Inflammation as a Trigger for Insulin Resistance and Cardiometabolic Disease

2014 ◽  
pp. 15-20 ◽  
Author(s):  
Thomas M. Stulnig
Keyword(s):  
Insulin Resistance ◽  
Cardiometabolic Disease

scholarly journals Perivascular Adipose Tissue and Cardiometabolic Disease

2013 ◽  
Vol 5 (1) ◽  
pp. 13
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Blood Vessels ◽  
Vascular Function ◽  
Immune Cell ◽  
The Body ◽  
Cardiometabolic Disease ◽  
Perivascular Adipose Tissue ◽  
Nitric Oxide Signaling ◽  
Fat Depots

BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity.CONTENT: Perivascular adipose tissue (PVAT) is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis.SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease.KEYWORDS: obesity, perivascular adipose tissue, PVAT, cardiometabolic disease, adipokine

scholarly journals Association of Lifestyle and Body Composition on Risk Factors of Cardiometabolic Diseases and Biomarkers in Female Adolescents

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Valter Paulo Neves Miranda ◽  
Paulo Roberto dos Santos Amorim ◽  
Ronaldo Rocha Bastos ◽  
Karina Lúcia Ribeiro Canabrava ◽  
Márcio Vidigal Miranda Júnior ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Body Composition ◽  
Uric Acid ◽  
Body Fat ◽  
Inflammatory Biomarkers ◽  
Female Adolescents ◽  
Cardiometabolic Disease ◽  
Hs Crp

Background. Female adolescents are considered a risk group for cardiometabolic disease due to their lifestyle (LS). Objective. To evaluate the association between LS classes and body composition groups with cardiometabolic disease risk factors and pro- and anti-inflammatory biomarkers in female adolescents. Methods. This cross-sectional study was carried out with female adolescents aged 14 to 19 years, from Viçosa-MG, Brazil. Latent class analysis assessed LS classes. Kinanthropometric measurements were taken together with the body fat percentage (BF%), being analyzed by the Dual Energy X-ray Absorptiometry (DEXA) equipment. Blood pressure and biochemical parameters were analyzed in the Health Division of the Federal University of Viçosa. The pro- and anti-inflammatory biomarkers were analyzed using Luminex technology. Associations with biomarkers were estimated by multiple linear regression. Results. 405 female adolescents were evaluated. The majority, 82.57%, 72.90%, and 65.31%, were classified as inactive by the number of steps, with high screen and cell phone time, respectively. Furthermore, 41.55% did meet the minimum of 60 minutes of moderate-to-vigorous physical activity (MVPA) and 54.69% had high values of BF% (DEXA). The “Sedentary & Inactive LS” class together with the high levels of weight and BF% were associated with increased levels of blood pressure, lipid profile, and uric acid. It was also found that “Inactive & Sedentary LS”, high BF%, insulin resistance, and ultra-sensitive C-reactive protein were associated with the concentrations of proinflammatory biomarkers of tumor necrosis factor-α, interleukin-6, and leptin. Conclusion. We concluded that female adolescents with overweight/obese and high BF% presented higher values of anthropometric indicators, levels of blood pressure, concentration of uric acid and hs-CRP, and lower concentration of HDL. Inactive and Sedentary lifestyle of these girls, along with excess body fat, insulin resistance, and higher concentrations of hs-CRP were associated with the higher concentration proinflammatory markers.

scholarly journals Clusterin as a Potential Biomarker of Obesity-Related Alzheimer’s Disease Risk

2020 ◽  
Vol 15 ◽  
pp. 117727192096410
Author(s):  
David Bradley
Keyword(s):  
Metabolic Disease ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
Smoking Status ◽  
Apoe Genotype ◽  
Cardiometabolic Disease ◽  
Potential Biomarker

Over 35% of the adult US population is obese. In turn, excess adiposity increases the risk of multiple complications including type 2 diabetes (T2D), insulin resistance, and cardiovascular disease; yet, obesity also independently heightens risk of Alzheimer’s Disease (AD), even after adjusting for other important confounding risk factors including blood pressure, sociodemographics, cholesterol levels, smoking status, and Apolipoprotein E (ApoE) genotype. Among patients over the age of 65 with dementia, 37% have coexisting diabetes, and an estimated 7.3% of cases of AD are directly attributable to midlife obesity. Clusterin, also known as apolipoprotein J (ApoJ), is a multifunctional glycoprotein that acts as a molecular chaperone, assisting folding of secreted proteins. Clusterin has been implicated in several physiological and pathological states, including AD, metabolic disease, and cardiovascular disease. Despite long-standing interest in elucidating clusterin’s relationship with amyloid beta (Aβ) aggregation/clearance and toxicity, significant knowledge gaps still exist. Altered clusterin expression and protein levels have been linked with cognitive and memory function, disrupted central nervous system lipid flux, as well as pathogenic brain structure; and its role in cardiometabolic disease suggests that it may be a link between insulin resistance, dyslipidemia, and AD. Here, we briefly highlight clusterin’s relevance to AD by presenting existing evidence linking clusterin to AD and cardiometabolic disease, and discussing its potential utility as a biomarker for AD in the presence of obesity-related metabolic disease.

