High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Assessment of Murine Colon Inflammation Using Intraluminal Fluorescence Lifetime Imaging.

Inflammatory bowel disease (IBD) is typically diagnosed by exclusion years after its onset. Current diagnostic methods are indirect, destructive, or target overt disease. Screening strategies that can detect low-grade inflammation in the colon would improve patient prognosis and alleviate associated healthcare costs. Here, we test the feasibility of fluorescence lifetime imaging (FLIm) to detect inflammation from thick tissue in a non-destructive and label-free approach based on tissue autofluorescence. A pulse sampling FLIm instrument with 355 nm excitation was coupled to a rotating side-viewing endoscopic probe for high speed (10 mm/s) intraluminal imaging of the entire mucosal surface (50-80 mm) of freshly excised mice colons. Current results demonstrate that tissue autofluorescence lifetime was sensitive to the colon anatomy and the colonocyte layer. Moreover, mice under DSS-induced colitis and 5-ASA treatments showed changes in lifetime values that were qualitatively related to inflammatory markers consistent with alterations in epithelial bioenergetics (switch between ß-oxidation and aerobic glycolysis) and physical structure (colon length). This study demonstrates the ability of intraluminal FLIm to image mucosal lifetime changes in response to inflammatory treatments and supports the development of FLIm as an in vivo imaging technique for monitoring the onset, progression, and treatment of inflammatory diseases.

Combined Impact of Telomere Length and Mitochondrial DNA Copy Number on Cognitive Function in Community-Dwelling Very Old Adults.

BACKGROUND: This study was conducted to investigate the combined impact of telomere length and mitochondrial DNA (mtDNA) copy number on cognitive function in community-dwelling very old adults. METHODS: In total, 186 subjects over 75 years participated in this study. Cognitive function was assessed using the Korean Mini-Mental State Examination, and leukocyte telomere length and mtDNA copy number were measured using real-time polymerase chain reaction methods. RESULTS: Both the fourth quartile of telomere length and mtDNA copy number were associated with cognitive dysfunction with an adjusted odds ratio of 0.23 (95% confidence interval (CI), 0.10-0.75) and 0.18 (95% CI, 0.03-0.54), respectively. Participants in the high telomere length/high mtDNA copy number group were more likely to have cognitive dysfunction than participants in the low telomere/low mtDNA copy number group with an adjusted odds ratio of 0.19 (95% CI, 0.07-0.58). CONCLUSION: Our results collectively suggest that the combination of telomere length and mtDNA copy number may be useful for monitoring cognitive decline in older adults.

The relationship between the presence of depressive symptoms and the severity of self-reported knee pain in the middle aged and elderly.

PURPOSE: Knee pain is a very common symptom of knee osteoarthritis (OA), and identification of the major contributors to knee pain is important to establish management plans for patients with knee OA. Among the potential contributors, we hypothesized that coexisting depressive symptoms might increase the severity of knee pain because the increased cytokine levels and neurotransmitter changes related to depression are known to influence the threshold of physical pain perception. Therefore, a possible relationship between self-reported depressive symptoms and self-reported knee pain has been explored. Additionally, we sought to determine factors influencing the severity of knee pain in a middle-aged and elderly Korean population using data from the fifth Korean National Health and Nutrition Examination Survey. METHODS: In total, 6599 persons aged ≥50 years were evaluated in terms of the radiographic severity of OA and pain severity using 10-point numerical rating scales. Depressive mood was assessed using a polar question: "Had the subject felt despair or depression every day for more than 2 weeks during the past year?" RESULTS: The Kellgren-Lawrence knee OA grade, depression, gender, educational level, household income, smoking status, marital status, living place, comorbidity status, BMI, and age were identified by multiple linear regression as variables affecting knee pain severity. The presence of depressive symptoms was associated with an increased risk of severe knee pain (odds ratio 2.55 [95 % confidence interval 1.77-3.66]). After stratifying the group in terms of the radiographic severity of knee OA, the relationship with depression persisted in the minimal (2.89 [1.90-4.32]) and moderate OA subgroups (2.29 [1.33-3.94]), but not in the severe OA subgroup. CONCLUSIONS: Severe knee pain was independently associated with the presence of depressive symptoms in middle-aged and elderly Korean subjects. This suggests that screening for and treatment of depression may help improve knee pain in elderly individuals. LEVEL OF EVIDENCE: II.

