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  • 1.

    【2hr】High Body Mass Index Masks Body Composition Differences in Physically Active Versus Sedentary Participants

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    机译 高体重指数掩盖了体育锻炼与久坐参与者的身体成分差异
    摘要：>Background: Despite the benefits of aerobic exercise on body composition, runners with high body mass index (BMI) remain understudied. We examined body composition differences between sedentary insulin-resistant [obese insulin-resistant sedentary (OS-IR)], sedentary insulin-sensitive [obese insulin-sensitive sedentary (OS-IS)], and trained [obese trained (OT)] individuals with high BMI (≥25 kg/m2). We hypothesized that after matching for high BMI, OT individuals would have less fat mass (absolute and relative) and greater lean mass than OS-IR or OS-IS individuals.>Methods: This is a retrospective analysis of OS-IR, OS-IS, and OT participants selected for similar age, sex, and BMI. Activity was self-reported. OT participants exercised at least 30 min/day (predominantly running) for 3–5 days/week. OS-IS and OS-IR participants actively exercised <0.5 hr/week. Body composition was measured by dual X-ray absorptiometry.>Results: Thirty-three participants were recruited [n = 11/group, mean age 31.7 years (standard error): (0.9)], 7 females/group, overall BMI [31.6 kg/m2 (0.7)]. Insulin resistance, quantified by the homeostatic model assessment for insulin resistance, was higher in the OS-IR [3.3 (0.2)] than the OS-IS [0.9 (0.2): P < 0.0001] or OT [1.6 (0.2): P < 0.0001] groups. We found the following: (i) Compared to the OS-IR group, the OT group had lower region-specific fat mass as measured by percent fat (trunk) or absolute fat mass (trunk, android region, and abdominal visceral region). (ii) OT and OS-IS groups had similar body composition. (iii) Total fat mass and percent body fat correlated with BMI, (iv) Visceral fat correlated with BMI (r = 0.80, P = 0.003) only in the OS-IR (P = 0.03 for BMI × group interaction).>Conclusions: Using BMI to classify obesity masks body composition differences in high BMI individuals discrepant for insulin resistance and physical activity status.
  • 2.

    【2hr】What Can Diabetes-Associated Genetic Variation in TCF7L2 Teach Us About the Pathogenesis of Type 2 Diabetes?

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    机译 TCF7L2中与糖尿病相关的遗传变异能教给我们2型糖尿病的发病机制吗？
    摘要：Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disorder characterized by hyperglycemia occurring as a result of impaired insulin secretion and/or insulin resistance. Among the various genetic factors associated with T2DM, a common genetic variant within the transcription factor 7-like 2 locus (TCF7L2) confers the greatest genetic risk for development of the disease. However, the mechanism(s) by which TCF7L2 predisposes to diabetes remain uncertain. Here we review the current literature pertaining to the potential mechanisms by which TCF7L2 confers risk of T2DM, using genetic variation as a probe to understand the pathogenesis of the disease.
  • 3.

    【2hr】Combination Therapies for Obesity

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    机译 肥胖的综合疗法
    摘要：The objective of this review is to examine advances in the development of combination therapies for the treatment of obesity beyond diet or lifestyle interventions. Experimental combination pharmacotherapies include combinations of pramlintide and phentermine as well as amylin and bupropion-naltrexone. Incretin and pancreatic hormones generally inhibit upper gastrointestinal motor functions, and combinations showing efficacy in obesity are coadministration of glucagon-like peptide-1 (GLP-1) with glucagon, a unimolecular dual incretin of PEGylated GLP-1/GIP coagonist, the combination of GLP-1 and PYY3-36, and, in proof of concept studies, combined infusions of GLP-1, peptide YY, and oxyntomodulin. Among bariatric procedures, repeat intragastric balloon (IGB) treatments are more efficacious than IGB plus diet, and endoscopic intervention can enhance the effects of Roux-en-Y gastric bypass when weight regain occurs. A first trial has provided promising results with combination of IGB plus the GLP-1 analog, liraglutide, compared to the balloon alone. Thus, combination therapies for the treatment of obesity hold promise for introduction into clinical practice.
  • 4.

