Publications by authors named "Wen-Harn Pan"

204 Publications

The Healthy Taiwanese Eating Approach is inversely associated with all-cause and cause-specific mortality: A prospective study on the Nutrition and Health Survey in Taiwan, 1993-1996.

PLoS One 2021 6;16(5):e0251189. Epub 2021 May 6.

Institute of Population Health Science, National Health Research Institutes, Miaoli, Taiwan, R.O.C.

Background: Few longitudinal studies have investigated the association between foods/dietary pattern and mortality risk in the Asian population. We investigated the prospective association between foods/dietary pattern and risk of death among ethnic Chinese adults in Taiwan.

Methods: The study population included 2475 young and middle-aged adults (aged 18-65 years at baseline) who completed the questionnaires and physical examinations in the Nutrition and Health Survey in Taiwan from 1993 to 1996. A food frequency questionnaire was administered to assess food consumption habits in a face-to-face interview. With survey data linked to the Taiwanese Death Registry, Cox proportional hazard model was used to identify the foods associated with all-cause mortality(followed until 2012), which were then tallied to calculate a dietary pattern score called Taiwanese Eating Approach(TEA) score. The TEA scores were then associated with various kinds of mortality outcomes. In addition, data from 431 elders (aged≥65 yrs) with 288 death endpoints were used to conduct a sensitivity analysis.

Results: A total of 385(15.6%) participants died (111 cardiovascular related deaths and 122 cancer related deaths) during the 17.8-year follow-up period(41274 person-years). Twelve foods (9 inverse [vegetables/fish/milk/tea](+1) and 3 positive[fatty meats/fermented vegetables/sweet drinks](-1)) were significantly associated with all-cause mortality risk. All adults were grouped by their cumulative food score into three diet groups: poor diet(29.3% of all subjects), average diet(44.0%), and healthy diet(26.70%). The better the diet, the lower the total, cardiovascular, and other cause mortality outcomes (trend-p < .001). The hazard ratio for the healthy diet was 0.64 (95% confidence interval:0.47-0.87) for total mortality, and 0.52(0.28-0.95) for cardiovascular death, compared with the poor diet in the multivariable models. This phenomenon was also seen in older adults for all-cause, cancer, and other cause mortalities.

Conclusion: Consuming a healthy Taiwanese Eating Approach (TEA) diet is negatively associated with all-cause, cardiovascular, and other-cause mortalities in Taiwan.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251189PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101962PMC
May 2021

Adequate protein intake in older adults in the context of frailty: cross-sectional results of the Nutrition and Health Survey in Taiwan 2014-2017.

Am J Clin Nutr 2021 Apr 13. Epub 2021 Apr 13.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Background: Emerging evidence suggests that a dietary protein intake higher than the current recommended dietary allowance of 0.8 g/kg body weight (BW)/d may be needed to maintain optimal muscle mass, strength, and function in older adults. However, defining optimal protein intake in this age group remains a challenge.

Objective: In this study we sought to describe the dietary protein intake in frail, prefrail, and robust older Taiwanese adults.

Methods: Data for 1920 older adults were collected from the Nutrition and Health Survey in Taiwan from 2014 to 2017. Dietary intake was assessed using the 24-h recall method. Frailty was determined using the modified Fried's criteria. Body composition was assessed using DXA. Sex-specific dietary protein intakes, measured as values/kg of BW, fat-free mass (FFM), and lean mass (LM), were estimated for the 3 age groups (65-69, 70-79, and ≥80y) and the 3 frailty levels.

Results: In both males (P for trend = 0.034) and females (P for trend = 0.015), there were significant downward trends for protein intake/kg of BW with the severity of frailty. The age-adjusted protein intake/kg of BW was still significant in males (P for trend = 0.009), but no longer in females. This phenomenon was also seen for protein intake at lunch and dinner but not at breakfast. Age-adjusted trends for protein intake/kg FFM or LM were not significant in either sex. The median protein intake in robust older males and females was 1.21 and 1.19 g/kg BW/d, respectively, and the mean intakes were even higher.

Conclusion: Median protein intake in robust Taiwanese older adults was approximately 1.2 g/kg BW/d, with higher mean values. The protein adequate intake in Taiwanese older adults was higher than the current recommended daily allowance (RDA) level but within the RDA range derived from the state-of art indicator amino acid oxidation technique.
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http://dx.doi.org/10.1093/ajcn/nqab070DOI Listing
April 2021

Isolated systolic hypertension and central blood pressure: Implications from the national nutrition and health survey in Taiwan.

J Clin Hypertens (Greenwich) 2021 Mar 22;23(3):656-664. Epub 2020 Dec 22.

Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

We aimed to investigate the association between isolated systolic hypertension (ISH) and central blood pressure (BP) in a nationally representative population, with a focus on the young and middle-aged adults (<50 years old). A total of 2029 adults without taking antihypertensive medications, aged ≥ 19 years old, participated in the 2013-2016 National Nutrition and Health Survey in Taiwan. Central and brachial BP were simultaneously measured using a cuff-based stand-alone central blood pressure monitor purporting to measure invasive central BP (type II device). Central hypertension was defined by central systolic (SBP)/diastolic BP (DBP) ≥130 or 90 mm Hg, and ISH was defined by brachial SBP ≥ 140 and DBP < 90 mm Hg. Overall, the prevalence rates of ISH, isolated diastolic hypertension (IDH, brachial SBP < 140 and DBP ≥ 90 mmHg), and systolic/diastolic hypertension (SDH, brachial SBP ≥ 140 and DBP ≥ 90 mmHg) were 6.51%, 1.92%, and 4.34%, respectively. ISH subjects had significantly higher central pulse pressure (PP) (62.8 ± 9.7 mm Hg for age < 50 years and 72.4 ± 13.5 mmHg for age ≥ 50 years) than those subjects with either IDH (44.7 ± 10.7 and 44.9 ± 10.6 mmHg) or SDH (55.2 ± 14.0 and 62.6 ± 17.1 mmHg). All ISH adults had central hypertension, and a higher prevalence of central obesity than the normotensives (80.95% vs. 26.15%, for age < 50 years; and 63.96% vs. 43.37% for age ≥ 50 years). All untreated subjects with ISH, whether younger or older, had central hypertension and had significantly higher central PP than those with IDH or SDH. Central obesity was one of the major characteristics of ISH, especially in the young- and middle-aged adults.
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http://dx.doi.org/10.1111/jch.14105DOI Listing
March 2021

Life course body mass index through childhood and young adulthood and risks of asthma and pulmonary function impairment.

