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  • 1.

    【2hr】Prediction of Proliferative Diabetic Retinopathy to Asymptomatic Obstructive Coronary Artery Disease in Chinese Type 2 Diabetes Individuals: An Exploratory Study

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    机译 中国2型糖尿病患者无症状性阻塞性冠状动脉疾病的增生性糖尿病视网膜病变预测研究：一项探索性研究
    摘要：Background: Patients with type 2 diabetes are prone to the asymptomatic obstructive coronary artery disease (AO-CAD). The association of proliferative diabetic retinopathy (PDR) with AO-CAD is unknown. The aim of the study is to explore the specific relationship of PDR with AO-CAD.Methods: We performed coronary angiography and retinal photographs in 1332 participants with unknown CAD status in a retrospective discovery set and 252 patients with non-CAD enrolled in a prospective validation cohort. Main outcome measures are prediction of PDR to AO-CAD.Results: In the case–control retrospective discovery set, investigation included 211 nondiabetic retinopathy (NDR) and 140 PDR. Individuals with PDR had a 2.16 times higher risk of AO-CAD compared with individuals without diabetic retinopathy (P < 0.01). Relative risk between individuals with PDR and the risk of AO-CAD varied by different adjusted covariates, 2.53 (1.48–4.32) by age and gender; 2.16 (1.10–4.31) by additionally other covariates. In the prospective validation set, after adjustment for covariates, the cumulative risk of AO-CAD was significantly higher in the PDR group compared with NDR group, followed up for a median of 4.3 years (hazard ratio = 3.07, 95% confidence interval 1.81–5.21, P < 0.001).Conclusions: PDR showed superior identification performance over traditional risk factors in screening for AO-CAD. PDR may predict persons at high risk of AO-CAD.
  • 2.

    【2hr】Correction to: Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release Across Glucose Tolerance in Man: Lack of Correlation with β Cell Function by Ruetten H, MD, PhD, Gebauer M, PhD, Raymond RH, MS, Calle RA, MD, Cobelli C, PhD, Ghosh A, PhD, Robertson RP, MD, Shankar SS, MD, Staten MA, MD, Stefanovski D, PhD, Vella A, MD, Wright K, MS, and Fryburg DA, MD; on behalf of the Foundation for the NIH Biomarkers Consortium Beta Cell Project Team Metab Syndr Relat Disord 2018;16:406–415 DOI 10.1089/met.2018.0022

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    机译 校正至：混合餐和静脉内L-精氨酸测试均刺激跨人的葡萄糖耐量的肠促胰激素释放：Ruetten H，MD，PhD，Gebauer M，PhD，Raymond RH，MS，Calle RA，MD缺乏与β细胞功能的相关性，Cobelli C，PhD，Ghosh A，PhD，Robertson RP，MD，Shankar SS，MD，Staten MA，MD，Stefanovski D，Phella A，MD，Wright K，MS和Fryburg DA。代表NIH生物标记物联盟Beta细胞项目团队Metab Syndr Relat Disord 2018; 16：406–415 DOI 10.1089 / met.2018.0022
    • 作者：
    • 刊名：Metabolic Syndrome and Related Disorders
    • 2019年第2期
    摘要：
  • 3.

    【2hr】Brain-Derived Neurotrophic Factor and Its Associations with Metabolism and Physical Activity in a Latino Sample

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    机译 拉丁裔样本中脑源性神经营养因子及其与代谢和体育活动的关系
    摘要：Background: Brain-derived neurotrophic factor (BDNF) is associated with body weight and other health conditions but remains understudied in the Latino population. The aim of this study was to examine the associations of BDNF serum levels with body mass index (BMI), physical activity, and the rs6265 nonconservative polymorphism among 349 Latinos aged ≥18 years enrolled in the Arizona Insulin Resistance Registry.Materials and Methods: Data on physical activity were acquired using a self-reported questionnaire. BDNF serum levels were measured utilizing a modified ELISA method, and the rs6265 polymorphism was genotyped by the Assay-by-Design service. Two sample t-tests or chi-squared tests were employed to compare demographics and outcomes between physically active and nonactive groups as well as between rs6265 CC and CT+TT groups.Results: BDNF levels and rs6265 polymorphism did not differ significantly between the physically active (N = 195) and nonactive group (N = 154). Participants with the rs6265 polymorphism did not show any significant difference in BDNF levels or BMI when compared with those with the normal functional variant. Higher BDNF levels were significantly associated with higher age (r = 0.11, P = 0.04) and higher 2-hr glucose level (r = 0.11, P = 0.04).Conclusions: In this cross-sectional study, the rs6265 polymorphism was not associated with a higher risk of obesity, or lower circulating levels of BDNF. Thus, the rs6265 polymorphism may have a different impact in Latinos as compared with other previously studied populations.
  • 4.