    【2hr】Longitudinal Associations of Metabolic Syndrome Severity Between Childhood and Young Adulthood: The Bogalusa Heart Study

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    机译 儿童和年轻成人之间代谢综合征严重程度的纵向关联：Bogalusa心脏研究
    摘要：>Background: Childhood metabolic syndrome (MetS) is associated with insulin resistance and increased risk for later development of type 2 diabetes (T2DM) and cardiovascular disease (CVD). In using MetS severity z-scores, our objective was to assess longitudinal associations in MetS severity, fasting insulin levels as a sign of insulin resistance and risk for T2DM, and uric acid levels as a biomarker of oxidative stress leading to CVD.>Methods: We used linear regression to analyze longitudinal data from 285 white and black participants from the Bogalusa Heart Study evaluated at baseline at ages 5–19 and as young adults after a mean of 12.0 years follow-up. We assessed correlations between childhood MetS severity and young-adult MetS severity, fasting insulin, and uric acid levels, both overall and by sex- and racial subgroups.>Results: Overall, childhood MetS z-scores were positively associated with young-adult MetS z-scores (r = 0.52), insulin (r = 0.34), and uric acid (r = 0.28) (all P < 0.001). These associations were consistent across all sex- and racial subgroups, except for young adult uric acid in white males in which childhood MetS-z was not associated (r = 0.15, P = 0.243). There was a strong cross-sectional association of young-adult MetS z-scores with insulin (r = 0.70) and uric acid (r = 0.57) (both P < 0.001), which was consistent for all sex- and racial subgroups.>Conclusions: These positive longitudinal correlations between childhood MetS z-scores and markers of later insulin resistance and oxidative stress suggest long-term durability of risk for CVD and T2DM. This suggests potential for MetS severity to serve as an indicator to monitor for future risk of T2DM and CVD.
  • 5.

    【2hr】Poor Sleep Quality is Associated with Insulin Resistance in Postmenopausal Women With and Without Metabolic Syndrome

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    机译 患有和不具有代谢综合征的绝经后妇女的睡眠质量差与胰岛素抵抗相关
    摘要：>Background: Poor sleep quality has previously been shown to be related to insulin resistance in apparently healthy adults. However, it is unclear whether an association between sleep quality and insulin resistance exists among adults with metabolic syndrome (MetS).>Methods: Participants included 347 overweight/obese postmenopausal women without type 2 diabetes (age: 57.5 ± 6.5 years; body mass index [BMI]: 31.7 ± 3.7 kg/m2; 54% with MetS). Sleep quality was assessed with the six-item Medical Outcomes Study Sleep Scale; values were categorized into quartiles. Insulin resistance was calculated from fasting glucose and insulin with the homeostasis model assessment of insulin resistance (HOMA2-IR) method. Analysis of covariance models were used to examine the association between sleep quality and HOMA2-IR after accounting for MetS and covariates (e.g., BMI, cardiorespiratory fitness, and energy intake).>Results: Women with the worst sleep quality had significantly higher HOMA2-IR values than women in all other quartiles (P ≤ 0.05 for each), and women with MetS had significantly higher HOMA2-IR values than women without MetS (P < 0.0001), but the relationship between sleep quality and HOMA2-IR did not differ between those with or without MetS (P = 0.26). Women with MetS in the worst quartile of sleep quality had higher HOMA2-IR values than all other women (P < 0.02). Taking >30 min to fall asleep, frequent restless sleep, and frequent daytime drowsiness were each related to higher HOMA2-IR values (each P < 0.04).>Conclusions: Sleep quality is an important correlate of insulin resistance in postmenopausal women with and without MetS. Intervention studies are needed to determine whether improving sleep improves insulin resistance in populations at elevated cardiometabolic risk.
  • 6.