Pediatr Pulmonol 2021 May 27;56(5):849-857. Epub 2021 Jan 27.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC.

Background: Adiposity is a key risk factor for asthma and impaired pulmonary function.

Objectives: We aimed to identify the critical period of life course adiposity for asthma in childhood and young adulthood, and to determine whether associations of adiposity and asthma vary across ages.

Methods: Birth weight and body mass index (BMI) from birth to 17 years of age were assessed in 6130 children from the Taiwan Children Health Study. Logistic regression for asthma outcome and linear regression for pulmonary function outcome were used to investigate associations of adiposity with asthma. Seventeen BMI-related single-nucleotide polymorphisms were used to obtain genetic instrumental variables for adiposity to perform Mendelian randomization (MR) analysis.

Results: Using both regression model and MR analyses, we confirmed that the critical period of adiposity in predicting childhood asthma would be before age 6 years. Further, we discovered that the sensitive period of adiposity gain related to young adulthood asthma was the prepubertal stage. Risks of asthma at age 17 per unit increase in z-score of the BMI increased from 0.94 (95% CI: 0.79-1.11) at birth, and became greater than 1.00 between age 11 and 12, then increased to 1.08 (95% CI: 0.95-1.22) at age 17. The associations of life course BMI with asthma and pulmonary function impairment at age 12 and with asthma at age 17 increased with age. The aforementioned association was most prominent among central obesity indicators.

Conclusions: To prevent asthma in childhood and young adulthood, we should aim at promoting healthy growth at the toddler period and prepubertal stage.
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http://dx.doi.org/10.1002/ppul.25197DOI Listing
May 2021

Sex difference in sympathetic nervous system activity and blood pressure in hypertensive patients.

J Clin Hypertens (Greenwich) 2021 Jan 15;23(1):137-146. Epub 2020 Nov 15.

Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non-diabetic hypertensive patients aged 20-50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24-h ambulatory BP monitoring, and 24-h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24-h ambulatory BP, and 24-h urine catecholamine excretion. In men, 24-h urine total catecholamine levels were correlated with 24-h SBP (r = 0.103, p = .008) and 24-h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24-h urine total catecholamine levels and 24-h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01-3.29, p = .048) and 24-h urine total catecholamine (β = 5.03, 95% CI 0.62-9.44, p = .025) were both independently associated with 24-h SBP; being male was independently associated with 24-h DBP (β = 3.55, 95% CI 2.26-4.85, p < .001). In conclusion, Chinese men with hypertension had higher SNS activity than women, and SNS activity was independently associated with 24-h ambulatory BP in men rather than in women. These findings suggest that different hypertensive treatment strategies should be considered according to patient sex.
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http://dx.doi.org/10.1111/jch.14098DOI Listing
January 2021

Body composition patterns among normal glycemic, pre-diabetic, diabetic health Chinese adults in community: NAHSIT 2013-2016.

PLoS One 2020 4;15(11):e0241121. Epub 2020 Nov 4.

School of Public Health, College of Public Health, Taipei Medical University, Taipei City, Taiwan.

Background: Central obesity is known to be associated with diabetes. Increasing lower extremity circumference was hypothesized in association with lower risk of diabetes.

Objective: This study determined which anthropometric patterns correlates the best with pre-diabetic and diabetic status among healthy adults.

Design: Cross-sectional study with nationwide population sampling of participants was designed.

Participants: In total, 1,358 ethnic Chinese adult participants were recruited from the Nutrition and Health Survey in Taiwan 2013-2016; the whole-body composition was measured through dual-energy X-ray absorptiometry.

Main Outcome Measures: Fat and lean mass in whole and specific parts of body among heathy Asian adults with normal glycemic, pre-diabetic, and diabetic states were measured, separately.

Statistical Analyses Performed: The generalized linear model was used to investigate the association between body composition (lean and fat mass) and hyperglycemic status. The reduced rank regression (RRR) was used to confirm the correlation between glycemic status and predicting factors (body composition parameters).

Results: Trunk fat positively correlated with the fasting glucose level (r = 0.327, P < 0.001) and HbA1c (r = 0.329, P < 0.001), whereas limb fat negatively correlated with the fasting glucose level (r = -0.325, P < 0.001) and HbA1c (ρ = -0.342, P < 0.001), respectively. In RRR analyses, fasting glucose and HbA1c exhibited a high positive association on fat amount per lean mass of the trunk (factor loading = 0.5319 and 0.5599, respectively) and of android area (0.6422 and 0.6104) and a high negative association fat amount per lean mass of the legs (-0.3863 and -0.3083) and gynoid area (-0.3414 and -0.3725).

Conclusions: For healthy community participants, increasing trunk fat had a greater risk of hyperglycemic status. Increasing lower extremity mass may confer lower risk of diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241121PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641370PMC
December 2020

Associations of Blood Pressure and Carotid Flow Velocity with Brain Volume and Cerebral Small Vessel Disease in a Community-Based Population.

Transl Stroke Res 2021 Apr 1;12(2):248-258. Epub 2020 Aug 1.

Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan.