scholarly journals Gut microbiome of a porcine model of metabolic syndrome and HF-pEF

2020 ◽  
Vol 318 (3) ◽  
pp. H590-H603
Author(s):  
Aoife N. O’Donovan ◽  
Florence M. Herisson ◽  
Fiona Fouhy ◽  
Paul M. Ryan ◽  
Derek Whelan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Bile Acid ◽  
Fatty Liver ◽  
Gut Microbiome ◽  
Porcine Model ◽  
Cardiometabolic Disease ◽  
Cardiometabolic Syndrome ◽  
Acid Producing Bacteria

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease. NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

21: DETERMINANTS OF VASCULAR INFLAMMATION BY 18-FLUORODEOXYGLUCOSE PET/MRI: FINDINGS FROM THE PSORIASIS, ATHEROSCLEROSIS AND CARDIOMETABOLIC DISEASE INITIATIVE

2016 ◽  
Vol 64 (3) ◽  
pp. 815.2-816
Author(s):  
MT Kabbany ◽  
AA Joshi ◽  
M Ahlman ◽  
J Rodante ◽  
JB Lerman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Fdg Pet ◽  
Particle Concentration ◽  
Vascular Inflammation ◽  
Chronic Inflammatory Disease ◽  
Human Model ◽  
Cardiometabolic Disease ◽  
Model Assessment ◽  
Mri Findings

Purpose of StudyPsoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a clinical human model to study inflammatory atherogenesis. We aimed to assess the major determinants of vascular inflammation (VI) measured by 18FDG PET-MRI in a well-phenotyped PSO cohort.Methods Used124 consecutive patients with PSO underwent 18FDG PET-MRI scans. We used target-to-background ratio to quantify VI 120 minutes post FDG injection. Homeostatic model assessment of insulin resistance (HOMA-IR) was measured, along with cholesterol efflux capacity (CEC) and HDL particle concentration by NMR (Liposcience) fasting.Summary of ResultsOur cohort was middle aged (mean 49±13.3 years) with mild to moderate PSO, and low CV risk (median Framingham Risk Score (FRS) 2, IQR 2–6). PSO was associated with increased VI (β=0.27, p<0.005), compared to healthy controls. VI was associated with HOMA-IR (β=0.26, p<0.001), CEC (β=−0.12, p=0.04) and HDL particle concentration (β=−0.19, p=0.003) beyond traditional CV risk factors (age, gender, FRS and BMI). Among these, HOMA-IR provided maximum incremental value in predicting VI beyond traditional risk factors (χ2=39.36, p<0.001).ConclusionsVI by FDG PET MRI is associated with traditional CV risk factors and cardiometabolic parameters. Insulin resistance and CEC were most strongly associated with VI by 18FDG PET-MRI beyond traditional CV risk factors and BMI in PSO suggesting that cardiometabolic disease increases CV risk in PSO.Abstract 21 Figure 1

Abstract 13783: Paradigms to Predict Cardiometabolic Disease in African Descent Populations Should Focus on HDL-Cholesterol Rather than Triglyceride

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Anne E Sumner ◽  
Caroline K Thoreson ◽  
Madia Ricks ◽  
Stephanie T Chung
Keyword(s):  
Insulin Resistance ◽  
African Americans ◽  
African Descent ◽  
African Ancestry ◽  
Density Lipoprotein ◽  
African Immigrants ◽  
Hdl Cholesterol ◽  
Cardiometabolic Disease ◽  
Sensitivity Index ◽  
Low Hdl