    【2hr】Metabolic Syndrome in Hispanic Youth: Results from the Hispanic Community Childrens Health Study/Study of Latino Youth

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    机译 西班牙裔青少年的代谢综合症：来自西班牙裔社区儿童健康研究/拉丁裔青少年的研究结果
    摘要：>Background: Metabolic syndrome (MetS), a cluster of cardiovascular risk factors, is being diagnosed in youth. Specific diagnostic criteria used to define MetS influence prevalence estimates and populations considered at risk for cardiovascular disease. The National Cholesterol Education Program's Adult Treatment Panel III (ATP), the World Health Organization (WHO), and the International Diabetes Federation (IDF) provide three MetS definitions used in medical research. This study examined concordance among these definitions in 1137 children 10–16 years of age, who participated in the Hispanic Community Children's Health Study/Study of Latino Youth.>Methods: Prevalence of MetS and of individual components was estimated using SAS. Mplus was used to test a single-factor model of MetS components (triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, waist circumference, and fasting glucose).>Results: The ATP definition identified most MetS cases in 10–15 (N = 19, 4.7%) and 16-year-old girls (N = 3, 7.3%). The IDF definition identified most cases of MetS in 10–15 (N = 16, 3.1%) and 16-year-old boys (N = 2, 2.8%). Fewest cases of MetS were identified with the WHO definition across age and sex groups.>Conclusion: Only one participant was classified as having MetS across all three definitions. Confirmatory factor analysis indicated fasting glucose and systolic blood pressure did not reliably cluster with other risk factors that define MetS in Hispanic/Latino adolescents. We conclude that prevalence estimates of MetS in youth are unstable across current criteria, calling into question the accuracy of defining and diagnosing MetS in youth.
  • 7.

    【2hr】Mast Cell and M1 Macrophage Infiltration and Local Pro-Inflammatory Factors Were Attenuated with Incretin-Based Therapies in Obesity-Related Glomerulopathy

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    机译 肥胖相关性肾小球病中肠抑素为基础的治疗减弱了肥大细胞和M1巨噬细胞浸润和局部促炎因素。
    摘要：>Background: The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists were well recognized to attenuate renal injury independent of glucose control in diabetic nephropathy. There are limited studies focusing on their effects on ORG. We explored the effects of incretin-based therapies on early ORG and the inflammatory responses involved mainly concentrated on mast cell (MC) and macrophage (M) infiltration and local pro-inflammatory factors.>Methods: ORG rat models were induced by high-fat diet and then divided into ORG vehicle, vildagliptin (3 mg/kg/day, qd) and liraglutide (200 μg/kg, bid) treated groups. After 8 weeks of treatments, albuminuria, glomerular histology, renal inflammatory cell infiltration, and pro-inflammatory factors were analyzed.>Results: Early ORG model was demonstrated by albuminuria, glomerulomegaly, foot process fusion, and mesangial and endothelial mild proliferation. Incretin-based therapies limited body weight gain and improved insulin sensitivity. ORG was alleviated, manifested by decreased average glomerular area, attenuated mesangial and endothelial cell proliferation, and revived cell-to-cell propagation of podocytes, which contributed to reduced albuminuria. Compared with ORG vehicle, MC and M1 macrophage (pro-inflammatory) infiltration and M1/M2 ratio were significantly decreased; M2 macrophage (anti-inflammatory) was not significantly increased after incretin-based treatments. Tumor necrosis factor-α (TNF-α) and IL-6 in renal cortex were significantly downregulated, while transforming growth factor-β1 (TGF-β1) remained unchanged.>Conclusions: Incretin-based treatments could alleviate high-fat diet-induced ORG partly through the systemic insulin sensitivity improvement and the attenuated local inflammation, mainly by the decrease of MC and M1 macrophage infiltration and reduction of TNF-α and IL-6.
  • 8.

    【2hr】Expression of MYD88 in Adipose Tissue of Obese People: Is There Some Role in the Development of Metabolic Syndrome?

