scholarly journals Increased Inflammation and Cardiometabolic Risk in Individuals with Low AMY1 Copy Numbers

2019 ◽  
Vol 8 (3) ◽  
pp. 382 ◽  
Author(s):  
Clara Marquina ◽  
Aya Mousa ◽  
Regina Belski ◽  
Harry Banaharis ◽  
Negar Naderpoor ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Fat Mass ◽  
Cardiometabolic Risk ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Copy Number Variations ◽  
Intravenous Glucose Tolerance Test ◽  
Healthy Population ◽  
Necrosis Factor Alpha ◽  
Intravenous Glucose

Lower copy number variations (CNVs) in the salivary amylase gene (AMY1) have been associated with obesity and insulin resistance; however, the relationship between AMY1 and cardiometabolic risk has not been fully elucidated. Using gold-standard measures, we aimed to examine whether AMY1 CNVs are associated with cardiometabolic risk factors in an overweight or obese, otherwise healthy population. Fifty-seven adults (58% male) aged 31.17 ± 8.44 years with a body mass index (BMI) ≥25 kg/m2 were included in the study. We measured AMY1 CNVs (qPCR); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, serum lipids by ELISA); insulin sensitivity (hyperinsulinaemic–euglycaemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (multiplex assays). Based on previous studies and median values, participants were divided into low (≤4) and high (>4) AMY1 CNV groups. Low AMY1 carriers (n = 29) had a higher fat mass (40.76 ± 12.11 versus 33.33 ± 8.50 kg, p = 0.009) and LDL-cholesterol (3.27 ± 0.80 versus 2.87 ± 0.69 mmol/L, p = 0.038), and higher serum levels of interleukin [IL]-6, IL-1β, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1) (all p < 0.05) compared with high AMY1 carriers (n = 28), but there were no differences in glycaemic measures, including insulin sensitivity or secretion (all p > 0.1). Except for MCP-1, the results remained significant in multivariable models adjusted for age, sex, and fat mass (all p < 0.05). Our findings suggest that low AMY1 CNVs are associated with increased cardiovascular disease risk and inflammation, but not glucose metabolism, in overweight or obese adults.

The effect of age and exercise training on insulin sensitivity, fat and muscle tissue cytokine profiles and body composition of old and young Standardbred mares

2012 ◽  
Vol 8 (3-4) ◽  
pp. 173-187 ◽  
Author(s):  
N.R. Liburt ◽  
M.N. Fugaro ◽  
K. Malinowski ◽  
E.K. Wunderlich ◽  
J.L. Zambito ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Repeated Measures ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Insulin Response ◽  
Intravenous Glucose Tolerance Test ◽  
Necrosis Factor Alpha ◽  
Intravenous Glucose ◽  
Cytokine Profiles

This study tested the hypothesis that old and young mares exhibit different endocrine responses to a frequently sampled intravenous glucose tolerance test (FSIGT) and different cytokine profiles in blood, adipose and muscle tissues. It was also hypothesised that exercise training alters endocrine and tissue cytokine profiles. Pilot data from 15 mixed background horses indicated tissue differences in cytokine profiles. For the main study, six old (22.0±0.7 years) and six young (7.3±0.6 years; mean±SE) unfit Standardbred mares were tested pre- and post-training. Exercise training occurred three days/week for 15 weeks at ~60% maximum heart rate. Plasma insulin and glucose concentrations were measured via radioimmunoassay and enzyme-electrode interface, respectively. Samples of blood, middle gluteal muscle (RM), and subcutaneous adipose tissue from the neck (NF) were collected pre- and post-training for mRNA quantification. Minimal model analysis of FSIGT, repeated measures ANOVA and Pearson Product Moment were used to analyse data. The null hypothesis was rejected when P≤l0.10. Post-training, old and young mares improved insulin sensitivity (SI) (P=0.08, P=0.01, respectively) and disposition index (P=0.04, P<0.001, respectively), but acute insulin response to glucose increased in young mares only (P=0.02). Old mares exhibited lower (P=0.06) average relative quantity (RQ) of tumour necrosis factor-alpha in NF compared to RM. Old mares showed greater RQ of interleukin-6 (IL-6) in NF compared to young (P=0.08). A negative correlation was observed between SI and IL-6 in NF post-training (P=0.07, R=-0.54), and a positive correlation occurred between SI and monocyte chemotactic protein-1 in NF post-training (P=0.08, R=0.53). Exercise training improved pancreatic beta cell function and insulin sensitivity in old and young horses. Cytokines associated with glucose metabolism may have varied roles in different tissues.

