scholarly journals Prader-Willi Syndrome Is Associated with Activation of the Innate Immune System Independently of Central Adiposity and Insulin Resistance

2010 ◽  
Vol 95 (7) ◽  
pp. 3392-3399 ◽  
Author(s):  
Alexander Viardot ◽  
Lisa Sze ◽  
Louise Purtell ◽  
Amanda Sainsbury ◽  
Georgina Loughnan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Arterial Stiffness ◽  
Innate Immune ◽  
Low Grade ◽  
Model Assessment ◽  
Central Adiposity ◽  
Activation Markers ◽  
Reactive Protein ◽  
Obese Subjects ◽  
Low Grade Inflammation

Background: Subjects with Prader-Willi syndrome (PWS) have a reduced life expectancy due to cardiovascular disease. Increased systemic low-grade inflammation is postulated as a contributor, despite reported lower visceral fat mass and increased insulin sensitivity. Objectives: Our aim was to compare inflammatory markers and arterial stiffness in PWS and adiposity-matched obese control subjects. Design: We conducted a cross-sectional cohort study comparing 12 PWS subjects, 12 obese subjects matched for percentage body fat and central abdominal fat mass, and 10 healthy normal-weight subjects. Main Outcome Measures: Dual-energy x-ray absorptiometry was used to assess body composition, flow cytometry to quantify activation markers on immune cells, and ELISA for measurement of C-reactive protein, adiponectin, and IL-6. Insulin resistance was estimated by homeostasis model assessment and arterial stiffness by applanation tonometry. Results: PWS and obese subjects had similarly increased homeostasis model assessment and arterial stiffness. Nevertheless, PWS subjects showed significantly higher IL-6 (4.9 ± 1.0 vs. 2.5 ± 0.4 pg/ml; P = 0.02) and nonsignificantly higher C-reactive protein (10.5 ± 3.2 vs. 4.0 ± 1.0 ng/ml; P = 0.08). Neutrophil activation markers CD66b and CD11b were higher in PWS compared to obese subjects (P < 0.01), reflecting an activated innate immune system. These markers were positively related to central adiposity in lean and obese subjects (r = 0.49; P < 0.05), but not in PWS subjects. Conclusions: PWS subjects compared to adiposity-matched obese subjects demonstrate similar insulin resistance but increased low-grade inflammation. The dissociation of inflammation and central adiposity suggests that activation of innate immunity may be either a specific genetic feature of PWS or linked to the commonly associated obstructive sleep apnea syndrome, and might offer a treatment target to reduce cardiovascular disease.

scholarly journals The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation

2014 ◽  
Vol 112 (10) ◽  
pp. 1724-1734 ◽  
Author(s):  
Eirini C. Spyridaki ◽  
Panagiotis Simos ◽  
Pavlina D. Avgoustinaki ◽  
Eirini Dermitzaki ◽  
Maria Venihaki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fluid Intelligence ◽  
Leisure Time Physical Activity ◽  
Resistance Index ◽  
Low Grade ◽  
Model Assessment ◽  
Inverse Association ◽  
Published Evidence ◽  
Activity Measurements ◽  
Low Grade Inflammation

Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.

scholarly journals Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

2012 ◽  
Vol 167 (4) ◽  
pp. 569-578 ◽  
Author(s):  
Francisco J Ortega ◽  
Mónica Sabater ◽  
José M Moreno-Navarrete ◽  
Neus Pueyo ◽  
Patricia Botas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Lipid Metabolism ◽  
Inflammatory Markers ◽  
Low Grade ◽  
Model Assessment ◽  
Glucose And Lipid Metabolism ◽  
Obese Subjects

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

scholarly journals PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiayu Huang ◽  
Lin Liu ◽  
Chunyan Chen ◽  
Ying Gao
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Predictive Biomarker ◽  
Normal Weight ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Model Assessment ◽  
Increased Risk ◽  
Homeostatic Model Assessment ◽  
Low Grade Inflammation

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into “nonobese” and “obese” arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normal-weight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

Association of Resting Heart Rate With Arterial Stiffness and Low-Grade Inflammation in Women With Systemic Lupus Erythematosus