Cerebral small vessel disease (CSVD) is a common finding on brain magnetic resonance imaging (MRI). We previously demonstrated that high blood pressure (BP) and low carotid flow velocity were associated with cerebrovascular disease. However, their associations with brain volume and CSVD remain to be determined. A total of 721 adults (≥ 50 years) from the community-based I-Lan Longitudinal Aging Study were included. Flow velocities at the common (CCA) and internal carotid artery (ICA), including peak systolic velocity (PSV) and end-diastolic velocity (EDV), were measured with Doppler ultrasound. We further detected the presence of CSVD including lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. General linear regression and logistic regression analysis were exploited to evaluate the association between carotid flow velocity, BP, brain volume, and CSVD. The mean of white matter, gray matter, and WMH volume were 422.2 cm, 546.9 cm, and 2.61 cm, respectively. The proportion of lacune and microbleed were 11.1% and 14.2%, respectively. The CSVD score were negatively associated with gray (r = - 0.121, p < .01) and white matter volume (r = 0.058, p = 0.12), but positively associated with systolic BP (beta = 1.02, p = 0.0017). EDV at common carotid artery associated positively with white matter volume (beta = 1.013, p = 0.0064) and negatively predicted the presence CSVD (odds ratio [OR] = 0.93, p = 0.0023). In the ordinal logistic regression analysis adjusting for age, sex, total intracranial volume education, low-density lipoprotein cholesterol, and fasting glucose, compared with hypertensive subjects with low EDV, normotensive subjects with low, middle, and high EDV had an odds ratio of 0.656 (0.327-1.318), 0.429 (0.261-0.705), and 0.272 (0.147-0.502) for CSVD score, respectively. High SBP and low carotid flow velocities were independently associated with brain volume and CSVD. These associations may be involved in the pathophysiology of cognitive function decline.
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http://dx.doi.org/10.1007/s12975-020-00836-7DOI Listing
April 2021

Quantifying the association of low-intensity and late initiation of tobacco smoking with total and cause-specific mortality in Asia.

Tob Control 2021 05 16;30(3):328-335. Epub 2020 Jun 16.

Division of Epidemiology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Background: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts.

Methods: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis.

Findings: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence.

Conclusions: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice.
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http://dx.doi.org/10.1136/tobaccocontrol-2019-055412DOI Listing
May 2021

Correction to: Individualized home-based exercise and nutrition interventions improve frailty in older adults: a randomized controlled trial.

Int J Behav Nutr Phys Act 2019 12 23;16(1):136. Epub 2019 Dec 23.

Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.

Following publication of the original article [1], the author reported that an abbreviation was incorrect in the original article.
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http://dx.doi.org/10.1186/s12966-019-0905-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927211PMC
December 2019

Genome-wide association study of morbid obesity in Han Chinese.

BMC Genet 2019 12 18;20(1):97. Epub 2019 Dec 18.

Institute of Biomedical Sciences, Academia Sinica, Taipei City, Taiwan.

Background: As obesity is becoming pandemic, morbid obesity (MO), an extreme type of obesity, is an emerging issue worldwide. It is imperative to understand the factors responsible for huge weight gain in certain populations in the modern society. Very few genome-wide association studies (GWAS) have been conducted on MO patients. This study is the first MO-GWAS study in the Han-Chinese population in Asia.

Methods: We conducted a two-stage GWAS with 1110 MO bariatric patients (body mass index [BMI] ≥ 35 kg/m) from Min-Sheng General Hospital, Taiwan. The first stage involved 575 patients, and 1729 sex- and age-matched controls from the Taiwan Han Chinese Cell and Genome Bank. In the second stage, another 535 patients from the same hospital were genotyped for 52 single nucleotide polymorphisms (SNPs) discovered in the first stage, and 9145 matched controls from Taiwan Biobank were matched for confirmation analysis.

Results: The results of the joint analysis for the second stage revealed six top ranking SNPs, including rs8050136 (p-value = 7.80 × 10), rs9939609 (p-value = 1.32 × 10), rs1421085 (p-value = 1.54 × 10), rs9941349 (p-value = 9.05 × 10), rs1121980 (p-value = 7.27 × 10), and rs9937354 (p-value = 6.65 × 10), which were all located in FTO gene. Significant associations were also observed between MO and RBFOX1, RP11-638 L3.1, TMTC1, CBLN4, CSMD3, and ERBB4, respectively, using the Bonferroni correction criteria for 52 SNPs (p < 9.6 × 10).

Conclusion: The most significantly associated locus of MO in the Han-Chinese population was the well-known FTO gene. These SNPs located in intron 1, may include the leptin receptor modulator. Other significant loci, showing weak associations with MO, also suggested the potential mechanism underlying the disorders with eating behaviors or brain/neural development.
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http://dx.doi.org/10.1186/s12863-019-0797-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921553PMC
December 2019

The Mediterranean diet reduces the genetic risk of chromosome 9p21 for myocardial infarction in an Asian population community cohort.

Sci Rep 2019 12 5;9(1):18405. Epub 2019 Dec 5.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

The interaction of genetic susceptibility and dietary habits in cardiovascular disease (CVD) remains undetermined. The purpose of this study was to investigate whether a Mediterranean dietary style modified the genetic risk of developing CVD in a Chinese cohort. A total of 2098 subjects with dietary information from a Chinese community cohort (CVDFACTS) were enrolled. Candidate genes, including SNP markers rs1333049 (CDKN2B, 9p21.3), rs17465637 (MIA3, 1q41) and rs501120 (CXCL12, 10q11.21), were genotyped to analyze the association with future CVD. The impact of dietary pattern was also analyzed according to adherence to the diet using the Mediterranean Diet Score (MDS). After an average follow-up of 7.8 years, only the C risk allele of rs1333049 at chromosome 9p21.3 was associated with a higher risk of MI with either an additive [HR = 1.78, 95% CI:1.23-2.5] or a recessive model [HR = 2.40, 95% CI: 1.42-4.04], and the CC genotype had a higher risk of developing MI (p = 0.009, log-rank test). There was no significant difference in the association of the lipid profile with future CV outcomes among the MDS tertiles. However, the high MI risk of the CC genotype in individuals consuming a less healthy diet (MDS1) (HR: 6.39, 95% CI: 1.74-23.43) significantly decreased to 2.38 (95% CI: 0.57-10.04) in individuals consuming a healthier diet (MDS3), indicating that a healthier dietary pattern (higher MDS) modified the risk of developing MI in carriers of variants in CDKN2B. In conclusion, genetic variants of CDKN2B at 9p21 were significantly associated with future MI risk in a Chinese cohort, and the genetic risk of MI could be modified by a healthier diet.
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http://dx.doi.org/10.1038/s41598-019-54938-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895036PMC
December 2019

Individualized home-based exercise and nutrition interventions improve frailty in older adults: a randomized controlled trial.

Int J Behav Nutr Phys Act 2019 12 2;16(1):119. Epub 2019 Dec 2.

Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan.

Background: Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults.