Association between serum vitamin D status and health-related quality of life (HRQOL) in an older Korean population with radiographic knee osteoarthritis: data from the Korean national health and nutrition examination survey (2010-2011).

BACKGROUND: Vitamin D is important in bone health and its relationship with osteoarthritis has recently been reported. Both vitamin D deficiency and knee osteoarthritis are age dependent and are known to affect quality of life (QOL) in older populations. In this study, we aimed to determine the association between vitamin D status and health-related quality of life (HRQOL) in an older Korean population with knee osteoarthritis. METHODS: A total of 2,165 participants aged ≥50 years with radiographic knee osteoarthritis defined as Kellgren-Lawrence (KL) grade ≥2 were selected from data from the 5th Korean National Health and Nutrition Examination Survey (KNHANES V), a representative cross-sectional nationwide survey conducted in 2010-2011. They stratified into two levels by vitamin D status (deficiency <10 ng/dL and normal ≥10 ng/dL). HRQOL was measured using the EuroQOL visual analogue scale (EQ-VAS) and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D). RESULTS: The vitamin D deficiency group was more likely to report problems with mobility, self-care, and usual activities. Vitamin D deficiency was significantly associated with poor HRQOL indicated by the lowest quartile of EQ-VAS (unadjusted odds ratio [OR] =1.832, p = 0.006) and the lowest quartile of the EQ-5D index (unadjusted OR = 1.992, p = 0.003). Theses associations of vitamin D status with EQ-VAS and EQ-5D index were maintained after adjustment for age and sex (Model 1: OR = 1.677, p = 0.022 and OR = 1.701, p = 0.021, respectively). The significant associations of vitamin D status with EQ-VAS were maintained after adjustment for other possible covariates (Model 3: OR = 1.562, p = 0.044). Also, a trend of associations between vitamin D status and EQ-5D index were shown after adjustment for other covariates (Model3: OR = 1.681, p = 0.056). CONCLUSION: This is the first study to reveal that vitamin D status is independently associated with HRQOL in an older Korean population with knee osteoarthritis. Our results suggest that the maintenance of sufficient vitamin D status may be important to prevent QOL decline in older populations with knee osteoarthritis.

Pericytes modulate endothelial inflammatory response during bacterial infection.

Pericytes are located around blood vessels, in close contact with endothelial cells. We discovered that pericytes dampen pro-inflammatory endothelial cell responses. Endothelial cells co-cultured with pericytes had markedly reduced expression of adhesion molecules (PECAM-1 and ICAM-1) and proinflammatory cytokines (CCL-2 and IL-6) in response to bacterial stimuli (Brucella ovis, Listeria monocytogenes, or Escherichia coli lipopolysaccharide). Pericyte-depleted mice intraperitoneally inoculated with either B. ovis, a stealthy pathogen that does not trigger detectable inflammation, or Listeria monocytogenes, developed peritonitis. Further, during Citrobacter rodentium infection, pericyte-depleted mice developed severe intestinal inflammation, which was not evident in control mice. The anti-inflammatory effect of pericytes required connexin 43, as either chemical inhibition or silencing of connexin 43 abrogated pericyte-mediated suppression of endothelial inflammatory responses. Our results define a mechanism by which pericytes modulate inflammation during infection, which shifts our understanding of pericyte biology: from a structural cell to a pro-active player in modulating inflammation. IMPORTANCE: A previously unknown mechanism by which pericytes modulate inflammation was discovered. The absence of pericytes or blocking interaction between pericytes and endothelium through connexin 43 results in stronger inflammation, which shifts our understanding of pericyte biology, from a structural cell to a player in controlling inflammation.