Angiology ◽  
2017 ◽  
Vol 69 (8) ◽  
pp. 672-676 ◽  
Author(s):  
José Antonio Vargas-Hitos ◽  
Alberto Soriano-Maldonado ◽  
Josefa Martínez-Bordonado ◽  
Isabel Sánchez-Berná ◽  
Daniel Fernández-Bergés ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Heart Rate ◽  
Arterial Stiffness ◽  
Lupus Erythematosus ◽  
Low Grade ◽  
Model Assessment ◽  
Resting Heart Rate ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Low Grade Inflammation

Resting heart rate (RHR) is associated with arterial stiffness, inflammation, and cardiovascular (CV) and all-cause mortality in the general population and in patients at high CV risk. We assessed the association of RHR with arterial stiffness and low-grade inflammation (LGI) in a cross-sectional study that included 101 women with systemic lupus erythematosus (SLE) without a history of CV disease or arrhythmia or who were under treatment that may cause bradycardia. Pulse wave velocity (PWV; a measure of arterial stiffness), RHR, and markers of LGI (ie, C-reactive protein, fibrinogen, erythrocyte sedimentation rate, insulin, and homeostatic model assessment index) were measured. The patients with the highest RHR (quartile 4; mean RHR = 87.2 bpm) had a PWV 0.61 m/s (95% confidence interval [CI]: 0.08-1.14; P = .024) greater than patients with the lowest RHR (quartile 1; RHR = 63.0 bpm), independent of age, systolic blood pressure, disease activity, smoking, and being physically inactive. Similarly, patients with the highest RHR (quartile 4) showed a significantly less favorable clustered LGI index than patients in quartile 1 ( b = .58; 95% CI: 0.212-0.948; P = .002). Higher RHR is associated with greater arterial stiffness and LGI in women with SLE. Further research to determine the prognostic value of RHR in this population is warranted.

scholarly journals Low-Grade Inflammation, Obesity, and Insulin Resistance in Adolescents

2007 ◽  
Vol 92 (12) ◽  
pp. 4569-4574 ◽  
Author(s):  
Christian Herder ◽  
Sophie Schneitler ◽  
Wolfgang Rathmann ◽  
Burkhard Haastert ◽  
Heiko Schneitler ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Immune Activation ◽  
Interferon Γ ◽  
Considerable Proportion ◽  
Low Grade ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Cross Sectional ◽  
Monocyte Chemoattractant Protein 1 ◽  
Low Grade Inflammation

Abstract Context: Low-grade inflammation is associated with insulin resistance and precedes the onset of type 2 diabetes mellitus in adults, but there are no comparable data in youth. Objective: The objective of the study was to characterize the pattern of subclinical immune activation that is associated with indices of obesity and insulin resistance in youth and analyze whether this association is explained by obesity. Design: This was a cross-sectional study. Setting: Medical check-up of schoolchildren was conducted by the Public Health Office in Düsseldorf (Germany). Participants: Participants included 519 adolescents (mean age 15.5 ± 0.8 yr). Main Outcome Measures: Measures included body mass index (BMI) and waist circumference (WC) as indices of obesity; fasting glucose, insulin, and homeostasis model assessment of insulin resistance; serum concentrations of TNFα, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1, interferon-γ-inducible protein (IP)-10 and adiponectin as immunological variables. Results: In age-, sex-, and lipid-adjusted analyses, IL-6, IL-18, IP-10, and adiponectin (inversely) were associated with both BMI and WC (all P ≤ 0.002). None of the immune markers was related to glucose, but IL-6, IL-18, and adiponectin (inversely) were associated with insulin and homeostasis model assessment of insulin resistance in age- and sex-adjusted models. Adjustment for BMI or WC indicated that a considerable proportion of these associations may be mediated by obesity. Conclusions: We found that a differential low-grade immune activation is associated with parameters of obesity in adolescents. Moreover, there is evidence that IL-6, IL-18, IP-10, and adiponectin (inversely) are associated with insulin resistance and that these associations can mainly be attributed to obesity.

scholarly journals Reversal of Insulin Resistance in Overweight and Obese Subjects by trans-Resveratrol and Hesperetin Combination—Link to Dysglycemia, Blood Pressure, Dyslipidemia, and Low-Grade Inflammation

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2374
Author(s):  
Naila Rabbani ◽  
Mingzhan Xue ◽  
Martin O. Weickert ◽  
Paul J. Thornalley
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Plasma Glucose ◽  
Quinone Reductase ◽  
Protein Glycation ◽  
Oral Glucose ◽  
Low Grade ◽  
Obese Subjects ◽  
Cox 2 ◽  
Low Grade Inflammation

