Yuan-Horng Yan

Effect of air pollution on blood pressure, blood lipids, and blood sugar: A population-based approach

Objective: To investigate changes in blood pressure, lipids, and sugar associated with changes in exposure to ambient air pollution. Methods: We conducted secondary analyses of blood pressure and biochemistry markers from Taiwanese Survey on Prevalence of Hyperglycemia, Hyperlipidemia, and Hypertension and air pollution monitoring data in 2002 by applying generalized additive models. Results: We observed increased particulate matter with aerodynamic diameters <10 &mgr;m was associated with elevated systolic blood pressure (an interquartile range, 34 &mgr;g/m3, for 0.47 mmHg; 95% CI, −0.09 to 1.02), triglyceride, apolipoprotein B, hemoglobin A1c, and reduced high-density lipoprotein cholesterol. Elevated ozone was associated with increased diastolic blood pressure, apolipoprotein B, and hemoglobin A1c. Conclusions: Alterations of atherosclerotic indicators are associated with particulate matter with aerodynamic diameters <10 &mgr;m and ozone changes. This might provide a link between air pollution and progression of atherosclerotic cardiovascular diseases.

Enhanced insulin resistance in diet-induced obese rats exposed to fine particles by instillation.

Context: Epidemiological studies indicate that diabetes is a sub-population at risk for particulate matter (PM)-associated cardiovascular disease (CVD). Recent animal studies suggested PM might impair glucose tolerance, which may lead to CVD. However, the mechanism remains unclear. Objective: To investigate further the PM effect on insulin resistance (IR) in obese and healthy rats. Materials and methods: Male Sprague–Dawley rats were fed with either a high fat diet (HFD) or normal chow diet (NCD) for 6 weeks. Both groups were then further assigned to receive PM10, PM2.5 or normal saline (n = 6 per group) by intratracheal instillation (IT) once per week for 3 weeks. Fasting glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was used to assess IR. Biochemistry tests and lipids profile were examined at sacrifice. The markers of fibrinogen and [nitrate+nitrite], an indicator of nitric oxide (NO) production, C-reactive protein (CRP) and white blood counts (WBCs) in peripheral blood were also determined. Results: Body weight, insulin and HOMA-IR of HFD rats were significantly increased compared with a NCD after 6 weeks. In HFD rats, PM2.5 increased HOMA-IR after first IT and further increased HOMA-IR at the end of exposure. However, this increase was not observed in NCD rats and after PM10 exposure. Increased fibrinogen was also noted after chronic PM2.5 exposure in both HFD and NCD rats. Discussion and conclusion: Exposure to PM2.5 enhanced IR in HFD rats but not in NCD rats. Obese subjects with IR may be a susceptible population to particulate air pollution.

Effects of Diesel Exhaust Particles on Left Ventricular Function in Isoproterenol-Induced Myocardial Injury and Healthy Rats

The associations between ambient particulate matter with an aerodiameter less than 2.5 μ m (PM2.5) and congestive heart failure (CHF) have been reported. However, the underlying mechanisms remain unclear. We investigated the effect of diesel exhaust particles (DEPs) on left ventricular function in isoproterenol (ISO)-induced myocardial injury and healthy rats. Male Sprague-Dawley (SD) rats were injected with ISO or normal saline. Seven days later, both groups were further assigned to receive either DEPs or normal saline by intratracheal instillation (IT). Echocardiography was used to measure fractional shortening (FS) and left ventricular end-diastolic diameter (LVDd) 24 h before and after IT in each rat. Fractional shortening (FS) was significantly decreased in SD rats treated with ISO as compared to those treated with normal saline (p < .05, t-test). When FS and LVDd before and after treatment were compared in each rat, there was no difference for normal saline treatment in healthy or ISO groups. However, there was significantly lower FS before and after DEPs exposure in both groups (p < .05, paired t-test). When using SD rats treated with normal saline as a reference group, both SD rats treated with DEPs and ISO rats treated with normal saline had lower FS (p < .05 and.0001, respectively, t-test), while ISO rats treated with DEPs had the lowest FS (p < .0001, t-test). Echocardiographic assessment revealed that left ventricular function was impaired by acute DEPs exposure, and this LV function was further compromised in rats with preexisting ISO-induced myocardial injury.