Serum carcinoembryonic antigen is associated with non-alcoholic fatty liver disease in healthy Korean non-smokers.

BACKGROUND: Carcinoembryonic antigen (CEA), a biomarker overexpressed in malignant tumors, exhibits increased levels in certain non-malignant conditions, including chronic inflammatory status. The elevation of CEA in chronic inflammatory conditions suggests that this marker may also be associated with non-alcoholic fatty liver disease (NAFLD). Therefore, we investigated the relationship between serum CEA concentrations and NAFLD in healthy Korean non-smokers. METHODS: A total of 200 healthy Korean non-smokers were enrolled during their routine health check-ups. Biomarkers of metabolic risk factors were assessed along with the presence of NAFLD using the liver Fibroscan®. Serum CEA levels were measured using a chemiluminescence immunoassay analyzer. RESULTS: The prevalence of NAFLD increased significantly with increasing CEA quartiles; the mean log CEA level increased gradually according to the grade of hepatic steatosis. Multivariate logistic regression analysis adjusted for age, gender, body mass index, exercise, blood pressure, fasting glucose, insulin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, white blood cell counts, aspartate aminotransferase, alanine aminotransferase and γ-glutamyltransferase showed that the fourth CEA quartile was associated with NAFLD, with an odds ratio of 2.98 (95% confidence interval 1.10-8.05, p<0.01). CONCLUSIONS: Our study showed independent associations between CEA and NAFLD by analyzing data from 200 healthy Korean non-smokers, suggesting that CEA functions in the pathophysiology of fatty liver disease. Further studies are required to better understand the clinical and pathophysiological significance of our findings.

The microbiome and gut homeostasis.

Changes in the composition of the gut microbiota are associated with many human diseases. So far, however, we have failed to define homeostasis or dysbiosis by the presence or absence of specific microbial species. The composition and function of the adult gut microbiota is governed by diet and host factors that regulate and direct microbial growth. The host delivers oxygen and nitrate to the lumen of the small intestine, which selects for bacteria that use respiration for energy production. In the colon, by contrast, the host limits the availability of oxygen and nitrate, which results in a bacterial community that specializes in fermentation for growth. Although diet influences microbiota composition, a poor diet weakens host control mechanisms that regulate the microbiota. Hence, quantifying host parameters that control microbial growth could help define homeostasis or dysbiosis and could offer alternative strategies to remediate dysbiosis.

The longitudinal and cross-sectional heterogeneity of the intestinal microbiota.

A central goal of microbiome research is to understand the factors that balance gut-associated microbial communities, thereby creating longitudinal and cross-sectional heterogeneity in their composition and density. Whereas the diet dictates taxa dominance, microbial communities are linked intimately to host physiology through digestive and absorptive functions that generate longitudinal heterogeneity in nutrient availability. Additionally, the host differentially controls the access to electron acceptors along the longitudinal axis of the intestine to drive the development of microbial communities that are dominated by facultatively anaerobic bacteria in the small intestine or obligately anaerobic bacteria in the large intestine. By secreting mucus and antimicrobials, the host further constructs microhabitats that generate cross-sectional heterogeneity in the colonic microbiota composition. Here we will review how understanding the host factors involved in generating longitudinal and cross-sectional microbiota heterogeneity helps define physiological states that are characteristic of or appropriate to a homeostatic microbiome.

The metabolic footprint of Clostridia and Erysipelotrichia reveals their role in depleting sugar alcohols in the cecum.