The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = −0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = −0.68, p < 0.05)—a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = −0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = −0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.

scholarly journals Aortic Stiffness, Inflammation, and Incidence of Cardiovascular Events in Elderly Participants From the General Population

Angiology ◽  
2021 ◽  
pp. 000331972110174
Author(s):  
Benjamin Nilsson Wadström ◽  
Margaretha Persson ◽  
Gunnar Engström ◽  
Peter M. Nilsson
Keyword(s):  
Arterial Stiffness ◽  
Disease Risk ◽  
High Sensitivity ◽  
Aortic Pulse Wave Velocity ◽  
Low Grade ◽  
Key Factors ◽  
Reactive Protein ◽  
Causal Pathways ◽  
Cv Disease ◽  
Low Grade Inflammation

Low-grade inflammation and arterial stiffness are key factors in the development of vascular aging. However, the interplay between arterial stiffness and inflammation for cardiovascular (CV) disease is unclear. Aortic pulse wave velocity (aPWV) and the inflammatory markers, high-sensitivity C-reactive protein (CRP) and orosomucoid, were measured in 2710 participants (median age: 72 years). These participants were followed up for a mean of 7.6 years for a composite CV disease end point. Per 1 interquartile range increment of CRP and orosomucoid, respectively, aPWV increased by 0.19 m/s (95% CI: 0.07-0.32) and 0.19 m/s (0.11-0.27), after multifactorial adjustment. Mediation analysis showed that aPWV, after multifactorial adjustment, mediated 8% (−4, 20) of the CV disease risk associated with CRP and 8% (−4, 18) of orosomucoid risk. The associated risk increased with combinations of high aPWV and high CRP or orosomucoid. We found no evidence that arterial PWV acted as an important mediator of the relationship between systemic inflammation and CV disease risk in this elderly population. The results instead indicate an additive effect. Our study supports the view that arterial stiffness and chronic inflammation affects CV risk mainly through separate causal pathways.

scholarly journals Cardiometabolic Risk Profile Among Young Adult Females With a History of Premature Adrenarche

2019 ◽  
Vol 3 (10) ◽  
pp. 1771-1783 ◽  
Author(s):  
Jani Liimatta ◽  
Pauliina Utriainen ◽  
Tomi Laitinen ◽  
Raimo Voutilainen ◽  
Jarmo Jääskeläinen
Keyword(s):  
Insulin Resistance ◽  
Young Adult ◽  
Fat Mass ◽  
Study Groups ◽  
Low Grade ◽  
Adult Women ◽  
Model Assessment ◽  
The Metabolic Syndrome ◽  
Premature Adrenarche ◽  
Low Grade Inflammation

Abstract Context Premature adrenarche (PA) is associated with childhood overweight and hyperinsulinemia; the long-term cardiometabolic outcome is unknown. Objective To study cardiometabolic profile in adult women with previous PA. Design and participants Thirty women with PA and 41 control subjects were followed from prepuberty to young adulthood. Main outcome measures Prevalence of the metabolic syndrome (MetS) and clinical and biochemical cardiovascular risk factors. Results There were no differences in the prevalence of MetS or in any parameters indicating dyslipidemia, hypertension, hepatosteatosis, atherosclerosis, or low-grade inflammation between the study groups. However, prevalence of insulin resistance (IR; P = 0.014) and acanthosis nigricans (P = 0.010) was higher in the PA group. Neither fasting glucose nor insulin concentrations differed between the study groups, but HbA1c [adjusted for body mass index (BMI) P = 0.011] and Homeostatic Model Assessment of Insulin Resistance (P = 0.044; BMI-adjusted P = nonsignificant) were higher in the PA group. Although BMI and fat percentage were comparable between the study groups, the PA group had higher central fat mass than the control group. In the whole study population, MetS and IR were associated with greater adult fat mass, but no prepubertal factors predicting later IR were found. Conclusion PA does not seem to be associated with MetS, dyslipidemia, hypertension, atherosclerosis, or low-grade inflammation in young adult women. However, some women with PA may be at an increased risk of unfavorable glucose metabolism, which is associated with increased central adiposity at adult age rather than determined by prepubertal factors.

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