Methods: This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition [combination]) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1 month, 3 months, and 6 months.

Results: At the 6-month measurement, the exercise (difference in frailty score change from baseline: - 0.23; 95% confidence interval [CI]: - 0.41, - 0.05; p = 0.012), nutrition (- 0.28; 95% CI: - 0.46, - 0.11; p = 0.002), and combination (- 0.34; 95% CI: - 0.52, - 0.16; p <  0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group.

Conclusions: The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance.

Trial Registration: Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.
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http://dx.doi.org/10.1186/s12966-019-0855-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889427PMC
December 2019

The causal role of elevated uric acid and waist circumference on the risk of metabolic syndrome components.

Int J Obes (Lond) 2020 04 21;44(4):865-874. Epub 2019 Nov 21.

Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, 11529, Taiwan.

Background/objectives: Hyperuricemia has been found to cluster with multiple components of metabolic syndrome (MetS). It is unclear whether hyperuricemia is a downstream result of MetS or may play an upstream role in MetS development. Using the Mendelian randomization (MR) method, we examined the causal relationship between elevated uric acid and the various components of MetS with waist circumference as a positive control.

Subjects/methods: Data from 10k participants of Taiwan Biobank was used to carry out MR analysis with uric acid risk score (wGRS) and waist circumference wGRS as instrumental variables and components of MetS as the outcomes.

Results: We found that genetically increased serum uric acid corresponds to a significant increment of triglyceride (β = 0.065, p < 0.0001), systolic blood pressure (β = 1.047, p = 0.0005), diastolic blood pressure (β = 0.857, p < 0.0001), and mean arterial pressure (β = 0.920, p < 0.0001), but a significant reduction of high-density lipoprotein cholesterol (β = -0.020, p = 0.0014). Uric acid wGRS was not associated with fasting serum glucose, HbA1C, waist circumference, or BMI. On the other hand, waist circumference was causally associated with all the components of MetS including uric acid.

Conclusions: Our MR investigation shows that uric acid increment may augment the risk of MetS through increasing blood pressure and triglyceride levels and lowering HDL-C value but not through accumulating fat or hyperglycemia. High waist circumference may be a causal agent for all the components of MetS including hyperuricemia.
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http://dx.doi.org/10.1038/s41366-019-0487-9DOI Listing
April 2020

Hyperuricemia and pulse pressure are predictive of incident heart failure in an elderly population.

Int J Cardiol 2020 02 6;300:178-183. Epub 2019 Nov 6.

Institution of Population Health Sciences Research, National Health Research Institutes, Miaoli, Taiwan; Institute of Biomedical Science, Academic Sinica, Taipei, Taiwan. Electronic address:

Objective: This study investigated the associations between hyperuricemia, pulse pressure (PP) and heart failure (HF) hospitalization among the elders in a community population.

Background: Hyperuricemia and PP have been related to the development of HF. Whether PP acts synergistically with hyperuricemia or mediates the causal relationship of HF, especially in the elderly, remains elucidated.

Methods: This cohort included 1665 adults aged ≥65 years from the National Nutrition and Health Survey in Taiwan Elderly were followed. HF hospitalization (ICD-9-CM:428) was defined by the National Health Insurance Dataset. A Cox proportional hazard model and a Fine and Grays model were adjusted for the conventional cardiovascular risk factors and death as a competing risk to estimate the association between hyperuricemia, PP and HF hospitalization.

Results: A total of 228 elders occurred HF hospitalization, and 692 died during a median of 12 years follow-up period, from 1999 to 2012. The incidence of HF was 14.2 per 1000 person-years. High PP (top quartile) and hyperuricemia (≥6.0 mg/dL [women] and 7.0 mg/dL [Men]) significantly correlated with incident HF (hazard ratio and 95% confidence intervals: 2.131;1.625-2.794 and 1.433;1.071-1.918, respectively). Compared with normal uric acid level and PP, combined hyperuricemia and high PP was additively related to incident HF (4.186:2.874-6.099). The associations remained after accounting for traditional cardiovascular risks, coronary heart disease as a time-dependent covariate, and mortality as a competing risk factor in the study population.

Conclusion: Both hyperuricemia and high PP were associated with HF hospitalization in this elderly population. Combine hyperuricemia and high PP would further improve the risk stratification in the prediction of incident HF.
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http://dx.doi.org/10.1016/j.ijcard.2019.11.001DOI Listing
February 2020

The Co-Occurrence Of Frailty (Accumulation Of Functional Deficits) And Depressive Symptoms, And Its Effect On Mortality In Older Adults: A Longitudinal Study.

Clin Interv Aging 2019 27;14:1671-1680. Epub 2019 Sep 27.

Institute of Population Health Sciences, National Health Research Institutes, Maoli, Taiwan.

Purpose: The co-occurrence of frailty and depression in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality have rarely been investigated. We aimed to examine the co-occurrence of frailty and depressive symptoms in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality using all the information from a longitudinal study.

Patients And Methods: We used the Taiwan Longitudinal Study of Aging (TLSA) for this study. TLSA was initiated in 1989 and followed periodically. We included participants from 1989 to 2007, who had data on frailty and depressive symptoms. Frailty was assessed by accumulation of functional deficits in 6 dimensions including disease status, sensory dysfunction, balance, functional limitations, health risk behaviors, and life satisfaction. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). A multistate model with interval censoring was used to examine the transition between states of frailty with or without depressive symptoms, and finally to death. A mixed model was used to examine the relationships between frailty and depressive symptoms.

Results: The coexistence of frailty and depressive symptoms was associated with higher mortality. Individuals with depressive symptom had a lower probability of reversal to a better state. Previous depression score predicted current frailty, but the coefficient was smaller than that of previous frailty. Previous frailty predicted current depression score, and the coefficient was stronger than that of previous depression.

Conclusion: Depressive symptoms increased the mortality and decreased the probability of reversal in the frail older adults.
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http://dx.doi.org/10.2147/CIA.S210072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775497PMC
December 2019

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis.

J Vis Exp 2019 09 6(151). Epub 2019 Sep 6.