BACKGROUND: The catabolic activity of the microbiota contributes to health by aiding in nutrition, immune education, and niche protection against pathogens. However, the nutrients consumed by common taxa within the gut microbiota remain incompletely understood. METHODS: Here we combined microbiota profiling with an un-targeted metabolomics approach to determine whether depletion of small metabolites in the cecum of mice correlated with the presence of specific bacterial taxa. Causality was investigated by engrafting germ-free or antibiotic-treated mice with complex or defined microbial communities. RESULTS: We noted that a depletion of Clostridia and Erysipelotrichia from the gut microbiota triggered by antibiotic treatment was associated with an increase in the cecal concentration of sugar acids and sugar alcohols (polyols). Notably, when we inoculated germ-free mice with a defined microbial community of 14 Clostridia and 3 Erysipelotrichia isolates, we observed the inverse, with a marked decrease in the concentrations of sugar acids and polyols in cecal contents. The carbohydrate footprint produced by the defined microbial community was similar to that observed in gnotobiotic mice receiving a cecal microbiota transplant from conventional mice. Supplementation with sorbitol, a polyol used as artificial sweetener, increased cecal sorbitol concentrations in antibiotic-treated mice, which was abrogated after inoculation with a Clostridia isolate able to grow on sorbitol in vitro. CONCLUSIONS: We conclude that consumption of sugar alcohols by Clostridia and Erysipelotrichia species depletes these metabolites from the intestinal lumen during homeostasis. Video abstract.

High-Fat-Diet-Induced Oxidative Stress Linked to the Increased Colonization of Lactobacillus sakei in an Obese Population.

Obesity is a major public health problem related to various chronic health conditions. Lactobacillus species has been reported in obese individuals; however, its role is unknown. We compared the abundance and composition of Lactobacillus species by analyzing feces from 64 healthy control subjects and 88 obese subjects. We isolated one Lactobacillus strain from the feces of a subject with obesity and further analyzed its genetic and molecular features. We found that an increased abundance and higher prevalence of Lactobacillus sakei distinguished the fecal microbiota of the obese group from that of healthy subjects and that it was related to the increased levels of reactive oxygen species (ROS) induced by higher fat intake. The L. sakei ob4.1 strain, isolated from the feces of a subject with obesity, showed high catalase activity, which was regulated by oxidative stress at the gene transcription level. L. sakei ob4.1 maintained colon epithelial cell adhesion ability under ROS stimulation, and treatment with saturated fatty acid increased colon epithelial ROS levels in a dose-dependent manner; however, L. sakei ob4.1 did not change the level of fat-induced colon epithelial ROS. Exposing mice to a high-fat diet revealed that high-fat-diet-induced colon ROS was associated with the increased colonization of L. sakei ob4.1 through catalase activity. Four-week supplementation with this strain in mice fed a high-fat diet did not change their body weights or ROS levels. A high-fat diet induces changes in the colon environment by increasing ROS levels, which provides a colonization benefit to an L. sakei strain with high catalase activity. IMPORTANCELactobacillus provides many health benefits; its various species are widely used as probiotics. However, an increased abundance of Lactobacillus has been reported in obesity, and the role of Lactobacillus strains in obesity remains unknown. We found a high abundance of the Lactobacillus sakei species in a group of obese subjects and examined its relationship with a high-fat diet and reactive oxygen species (ROS) in the feces. To find the underlying mechanism, we analyzed and characterized an L. sakei strain isolated from a severely obese individual. We found that higher gut oxidative stress could link high-fat-diet-induced obesity and L. sakei. This translational research identifies the roles of the host gut environment in the colonization and survival of L. sakei.

5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium.

