Chih Hsing Wu

Smoking, habitual tea drinking and metabolic syndrome in elderly men living in rural community: the Tianliao old people (TOP) study 02.

The literature shows an inconsistent relationship between lifestyle behaviors and metabolic syndrome (MetS), especially in the elderly. We designed this study to investigate the interrelationships among cigarette smoking, tea drinking and MetS, and to verify the factors associated with MetS in elderly males dwelling in rural community. In July 2010, with a whole community sampling method, 414 male subjects aged over 65 dwelling in Tianliao township were randomly sampled. The response rate was 60.8%. Each subject completed the structured questionnaires including sociodemographic characteristics, habitual behaviors (including cigarette smoking and tea drinking habits) and medical history. After an overnight fast, the laboratory and anthropometric data were obtained. MetS was confirmed according to the criteria defined by the modified NCEP ATP III for the male Chinese population. Subjects were split into either non-MetS or MetS groups for further analysis. Of the 361 subjects with complete data, 132 (36.6%) elderly men were classified as having MetS. Using binary logistic regression, body mass index, serum uric acid, high sensitivity C-reactive protein, HOMA index, current smokers (ORu200a=u200a2.72, 95%CI: 1.03 ∼ 7.19), total smoking amount >u200a=u200a30 (ORu200a=u200a2.78, 95%CI: 1.31 ∼ 5.90) and more than 20 cigarettes daily (ORu200a=u200a2.54, 95%CI: 1.24 ∼ 5.18) were positively associated with MetS. Current un- or partial fermented tea drinker (ORu200a=u200a0.42, 95%CI: 0.22 ∼ 0.84), tea drinking habit for 1–9 years (ORu200a=u200a0.36, 95%CI: 0.15 ∼ 0.90) and more than 240cc daily (ORu200a=u200a0.35, 95%CI: 0.17 ∼ 0.72) were negatively associated with MetS. In conclusion, this study suggests that smoking habit was positively associated with MetS, but tea drinking habit was negatively associated with MetS in elderly men dwelling in rural community.

Detection of Total and A1c-Glycosylated Hemoglobin in Human Whole Blood Using Sandwich Immunoassays on Polydimethylsiloxane-Based Antibody Microarrays

The percentage of glycosylated hemoglobin A1c (%GHbA1c) in human whole blood indicates the average plasma glucose concentration over a prolonged period of time and is used to diagnose diabetes. However, detecting GHbA1c in the whole blood using immunoassays has limited detection sensitivity due to its low percentage in total hemoglobin (tHb) and interference from various glycan moieties in the sample. We have developed a sandwich immunoassay using an antibody microarray on a polydimethylsiloxane (PDMS) substrate modified with fluorinated compounds to detect tHb and glycosylated hemoglobin A1c (GHbA1c) in human whole blood without sample pretreatment. A polyclonal antibody against hemoglobin (Hb) immobilized on PDMS is used as a common capture probe to enrich all forms of Hb followed by detection via monoclonal anti-Hb and specific monoclonal anti-GHbA1c antibodies for tHb and GHbA1c detection, respectively. This method prevents the use of glycan binding molecules and dramatically reduces the background interference, yielding a detection limit of 3.58 ng/mL for tHb and 0.20 ng/mL for GHbA1c. The fluorinated modification on PDMS is superior to the glass substrate and eliminates the need for the blocking step which is required in commercial enzyme linked immunosorbent assay (ELISA) kits. Moreover, the detection sensitivity for GHbA1c is 4-5 orders of magnitude higher, but the required sample amount is 25 times less than the commercial method. On the basis of patient sample data, a good linear correlation between %GHbA1c values determined by our method and the certified high performance liquid chromatography (HPLC) standard method is shown with R(2) > 0.98, indicating the great promise of the developed method for clinical applications.