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model

Epidemiological studies have reported associations between particulate matter (PM) and cardiovascular effects, and diabetes mellitus (DM) patients might be susceptible to these effects. The chief chronic injuries resulting from DM are small vascular injuries (micro-vascular complications) or large blood vessel injuries (macro-vascular complications). However, toxicological data regarding the effects of PM on DM-related cardiovascular complications is limited. Our objective was to investigate whether subchronic PM exposure alters glucose homeostasis and causes cardiovascular complications in a type 1 DM rat model. We constructed a real world PM2.5 exposure system, the Taipei Air Pollution Exposure System for Health Effects (TAPES), to continuously deliver non-concentrated PM for subchronic exposure. A type 1 DM rat model was induced using streptozotocin. Between December 22, 2009 and April 9, 2010, DM rats were exposed to PM or to filtered air (FA) using TAPES in Taipei, Taiwan, 24h/day, 7days/week, for a total of 16weeks. The average concentrations (mean [SD]) of PM2.5 in the exposure and control chambers of the TAPES were 13.30 [8.65] and 0.13 [0.05]μg/m(3), respectively. Glycated hemoglobin A1c (HbA1c) was significantly elevated after exposure to PM compared with exposure to FA (mean [SD], 7.7% [3.1%] vs. 4.7% [1.0%], P<0.05). Interleukin 6 and fibrinogen levels were significantly increased after PM exposure. PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney (tubular damage index: 1.76 [0.77] vs. 1.15 [0.36], P<0.001). PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation.

Association of temporal distribution of fine particulate matter with glucose homeostasis during pregnancy in women of Chiayi City, Taiwan

Background To investigate the effects of fine particulate matter (PM2.5) on the indicators of glucose homeostasis during pregnancy. Methods: A total of 3589 non‐diabetic pregnant women who underwent a 3‐h 100‐g oral glucose tolerance test (OGTT) were enrolled from a tertiary teaching hospital in Chiayi City, Taiwan between 2006 and 2014. Fasting, 1‐h, 2‐h, and 3‐h glucose levels after an OGTT were used as indicators of glucose homeostasis. PM2.5 and other air pollution data were obtained from one fixed‐site monitoring station (Chiayi City station) operated by Taiwan Environmental Protection Administration (EPA). We used mixed models for indicators of glucose homeostasis to estimate the effects of PM2.5. The models were adjusted for individual‐specific effects (nulliparous status, age, body mass index, season, and year) and the moving averages of temperature and relative humidity in the corresponding study period. Results There were significant relationships between PM2.5 and the glucose homeostasis indicators, including fasting, 1‐h, 2‐h, and 3‐h glucose levels in the single‐pollutant covariate‐adjusted model. The pre‐screening 1‐month to 1‐year moving averages of IQR increases in PM2.5 were significantly associated with elevated fasting OGTT glucose levels (1.32–5.87 mg/dL). The two‐pollutant covariate‐adjusted models had similar results. Conclusions We found positive associations between PM2.5 and OGTT glucose levels during pregnancy. The association was especially pronounced for the fasting and 1‐h glucose levels. PM2.5 exposure in the second trimester may enhance this effect. Exposure to PM2.5 was associated with glucose homeostasis during pregnancy. HighlightsPM2.5 was associated with OGTT, especially the fasting and 1‐h glucose levels.PM2.5 exposure in the second trimester may enhance this effect.Our findings provided evidence linking PM2.5 exposure, glucose homeostasis and GDM.

Abnormal glucose tolerance is associated with preterm labor and increased neonatal complications in Taiwanese women

OBJECTIVE To investigate the relationship between abnormal degrees of oral glucose tolerance test (OGTT) results and pregnancy outcomes. MATERIALS AND METHODS A total of 7513 singleton pregnancies screened for gestational diabetes mellitus were enrolled in this retrospective observational study. The pregnancy outcomes of six different groups with different degrees of glucose intolerance using the OGTT were compared [both the National Diabetes Data Group (NDDG) and Carpenter and Coustan (C&C) criteria were used]. The pregnancies were classified into the following groups: the normal group, consisting of pregnancies with a negative 50-g glucose challenge test (GCT), and Grade 0, 1, 2, 3 and 4 groups, consisting of pregnancies with positive 50-g GCT, and abnormal values of 0, 1, 2, 3 and 4 from the 100-g OGTT, respectively. RESULTS The adjusted odds ratios (95% confidence interval) for preterm labor and admission to the neonatal intensive care unit (NICU) were shown to be increased in the Grade 4 groups [3.31 (1.47-7.43) and 6.31 (3.14-12.70) by the NDDG criteria; 4.13 (2.30-7.43) and 5.25 (3.00-9.19) by the C&C criteria] compared with the normal group. CONCLUSION The results indicated an increased risk for preterm labor and admission to the NICU as the abnormal value of the OGTT increased.

