogeneity of the results among the different studies and evaluated for publication bias using Begg funnel plot and Egger test.
Testing for heterogeneity showed significance (p<0.001); thus, we applied a random-effects model. RR (95% CI) per 10 µg/m3 increase of daily PM10 for both the time-series and case-crossover studies combined, time-series studies relative risk only, and case-crossover studies only, were 1.0047 (1.0033 to 1.0062), 1.0057 (1.0029 to 1.0086), and 1.0027 (1.0010 to 1.0043), respectively. The non-significant Egger test suggested that this analysis was not likely to have a publication bias.
We found a significant positive association between PM10 exposure and non-accidental mortality among Asian populations. Continued investigations are encouraged to contribute to the health impact assessment and public health management of air pollution in Asian countries.
PMCID: PMC3567321  PMID: 23407325
PM10; Non-accidental mortality; Asia; Meta-analysis
4.  Socioeconomic Inequalities in Adolescent Depression in South Korea: A Multilevel Analysis 
PLoS ONE  2012;7(10):e47025.
In recent years, South Korea has witnessed a sustained rise in the prevalence of adolescent depression. In the present study, we sought to investigate family and school environmental influences on adolescent depression.
Methods and Findings
Middle and high school students (N = 75,066) were randomly selected respondents to a web-based survey and answered questions on their academic and socioeconomic backgrounds, parental support, parental education level, physical activities, lifestyle habits and their experience of depression in the past one year. Two-level multilevel analysis was used to investigate the relationship between depression and individual (level 1) and school (level 2) factors. Girls reported having experienced depression in greater numbers than boys (43.96% vs. 32.03%). A significant association was found between adolescent depression experience and gender, grade, self-rated academic achievement, family affluence scale, parental support, parental education level, lifestyle habits, physical activity and sleep dissatisfaction. The students living with rich parents were more likely to be depressive, and maternal higher education was significantly associated with higher probability of boys’ depression experience. Low academic achievement was highly associated with the experience of depression. In school level contexts, girls were found to be less likely to be depressive in girls-only schools.
The adolescent depression experience is not only an individual phenomenon but is highly associated with other factors such as parents, peers, academic achievement, and even gender mix in the school. Thus, prevention measures on youth depression need to focus on emphasizing less pressure from parents on academic performance, and establishing healthy inter-gender relationships within co-education schools.
PMCID: PMC3471941  PMID: 23077540
5.  Air Pollution and Symptoms of Depression in Elderly Adults 
Environmental Health Perspectives  2012;120(7):1023-1028.
Background: Although the effect of air pollution on various diseases has been extensively investigated, few studies have examined its effect on depression.
Objectives: We investigated the effect of air pollution on symptoms of depression in an elderly population.
Methods: We enrolled 537 participants in the study who regularly visited a community center for the elderly located in Seoul, Korea. The Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was used to evaluate depressive symptomatology during a 3-year follow-up study. We associated ambient air pollutants with SGDS-K results using generalized estimating equations (GEE). We also conducted a factor analysis with items on the SGDS-K to determine which symptoms were associated with air pollution.
Results: SGDS-K scores were positively associated with interquartile range (IQR) increases in the 3-day moving average concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) [17.0% increase in SGDS-K score, 95% confidence interval (CI): 4.9%, 30.5%], the 0–7 day moving average of nitrogen dioxide [NO2; 32.8% (95% CI: 12.6%, 56.6%)], and the 3-day moving average of ozone [O3; 43.7% (95% CI: 11.5%, 85.2%)]. For these three pollutants, factor analysis showed that air pollution was more strongly associated with emotional symptoms such as feeling happy and satisfied than with somatic or affective symptoms.
Conclusions: Our study suggests that increases in PM10, NO2, and O3 may increase depressive symptoms among the elderly. Of the symptoms evaluated, ambient air pollution was most strongly associated with emotional symptoms.
PMCID: PMC3404652  PMID: 22514209
air pollution; depressive symptoms; elderly; factor analysis; panel study
6.  Association of Serum 25-Hydroxyvitamin D Levels with Markers for Metabolic Syndrome in the Elderly: A Repeated Measure Analysis 
Journal of Korean Medical Science  2012;27(6):653-660.
The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects.
PMCID: PMC3369452  PMID: 22690097
Vitamin D; Insulin Resistance; Metabolic Syndrome; Elderly; Mixed Effect Model

Results 1-6 (6)