Hsu-Ko Kuo

Diabetes and the Risk of Multi-System Aging Phenotypes: A Systematic Review and Meta-Analysis

Background Observational studies suggested an association between diabetes and the risk of various geriatric conditions (i.e., cognitive impairment, dementia, depression, mobility impairment, disability, falls, and urinary incontinence). However, the magnitude and impact of diabetes on older adults have not been reviewed. Methodology/Principal Findings MEDLINE and PSYCINFO databases were searched through November 2007 for published studies, supplemented by manual searches of bibliographies of key articles. Population-based, prospective cohort studies that reported risk of geriatric outcomes in relation to diabetes status at baseline were selected. Two authors independently extracted the data, including study population and follow-up duration, ascertainment of diabetes status at baseline, outcomes of interest and their ascertainment, adjusted covariates, measures of association, and brief results. Fifteen studies examined the association of DM with cognitive dysfunction. DM was associated with a faster decline in cognitive function among older adults. The pooled adjusted risk ratio (RR) for all dementia when persons with DM were compared to those without was 1.47 (95% CI, 1.25 to 1.73). Summary RRs for Alzheimers disease and vascular dementia comparing persons with DM to those without were 1.39 (CI, 1.16 to 1.66) and 2.38 (CI, 1.79 to 3.18), respectively. Four of 5 studies found significant association of DM with faster mobility decline and incident disability. Two studies examined the association of diabetes with falls in older women. Both found statistically significant associations. Insulin users had higher RR for recurrent falls. One study for urinary incontinence in older women found statistically significant associations. Two studies for depression did not suggest that DM was an independent predictor of incident depression. Conclusions/Significance Current evidence supports that DM is associated with increased risk for selected geriatric conditions. Clinicians should increase their awareness and provide appropriate care. Future research is required to elucidate the underlying pathological pathway.

Serum bilirubin is inversely associated with insulin resistance and metabolic syndrome among children and adolescents.

OBJECTIVE Bilirubin is a potent antioxidant and a cyroprotectant. Low serum bilirubin is associated with atherosclerosis. Little is known about its role in metabolic syndrome (MS) among children and adolescents. METHODS We examined 4723 children and adolescents aged 12-17 years with reliable measures of various serum hepatic profiles and metabolic risks from Health and Nutrition Examination Survey 1999-2004. RESULTS The results showed that the prevalence of the MS was from 6.6+/-1.2% in the lowest quartile to 2.1+/-1.9% in the highest quartile of the concentration of total bilirubin. The graded association remained significant after the adjustment of other co-variates. The odds ratios for the MS were around 0.29 (0.08-0.99) and 0.23 (0.08-0.65) for the upper two quartiles when using the lowest quartile as reference for the concentration of total bilirubin. The quartiles of the serum total bilirubin levels were inversely correlated with the homeostasis model assessment (HOMA-IR) and insulin while not associated with the serum C-reactive protein (CRP) levels. CONCLUSIONS The serum total bilirubin levels are inversely correlated with the prevalence of the MS. The mechanism of the association between MS and total bilirubin may be related to the insulin resistance status.

Exploring How Peak Leg Power and Usual Gait Speed Are Linked to Late-Life Disability: Data from the National Health and Nutrition Examination Survey (NHANES), 1999–2002

Kuo HK, Leveille SG, Yen CJ, Chai HM, Chang CH, Yeh YC, Yu YH, Bean JF: Exploring leg power and gait speed in late-life disability: Data from the National Health and Nutrition Examination Survey (NHANES), 1999–2002. Am J Phys Med Rehabil 2006;85:650–658. Objective:To investigate the relation of both peak leg power and usual gait speed in their association with varying domains of late-life disability. Design:Participants (≥60 yrs of age, n = 1753) were from the National Health and Nutrition Examination Survey, 1999–2002. Disability in activities of daily living, instrumental activities of daily living, leisure and social activities, lower limb mobility, and general physical activities was obtained by self-report. Peak muscle power was the product of isokinetic peak leg torque and peak force velocity. Functional limitations were evaluated via usual gait speed, which was obtained from a 20-foot timed walk. Results:Low usual gait speed was associated with disability independent of basic demographics, cognitive performance, co-morbidities, health behaviors, and inflammatory markers. The odds ratios for disabilities in activities of daily living, instrumental activities of daily living, leisure and social activities, lower limb mobility, and general physical activities for each standard-deviation increase in walking speed were 0.72 (95% confidence interval [CI], 0.59–0.87), 0.63 (95% CI, 0.52–0.77), 0.57 (95% CI, 0.45–0.72), 0.56 (95% CI, 0.47–0.67), and 0.74 (95% CI, 0.64–0.85), respectively. The odds ratios for disabilities in activities of daily living, instrumental activities of daily living, leisure and social activities, lower limb mobility, and general physical activities for each standard-deviation increase in leg power were 0.70 (95% CI, 0.55–0.89), 0.67 (95% CI, 0.53–0.86), 0.62 (95% CI, 0.47–0.83), 0.58 (95% CI, 0.47–0.72), and 0.73 (95% CI, 0.61–0.87), respectively. Supplementary adjustment for walking speed mildly attenuated the relation of leg power to disability. Conclusion:Peak leg power and habitual gait speed were associated with varying domains of late-life disability. The association between peak leg power and disability seems to be partially mediated through usual gait speed.