    【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.
  • 5.

    【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.
  • 6.

    【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.
  • 7.

    【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.
  • 8.

    【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.
  • 9.

    【2hr】A Common Variation in the Caveolin 1 Gene Is Associated with High Serum Triglycerides and Metabolic Syndrome in an Admixed Latin American Population

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    机译 Caveolin 1基因的常见变异与混合的拉丁美洲人口中高血清甘油三酸酯和代谢综合征相关。
    摘要：Background: The caveolin 1 (CAV1) gene has been associated with metabolic traits in animal models and human cohorts. Recently, a prevalent variant in CAV1 has been found to be related to metabolic syndrome in Hispanics living in North America. Since Hispanics represent an admixed population at high risk for cardiovascular diseases, in this study a Latin American population with a similar genetic background was assessed.Objective: To analyze a genetic association between CAV1 and metabolic traits in an admixed Latin American population.Methods: A cross-sectional study was carried out with adults from the Colombian Caribbean Coast, selected in urban clusters and work places through a stratified sampling to include diverse ages and socioeconomic groups. Blood pressure and waist circumference were registered. Serum concentrations of glucose, triglycerides, and high-density lipoprotein cholesterol were measured from an 8-hr fasting whole-blood sample. Two previously analyzed CAV1 single nucleotide polymorphisms were genotyped (rs926198 and rs11773845). A logistic regression model was applied to estimate the associations. An admixture adjustment was performed through a Bayesian model.Results: A total of 605 subjects were included. rs11773845 was associated with hypertriglyceridemia [odds ratio (OR) = 1.33, p = 0.001] and the metabolic syndrome (OR = 1.53, p = 0.02). When admixture adjustment was performed these genetic associations preserved their statistical significance. There were no significant associations between rs926198 and metabolic traits.Conclusions: The CAV1 variation rs11773845 was found to be consistently associated with high serum triglycerides and the metabolic syndrome. This is the first report of a relationship between CAV1 variants and serum triglycerides in Latin America.
  • 10.

    【2hr】Chronic Obesity and Incident Hypertension in Latina Women Are Associated with Accelerated Telomere Length Loss over a 1-Year Period

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    机译 拉丁裔妇女的慢性肥胖和突发性高血压与1年期间端粒长度增加加速有关
    摘要：Aims: Shorter telomere length is associated with increased chronic disease risk in adulthood including diabetes mellitus and cardiovascular risk. Few studies have evaluated the relationship between telomere length change and incident disease risk in populations with a high percentage of overweight and obesity.Results: In an urban Latina population recruited in San Francisco (n = 82) with a high prevalence of overweight and obesity (78.4%), we assessed leukocyte telomere length and telomere length change over a 1-year period in relation to obesity, chronicity of obesity, and incident metabolic disease risk 5–6 years later. We also assessed the relationship between telomere length change over a 1-year period and weight loss. There were no significant associations between baseline telomere length and socio-demographics including age and ethnicity, or current weight status. Telomere length change, however, was associated with being obese at baseline and previous years of chronic obesity. A high percentage of women who were obese at baseline were also obese the year before (90%) and 2 years before (85%). Obesity at baseline was an independent predictor for increased telomere length attrition (β = −346.9, −568.4 to −125.4; P < 0.01). Similarly, chronic obesity was associated with increased risk for accelerated attrition (β = −280.6, −518.4 to −42.8; P < 0.01).Innovation: We speculate that accelerated attrition may be a harbinger of metabolic disease. We also found that those who had or developed hypertension had accelerated attrition [−407.4 ± 464.0 vs. −168.1 ± 643.6 (P = 0.03)].Conclusion: In populations with chronic and long-standing obesity, telomere length attrition rate, rather than baseline telomere length may be a more sensitive indicator of health status including chronic disease development.
  • 11.