Association of plasma acylcarnitines with insulin sensitivity, insulin secretion, and prediabetes in a biracial cohort

2021 ◽  
pp. 153537022110094
Author(s):  
Ibiye Owei ◽  
Nkiru Umekwe ◽  
Frankie Stentz ◽  
Jim Wan ◽  
Sam Dagogo-Jack
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Intravenous Glucose Tolerance Test ◽  
Cross Sectional ◽  
Parental History ◽  
Intravenous Glucose

The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.

scholarly journals Improvements in cholesterol efflux capacity of HDL and adiponectin contribute to mitigation in cardiovascular disease risk after bariatric surgery in a cohort with morbid obesity

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Himani Thakkar ◽  
Vinnyfred Vincent ◽  
Sakshi Sukhla ◽  
Manraj Sra ◽  
Uma Kanga ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Insulin Sensitivity ◽  
Cholesterol Efflux ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cvd Risk ◽  
Cholesterol Efflux Capacity ◽  
Post Surgery ◽  
Inflammatory Status

Abstract Background Bariatric surgery can alleviate cardiovascular risk via effects on cardiovascular disease (CVD) risk factors such as diabetes mellitus, hypertension, and dyslipidemia. Our study aimed to assess the cholesterol efflux capacity (CEC) of HDL as a negative risk factor for CVD in individuals with obesity and identify the factors associated with improvement in CEC 3 months following bariatric surgery. Methods We recruited 40 control individuals (mean BMI of 22.2 kg/m2) and 56 obese individuals (mean BMI of 45.9 kg/m2). The biochemical parameters, inflammatory status and CEC of HDL was measured for the obese individuals before bariatric surgery and at 3 months after surgery. The CEC was measured using a cell-based cholesterol efflux system of BODIPY-cholesterol-labelled THP-1 macrophages. Results A significant reduction in BMI (− 17%, p < 0.001), resolution of insulin sensitivity (HOMA2-IR = − 23.4%, p = 0.002; Adipo IR = − 16%, p = 0.009) and inflammation [log resistin = − 6%, p = 0.07] were observed 3 months post-surgery. CEC significantly improved 3 months after surgery [Pre: 0.91 ± 0.13; Post: 1.02 ± 0.16; p = 0.001] despite a decrease in HDL-C levels. The change in CEC correlated with the change in apo A-I (r = 0.39, p = 0.02) and adiponectin levels (r = 0.35, p = 0.03). Conclusion The results suggest that improvements in CEC, through improvement in adipose tissue health in terms of adipokine secretion and insulin sensitivity could be an important pathway in modulating obesity-related CVD risk.

Abstract 610: Ineffective Suppression of Adipocyte Lipolysis in Metabolic Syndrome: An in vivo Test for Adipocyte Insulin Resistance

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jennifer L Ford ◽  
Raymond C Boston ◽  
Rachel E Walker ◽  
Gregory C Shearer
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Lipid Droplet ◽  
Minimal Model ◽  
Initial Rate ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
In Vivo Test

Background: Insulin resistance is a major contributor to metabolic syndrome, disrupting both glucose and non-esterified fatty acid (NEFA) dynamics through ineffective glucose clearance and decreased suppression of lipid droplet lipolysis. The minimal model of glucose dynamics is used for glycemic insulin sensitivity however it does not measure adipocyte insulin sensitivity, the primary determinant of plasma NEFA. An in-vivo approach to measuring adipocyte insulin sensitivity using NEFA is employed, comparing healthy and metabolic syndrome subjects. Both the models are employed to estimate insulin sensitivity and validate the NEFA approach. Objective: To test the use of NEFA kinetics to measure adipocyte insulin sensitivity compared to the glucose minimal model. Approach and results: Metabolic syndrome (n=56) and optimally healthy (n=14) subjects underwent a frequently sampled intravenous glucose tolerance test, and plasma analyzed for insulin, glucose, and NEFA. Insulin sensitivity ( S I ) and glucose effectiveness ( S G ) were calculated from the glucose minimal model. S I was 1.7 (mU/L) -1 min -1 and 0.40 (mU/L) -1 /min -1 and S G was 0.027 min -1 and 0.017 min -1 for the healthy and metabolic syndrome groups, respectively, indicating substantial glycemic insulin resistance in the latter. A model using glucose as the driver for NEFA kinetics was then applied. We found the initial rate of NEFA utilization by tissues (NU) was less, but the threshold glucose (tG) and glucose concentration required for a unit change in lipolysis inhibition ( G i ) were greater in metabolic syndrome verses healthy (NU: 0.050[0.045, 0.057] vs. 0.068[0.054, 0.086] p=0.03; tG: 6.7[6.2, 7.2] vs. 5.0[4.3, 5.9] p=0.001; G i : 0.30[0.25, 0.35] vs. 0.17[0.07, 0.27] p=0.02). No differences were found in initial rate of NEFA production or glucose utilization. Conclusion: Our results indicate that suppression of lipid-droplet lipolysis requires greater stimulus in metabolic syndrome compared to insulin sensitive adipocytes. Further, the rate of NEFA removal is less in metabolic syndrome. These results reveal components of insulin sensitivity not demonstrated by the glucose model. The NEFA model provides a measurement of adipocyte insulin sensitivity not captured by glycemic indices.

Differential DNA Methylation and Cardiometabolic Risk in African American Mother-Adolescent Dyads

2021 ◽  
pp. 109980042110390
Author(s):  
Amanda Elswick Gentry ◽  
Jo Robins ◽  
Mat Makowski ◽  
Wendy Kliewer
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
African American ◽  
African Americans ◽  
Waist Circumference ◽  
Low Income ◽  
Cardiometabolic Risk ◽  
Disease Risk ◽  
Cardiovascular Disease Risk

Background: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations. Materials and Methods: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance. Results: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents. Conclusion: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads.

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