Cognitive Function, Habitual Gait Speed, and Late-Life Disability in the National Health and Nutrition Examination Survey (NHANES) 1999–2002

Background: Both cognitive function and gait speed are important correlates of disability. However, little is known about the combined effect of cognitive function and gait speed on multiple domains of disability as well as about the role of gait speed in the association between cognitive function and late-life disability. Objective: To investigate (1) how cognition and habitual gait speed are related to late-life disability; (2) the role of habitual gait speed in the cognitiondisability association; and (3) the combined effect of cognitive function and habitual gait speed on late-life disability. Method: Participants (>60 years, n = 2,481) were from the National Health and Nutrition Examination Survey 1999–2002. Disability in activities of daily living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), and lower extremity mobility (LEM) was obtained by self-report. Cognitive function was measured by a 2-min timed Digit Symbol Substitution Test (DSST), an executive function measure from the Wechsler Adult Intelligence Test. Habitual gait speed was obtained from a 20-foot timed walk. Multiple logistic regression was used to assess the association between cognitive function and disability. Results: Cognitive function was associated with decreased likelihood for disability in each domain. The odds ratios (ORs) for disability in ADL, IADL, LSA, and LEM for each standard deviation (SD) increase in the DSST score were 0.47 (95% confidence interval [CI] = 0.34–0.64), 0.53 (95% CI = 0.42–0.67), 0.61 (95% CI = 0.47–0.79), and 0.73 (95% CI = 0.61–0.86), respectively, in the multi-variable models. After additional adjustment for habitual gait speed in the cognition-disability relationship, DSST score was no longer a significant correlate for LSA and LEM disability. The strength of the association between DSST score and disability in ADL/IADL was also diminished. The attenuated association between cognition and disability implies that limitation in gait speed likely mediates the association between cognitive function and disability. We found additive effects of cognition and habitual gait speed on late-life disability. The OR of disability in respective domains were lowest among participants with high-DSST score (high executive function) and with high gait speed. In contrast, the OR tended to be highest among participants with low-DSST score (low executive function) and low gait speed. Conclusion: Cognitive function was associated with multiple domains of disability. There was a joint effect of cognitive function and gait speed on late-life disability. This study also suggested that habitual gait speed partially mediated the inverse association between cognitive function and late-life disability, providing a mechanistic explanation in the context of disablement process.

The Evolving Transcriptome of Head and Neck Squamous Cell Carcinoma: A Systematic Review

Background Numerous studies were performed to illuminate mechanisms of tumorigenesis and metastases from gene expression profiles of Head and Neck Squamous Cell Carcinoma (HNSCC). The objective of this review is to conduct a network-based meta-analysis to identify the underlying biological signatures of the HNSCC transcriptome. Methods and Findings We included 63 HNSCC transcriptomic studies into three specific categories of comparisons: Pre, premalignant lesions v.s. normal; TvN, primary tumors v.s. normal; and Meta, metastatic or invasive v.s. primary tumors. Reported genes extracted from the literature were systematically analyzed. Participation of differential gene activities across three progressive stages deciphered the evolving nature of HNSCC. In total, 1442 genes were verified, i.e. reported at least twice, with ECM1, EMP1, CXCL10 and POSTN shown to be highly reported across all three stages. Knowledge-based networks of the HNSCC transcriptome were constructed, demonstrating integrin signaling and antigen presentation pathways as highly enriched. Notably, functional estimates derived from topological characteristics of integrin signaling networks identified such important genes as ITGA3 and ITGA5, which were supported by findings of invasiveness in vitro [1]. Moreover, we computed genome-wide probabilities of reporting differential gene activities for the Pre, TvN, and Meta stages, respectively. Results highlighted chromosomal regions of 6p21, 19p13 and 19q13, where genomic alterations were shown to be correlated with the nodal status of HNSCC [2]. Conclusions By means of a systems-biology approach via network-based meta-analyses, we provided a deeper insight into the evolving nature of the HNSCC transcriptome. Enriched canonical signaling pathways, hot-spots of transcriptional profiles across the genome, as well as topologically significant genes derived from network analyses were highlighted for each of the three progressive stages, Pre, TvN, and Meta, respectively.

Levels of homocysteine are inversely associated with cardiovascular fitness in women, but not in men: data from the National Health and Nutrition Examination Survey 1999-2002.

Objectives.  Cardiovascular fitness represents the ability of active skeletal muscle to utilize oxygen during aerobic exercise. Elevated homocysteine, causing tissue injury by such mechanisms as oxidative stress, endothelial damage, and protein homocysteinylation, is associated with increased risk of cardiovascular disease, dementia and osteoporotic fracture. However, the association between elevated homocysteine and cardiovascular fitness has not been reported.