The impacts of sarcopenia and obesity on physical performance in the elderly

OBJECTIVE/BACKGROUNDnThe current definition of sarcopenic obesity in the elderly does not seem to take the ageing difference of body composition into sufficient consideration. The study accordingly attempted to better define sarcopenia/obesity based on various references, and the impacts of sarcopenia/obesity on elderly physical performance were also examined.nnnDESIGN AND METHODSn2629 elderly subjects (age ≧65) and 998 young adults were recruited for Sarcopenia and Translational Ageing Research in Taiwan (START). For each eligible subject, body composition was measured by bio-impedance analysis and physical performance, including upper and lower extremity function, was examined. The thresholds of sarcopenic obesity were defined as a value at two standard deviations from the gender-specific means of the young population or at the adopted value of our elderly population.nnnRESULTSnCompared to the young adults, the elderly subjects reported a lower appendicular skeletal muscle index (ASMI, kg/m(2)) and a significantly higher fat percentage (%). From three different criteria, thresholds of obesity or sarcopenia were 31.41%, 30.16%, 30.64% (fat percentage) or 6.76kg/m(2), 7.36kg/m(2), 7.09kg/m(2) (ASMI) for men and 39.17%, 41.43%, 43.25% or 5.28kg/m(2), 5.74kg/m(2), 5.70kg/m(2) for women. The elderly subjects were classified into four groups. With covariates adjusted, the sarcopenia only, obesity only, and sarcopenic obesity elderly subjects were worse than their normal counterparts in physical performance (all p<0.05 except for the handgrip strength compared in groups 1 and 3).nnnCONCLUSIONSnSarcopenic obesity seems to exert a synergistic impact on elderly physical performance. Body composition should be an essential part in geriatric assessment and elderly care.

Combined association of chronic disease and low skeletal muscle mass with physical performance in older adults in the Sarcopenia and Translational Aging Research in Taiwan (START) study.

BackgroundMultiple chronic conditions and low skeletal muscle mass are common features of aging that are detrimental to physical performance. This study evaluates the simultaneous impact of these conditions on physical performance in older adults.MethodsFive studies from 2003 to 2012 were pooled to include 2,398 adults aged ≥65xa0years with diagnosed chronic diseases measured by self-administered questionnaire. Low muscle mass was defined as an appendicular skeletal muscle mass index less than that of the sex-specific lowest quintile in the population of older adults. Poor physical performances were defined as the lowest quintile of grip strength and gait speed in the population of older adults and the slowest sex-specific 20% of Timed Up and Go (TUG) test at each study site. Chi-squared and logistic regression tests were applied for data analysis.ResultsMean age of the study participants, of whom approximately 50% were men, was 74.3xa0years. Slow gait speed was nearly three times more likely to occur in the presence of low muscle mass coupled with chronic disease than in the absence of both factors after adjustment for study site, age, sex, education, marital status, body mass index, tobacco and alcohol use, and comorbidities. The independent effect of low muscle mass was generally stronger than that of each disease. Participants with more than two chronic diseases and low muscle mass were significantly more likely to perform poorly than those with no risk factors (odds ratio [OR]u2009=u20092.51 in patients with low grip strength, ORu2009=u20093.89 in patients with low gait speed, and ORu2009= 3.67 in patients with poor TUG test scores, all Pu2009<u20090u2009.05) after adjustment.ConclusionsThe combined association of chronic disease and low skeletal mass with physical performance was stronger than the effect of either factor alone.

In-Depth Comparative Characterization of Hemoglobin Glycation in Normal and Diabetic Bloods by LC-MSMS