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    机译 MYD88在肥胖人群脂肪组织中的表达：在代谢综合征的发生中有作用吗？
    摘要：>Background: The mechanism leading to the development of metabolic complications in obese individuals is not fully understood. Thus, the objective of this study was to examine differences in insulin resistance, inflammation, cytokine and adipokine levels, and expression of selected genes across obese individuals with different number of metabolic syndrome (MetS) components.>Methods: Forty obese individuals who underwent bariatric surgery, divided in three groups based on the number of components of MetS, in addition to abdominal obesity (0, 1, and 2–3 additional components), were studied. Levels of inflammatory proteins, insulin resistance, cytokines, adipokines, and gene expression in subcutaneous (SAT) and visceral adipose tissue (VAT) were compared.>Results: There was a significantly higher expression of MYD88 in SAT among those with more components of MetS (P = 0.008). In SAT, but not in VAT, MYD88 expression was significantly correlated with toll-like receptor 4 expression (r = 0.7, P < 0.05). Expression of adipsin in SAT was also associated with the presence of more components of MetS, but with borderline statistical significance (P = 0.05). There were no significant differences in insulin resistance, inflammation, and cytokine and adipokine levels by the number of components of MetS.>Conclusions: Our study suggests that MYD88 expression in SAT of obese subjects could be associated with the development of components of MetS.
  • 9.

    【2hr】Adipose Tissue Insulin Resistance in Gestational Diabetes

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    机译 妊娠糖尿病患者的脂肪组织胰岛素抵抗
    摘要：>Background: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose–lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1.>Methods: AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose–lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice.>Results: We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01—ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01—ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046—t test on area under curve [AUC]glucose).>Conclusions: Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.
  • 10.

    【2hr】Response to Wood re: Oxidative Priority Meal Frequency and the Energy Economy of Food and Activity: Implications for Longevity Obesity and Cardiometabolic Disease

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    机译 对木材的回应：氧化性优先进餐频率以及食物和活动的能源经济：对长寿肥胖和心脏代谢疾病的影响
    摘要：
  • 11.

    【2hr】Comparison of Endothelial Function in Asian Indians Versus Caucasians

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    机译 亚洲印第安人与白种人的内皮功能比较
    摘要：>Background: Asian Indians have markedly increased mortality due to coronary artery disease (CAD). Impaired endothelial function has been linked to an increased risk of acute cardiovascular events. We tested the hypothesis that endothelial function was attenuated in Asian Indians and Caucasians.>Methods: We studied 14 Asian Indians [mean age: 30 ± 6 years; mean body mass index (BMI): 25 ± 3 kg/m2] and 11 Caucasians (mean age: 30 ± 5 years; mean BMI: 26 ± 2 kg/m2). All 25 subjects were healthy men and nonsmokers without any history of CAD or diabetes and were not taking medications. Endothelial function was evaluated by ultrasound measures of flow-mediated dilatation (FMD) and endothelium-independent nonflow mediated vasodilatation (NFMD) of the brachial artery, in the morning immediately after awakening (6 a.m.) in a fasting state.>Results: Mean age, BMI, apnea–hypopnea index, heart rate, and blood pressure were similar in both groups (P = >0.05). When correcting for body surface area, brachial artery diameter was not different between the two groups (2.1% ± 0.3% vs. 2.2% ± 0.4%; P = 0.29). FMD and NFMD were similar in Asian Indians and Caucasians (5.9% ± 4.1% vs. 5.7% ± 2.6%, P = 0.70; 16.4% ± 8% vs. 14.8% ± 4.1%, P = 0.58, respectively).>Conclusion: Endothelial function in Asian Indian men is not attenuated in comparison to Caucasian men.
  • 12.

    【2hr】Alcohol Consumption and Metabolic Syndrome Among Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

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    机译 西班牙裔/拉丁裔的饮酒量和代谢综合症：西班牙裔社区健康研究/拉丁裔的研究
    摘要：>Background: The association between alcohol consumption and metabolic syndrome (MetS) among Hispanic/Latino populations has not been studied in great detail. Our study examined the relationship between alcohol consumption and MetS among U.S. Hispanics/Latinos and explored whether this relationship varied by age, body mass index, gender, and Hispanic/Latino backgrounds.>Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a multisite, prospective, population-based, cohort study of Hispanics/Latinos, ages 18–74 years from four U.S. communities. Participants were categorized into never, former, occasional, low, moderate, and high alcohol consumption categories. A cross-sectional analysis of 15,905 participants with complete data was conducted. Survey design appropriate chi-squared and logistic regression models were run to detect significant associations between alcohol consumption categories and cases of MetS.>Results: Almost half (47.4%) of the sample was classified as occasional, low, moderate, or heavy drinkers. Low and moderate alcohol consumers had lower odds of MetS than never drinkers. Low and heavy drinkers had higher odds of presenting with elevated central obesity, while occasional, low, moderate, and heavy drinkers had higher odds of having low high-density lipoprotein cholesterol levels compared to never drinkers. Low and moderate wine drinkers had lower odds of MetS compared to never drinkers. There were no significant findings among beer or liquor drinkers, or with binge drinking after model adjustments.>Conclusions: Our findings suggest that low and moderate alcohol consumption may lower the odds of MetS in a sample of Hispanic/Latino adults, but that the relationship of alcohol consumption varies with the individual components of MetS.
  • 13.