5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of Escherichia coli, which could be ameliorated by treatment with 5-ASA. However, 5-ASA was no longer able to reduce inflammation, restore epithelial hypoxia, or blunt an expansion of E. coli in DSS-treated mice that lacked Pparg expression specifically in the intestinal epithelium. These data suggest that the anti-inflammatory activity of 5-ASA requires activation of epithelial PPAR-γ signaling, thus pointing to the intestinal epithelium as a potential target for therapeutic intervention in ulcerative colitis.IMPORTANCE An expansion of Enterobacterales in the fecal microbiota is a microbial signature of dysbiosis that is linked to many noncommunicable diseases, including ulcerative colitis. Here, we used Escherichia coli, a representative of the Enterobacterales, to show that its dysbiotic expansion during colitis can be remediated by modulating host epithelial metabolism. Dextran sulfate sodium (DSS)-induced colitis reduced mitochondrial activity in the colonic epithelium, thereby increasing the amount of oxygen available to fuel an E. coli expansion through aerobic respiration. Activation of epithelial peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling with 5-aminosalicylic acid (5-ASA) was sufficient to restore mitochondrial activity and blunt a dysbiotic E. coli expansion. These data identify the host's epithelial metabolism as a potential treatment target to remediate microbial signatures of dysbiosis, such as a dysbiotic E. coli expansion in the fecal microbiota.

High-Fat Diet and Antibiotics Cooperatively Impair Mitochondrial Bioenergetics to Trigger Dysbiosis that Exacerbates Pre-inflammatory Bowel Disease.

The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-γ (peroxisome proliferator-activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.

Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria.

Intestinal inflammation is a risk factor for colorectal cancer formation, but the underlying mechanisms remain unknown. Here, we investigated whether colitis alters the colonic microbiota to enhance its cancer-inducing activity. Colitis increased epithelial oxygenation in the colon of mice and drove an expansion of Escherichia coli within the gut-associated microbial community through aerobic respiration. An aerobic expansion of colibactin-producing E. coli was required for the cancer-inducing activity of this pathobiont in a mouse model of colitis-associated colorectal cancer formation. We conclude that increased epithelial oxygenation in the colon is associated with an expansion of a prooncogenic driver species, thereby increasing the cancer-inducing activity of the microbiota.IMPORTANCE One of the environmental factors important for colorectal cancer formation is the gut microbiota, but the habitat filters that control its cancer-inducing activity remain unknown. Here, we show that chemically induced colitis elevates epithelial oxygenation in the colon, thereby driving an expansion of colibactin-producing Escherichia coli, a prooncogenic driver species. These data suggest that elevated epithelial oxygenation is a potential risk factor for colorectal cancer formation because the consequent changes in the gut habitat escalate the cancer-inducing activity of the microbiota.

Serum γ-glutamyltransferase level and metabolic syndrome in children and adolescents: Korean National Health and Nutrition Examination Survey.

AIMS/INTRODUCTION: Serum γ-glutamyltransferase (GGT) is positively related to cardiometabolic diseases, such as type 2 diabetes mellitus, hypertension and metabolic syndrome (MetS), in adult populations. Our aim was to investigate whether serum GGT is independently associated with MetS and its components in a nationally representative sample of Korean children and adolescents. MATERIALS AND METHODS: The study included data from 1,618 participants (867 boys, 751 girls) aged 10-18 years from the 2010-2011 Korean National Health and Nutrition Examination Survey. MetS was diagnosed by the 2007 International Diabetes Federation criteria for children and adolescents. Participants were stratified using a cut-off value of the 75th percentile of serum GGT levels (19 IU/L for boys, 15 IU/L for girls). The odds ratios and 95% confidence intervals for MetS and its components were determined with multiple logistic regression analyses. RESULTS: The mean values of most cardiometabolic variables were significantly higher in the upper stratum. Except for low high-density lipoprotein cholesterol in boys and elevated blood pressure in girls, participants in the upper GGT stratum had significantly higher odds of MetS and its components than those in the lower stratum. The multivariate-adjusted odds ratios for MetS for the upper stratum were 5.79 (95% confidence interval 1.21-27.02) in boys and 6.20 (95% confidence interval 1.71-22.47) in girls, after adjusting for age, household income and residential area. CONCLUSIONS: Serum GGT was positively associated with MetS and its components in Korean children and adolescents. Serum GGT could be a useful measure for identifying children and adolescents with MetS.

Serum chemerin levels are independently associated with quality of life in colorectal cancer survivors: A pilot study.