AbstractThe glycation level at β-Val-1 of the hemoglobin β chain in human blood (HbA1c%) is used to diagnose diabetes and other diseases. However, hemoglobin glycation occurs on multiple sites on different isoforms with different kinetics, but its differential profile has not been clearly demonstrated. In this study, hemoglobin was extracted from the blood of normal and diabetic individuals by protein precipitation. Triplicate solutions prepared from each sample were directly analyzed or digested with multiple enzymes and then analyzed by nano-LC/MS via bottom-up approach for side-by-side characterization. Intact hemoglobin analysis indicated a single glucose-dominant glycation, which showed good correlation with the HbA1c% values. Moreover, full sequence (100xa0%) of α/β globin was mapped and seven glycation sites were unambiguously assigned. In addition to β-Val-1, two other major sites at α-Lys-61 and β-Lys-66, which contain the common sequence HGKK, and four minor sites (<1xa0%) on α-Val-1, β-Lys-132, α-Lys-127, and α-Lys-40 were identified. All sites were shown to exhibit similar patterns of site distribution despite different glucose levels. Both the intact mass measurement and bottom-up data consistently indicated that the total glycation percentage of the β-globin was twice higher than the α-globin. Using molecular modeling, the 3D structure of the consensus sequence (HGKK) was shown to contain a phosphate triangle cavity, which helps to catalyze the glycation reaction. For the first time, hemoglobin glycation in normal and diabetic bloods was comparatively characterized in-depth with 100xa0% sequence coverage. The results provide insight about the HbA1c parameter and help define the new and old markers.n Figureᅟ

Epidemiological survey of quantitative ultrasound in risk assessment of falls in middle-aged and elderly people.

The risk assessment of falls is important, but still unsatisfactory and time-consuming. Our objective was to assess quantitative ultrasound (QUS) in the risk assessment of falls. Our study was designed as epidemiological cross-sectional study occurring from March 2009 to February 2010 by community survey at a medical center. The participants were collected from systemic sample of 1,200 community-dwelling people (Male/Femaleu200a=u200a524/676) 40 years old and over in Yunlin County, Mid-Taiwan. Structural questionnaires including socioeconomic status, living status, smoking and drinking habits, exercise and medical history were completed. Quantitative ultrasound (QUS) at the non-dominant distal radial area (QUS-R) and the left calcaneal area (QUS-C) were measured. The overall prevalence of falls was 19.8%. In men, the independently associated factors for falls were age (OR: 1.04; 95%CI: 1.01∼1.06), fracture history (OR: 1.89; 95%CI: 1.12∼3.19), osteoarthritis history (OR: 3.66; 95%CI: 1.15∼11.64) and speed of sound (OR: 0.99; 95%CI: 0.99∼1.00; p<0.05) by QUS-R. In women, the independently associated factors for falls were current drinking (OR: 3.54; 95%CI: 1.35∼9.31) and broadband ultrasound attenuation (OR: 0.98; 95%CI: 0.97∼0.99; p<0.01) by QUS-C. The cutoffs at -2.5< T-score<-1 derived using QUS-R (OR: 2.85; 95%CI: 1.64∼4.96; p<0.01) in men or T-score ≦-2.5 derived using QUS-C (OR: 2.72; 95%CI: 1.42∼5.21; p<0.01) in women showed an independent association with falls. The lowest T-score derived using either QUS-R or QUS-C was also revealed as an independent factor for falls in both men (OR: 2.13; 95%CI: 1.03∼4.43; p<0.05) and women (OR: 2.36; 95%CI: 1.13∼4.91; p<0.05). Conclusions: Quantitative ultrasounds, measured either at the radial or calcaneal area, are convenient tools by which to assess the risk of falls in middle-aged and elderly people.

Role of adiponectin gene variants, adipokines and hydrometry-based percent body fat in metabolically healthy and abnormal obesity

OBJECTIVEnMetabolically healthy obesity (MHO) subjects have better metabolic parameters than metabolically abnormal obesity (MAO) subjects, but the possible mechanisms underlying this remain unknown. Our study was designed to investigate the interrelationships among genes, adipokines, body fat and its distribution in MHO and MAO.nnnMETHODSnFrom 2007 to 2009, 103 males and 131 females aged 18-50 years were enrolled by an intention-to-treat design in a weight management clinic. Participants were divided into MHO and MAO groups. Percent body fat (PBF) was measured by a deuterium oxide dilution method. Four polymorphic variants, including PPARγ2 (Pro12Ala and C1431T) and adiponectin (T45G and G276T) genes, and three adipokines (adiponectin, leptin and resistin) were obtained.nnnRESULTSnOf the 234 obese subjects, 130 (55.6%) were MHO. In the univariate analysis, the MAO group has significantly higher anthropometric, metabolic indices and leptin levels than the MHO group. Logistic regression analysis revealed that age, male gender, the T allele of adiponectin T45G polymorphism, leptin and PBF were positively associated with MAO. ANCOVA analysis revealed that the T allele of adiponectin T45G polymorphism was associated with higher fasting and postprandial glucose levels. We further found that TT genotype has a lower high molecular weight (HMW)/low molecular weight (LMW) adiponectin ratio than GG genotype.nnnCONCLUSIONSnThe factors associated with MAO are age, male gender, the T allele of adiponectin T45G polymorphism, leptin, and PBF. The net effects of T45G polymorphism on the MAO phenotype may be achieved by changes in the adiponectin oligomer ratio and glucose levels.