    【2hr】Low Cardiorespiratory Fitness Is Associated with Markers of Insulin Resistance in Young Normal Weight Hispanic Women

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    机译 低心肺健康与年轻正常体重西班牙裔妇女的胰岛素抵抗相关
    摘要：>Background: Low cardiorespiratory fitness (CRF) and its decline over time are predictors of the development of diabetes in black and Caucasian women, independent of obesity. It is unclear, however, if the adverse effect of low CRF on the risk of diabetes in Hispanic women is mediated by obesity. Our purpose was to determine the associations of CRF with markers of insulin resistance in 68 normal weight Hispanic women.>Methods: Obesity indicators included body mass index (BMI), body composition by DXA, and waist circumference. CRF was measured by indirect calorimetry. A glucose tolerance test was used to measure markers of insulin resistance: homeostasis model assessment, fasting insulin, 2-hr insulin, area under the curve insulin, qualitative insulin sensitivity check, and insulin sensitivity index. Pearson correlation and multiple regression analyses were used to identify associations between CRF and markers of insulin resistance. Multivariate ANOVA was used to compare markers of insulin resistance over quartiles of CRF.>Results: Low CRF was significantly associated with all markers of insulin resistance (P < 0.01). These associations were independent of age, BMI, waist circumference, family history of T2DM, and triglycerides (CRF standardized beta range: −0.27 to −0.46, P < 0.05). However, these associations were attenuated when body composition, specifically fat-free mass, was entered into the model (CRF standardized beta range: −0.03 to 0.21, P > 0.05). All markers of insulin resistance improved linearly across CRF quartiles (P < 0.05).>Conclusions: Our findings suggest that low CRF may be an important predictor of diabetes risk in Hispanic women and that fat-free mass rather than overall body adiposity mediates these relationships.
  • 14.

    【2hr】Major Increase in Microbiota-Dependent Proatherogenic Metabolite TMAO One Year After Bariatric Surgery

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    机译 减肥手术一年后微生物群依赖的促动脉粥样硬化代谢物TMAO的大量增加
    摘要：>Background: Trimethylamine-N-oxide (TMAO) is formed in the liver from trimethylamine (TMA), a product exclusively generated by the gut microbiota from dietary phosphatidylcholine and carnitine. An alternative pathway of TMAO formation from carnitine is via the microbiota-dependent intermediate γ-butyrobetaine (γBB). Elevated TMAO levels are associated with cardiovascular disease (CVD), but little is known about TMAO in obesity. Given the proposed contribution of microbiota alterations in obesity and type 2 diabetes (T2D), we investigated the potential impact of obesity, lifestyle-induced weight loss, and bariatric surgery on plasma levels of TMAO, its microbiota-dependent intermediate γBB, and its diet-dependent precursors carnitine and choline.>Methods: TMAO, γBB, carnitine, and choline were measured by high-performance liquid chromatography in 34 obese individuals (17 with and 17 without T2D) undergoing bariatric surgery and 17 controls.>Results: TMAO was not elevated in obese patients or reduced by lifestyle interventions but increased approximately twofold after bariatric surgery. Similar to TMAO, plasma levels of γBB were not influenced by lifestyle interventions but increased moderately after bariatric surgery. In contrast, carnitine and choline, which are abundant in nutrients, such as in red meat and eggs, and not microbiota dependent, were reduced after lifestyle interventions and rebounded after bariatric surgery.>Conclusions: The major increase in TMAO after bariatric surgery was unexpected because high TMAO levels have been linked to CVD, whereas bariatric surgery is known to reduce CVD risk. Prospective studies of gut microbiota composition and related metabolites in relation to long-term cardiovascular risk after bariatric surgery are warranted.
  • 15.

