Meng-Chuan Huang

Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan

A multicenter case‐control study was conducted in northern and southern Taiwan to clarify the independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer. A total of 513 patients with newly diagnosed and histopathologically confirmed squamous cell carcinoma of the esophagus and 818 gender, age and study hospital‐matched controls were included. We found a significant dose‐response relationship between the duration and intensity of consumption of the 3 substances and the development of this neoplasm in this site. Although the amount of alcohol consumed had a stronger effect on the risk of esophageal cancer than the number of years it was consumed, however, the number of years one smoked had a stronger effect on the risk than the amount of cigarettes consumed. The strongest risk factor of esophageal cancer was alcohol intake, with highest risk (OR = 13.9) being for those who consumed more than 900 g/day‐year. Combined exposure to any 2 of 3 substances brought the risks up to 8.8–19.7 fold and, to all 3 substances, to 41.2‐fold. A multiplicative interaction effect for alcohol drinkers who smoked on cancer risk was detected, whereas an additive interaction effect was found among drinkers who chewed. The combined effect of all 3 substances accounted for 83.7% of the attributable fraction of contracting esophageal cancer in this population. In conclusion, these results suggest that the intensity and the length of time alcohol and tobacco are used play different roles in the etiology of esophageal cancer. Alcohol separately interacts with tobacco and betel quid in a differently synergistic way in determining the development of this site of cancer.

Efficacy of Dietary Arachidonic Acid Provided as Triglyceride or Phospholipid as Substrates for Brain Arachidonic Acid Accretion in Baboon Neonates

Arachidonic acid (AA) is a long-chain polyunsaturate (LCP) present in human breast milk as both triglyceride (TG) and as phospholipid (PL). There has been little attention to the metabolic consequences of lipid form of AA in infant formulas. Our objective was to investigate the efficacy of dietary TG and PL as carriers of AA for accretion in the brain and associated organs of term baboon neonates consuming a formula with LCP composition typical of human milk. TG and phosphatidylcholine (PC) with [U-13C]-AA in the sn-2 position and with unlabeled 16:0 in the remaining positions (TG-AA* or PL-AA*, respectively) were used as tracers to study the tissue AA* incorporation. Baboon neonates received a single oral dose of either TG-AA* (n = 3) or PL-AA* (n = 4) at 18–19 d of life. Tissues were obtained 10 d later (28–29 d of life) and isotopic enrichment was measured. In the brain, 4.5% of the PL-AA* dose and 2.1% of the TG-AA* dose were recovered as brain AA*, respectively, indicating that PL was about 2.1-fold more effective than TG as a substrate for brain AA accretion. Preferential incorporation of PL-derived AA* over TG source of AA* was also observed in the liver, lung, plasma, and erythrocytes. Because of the quantitative predominance of TG-AA in formula, total brain AA accretion, expressed as absolute weight, was 5.0-fold greater from TG-AA than from PL-AA. We estimate that about half of postnatal brain AA accretion is derived from dietary preformed AA in term baboon neonates consuming a formula with lipid composition similar to that of human milk.

Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid

The consumption of alcohol, tobacco and betel quid has been found to be an important contributor to esophageal squamous cell carcinoma (ESCC) in Taiwan. The genotoxic effect of the ADH1B and ALDH2 genes modulating an individuals alcohol‐metabolizing capacity on ESCC may be linked to drinking behavior, intake pattern and other exogenous factors. To investigate the interplay of these genetic and environmental factors in determining the risk of ESCC, a multicenter case‐control study was conducted. Here, 406 patients with pathology‐proven ESCC, as well as 656 gender, age and study hospital matched controls were recruited. Genetic polymorphisms of ADH1B and ALDH2 appeared to correlate with the abstinence of alcohol, though not with tobacco and betel quid. Within the same levels of alcohol consumption, carcinoma risks increased along with an increase in the numbers of ADH1B*1 and ALDH2*2 alleles. The inactive ALDH2*1/*2 genotype was found to multiplicatively interact with a low‐to‐moderate (0.1–30 g/day) and a heavy (>30 g/day) ethanol intake to increase the ESCC risk (the joint aOR = 14.5 and 102.6, respectively). Among low‐to‐moderate drinkers, a smoking‐dependent carcinogenetic effect for the ADH1B*1/*1 and ALDH2*1/*2+*2/*2 genotypes was recognized, with significant risks found in smokers, but not in nonsmokers. Further, a supra‐multiplicative combined risk of ESCC for alcohol and tobacco use was identified among carriers of the ADH1B*1/*1 genotype (p for interaction = 0.042). In conclusion, the interplay of the ADH1B and ALDH2 genotypes, in conjunction with a behaved drinking habit and a practiced drinking pattern, along with continued tobacco consumption, plays an important pathogenic role in modulating ESCC risk.