Genomics Research Center, Academia Sinica; Department of Chemistry, Scripps Research Institute;

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for generating potential synthetic solutions. The programmable one-pot oligosaccharide synthesis approach is designed to empower fast oligosaccharide synthesis of large amounts using thioglycoside building blocks (BBLs) with the appropriate sequential order of relative reactivity values (RRVs). Auto-CHO is a cross-platform software with a graphical user interface that provides possible synthetic solutions for programmable one-pot oligosaccharide synthesis by searching a BBL library (containing about 150 validated and >50,000 virtual BBLs) with accurately predicted RRVs by support vector regression. The algorithm for hierarchical one-pot synthesis has been implemented in Auto-CHO and uses fragments generated by one-pot reactions as new BBLs. In addition, Auto-CHO allows users to give feedback for virtual BBLs to keep valuable ones for further use. One-pot synthesis of stage-specific embryonic antigen 4 (SSEA-4), which is a pluripotent human embryonic stem cell marker, is demonstrated in this work.
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http://dx.doi.org/10.3791/59987DOI Listing
September 2019

Association between educational level and total and cause-specific mortality: a pooled analysis of over 694 000 individuals in the Asia Cohort Consortium.

BMJ Open 2019 08 22;9(8):e026225. Epub 2019 Aug 22.

Armed Forces Capital Hospital, Seoul National University College of Medicine, Seoul, The Republic of Korea.

Objective: To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations.

Design: A pooled analysis of 15 population-based cohort studies.

Setting And Participants: 694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium.

Interventions: None.

Main Outcome Measures: HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality.

Results: A total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (p=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both p <0.01). The pattern of the association among East Asians and South Asians was similar compared with ≤primary education; HR (95% CI) for all-cause mortality associated with ≥university education was 0.72 (0.63 to 0.81) among 539 724 East Asians (Chinese, Japanese and Korean) and 0.61 (0.54 to 0.69) among 154 710 South Asians (Indians and Bangladeshis).

Conclusion: Higher educational level was associated with substantially lower risk of death among Asian populations.
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http://dx.doi.org/10.1136/bmjopen-2018-026225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707688PMC
August 2019

Assessing causality between childhood adiposity and early puberty: A bidirectional Mendelian randomization and longitudinal study.

Metabolism 2019 11 15;100:153961. Epub 2019 Aug 15.

Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Aims: Obesity and early puberty have been reported to be mutually causative. We investigated the causal relationship between adiposity and early puberty by performing bidirectional Mendelian randomization (MR) and longitudinal data analyses.

Methods: We used information from the Taiwan Children Health Study (3109 adolescents aged 11-12 years) with 17 body mass index (BMI)- and 10 puberty-related single-nucleotide polymorphisms (SNPs) to produce genetic instrumental variables (IVs). The two-stage least squares (2SLS) method, MR sensitivity analysis, and survival analysis were used to explore and confirm causality.

Results: Regression estimates from IVs revealed that significantly increased association of BMI with early puberty was noted (coefficients: 0.13, 0.10, and 0.09; 95% CI: 0.07-0.19, 0.02-0.19, and 0.02-0.16 for all participants, male adolescents, and female adolescents, respectively). Genetic IVs for puberty were not associated with BMI. MR sensitivity and two-sample MR analyses produced similar results. Longitudinal analysis results revealed that prepubertal overweight and obesity could predict early onset of puberty. However, after excluding children with a history of overweight and obesity at the age of 7-12 years, early puberty was not found to trigger new-onset of overweight and obesity at the age of 18 years in either sex.

Conclusions: Higher adiposity may lead to early puberty. However, the causal effects of early puberty on adiposity accumulation were not supported by our data. Targeted interventions to reduce childhood obesity are strongly recommended to prevent obesity-related comorbidities, as well as early puberty onset.
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http://dx.doi.org/10.1016/j.metabol.2019.153961DOI Listing
November 2019

Is Hyperuricemia, an Early-Onset Metabolic Disorder, Causally Associated with Cardiovascular Disease Events in Han Chinese?

J Clin Med 2019 Aug 12;8(8). Epub 2019 Aug 12.

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

Background: Serum uric acid (SUA) has gradually been recognized as a potential risk factor for cardiovascular disease (CVD). However, whether the relationship is causal remains controversial.

Methods: We employed two methods to demonstrate the importance of SUA in CVD development. First, we examined the onset sequence of hyperuricemia in relation to five cardiometabolic (CM) diseases. Second, we conducted a Mendelian randomization (MR) study to causally infer the relationship between SUA and CVD. The information collected from the Cardiovascular Disease Risk Factors Two-Township Study (CVDFACTS) and Taiwan Biobank was used, respectively.

Results: The onset sequence study showed that hyperuricemia and hypo-alpha-lipoproteinemia (low HDL-C) have earlier ages of onset than other CM diseases. For the MR analysis, the high weighted genetic risk score (WGRS) group had a significantly increased cumulative lifetime risk of CVD compared with the low WGRS group (OR = 1.62, (1.17-2.23), = 0.003). Sensitivity analysis using the WGRS derived from other populations' SUA-influential SNPs revealed similar results.

Conclusions: We showed that hyperuricemia is an earlier-onset metabolic disorder than hypertension, hypertriglyceridemia, and diabetes mellitus, indicating that high SUA plays an upstream role in CM development. Moreover, our MR study results support the idea that hyperuricemia may play a causal role in CVD development. Further validation studies in more populations are needed.
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http://dx.doi.org/10.3390/jcm8081202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723695PMC
August 2019

Increased coffee, tea, or other sugar-sweetened beverage consumption in adolescents is associated with less satisfactory dietary quality, body fatness and serum uric acid profiles over the past 18 years in Taiwan.

Asia Pac J Clin Nutr 2019 ;28(2):371-382

Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.

Background And Objectives: Taiwan has a high density of convenience stores and beverage shops, which makes sugar-sweetened beverages (SSBs) very accessible to teenagers. This study examined the changes and the association between SSBs and biomarkers and nutrient intake, for teenagers over the course of 18 years using a national representative sample.

Methods And Study Design: This cross-sectional study used data from the Nutrition and Health Survey in Taiwan (NAHSIT). Complete data for teenagers aged 13 to 19 years including a 24-hour dietary recall, anthropometric and clinical measurements, and SSBs from two periods were analyzed (1993-1996: N=1820; 2010-2011: N=2513). SAS callable SUDAAN was used for statistical analysis, adjusting for the sampling scheme. Log transformation was used for non-normal variables before linear models were used. Coffee or tea and SSB (excluding tea or coffee) consumers were categorized as non-drinkers, low (below), or high (above) consumers based on median intake during 1993-1996.