    【2hr】Risk Factors for Insulin Resistance Metabolic Syndrome and Diabetes in 248 HFE C282Y Homozygotes Identified by Population Screening in the HEIRS Study

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    机译 HEIRS研究中通过人群筛选确定了248个HFE C282Y纯合子中胰岛素抵抗代谢综合症和糖尿病的危险因素
    摘要：>Background: We sought to identify risk factors for insulin resistance, metabolic syndrome (MetS), and diabetes mellitus in 248 non-Hispanic white HFE C282Y homozygotes identified by population screening.>Methods: We analyzed observations obtained prospectively in a postscreening examination: age; sex; body mass index (BMI); systolic/diastolic blood pressure; metacarpophalangeal (MP) joint hypertrophy; hepatomegaly; complete blood counts; alanine/aspartate aminotransferase levels; elevated C-reactive protein (>0.5 mg/dL); transferrin saturation; serum ferritin; homeostasis model assessment-insulin resistance (HOMA-IR); and MetS.>Results: Twenty-six participants (10.5%) had diabetes diagnoses. A significant trend across HOMA-IR quartiles was observed only for blood neutrophils. Logistic regression on HOMA-IR fourth quartile revealed positive associations: age (P = 0.0002); male sex (P = 0.0022); and BMI (P < 0.0001). HOMA-IR fourth quartile predicted MetS (P < 0.0001). Logistic regression on diabetes revealed positive associations: age (P = 0.0012); male sex (P = 0.0068); MP joint hypertrophy (P = 0.0167); neutrophils (P = 0.0342); and MetS (P = 0.0298). Serum ferritin did not predict HOMA-IR fourth quartile, MetS, or diabetes.>Conclusions: In screening C282Y homozygotes, age, male sex, and BMI predicted HOMA-IR fourth quartile. HOMA-IR fourth quartile alone predicted MetS. Diabetes was associated with greater age, male sex, MP joint hypertrophy, greater blood neutrophil counts, and MetS.
  • 16.

    【2hr】Obesity Oxidative Stress Adipose Tissue Dysfunction and the Associated Health Risks: Causes and Therapeutic Strategies

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    机译 肥胖氧化应激脂肪组织功能障碍和相关的健康风险：病因和治疗策略
    摘要：Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.
  • 17.

    【2hr】Endogenous Sex Steroid Hormones Lipid Subfractions and Ectopic Adiposity in Asian Indians

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    机译 亚洲印第安人的内源性类固醇激素脂质亚组分和异位肥胖
    摘要：>Background: Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians.>Methods: We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity.>Results: Among women, lower logSHBG levels were associated with smaller logLDL particle size and higher logtriglycerides, logVLDL, and logIDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower logSHBG levels was significantly associated with lower logmedium LDL and logsmall LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower logSHBG was also associated with smaller logLDL peak diameter size and higher logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR.>Conclusions: Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.
  • 18.

    【2hr】Effect of Selective Mineralocorticoid Receptor Blockade on Flow-Mediated Dilation and Insulin Resistance in Older Adults with Metabolic Syndrome