G-2548A Polymorphism of the Leptin Gene Is Correlated with Extreme Obesity in Taiwanese Aborigines

We examined the genetic associations of the G‐2548A polymorphism in the promoter of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin receptor (LEPR) gene with obesity. Two hundred twenty‐six obese aboriginal subjects (BMI ≥ 27 kg/m2) and 182 aboriginal subjects with normal weight (BMI < 25 kg/m2) participated in this study. The polymorphisms of LEP G‐2548A and LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment length polymorphism, and their anthropometric characteristics were measured. Levels of leptin, triglycerides, and cholesterol were measured after overnight fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with Mendelian recessive (χ2 = 7.89, p = 0.005) and codominant (χ2 = 7.93, p = 0.02) models to be higher in the extremely obese subjects (BMI ≥ 35 kg/m2) than in normal weight subjects (6.9%) but not in moderately obese subjects (35 > BMI ≥ 27 kg/m2). There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups. We suggest that the LEP −2548 G/G homozygote plays a genetic recessive role in the development of extreme obesity in Taiwanese aborigines.

Prospective Randomized Controlled Trial to Evaluate Effectiveness of Registered Dietitian–Led Diabetes Management on Glycemic and Diet Control in a Primary Care Setting in Taiwan

OBJECTIVE In this randomized controlled trial we evaluated the effect of registered dietitian–led management of diabetes on glycemic control and macronutrient intake in type 2 diabetic patients in primary care clinics in Taiwan and studied the association between changes in macronutrient intake and glycemic measures. RESEARCH DESIGN AND METHODS We recruited 154 adult patients with type 2 diabetes and randomly assigned them to a routine care control group (n = 79) or a registered dietitian–led intervention group (n = 75) who received on-site diabetic self-management education every 3 months over 12 months. RESULTS Over the 1-year period, neither the intervention group (n = 75) nor the control group (n = 79) had significant changes in A1C, whereas the intervention patients with poorly controlled baseline A1C (≥7%) (n = 56) had significantly greater improvements in A1C and fasting plasma glucose than the control subjects (n = 60) (−0.7 vs. −0.2%, P = 0.034; −13.4 vs. 16.9 mg/dl, P = 0.007) during the same period. We also found significant net intervention-control group differences in overall energy intake (−229.06 ± 309.16 vs. 56.10 ± 309.41 kcal/day) and carbohydrate intake (−31.24 ± 61.53 vs. 7.15 ± 54.09 g/day) (P < 0.001) in patients with poorly controlled A1C. Multivariable adjusted modeling revealed an independent association between changes in carbohydrate intake and A1C in the intervention group (n = 56; β = 0.10, SEM = 0.033, P = 0.004). CONCLUSIONS On-site registered dietitian–led management of diabetes can improve glycemic control in patients with poorly managed type 2 diabetes in primary care clinics in Taiwan. A reduction in carbohydrate intake may improve glycemic status.

Association between Insulin Resistance and Development of Microalbuminuria in Type 2 Diabetes: A Prospective Cohort Study.

OBJECTIVE An association between insulin resistance and microalbuminuria in type 2 diabetes has often been found in cross-sectional studies. We aimed to reassess this relationship in a prospective Taiwanese cohort of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS We enrolled 738 normoalbuminuric type 2 diabetic subjects, aged 56.6 ± 9.0 years, between 2003 and 2005 and followed them through the end of 2009. Average follow-up time was 5.2 ± 0.8 years. We used urine albumin-to-creatinine ratio to define microalbuminuria and the homeostasis model assessment of insulin resistance (HOMA-IR) to assess insulin resistance. The incidence rate ratio and Cox proportional hazards model were used to evaluate the association between HOMA-IR and development of microalbuminuria. RESULTS We found incidences of microalbuminuria of 64.8, 83.5, 93.3, and 99.0 per 1,000 person-years for the lowest to highest quartiles of HOMA-IR. Compared with those in the lowest quartile of HOMA-IR, the incidence rate ratios for those in the 2nd, 3rd, and highest quartiles were 1.28 (95% CI 0.88–1.87), 1.44 (0.99–2.08), and 1.52 (1.06–2.20), respectively (trend test: P < 0.001). By comparison with those in the lowest quartile, the adjusted hazard ratios were 1.37 (0.93–2.02), 1.66 (1.12–2.47), and 1.76 (1.20–2.59) for those in the 2nd, 3rd, and highest HOMA-IR quartiles, respectively. CONCLUSIONS According to the dose-response effects of HOMA-IR shown in this prospective study, we conclude that insulin resistance could significantly predict development of microalbuminuria in type 2 diabetic patients.

Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup.

Objective:The dietary intake of fructose-rich sugar-sweetened beverages (SSB) may have a significant role in raising serum uric acid (SUA) levels as well as the risk of contracting gout and cardiovascular risk factors. Our objective was to investigate the impact of SSB intake on SUA, body mass index (BMI) and systolic blood pressure (SBP) among adolescents in Taiwan.Methods:We evaluated data from 2727 representative adolescents who were multistage sampled from 36 Junior High schools in Taiwan. We cross-sectionally collected demographic, physical, dietary and anthropometric variables, and prospectively measured clinical outcomes. Data were analyzed using multiple regression and logistic models adjusted for covariates.Results:We found that 87.7% of adolescents were SSB drinkers, with 25.1% drinking >500 ml per day of such beverages. Increased SSB intake was associated with increased waist and hip circumferences, body fat, BMI, SBP and SUA. As compared with non-drinkers, SSB drinkers had a 3.2–4.9 elevated risk of obesity. The prevalence of hyperuricemia in heavy SSB users (40.2–49.4%) was appreciably greater than that for non-users (24.2%). Adolescents who consumed >500 ml per day of heavy high-fructose corn syrup (HFCS) containing beverages had a 0.42 mg dl−1 higher SUA level and a 2.0–2.1 increased risk of developing hyperuricemia than non-drinkers. The consumption of HFCS-rich beverages was also found to interact with obesity in determining higher levels of SUA (2.2–2.4 mg dl−1 increases).Conclusion:High SSB consumption has a notable effect on increased levels of BMI and SUA. The intake of HFCS-rich beverages and BMI were likely to interactively strengthen SUA levels among obese adolescents.

Association between diet and esophageal cancer in Taiwan

Background:  Several studies have reported the importance of dietary factors in the development of esophageal cancer. The purpose of the present study was to evaluate the effects of several common dietary factors on the risk of squamous cell carcinoma of the esophagus in a Taiwanese population.

Inadequate Energy and Excess Protein Intakes May Be Associated With Worsening Renal Function in Chronic Kidney Disease

OBJECTIVES Dietary energy and protein play important roles in chronic kidney disease (CKD). This study investigates the relationship between energy/protein intake status and renal function in CKD. DESIGN AND STUDY POPULATION This cross-sectional study included 599 adult patients diagnosed with stage 3 to 5 CKD in nephrology and nutrition outpatient clinics in Taiwan. MAIN OUTCOME MEASURE Energy and protein intakes were assessed using 24-h dietary recall. We recorded recommended calorie/protein amounts and renal function indices, glomerular filtration rate (GFR), creatinine, and blood urea nitrogen (BUN). Patients were categorized into three intake calorie/protein groups by a ratio of actual intake vs. recommended intake. High intake was defined as a ratio of actual intake/recommended intake > or = 110%, moderate intake as > or = 90% to <110%, and low intake as <90%. Data were analyzed by paired t test, one-way analysis of variance, least significant differences, and multiple linear regression. RESULTS The energy and protein intakes in CKD patients were significantly higher and lower than recommended levels (P < .001). Low energy intake was significantly related to worsening GFR at increments of -4.41 mL/min/1.73 m(2), compared with moderate and high energy intake (P = .008); high protein intake was also associated with worsening GFR at increments of -3.50 mL/min/1.73m(2), compared with moderate and low protein intake (P < .001). Low energy intake and high protein intake were significantly positively correlated with elevations in creatinine and BUN. CONCLUSION Lower energy and higher protein intakes than recommended may be associated with deteriorating renal function.

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

Objective: To investigate whether vitamin B6 supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients.Design: A single-blind intervention study.Setting: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan.Subjects: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study.Interventions: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B6 (n=8), 10 mg vitamin B6 (n=8), 50 mg vitamin B6 (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B12 (n=9) for 12 weeks.Main outcome measures: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5′-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B12 were measured.Results: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B6 when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B12 supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B6 supplemented groups, respectively; whereas folic acid combined with vitamin B12 supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001).Conclusions: Our results indicate that vitamin B6 supplementation alone is less effective than folic acid combined with vitamin B12 in lowering plasma homocysteine concentrations in CAD patients.Sponsorship: This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).