Results: Intake of coffee or tea increased significantly in the 18 years of this study (p<0.01), whereas intake of SSBs (excluding coffee or tea) decreased significantly (p<0.05). Intake was significantly higher among second survey and those with high total energy intakes (p<0.01). For both coffee/tea and SSB, the high-intake groups had higher serum uric acid and intake of carbohydrates (p<0.05), lower intake of protein and phosphorus and lower dietary diversity score (p<0.05).

Conclusions: Consumption of coffee or tea increased in adolescents during the 18 years. High intakes of SSB, coffee or tea was associated with high serum uric acid values and worse dietary quality.
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http://dx.doi.org/10.6133/apjcn.201906_28(2).0020DOI Listing
January 2020

Dietary Profiles, Nutritional Biochemistry Status, and Attention-Deficit/Hyperactivity Disorder: Path Analysis for a Case-Control Study.

J Clin Med 2019 May 18;8(5). Epub 2019 May 18.

Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

This study aims to investigate dietary and nutritional biochemistry profiles of attention-deficit/hyperactivity disorder (ADHD) and to explore their potential relationship by path analysis. We enrolled 216 children with ADHD and 216 age-, height- and gender-matched controls from 31 elementary schools in Taiwan. Dietary intake of the participants was assessed using a food frequency questionnaire (FFQ). Fasting blood samples were collected to determine the serum levels of multiple nutritional markers. Moreover, we employed a structural equation model (SEM) to link diet, nutritional markers and ADHD. Compared to healthy control, ADHD children had significantly lower serum levels of vitamin B12, folate, vitamin B6, ferritin concentration, and monounsaturated fatty acids (MUFA), but higher levels of serum saturated fatty acids (SFA), n-6/n-3 fatty acid ratio, and inorganic phosphorous concentration. Children with ADHD had more intake of nutrient-poor foods such as high sugar and high fat foods, and had less intake of vegetable, fruit, protein-rich foods than their counterpart. SEM analysis showed that the poor nutritional biochemistry profiles linked the association between unhealthy dietary patterns and ADHD. In conclusion, an unhealthy dietary pattern may be a predecessor of the poor nutritional biochemistry status, and managing diet and nutrition conditions should be considered to improve ADHD symptoms in children.
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http://dx.doi.org/10.3390/jcm8050709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572510PMC
May 2019

Association of Diabetes With All-Cause and Cause-Specific Mortality in Asia: A Pooled Analysis of More Than 1 Million Participants.

JAMA Netw Open 2019 04 5;2(4):e192696. Epub 2019 Apr 5.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Importance: Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations.

Objectives: To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status.

Design, Setting, And Participants: This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018.

Exposures: Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status.

Main Outcomes And Measures: All-cause and cause-specific mortality.

Results: Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age.

Conclusions And Relevance: This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.2696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481439PMC
April 2019

Tobacco Smoking and Mortality in Asia: A Pooled Meta-analysis.

JAMA Netw Open 2019 03 1;2(3):e191474. Epub 2019 Mar 1.

State Key Laboratory of Oncogene and Related Genes, Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Importance: Understanding birth cohort-specific tobacco smoking patterns and their association with total and cause-specific mortality is important for projecting future deaths due to tobacco smoking across Asian populations.

Objectives: To assess secular trends of tobacco smoking by countries or regions and birth cohorts and evaluate the consequent mortality in Asian populations.

Design, Setting, And Participants: This pooled meta-analysis was based on individual participant data from 20 prospective cohort studies participating in the Asia Cohort Consortium. Between September 1, 2017, and March 31, 2018, a total of 1 002 258 Asian individuals 35 years or older were analyzed using Cox proportional hazards regression analysis and random-effects meta-analysis. The pooled results were presented for mainland China; Japan; Korea, Singapore, and Taiwan; and India.

Exposures: Tobacco use status, age at starting smoking, number of cigarettes smoked per day, and age at quitting smoking.

Main Outcomes And Measures: Country or region and birth cohort-specific mortality and the population attributable risk for deaths from all causes and from lung cancer.

Results: Of 1 002 258 participants (51.1% women and 48.9% men; mean [SD] age at baseline, 54.6 [10.4] years), 144 366 deaths (9158 deaths from lung cancer) were ascertained during a mean (SD) follow-up of 11.7 (5.3) years. Smoking prevalence for men steadily increased in China and India, whereas it plateaued in Japan and Korea, Singapore, and Taiwan. Among Asian male smokers, the mean age at starting smoking decreased in successive birth cohorts, while the mean number of cigarettes smoked per day increased. These changes were associated with an increasing relative risk of death in association with current smoking in successive birth cohorts of pre-1920, 1920s, and 1930 or later, with hazard ratios for all-cause mortality of 1.26 (95% CI, 1.17-1.37) for the pre-1920 birth cohort, 1.47 (95% CI, 1.35-1.61) for the 1920s birth cohort, and 1.70 (95% CI, 1.57-1.84) for the cohort born in 1930 or later. The hazard ratios for lung cancer mortality were 3.38 (95% CI, 2.25-5.07) for the pre-1920 birth cohort, 4.74 (95% CI, 3.56-6.32) for the 1920s birth cohort, and 4.80 (95% CI, 3.71-6.19) for the cohort born in 1930 or later. Tobacco smoking accounted for 12.5% (95% CI, 8.4%-16.3%) of all-cause mortality in the pre-1920 birth cohort, 21.1% (95% CI, 17.3%-24.9%) of all-cause mortality in the 1920s birth cohort, and 29.3% (95% CI, 26.0%-32.3%) of all-cause mortality for the cohort born in 1930 or later. Tobacco smoking among men accounted for 56.6% (95% CI, 44.7%-66.3%) of lung cancer mortality in the pre-1920 birth cohort, 66.6% (95% CI, 58.3%-73.5%) of lung cancer mortality in the 1920s birth cohort, and 68.4% (95% CI, 61.3%-74.4%) of lung cancer mortality for the cohort born in 1930 or later. For women, tobacco smoking patterns and lung cancer mortality varied substantially by countries and regions.