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    机译 选择性盐皮质激素受体阻滞剂对老年人代谢综合征的血流介导的扩张和胰岛素抵抗的影响
    摘要：>Background: The prevalence of metabolic syndrome is especially high in older adults. Metabolic syndrome is associated with impaired vascular endothelial function, insulin resistance, and increased risk for cardiovascular disease but the underlying mechanisms are not fully elucidated. Plasma aldosterone is independently associated with metabolic syndrome and is linked to endothelial dysfunction and insulin resistance. Thus, we hypothesized that mineralocorticoid receptor (MR) blockade would improve flow-mediated dilation and insulin resistance in older adults with metabolic syndrome.>Methods: To test this hypothesis, we conducted a balanced, randomized, double-blind, placebo-controlled, crossover study using selective MR blockade (eplerenone; 100 mg/day) for 1 month with 1 month washout in older adults with metabolic syndrome (62.6 ± 3.2 yrs; mean ± standard error). We evaluated brachial artery flow-mediated dilation (ultrasonography), oxidative stress (oxidized low-density lipoproteins and F2-isoprostanes) and insulin resistance (homeostatic model assessment).>Results: In response to MR blockade, flow-mediated dilation (5.37 ± 0.85 vs. 5.98 ± 1.29%; placebo vs. eplerenone; P = 0.4), oxidized low-density lipoproteins (51.6 ± 11.5 vs. 56.1 ± 10.9 U/L; P = 0.6), and F2-isoprostanes (0.07 ± 0.02 vs. 0.06 ± 0.01 pg/mL; P = 0.3) did not improve. Insulin resistance also did not change following MR blockade (1.04 ± 0.26 vs. 1.38 ± 0.50; P = 0.6). However, MR blockade resulted in a large reduction (10 mmHg) in systolic blood pressure (140 ± 6 vs. 130 ± 6 mmHg; P = 0.02), with no significant change in diastolic blood pressure (81 ± 3 vs. 75 ± 2 mmHg; P = 0.2).>Conclusions: Our data do not support a contributing role for MRs in endothelial dysfunction and insulin resistance in older adults with metabolic syndrome. However, our findings suggest MR activation is an important contributor to systolic hypertension in this patient group.
  • 19.

    【2hr】Circuit Resistance Training Attenuates Acute Exertion-Induced Reductions in Arterial Function but Not Inflammation in Obese Women

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    机译 电路阻力训练可减轻肥胖女性急性运动引起的动脉功能减少但不会减轻炎症
    摘要：>Background: Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response.>Methods: Eighteen obese [body mass index (BMI) 30.0–40.0 kg·m−2] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed.>Results: Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics.>Conclusions: This study shows that CRT alleviates acute exertion-induced reductions in endothelial function among obese sedentary women in the absence of changes in inflammation.
  • 20.

    【2hr】Serum Ferritin Insulin Resistance and Metabolic Syndrome: Clinical and Laboratory Associations in 769 Non-Hispanic Whites Without Diabetes Mellitus in the HEIRS Study

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    机译 血清铁蛋白胰岛素抵抗和代谢综合症：HEIRS研究中的769名无糖尿病的非西班牙裔白人的临床和实验室关联
    摘要：>Background: In some reports, serum ferritin (SF) has been associated with insulin resistance and metabolic syndrome.>Methods: We studied non-Hispanic whites without diabetes mellitus in a postscreening examination. Participants included cases [HFE C282Y homozygosity; and transferrin saturation (TS) >50% and SF >300 μg/L (males) and TS >45% and SF >200 μg/dL (females), regardless of HFE genotype] and controls [HFE wild-type (wt/wt) and TS/SF 25th–75th percentiles]. We excluded participants with overnight fasts <8 hr, cirrhosis, hepatitis B or C, pregnancy, or missing data. Observations were age, sex, C282Y homozygosity, body mass index (BMI), systolic and diastolic blood pressures (SBP, DBP), lymphocytes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), TS, SF, and glucose/insulin. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR) 4th quartile (≥2.70).>Results: A total of 407 women and 362 men (mean age 54 years) included 188 C282Y homozygotes and 371 wt/wt. Significant trends across HOMA-IR quartiles included age, male sex, BMI, SBP, DBP, lymphocytes, ALT, CRP >0.5 mg/dL (positive), and TS (negative). Multiple regression on HOMA-IR revealed significant associations with male sex, BMI, SBP, lymphocytes, ALT, CRP>0.5 mg/dL (positive), and DBP and SF (negative). Logistic regression on HOMA-IR 4th quartile revealed significant positive associations with age, male sex, BMI, and lymphocytes. Metabolic syndrome occurred in 53 participants (6.9%). Logistic regression on metabolic syndrome revealed these odds ratios: HOMA-IR 4th quartile [9.1 (4.8, 17.3)] and CRP >0.5 mg/dL [2.9 (1.6, 5.4)].>Conclusions: Age, male sex, BMI, and lymphocytes were positively associated with HOMA-IR after correction for other factors. HOMA-IR 4th quartile and CRP >0.5 mg/dL predicted metabolic syndrome.
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