    【2hr】Insulin Resistance and Metabolic Syndrome: Clinical and Laboratory Associations in African Americans Without Diabetes in the Hemochromatosis and Iron Overload Screening Study

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    机译 胰岛素抵抗和代谢综合症：血色素沉着症和铁超负荷筛选研究中无糖尿病的非洲裔美国人的临床和实验室协会
    摘要：Background: We sought to determine associations with insulin resistance (IR) and metabolic syndrome (MetS) in African Americans.Methods: We studied African American adults without diabetes in a postscreening examination. Participants included Cases: transferrin saturation (TS) >50% and serum ferritin (SF) >300 μg/L (M), and TS >45% and SF >200 μg/L (F), regardless of HFE genotype; and Controls: TS/SF 25th to 75th percentiles and HFE wt/wt (wild type). We excluded participants with fasting <8 h; fasting glucose >126 mg/dL; hepatitis B or C; cirrhosis; pregnancy; or incomplete datasets. We analyzed age; sex; Case/Control; body mass index (BMI); systolic and diastolic blood pressures; neutrophils; lymphocytes; alanine aminotransferase; aspartate aminotransferase; elevated C-reactive protein (CRP >0.5 mg/L); TS; and SF. We computed homeostasis model assessment of insulin resistance (HOMA-IR) using fasting serum glucose and insulin, and defined IR as HOMA-IR fourth quartile (≥2.42).Results: There were 312 Cases and 86 Controls (56.3% men). Ninety-one percent had HFE wt/wt. None had HFE p.C282Y. A significant increasing trend across HOMA-IR quartiles was observed for BMI only. Multivariable regression on HOMA-IR revealed significant positive associations: age; BMI; lymphocytes; SF; and CRP >0.5 mg/L; and significant negative associations: neutrophils and TS. Logistic regression on IR revealed BMI [odds ratio (OR) 1.3 (95% confidence interval 1.2–1.4)] and CRP >0.5 mg/L [OR 2.7 (1.2–6.3)]. Fourteen participants (3.5%) had MetS. Logistic regression on MetS revealed one association: IR [OR 7.4 (2.1–25.2)].Conclusions: In African Americans without diabetes, IR was associated with BMI and CRP >0.5 mg/L, after adjustment for other variables. MetS was associated with IR alone.
  • 12.

    【2hr】International Comparison of Abdominal Fat Distribution Among Four Populations: The ERA-JUMP Study

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    机译 四个人群腹部脂肪分布的国际比较：ERA-JUMP研究
    摘要：Background: Abdominal fat distribution varies across groups with different races or environments. Whether environmental factors, apart from racial differences, affect abdominal fat distribution is unknown.Methods: We compared the abdominal fat distribution of four groups; different races with similar environments (Caucasians vs. Japanese Americans), different environments with an identical race (Japanese Americans vs. Japanese), and similar races with similar environments (Japanese vs. Koreans). A population-based sample of 1212 men aged 40–49 were analyzed: 307 Caucasians and 300 Japanese Americans in the United States, 310 Japanese in Japan, and 295 Koreans in Korea. We compared the proportion of visceral adipose tissue area to total abdominal adipose tissue area (VAT%) and other factors that can affect abdominal fat distribution (smoking, alcohol use, physical activity levels, and metabolic factors).Results: VAT% was significantly higher in Japanese and Koreans than in Japanese Americans and Caucasians (50.0, 48.5, 43.2, 41.0%, respectively, P < 0.001). Even after adjustment for possible confounders, the significant VAT% difference remained in comparing groups with identical race but different environments (i.e., Japanese vs. Japanese Americans). In contrast, comparing groups with different races but similar environments (i.e., Caucasians vs. Japanese Americans), VAT% was not significantly different. Comparing groups with similar races and similar environments (i.e., Japanese vs. Koreans), VAT% did not significantly differ.Conclusions: Environmental differences, apart from racial differences, affect the difference in abdominal fat distribution across different groups in middle-aged men.
  • 13.

    【2hr】Association Between Carotid Intima Media Thickness, Age, and Cardiovascular Risk Factors in Children and Adolescents

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    机译 儿童和青少年的颈动脉内膜中层厚度，年龄和心血管危险因素之间的关联
    摘要：Background: Measures of carotid intima media thickness (cIMT) in adults are correlated with adiposity and the metabolic syndrome (MetS) and predict cardiovascular (CV) events. Relations in children are not as well studied. Our objective was to determine the relations of cIMT with body mass index (BMI) and CV risk score in children.Methods: The study included 291 children (158 M/133 F) 6–18 years of age (140 aged 6–11/151 aged 12–18) with measurements of height, weight, waist circumference; fasting lipids, glucose, insulin, and cIMT. A CV risk cluster score was developed from sum of the z-scores of the five MetS components (waist circumference, blood pressure, serum triglycerides, high-density lipoprotein cholesterol, and insulin). Partial Pearson correlation coefficients were adjusted for age, sex, and race.Results: There was no significant age difference in cIMT from 6 to 18 years of age. BMI and CV risk score were significantly correlated (P < 0.0001), and both were correlated with cIMT (r = 0.14, P = 0.02 and r = 0.16, P = 0.006, respectively). Slight age-related differences in associations of cIMT with CV risk score and BMI were explained by unusual values in a few children.Conclusions: These cross-sectional data in normal children show that cIMT was stable from childhood into adolescence. However, both BMI and CV risk score had small, but significant positive correlations with cIMT. Therefore, maintaining normal levels of adiposity and other risk variables may be useful in preventing early changes associated with preclinical atherosclerosis.
  • 14.