Conclusions And Relevance: In this study, mortality associated with tobacco smoking continued to increase among Asian men in recent birth cohorts, indicating that tobacco smoking will remain a major public health problem in most Asian countries in the coming decades. Implementing comprehensive tobacco-control programs is warranted to end the tobacco epidemic.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.1474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450311PMC
March 2019

Type 2 diabetes occurrence and mercury exposure - From the National Nutrition and Health Survey in Taiwan.

Environ Int 2019 05 27;126:260-267. Epub 2019 Feb 27.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan; Department of Public Health, National Defense Medical Center, Taipei, Taiwan; Department of Safety, Health, and Environmental Engineering, National United University, Miaoli, Taiwan. Electronic address:

Background: The global prevalence of type 2 diabetes continues to increase in both developed and developing countries. Environmental exposure to mercury may be an important and modifiable risk factor for type 2 diabetes. However, the epidemiological results are controversial.

Objectives: This study aimed to examine the association between blood mercury levels and prevalence of type 2 diabetes.

Methods: A total of 646 adult participants were selected from the National Nutrition and Health Survey in Taiwan (NAHSIT) 2005-2008. The participants were interviewed using structured questionnaires to record data on basic demographics, socioeconomic status, lifestyle, medical history, and 24-h dietary recall. Specimens of blood and urine were collected at the health examination. Type 2 diabetes was defined as a fasting blood glucose level ≥ 126 mg/dL or intake of hypoglycemic medications. The mercury concentration in red blood cells (RBC-Hg) was quantified by cold vapor atomic absorption spectrometry.

Results: Participants with type 2 diabetes had a significantly higher RBC-Hg than those without type 2 diabetes. A significant association between the RBC-Hg and prevalence of type 2 diabetes was observed [odds ratio (OR): 1.64; 95% confidence intervals: 1.14-2.35] after potential confounders were well considered, including age, sex, body mass index (BMI), hypertension, total cholesterol, saltwater fish consumption, geographical strata, seasonality and hemoglobin (Hb) level.

Conclusion: Our findings showed that elevated RBC-Hg is significantly associated with type 2 diabetes prevalence. Future research, particularly for longitudinal cohort studies with suitable specimens, needs to be performed to verify our findings.
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http://dx.doi.org/10.1016/j.envint.2019.02.038DOI Listing
May 2019

Secular trends and associated factors of age at natural menopause in Taiwanese women.

Menopause 2019 05;26(5):499-505

Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Objective: Age at natural menopause (ANM) is considered an indicator for chronic disease and mortality risk in later life. Research suggests that ANM appears to vary across geographic regions and ethnicities. The aim of this study was to explore the secular trends and factors associated with ANM in Taiwanese women.

Methods: We used data from three cross-sectional phases of the Nutrition and Health Survey in Taiwan. In all, 4,111 women aged 35 years and over were included. Information on ANM and sociodemographics, lifestyle, and health factors were collected using household questionnaires. A Cox proportional-hazards model was used to determine the association of ANM with relevant factors, and a life table method was used to estimate median ANM.

Results: Life table method estimated the median ANM to be 50 years. ANM was getting later for women born in younger cohorts (hazard ratio [HR] 0.87 per 10-year difference, 95% confidence interval [CI] 0.81-0.95). ANM was also later among women who achieved higher educational levels (HR 0.91 per one-category difference, 95% CI 0.86-0.96) and who had been married (HR 0.64, 95% CI 0.42-0.96). ANM occurred later for parous than for nulliparous women. Multivariable analysis found no significant associations of ANM with age at menarche, smoking, or alcohol drinking.

Conclusions: The results suggest that women in the younger cohorts, with higher educational levels, and who are parous and married may have later ANM. The trend effect of secular time and educational levels on ANM may reflect the influences of socioeconomic/nutritional status in their childhood or throughout their lifetime.
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http://dx.doi.org/10.1097/GME.0000000000001307DOI Listing
May 2019

Impacts of the New 2017 ACC/AHA Hypertension Guideline on the Prevalence of Brachial Hypertension and Its Concordance with Central Hypertension.

Am J Hypertens 2019 03;32(4):409-417

Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan.

Objectives: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline lowers the blood pressure (BP) thresholds for defining brachial hypertension. We therefore aimed to investigate how the new guideline influences the prevalence of brachial hypertension and whether it improves the identification of central hypertension in an Asian national representative population.

Methods: A total of 2,742 adults older than 19 years participated in the 2013-2016 National Nutrition and Health Survey in Taiwan. Central and brachial BPs were simultaneously measured twice and averaged using a cuff-based stand-alone central BP monitor purporting to measure invasive central BP (type II device). Brachial hypertension was defined by brachial systolic/diastolic BP ≥ 130 or 80 mm Hg or using antihypertensive medication, and central hypertension was defined by central systolic/diastolic BP ≥ 130 or 90 mm Hg or using antihypertensive medication.

Results: The national weighted prevalence rates of brachial hypertension according to the 2017 AHA/ACC guideline were 48.7% in men and 30.7% in women. The prevalence of brachial hypertension increased by 18.8% in men and 9.4% in women, when compared with the prevalence defined by the conventional thresholds of brachial systolic/diastolic BP ≥ 140 or 90 mm Hg. In comparison with the conventional criteria, the new hypertension criteria had a higher sensitivity (93.0% vs. 77.4%) and a lower specificity (86.7% vs. 99.6%) for detecting central hypertension.

Conclusions: Adoption of the 2017 AHA/ACC BP thresholds substantially increases the prevalence of brachial hypertension, especially in men, and identifies over 90% of those with central hypertension at the expense of lesser specificity.
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http://dx.doi.org/10.1093/ajh/hpz008DOI Listing
March 2019

Dietary Patterns and Foods Associated With Cognitive Function in Taiwanese Older Adults: The Cross-sectional and Longitudinal Studies.

J Am Med Dir Assoc 2019 05 7;20(5):544-550.e4. Epub 2019 Jan 7.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Objectives: To find dietary patterns and foods associated with cognitive function.

Design: A cross-sectional study of short-term effects and a prospective study for long-term effects.