Metabolic risks, white matter hyperintensities, and arterial stiffness in high-functioning healthy adults

BACKGROUND Arterial stiffness, an age-related feature and measured noninvasively by pulse wave velocity (PWV), is associated with a variety of cardiovascular diseases. Although white matter lesion (WML), representing cerebrovascular micro-angiopathy, is typically considered as a preclinical cardiovascular disease, little is know about the association between PWV and WML. The aim of this study is to examine the association between PWV and WML. METHOD We examined the extent of white matter lesion on cranial magnetic resonance imaging of 93 participants (mean 72.46 years) from the annual Health Examination for the Elderly Program in the National Taiwan University Hospital. Two subtypes of WML including periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) were graded according to Fazekas et al. The brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV) were measured using an automatic waveform analyzer. RESULTS PVH and DWHM were found in 71 (76%) and 58 (62%) participants. Various degree of WML was observed in 80 (86%) participants. Hypertension, use of anti-hypertensive medications, and elevated blood pressure were identified as risk factors of WML. The baPWV and haPWV were correlated with many metabolic risks, including systolic blood pressure, pulse pressure, and serum triglycerides. The baPWV and haPWV were greater in participants with higher grades of WML in the multivariate analyses. The receiver operating characteristics analyses demonstrated that area under curves for haPWV to identify moderate-to-severe PVH and DWMH were 0.78 (95% confidence interval [CI] 0.66-0.91) and 0.72 (95% CI 0.59-0.85), respectively. CONCLUSION Greater PWV is associated with higher grades of WML among high-functioning older adults. Our findings support the notion that measurement of arterial stiffness is useful in clinical practice for detection of preclinical cerebrovascular disease.

Effects of obesity, physical activity, and cardiorespiratory fitness on blood pressure, inflammation, and insulin resistance in the National Health and Nutrition Survey 1999-2002.

BACKGROUND AND AIMS This study was designed to elucidate the effects of obesity, self-reported physical activity and cardiorespiratory fitness on blood pressure, inflammation, and insulin resistance. METHODS AND RESULTS Data from 950 Caucasian subjects ranging in age from 19 to 49 years from the National Health and Nutrition Survey (NHANES), 1999-2002, were included to construct a population-based observational study. Cardiorespiratory fitness (VO(2) max) was predicted from a submaximal exercise stress test. Self-reported physical activity was measured by metabolic equivalent score transformed from a questionnaire. A structural equation model (SEM) was developed to examine the relationship between obesity, cardiorespiratory fitness, self-reported physical activity, and hypertension, inflammation, and insulin resistance. The model showed that obesity was positively linked to hypertension (B=0.50, P<0.001) and C-reactive protein (CRP; B=0.15, p<0.05), which in turn led to insulin resistance (B=0.44, P<0.05). Increased cardiorespiratory fitness was negatively associated with CRP (Γ=-0.23, P<0.01), but not correlated to hypertension after adjustment for potential confounding factors. No significant association was found between self-reported physical activity and hypertension, insulin resistance, and CRP. CONCLUSION Obesity contributes to the development of hypertension, inflammation, and insulin resistance. Improved cardiorespiratory fitness might lead to clinical and biochemical improvement in insulin resistance by reducing the inflammatory state.

Inverse association between insulin resistance and gait speed in nondiabetic older men: results from the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2002

BackgroundRecent studies have revealed the associations between insulin resistance (IR) and geriatric conditions such as frailty and cognitive impairment. However, little is known about the relation of IR to physical impairment and limitation in the aging process, eg. slow gait speed and poor muscle strength. The aim of this study is to determine the effect of IR in performance-based physical function, specifically gait speed and leg strength, among nondiabetic older adults.MethodsCross-sectional data were from the population-based National Health and Nutrition Examination Survey (1999-2002). A total of 1168 nondiabetic adults (≥ 50 years) with nonmissing values in fasting measures of insulin and glucose, habitual gait speed (HGS), and leg strength were analyzed. IR was assessed by homeostasis model assessment (HOMA-IR), whereas HGS and peak leg strength by the 20-foot timed walk test and an isokinetic dynamometer, respectively. We used multiple linear regression to examine the association between IR and performance-based physical function.ResultsIR was inversely associated with gait speed among the men. After adjusting demographics, body mass index, alcohol consumption, smoking status, chronic co-morbidities, and markers of nutrition and cardiovascular risk, each increment of 1 standard deviation in the HOMA-IR level was associated with a 0.04 m/sec decrease (p = 0.003) in the HGS in men. We did not find such association among the women. The IR-HGS association was not changed after further adjustment of leg strength. Last, HOMA-IR was not demonstrated in association with peak leg strength.ConclusionIR is inversely associated with HGS among older men without diabetes. The results suggest that IR, an important indicator of gait function among men, could be further investigated as an intervenable target to prevent walking limitation.

Nationwide epidemiological study of severe gallstone disease in Taiwan

BackgroundOur study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20.MethodsA retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution.ResultsThe hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy.ConclusionThis population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.