BACKGROUND: Colorectal cancer (CRC) survivors are known to experience various symptoms that significantly affect their quality of life (QOL); therefore, it is important to identify clinical markers related with CRC survivor QOL. Here we investigated the relationship between serum chemerin levels, a newly identified proinflammatory adipokine, and QOL in CRC survivors. METHODS: A data of total of 110 CRC survivors were analysed in the study. Serum chemerin levels were measured with an enzyme immunoassay analyser. Functional Assessment of Cancer Therapy (FACT) scores were used as an indicator of QOL in CRC survivors. RESULTS: Weak but not negligible relationships were observed between serum chemerin levels and FACT-General (G) (r = -0.22, p<0.02), FACT-Colorectal cancer (C) (r = -0.23, p<0.02) and FACT-Fatigue (F) scores (r = -0.27, p<0.01) after adjusting for confounding factors. Both stepwise and enter method multiple linear regression analyses confirmed that serum chemerin levels were independently associated with FACT-G (stepwise: ß = -0.15, p<0.01; enter: ß = -0.12, p = 0.02), FACT-C (stepwise: ß = -0.19, p<0.01; enter; ß = -0.14, p = 0.02) and FACT-F scores (stepwise: ß = -0.23, p<0.01; enter: ß = -0.20, p<0.01). CONCLUSIONS: Our results demonstrate a weak inverse relationship between serum chemerin and CRC survivor QOL. Although it is impossible to determine causality, our findings suggest that serum chemerin levels may have a significant association with CRC survivor QOL. Further prospective studies are required to confirm the clinical significance of our pilot study.

Comparing the Trend of Physical Activity and Caloric Intake between Lipid-Lowering Drug Users and Nonusers among Adults with Dyslipidemia: Korean National Health and Nutrition Examination Surveys (2010-2013).

BACKGROUND: The purpose of this study was to compare the physical activity and caloric intake trends of lipid-lowering drug users with those of non-users among Korean adults with dyslipidemia. METHODS: This study was a repeated cross-sectional study with a nationally representative sample of 2,635 Korean adults with dyslipidemia based on the 2010-2013 Korea National Health and Nutrition Examination Survey. Physical activity was assessed using the International Physical Activity Questionnaire, and caloric intake was estimated through 24-hour dietary recall. All statistical analyses were conducted using IBM SPSS ver. 21.0 (IBM Co., Armonk, NY, USA). The changes in physical activity and caloric intake were investigated for lipid-lowering drug users and non-users using generalized linear models. RESULTS: The proportion of lipid-lowering drug users in the 2010-2013 survey population increased from 3.5% to 5.0% (P<0.001). Among adults of dyslipidemia, total of 1,562 participants (56.6%) reported taking lipid-lowering drugs, and 1,073 (43.4%) reported not taking lipid-lowering drugs. Drug users were more likely to be older and less educated and to have a diagnosis of diabetes, higher body mass index, and lower low density lipoprotein cholesterol level. Physical activity trends were tested separately for the lipid-lowering drug users and non-users, and a significant decrease was found among the drug users during the study period. Physical activity among the drug users in 2013 was 38% lower (1,357.3±382.7 metabolic equivalent [MET]; P for trend=0.002) than in 2010 (2,201.4±442.6 MET). In contrast, there was no statistically significant difference between drug users and non-users in the trend of caloric intake during the same period. CONCLUSION: Physical activity significantly decreased among lipid-lowering drug users between 2010 and 2013, which was not observed among non-users. The importance of physical activity may need to be re-emphasized for lipid-lowering drug users.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and insulin resistance in Korean adolescents: a nationwide population-based study.