Setting: Nutrition and Health Survey in Taiwan (NAHSIT) 2014-2016 and NAHSIT 1999-2000.

Participants: A total of 1245 older patients enrolled in the NAHSIT 2014-2016 and 1436 in the NAHSIT 1999-2000.

Measurements: Dietary intake was appraised with a food-frequency questionnaire. Cognitive function was assessed by the Mini-Mental State Examination score (MMSE).

Results: Using reduced rank regression to data-mine NAHSIT 2014-2016 cross-sectional data, we found in both genders a dietary pattern associated with high MMSE score, which was characterized by higher intakes of fresh fruits, nuts and seeds, whole grains, breakfast cereals, coffee, dairy products, seafood products, and fish. Moreover, in women, the pattern included a few additional items: tea, eggs, soybean products, and vegetables. Presence of mild cognitive impairment was inversely associated with the dietary pattern score, with declined adjusted odds ratio (95% confidence interval) from tertile 1 (as reference), tertile 2, to tertile 3 in both men [1 → 0.85(0.45-1.61) → 0.32 (0.14-0.78)] and women [1→0.44 (0.25-0.76) → 0.39 (0.20-0.75)]. Using the NAHSIT 1999-2000 as a baseline, along with 11 years of follow-up, we found with the Cox proportional hazards model that higher intake (≥4 vs <1 time/wk) of either tea or fish, but not other foods, was associated with a lower risk of developing dementia. Higher intakes of both tea and fish were associated with an even lower risk.

Conclusions/implications: A dietary pattern characterized by high intakes of phytonutrient-rich plant foods (fruits, whole grains, nuts/seeds, and vegetables), tea and coffee, and protein-rich foods such as eggs, dairy products, and fish, was associated with the presence of better cognitive function in older adult. Higher intakes of fish and tea combined showed a long-term protective effect. Further research is warranted to understand the long- and short-term effects of diet.
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http://dx.doi.org/10.1016/j.jamda.2018.10.017DOI Listing
May 2019

Levels and temporal variations of urinary lead, cadmium, cobalt, and copper exposure in the general population of Taiwan.

Environ Sci Pollut Res Int 2019 Feb 6;26(6):6048-6064. Epub 2019 Jan 6.

National Institute of Environmental Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35035, Taiwan.

Toxic metal contamination in food products and the environment is a public health concern. Therefore, understanding human exposure to cadmium (Cd), lead (Pb), cobalt (Co), and copper (Cu) levels in the general population of Taiwan is necessary and urgent. We aimed to establish the human biomonitoring data of urine toxic metals, exposure profile changes, and factors associated with metal levels in the general population of Taiwan. We randomly selected 1601 participants older than 7 years of age (36.9 ± 18.7 years (7-84 years)) from the Nutrition and Health Survey in Taiwan (NAHSIT) conducted during 1993-1996 (93-96) and 2005-2008 (05-08) periods and measured the levels of four metals in the participants' urine samples using inductively coupled plasma-mass spectrometry. The median (range) levels of urinary Cd, Pb, Co, and Cu in participants from the NAHSIT 93-96 (N = 821)/05-08 (N = 780) were 0.60 (ND-13.90)/0.72 (ND-7.44), 2.28 (ND-63.60)/1.09 (0.04-48.88), 0.91 (0.08-17.30)/1.05 (0.05-22.43), and 16.87 (2.62-158.28)/13.66 (1.67-189.70) μg/L, respectively. We found that the urinary median levels of Pb and Cu in our participants were significantly lower in the NAHSIT 05-08 (Pb 1.09 μg/L, Cu 13.66 μg/L) than in the NAHSIT 93-96 (Pb 2.28 μg/L, Cu 16.87 μg/L; P < 0.01), whereas those of Cd and Co were significantly higher in the NAHSIT 05-08 (Cd 0.72 μg/L, Co 1.05 μg/L; P < 0.01). Youths had higher exposure levels of Pb, Co, and Cu than adults. Participants with alcohol consumption, betel quid chewing, or cigarette smoking had significantly higher median levels of urinary Pb or Cu (P < 0.01) than those without. Principal components and cluster analysis revealed that sex had different exposure profiles of metals. We concluded that levels of urinary Cd, Pb, Co, and Cu exposure in the general Taiwanese varied by age, sex, and lifestyles.
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http://dx.doi.org/10.1007/s11356-018-3911-0DOI Listing
February 2019

Hierarchical and programmable one-pot synthesis of oligosaccharides.

Nat Commun 2018 12 6;9(1):5202. Epub 2018 Dec 6.

Genomics Research Center, Academia Sinica, Taipei, 11529, Taiwan.

The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.
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http://dx.doi.org/10.1038/s41467-018-07618-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283847PMC
December 2018

Vegetable Signatures Derived from Human Urinary Metabolomic Data in Controlled Feeding Studies.

J Proteome Res 2019 01 17;18(1):159-168. Epub 2018 Dec 17.

Institute of Biomedical Sciences , Academia Sinica , Taipei 11529 , Taiwan.

Examination of changes in urinary metabolomic profiles after vegetable ingestion may lead to new methods of assessing plant food intake. To this regard, we developed a proof-of-principle methodology to identify urinary metabolomic signatures for spinach, celery, and onion. Three feeding studies were conducted. In the first study, healthy individuals were fed with spinach, celery, onion, and no vegetables in four separate experiments with pooled urinary samples for metabolite discovery. The same protocol was used to validate the finding at the individual level in the second study and when feeding all three vegetables simultaneously in the third study. An LC-MS-based metabolomics approach was adopted to search for indicative metabolites from urine samples collected during multiple time periods before and after the meal. Consequently, a total of 1, 9, and 3 nonoverlapping urinary metabolites were associated with the intake of spinach, celery, and onion, respectively. The PCA signature of these metabolites followed a similar "time cycle" pattern, which maximized at approximately 2-4 h after intake. In addition, the metabolite profiles for the same vegetable were consistent across samples, regardless of whether it was consumed individually or in combination. The developed methodology along with the identified urinary metabolomic signatures were potential tools for assessing plant food intake.
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http://dx.doi.org/10.1021/acs.jproteome.8b00470DOI Listing
January 2019