    【2hr】Relationship of Circulating miRNAs with Insulin Sensitivity and Associated Metabolic Risk Factors in Humans

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    机译 人体内循环miRNA与胰岛素敏感性和相关代谢危险因素的关系
    摘要：Background: Insulin resistance disrupts metabolic processes and leads to various chronic disease states such as diabetes and metabolic syndrome (MetS). However, the mechanism linking insulin resistance with cardiometabolic disease pathophysiology is still unclear. One possibility may be through circulating microRNAs (c-miRs), which can alter gene expression in target tissues. Our goal was to assess the relationship of c-miRs with insulin sensitivity, as measured by the gold standard, hyperinsulinemic-euglycemic clamp technique.Methods: Eighty-one nondiabetic, sedentary, and weight-stable patients across a wide range of insulin sensitivities were studied. Measurements were taken for blood pressure, anthropometric data, fasting glucose and lipids, and insulin sensitivity measured by clamp. After an initial screening array to identify candidate miRs in plasma, all samples were assessed for relationships between these c-miRs and insulin sensitivity, as well as associated metabolic factors.Results: miR-16 and miR-107 were positively associated with insulin sensitivity (R2 = 0.09, P = 0.0074 and R2 = 0.08, P = 0.0417, respectively) and remained so after adjustment with body mass index (BMI). After adjusting for BMI, miR-33, -150, and -222 were additionally found to be related to insulin sensitivity. Regarding metabolic risk factors, miR-16 was associated with waist circumference (r = −0.25), triglycerides (r = −0.28), and high-density lipoprotein (r = 0.22), while miR-33 was inversely associated with systolic blood pressure (r = −0.29). No significant relationships were found between any candidate c-miRs and BMI, diastolic blood pressure, or fasting glucose.Conclusions: Our results show that relative levels of circulating miR-16, -107, -33, -150, and -222 are associated with insulin sensitivity and metabolic risk factors, and suggest that multiple miRs may act in concert to produce insulin resistance and the clustering of associated traits that comprise the MetS. Therefore, miRs may have potential as novel therapeutic targets or agents in cardiometabolic disease.
  • 15.

    【2hr】Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release Across Glucose Tolerance in Man: Lack of Correlation with β Cell Function

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    机译 混合餐和静脉内L-精氨酸测试均刺激跨人糖耐量的肠促胰岛素释放：缺乏与β细胞功能的相关性
    摘要：Background: The aims of this study were to 1. define the responses of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and peptide YY (PYY) to an oral meal and to intravenous L-arginine; and 2. examine correlation of enteroendocrine hormones with insulin secretion. We hypothesized a relationship between circulating incretin concentrations and insulin secretion.Methods: Subjects with normal glucose tolerance (NGT, n = 23), prediabetes (PDM, n = 17), or with type 2 diabetes (T2DM, n = 22) were studied twice, following a mixed test meal (470 kCal) (mixed meal tolerance test [MMTT]) or intravenous L-arginine (arginine maximal stimulation test [AST], 5 g). GLP-1 (total and active), PYY, GIP, glucagon, and β cell function were measured before and following each stimulus.Results: Baseline enteroendocrine hormones differed across the glucose tolerance (GT) spectrum, T2DM generally >NGT and PDM. In response to MMTT, total and active GLP-1, GIP, glucagon, and PYY increased in all populations. The incremental area-under-the-curve (0–120 min) of analytes like total GLP-1 were often higher in T2DM compared with NGT and PDM (35–51%; P < 0.05). At baseline glucose, L-arginine increased total and active GLP-1 and glucagon concentrations in all GT populations (all P < 0.05). As expected, the MMTT and AST provoked differential glucose, insulin, and C-peptide responses across GT populations. Baseline or stimulated enteroendocrine hormone concentrations did not consistently correlate with either measure of β cell function.Conclusions/interpretation: Both MMTT and AST resulted in insulin and enteroendocrine hormone responses across GT populations without consistent correlation between release of incretins and insulin, which is in line with other published research. If a defect is in the enteroendocrine/β cell axis, it is probably reduced response to rather than diminished secretion of enteroendocrine hormones.
  • 16.

    【2hr】Metabolic Syndrome in Hispanic Youth: Results from the Hispanic Community Children's 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.
  • 17.

    【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.
  • 18.

    【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.
  • 19.

    【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.
  • 20.

    【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：
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