BACKGROUND: Studies have suggested the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) as a surrogate marker of insulin resistance. However, few studies have examined the association between TG/HDL-C and insulin resistance in the general adolescent population. This study aimed to examine the association between TG/HDL-C and insulin resistance in a nationally representative sample of Korean adolescents. METHODS: A total of 2649 participants aged 12-18 years were selected from the 2007 to 2010 Korean National Health and Nutrition Examination Survey (KNHANES). Insulin resistance was defined as the homeostatic model assessment of insulin resistance (HOMA-IR) values greater than the 80th percentile. RESULTS: The mean values of most cardiometabolic variables increased proportionally with TG/HDL-C quartiles. Compared to individuals in the lowest TG/HDL-C quartile, the odds ratio for insulin resistance for individuals in the highest quartile was 2.91 in boys and 2.38 in girls after adjusting for confounding variables. CONCLUSIONS: This study suggests that TG/HDL-C could be a convenient marker for identifying Korean adolescents with insulin resistance.

Comparison of Surrogate Markers as Measures of Uncomplicated Insulin Resistance in Korean Adults.

BACKGROUND: Metabolic syndrome (MS) is known to increase the risk of various cardiometabolic diseases and in-sulin resistance (IR) has known to have central role in the development of MS. Many surrogate indices of IR have been proposed and the detection of MS might be a suitable model for assessing the accuracy of surrogate indices. The aims of our study are to invest the most appropriate index by assessment of the diagnostic capacity of IR among each surrogate index and identifying cut-off values for discriminating uncomplicated MS in Korean adults. METHODS: A cross-sectional study was performed, assessing 294 Korean adults, 85 of whom were diagnosed with uncomplicated MS. The sensitivities and specificities of five surrogate IR indices were compared to discriminate MS from healthy subjects; these included fasting serum insulin, homeostasis model assessment-insulin resistance index, quantitative insulin sensitivity check index, McAuley index, and Disse index. Correlations between each index value were assessed using Pearson's and Spearman's correlation methods. RESULTS: The McAuley index showed the highest area under the curve (0.85), specificity (86.12%), accuracy (82.31%), positive predictive value (68.13%), and negative predictive value (88.67%) to distinguish MS, with a cut-off point of 5.3 defined. Correlation coefficients of the five indices showed that the McAuley index had the strongest correlation with IR. CONCLUSION: The McAuley index showed the best accuracy in the detection of MS as a surrogate marker of IR. To establish more effective and accurate standards of measuring IR, comprehensive and multi-scaled studies are required.

The Association between Atopic Dermatitis and Depressive Symptoms in Korean Adults: The Fifth Korea National Health and Nutrition Examination Survey, 2007-2012.

BACKGROUND: Atopic dermatitis (AD) is characterized by pruritic and eczematous skin lesions, which often cause depressive symptoms, anxiety, stress, sleep disturbances, social withdrawal, and stigmatization. METHODS: In total, 23,442 subjects (434 AD patients and 23,008 control subjects) aged 19 years or older and without a history of major medical illness or depressive disorders were selected from The Fifth Korea National Health and Nutrition Examination Survey 2007-2012. Following the initial selection, 2,170 age- and sex-matched control subjects were selected using 1:5 propensity score matching. Multiple logistic regression analysis was performed to identify the presence of depressive symptoms of at least 2 weeks in duration. RESULTS: The demographic, socioeconomic, and clinical characteristics of AD patients and control subjects were presented and compared, and some variables differed significantly between groups. Presence of depressive symptoms was set as dependent variable, and multiple logistic regression analysis was performed as follows: (1) unadjusted; (2) with alcohol use, exercise status, smoking status, and body mass index (BMI) adjusted for; and (3) with alcohol use, exercise status, smoking status, marital status, occupation, BMI, total caloric intake, history of hypertension, and history of diabetes mellitus adjusted for. Depressive symptoms were significantly higher (odds ratios, 1.46, 1.40, and 1.36; 95% confidence intervals, 1.09-1.95, 1.0.4-1.88, and 1.01-1.85, respectively) in AD patients relative to those of matched controls. CONCLUSION: AD and clinical depression interact closely, and causal relationships between the two conditions have frequently been observed. Physicians should consider mental health interventions cautiously. It is particularly important that primary care physicians provide comprehensive, continuous long-term care.