Paradigms for the early detection of cardiometabolic disease usually incorporate both elevated triglyceride (TG) and low high density lipoprotein -cholesterol (HDL-C). However, African-Americans with cardiometabolic disease usually have normal TG levels. The HDL-C pattern of African-Americans with cardiometabolic disease is uncertain. The TG and HDL-C pattern in Africans with cardiometabolic disease is unknown. To clarify the TG and HDL-C pattern in African descent populations with cardiometabolic disease, 377 blacks (167 African-Americans, 210 African immigrants, 59% male, age 36±9y, mean±SD, range 20-64y, BMI 29.0±6.3 kg/m2, range 18.5-54.7) had glucose tolerance status determined by OGTT, lipid profiles and insulin resistance determined by the insulin sensitivity index (SI). Insulin resistance was defined as the lowest quartile of SI (<2.18 L/mU - 1min- 1). Metabolic triad was defined as hyperinsulinemia (fasting insulin≥3.7 μU/mL), hyperapolipoproteinB (≥64 mg/dL) and sdLDL(≥21.5 nm) based on the median values of the group with normal BMI. Cardiometabolic disease was defined as one or more of the following: pre-diabetes, diabetes, insulin resistance or metabolic triad. The frequency with which hypertriglyceridemia (TG≥150 mg/dL) or low HDL-C (<40 mg/dL in men or <50 mg/dL in women) occurred in the presence of cardiometabolic disease was determined. The prevalence of cardiometabolic disease did not differ in African-Americans and African immigrants (63% vs. 60%, P=0.51). TG and HDL-C levels in blacks with cardiometabolic disease did not differ by African ancestry. In the presence of cardiometabolic disease, TG levels were 80±40 vs. 87±43, P=0.24, resp. while HDL-C levels in men were: 45±11 vs. 44±12, P=0.63, and in women: 48±10 vs. 49±10, P=0.86). Less than 10% of people with cardiometabolic disease had TG≥150 mg/dL. However, 42% of people with cardiometabolic disease had low HDL-C. If HDL-C levels were low, the odds of having cardiometabolic disease was 2.84 (95% CI 1.76, 4.59. P<0.001). Overall, more than 40% of people with cardiometabolic disease had low HDL while <10% had elevated TG levels. Therefore, paradigms to detect cardiometabolic disease in African descent populations should focus on HDL-C rather than TG.

scholarly journals Lipoprotein Insulin Resistance Score: Validation and Utility in African Ancestry Populations

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A291-A292
Author(s):  
Vandhna Rani Sharma ◽  
Celeste K L Cravalho ◽  
Joshua Dawson ◽  
Alfredo Villalobos-Perez ◽  
Lilian Mabundo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
African Ancestry ◽  
European Ancestry ◽  
Whole Body ◽  
Cardiometabolic Disease ◽  
Screening Methods ◽  
Lower Sensitivity ◽  
Sensitivity Index ◽  
Abnormal Glucose Tolerance

Abstract Lipoprotein insulin resistance (LPIR) is an emerging biomarker of insulin resistance (IR), and a score of &gt;48 is a strong predictor of incident cardiometabolic disease disease in a predominantly European ancestry population. LPIR is derived from a composite score of nuclear magnetic resonance (NMR) lipoprotein (Lp) parameters: triglyceride-rich (TRLp), low density (LDLp), and high density (HDLp). Yet, there is a paucity of data in African ancestry population, in whom there is low-normal TRLp despite high rates of IR and diabetes. Therefore, we examined Lp profiles and LPIR in a large African ancestry cohort, stratified by sex to determine the relationship of LPIR with established markers of IR. This is a secondary analysis from 2 studies (The Africans in America and Federal Women’s Study) designed to evaluate the genetic, biological and socio-environmental factors of diabetes risk in those of African ancestry. All participants self-identified as healthy and lived in the DC metro area, n= 518: 87.7% African immigrant,12.3% African American; age 39±10 (20-65y); BMI 28.1±4.8 (18.2–45.2 kg/m2); 58% male; 31% with obesity, and 37% with abnormal glucose tolerance; mean±SD (range); median (25th-75th percentile). Fasting measures of IR (LPIR, triglyceride/HDL (TG/HDL) ratio and homeostasis model of insulin resistance (HOMA-IR)) were compared with the whole-body insulin sensitivity index (WBISI) obtained during a multi-sample 75g OGTT, using spearman correlations. Lp particle size and subclass concentrations were measured by the amplitudes of the lipid-methyl group signals (NMR LipoProfile®). Men had lower BMI (27.1±3.9 vs 29.3±5.6 kg/m2), fat mass (23.5±5.5 vs 37.9±6.8 %), insulin resistance (WBISI: 6.2 (3.7–10.1) vs 4.9 (3.2–8.6), HOMA-IR: 1.3 (0.7–2.0) vs 1.6 (0.9–2.4), TG/HDL: 1.4 (1.0–2.2) vs 1.1 (0.8–1.5)), all P&lt;0.001. LDLp (1226 (959–1531) vs 1239 (981–1553) nmol/L) and HDLp (17.6 (16.2–19) vs 17.5 (15.9–19.7) µmol/L) were similar by sex, P&gt;0.6, while small LDLp 734 (523–1039) vs 541 (370–805) nmol/L and TRLp 80.5 (52.2–116.4) vs 53.6 (28.7 -89.3) nmol/L were higher in men. The total mean LPIR score was 28.9±18.7 and was higher in men (34±19 vs. 23±17), P&lt;0.001. LPIR and TG/HDL ratio correlated with WBISI (r≥-0.40) and HOMA-IR (r≥0.40), P&lt;0.001 with no differences by sex. HOMA-IR correlated with WBISI (r=-0.95, P&lt;0.001). Overall, African ancestry individuals had high rates of abnormal glucose tolerance, obesity and LDLp but LPIR was 20 points lower than the established score for predicting cardiometabolic disease. It’s utility for detecting IR was modest but it may be an important adjunct for early cardiometabolic risk stratification in African ancestry populations in whom traditional screening methods have lower sensitivity.

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