The interplay between inflammation, physical activity and metabolic syndrome in a remote male geriatric community in Southern Taiwan: the Tianliao Old People (TOP) study 03

BackgroundBoth physical activity and inflammation are important in the pathophysiology of metabolic syndrome (MetS). Our study aim is to explore their associations in an elderly male (≥ 65xa0years old) cohort.MethodsWe enrolled 309 elderly male residents (mean age: 74.4u2009±u20096.0xa0years) in a remote southern Taiwan community. The physical activity was recorded by a standard questionnaire. A high-sensitivity C-reactive protein (hsCRP) levelu2009>u20093.0xa0mg/L indicated a high inflammatory status.ResultsThe total prevalence rate of MetS was 27.8% in this male geriatric cohort. Median hsCRP levels were significantly higher in the MetS group (1.60u2009±u20090.7 vs. 1.0u2009±u20090.3xa0mg/L, pu2009<u20090.01), and the risk of elevated hsCRP increased with escalating MetS components (p for trendu2009<u20090.001). The non-MetS group had higher amount of median weekly physical activity (183.1u2009±u200919.0 vs. 173.5u2009±u200910.6 MET-hr/week, pu2009=u20090.029), which was also higher among those with lower hsCRP levels (186.1u2009±u200914.1 vs. 167.8u2009±u200938.5 MET-hr/week, pu2009=u20090.013). Multivariate analysis showed that higher body mass index (ORs: 1.527, 95% CI: 1.319-1.768, pu2009<u20090.01) insulin (OR: 1.128, 95% CI: 1.045-1.218, pu2009<u20090.01) and physical activity (ORs: 0.997, 95% IC: 0.994-0.999, pu2009<u20090.05) were independent predictors of MetS, but not hsCRP level (pu2009>u20090.05).ConclusionsReduced physical activity was one major pathophysiological MetS factor in our Asian geriatric participants.

Serum Vitamin D, intact parathyroid hormone, and Fetuin A concentrations were associated with geriatric sarcopenia and cardiac hypertrophy

With aging, intact parathyroid hormone (iPTH) increases. It plays a crucial role in left ventricular hypertrophy (LVH). Also, 25-hydroxy vitamin D (Vit-D) and iPTH have been observed to be determinants of muscle wasting known as sarcopenia. Fetuin A (FetA), a systemic calcification inhibitor, involves in the development of diastolic heart failure. Hence, we hypothesized that the interplay among FetA, Vit-D and iPTH may contribute to sarcopenic LVH among the elders. We analyzed a database from the Tianliao Old People study with 541 elders (≥65 years) in a Taiwan’s suburban community. After excluding patients with renal function impairment, 120/449 (26.7%) patients were diagnosed with sarcopenia. Sarcopenic patients had lower serum Vit-D levels but higher FetA as well as iPTH. Notably, sarcopenic patients with LVH had significantly lower FetA and higher iPTH levels. In multivariate logistic regression analysis, only the increase in iPTH was independently associated with sarcopenic LVH (Odds ratio: 1.05; confidence interval: 1.03–1.08, pu2009=u20090.005). Using iPTH >52.3u2009ng/l as a cutoff point, the sensitivity and specificity was 66% and 84%, respectively. In conclusion, FetA, Vit-D, and iPTH levels were all associated with sarcopenia in this geriatric population. Among them, iPTH specifically indicates patients with sarcopenic LVH.

Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes

Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.