Sustained renal inflammation following 2 weeks of inhalation of occupationally relevant levels of zinc oxide nanoparticles in Sprague Dawley rats

Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4.9 mg/m3 (high dose) ZnONPs or high-efficiency particulate arresting-filtered air (HEPA-FA) via inhalation for 2 weeks. Histopathological examinations of rat kidneys were performed at 24 hours, 7 days, and 1 month after exposure. A significant increase in microscopic inflammatory foci with pronounced periglomerular inflammation and interstitial lymphocytic infiltration was found in rats exposed to low and high doses of ZnONPs compared with rats exposed to HEPA-FA at the three time points following 2 weeks of exposure. Tubulitis featuring lymphocytic infiltrate within the tubular epithelium was found after 24 hours but had disappeared at 7 and 30 days in both the low- and high-dose exposure groups. Our findings demonstrate that inhaled ZnONPs cause sustained renal periglomerular and interstitial inflammation through lymphocytic infiltration. These findings provide histopathological evidence regarding sustained renal inflammation of nanoparticle exposure in rats and may provide some insight into the occupational health effects of ZnONPs on exposed workers.

Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse pregnancy outcomes in high-risk Taiwanese women

Background The objective of this study was to investigate the associations among the mid-pregnancy glycated hemoglobin A1c (HbA1c) level, gestational diabetes (GDM), and risk of adverse pregnancy outcomes in women without overt diabetes and with positive 50-g, 1-h glucose challenge test (GCT) results (140 mg/dL or greater). Methods This prospective study enrolled 1,989 pregnant Taiwanese women. A two-step approach, including a 50-g, 1-h GCT and 100-g, 3-h oral glucose tolerance test (OGTT), was employed for the diagnosis of GDM at weeks 23–32. The mid-pregnancy HbA1c level was measured at the time the OGTT was performed. A receiver operating characteristic (ROC) curve was used to determine the relationship between the mid-pregnancy HbA1c level and GDM. Multiple logistic regression models were implemented to assess the relationships between the mid-pregnancy HbA1c level and adverse pregnancy outcomes. Results An ROC curve demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM, as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was 5.7%. The area under the ROC curve of the mid-pregnancy HbA1c level for GDM was 0.70. Compared with the levels of 4.5–4.9%, higher mid-pregnancy HbA1c levels (5.0–5.4, 5.5–5.9, 6.0–6.4, 6.5–6.9, and >7.0%) were significantly associated with increased risks of gestational hypertension or preeclampsia, preterm delivery, admission to the neonatal intensive care unit, low birth weight, and macrosomia (the odds ratio [OR] ranges were 1.20–9.98, 1.31–5.16, 0.88–3.15, 0.89–4.10, and 2.22–27.86, respectively). Conclusions The mid-pregnancy HbA1c level was associated with various adverse pregnancy outcomes in high-risk Taiwanese women. However, it lacked adequate sensitivity and specificity to replace the two-step approach in the diagnosis of GDM. The current study comprised a single-center prospective study; thus, additional, randomized control design studies are required.

Influence of food intake on the predictive value of the gestational diabetes mellitus screening test.

OBJECTIVE: To investigate the influence of prior food ingestion on the predictive value of a screening test for gestational diabetes mellitus. METHODS: This prospective, nonrandomized study enrolled 1,387 pregnant women who underwent the 50-g glucose challenge test. Gestational diabetes mellitus was diagnosed according to the National Diabetes Data Group criteria. A nutritional survey of dietary information before the glucose challenge test was conducted. The patients were stratified into three groups based on the time of last food ingestion (fasting interval): 1 hour or less, 1–2 hours, and more than 2 hours. The more than 2-hours fasting interval group was defined as the “fasting” group, and the combined 1 hour or less and 1–2 hours fasting interval groups were defined as the “fed” group. We calculated the positivity rate and the positive predictive value to detect the predictive value. RESULTS: Among women who fasted 1 hour or less, 1–2 hours, and more than 2 hours before a glucose challenge test, 2.5%, 3.1%, and 6.9% were diagnosed with gestational diabetes mellitus, respectively. The positive predictive value of the glucose challenge test was greater in the fasting group than in the fed group (27.1% compared with 13.7%, P=.003). A multinomial logistic analysis showed that gestational diabetes mellitus was more prevalent in the fasting group than in the fed group (adjusted odds ratio 2.86, 95% confidence interval 1.65–4.95). CONCLUSION: Our findings suggest that food intake influences the predictive value of the gestational diabetes screening test. LEVEL OF EVIDENCE: II