Preliminary experience with a new stable isotope breath test for chylomicron remnant metabolism: a study in central obesity

2001 ◽  
Vol 101 (6) ◽  
pp. 683-690 ◽  
Author(s):  
G.F. WATTS ◽  
D.C.F. CHAN ◽  
P.H.R. BARRETT ◽  
I.J. MARTINS ◽  
T.G. REDGRAVE

We aimed to investigate the metabolism of chylomicron remnants in the postabsorptive state employing a new stable isotope breath test in centrally obese men without overt hyperlipidaemia. Groups of 12 centrally obese and 12 non-obese men of similar age and with similar plasma cholesterol and triacylglycerol (triglyceride) levels were studied. The catabolism of chylomicron remnants was measured using an intravenous injection of a remnant-like emulsion containing cholesteryl [13C]oleate. Isotopic enrichment of 13CO2 in breath was determined using isotope-ratio mass spectrometry, and a multi-compartmental model (SAAM II program) was used to estimate the fractional catabolic rate (FCR) of the chylomicron remnant-like particles. The plasma concentrations of low-density lipoprotein (LDL)-cholesterol, non-high-density lipoprotein (HDL)-cholesterol and insulin were significantly higher (P < 0.05) in the obese than the control subjects. The obese subjects had significantly lower HDL-cholesterol (P < 0.05) and, in particular, a decreased FCR of the remnant-like particles compared with lean subjects (0.061±0.014 and 0.201±0.048pools/h respectively; P = 0.016). In the obese group, the FCR of remnant-like particles was inversely associated with the waist/hip ratio, and with plasma triacylglycerol, cholesterol, LDL-cholesterol and non-HDL-cholesterol levels. In multiple regression analysis, the waist/hip ratio was the best predictor of the FCR of the emulsion. In conclusion, this new test suggests that postabsorptive chylomicron remnant catabolism is impaired in centrally obese subjects without overt hyperlipidaemia. This defect may be due to the degree of adiposity.

2000 ◽  
Vol 151 (1) ◽  
pp. 95-96 ◽  
Author(s):  
G.F. Watts ◽  
P.H.R. Barrett ◽  
D. Chan ◽  
B. Stuckey ◽  
I. Martins ◽  
...  

2018 ◽  
Vol 9 (4) ◽  
pp. 143
Author(s):  
Adediji Isaac Oluwole ◽  
Ayodele Ademola Adelakun ◽  
Afolabi Joy Oluwaseyifunmi ◽  
Akinleye Waheed A ◽  
Taiwo Timilehin Darasimi

Background: Type II DM and obesity are metabolic disorders characterized by insulin resistance, dyslipidaemia, and metabolic stress. These features were assessed in patients using fasting plasma glucose, fasting lipid profile and serum cortisol as their markers.Materials and methods: Ninety participants were recruited and classified into 3 groups of thirty each – Obese with type II DM, Non-obese with type II DM, non-obese and non-diabetics who served as controls. Anthropometric measures of weight and height were taken using standard procedures and body mass index was calculated thereafter. Blood samples were collected after an overnight fast for the in vitro assay of serum cortisol, plasma glucose, triglycerides, total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol using enzyme linked immunosorbent assay and colorimetry as appropriate. Data obtained were analyzed statistically using ANOVA and post hoc test for comparison of variables between groups. Pearson’s correlation was performed to assess the relationship between variables and p<0.05 was considered significant.Results: Serum cortisol, plasma glucose, total cholesterol, triglycerides and LDL-cholesterol were elevated while HDL-cholesterol was reduced in both obese and non-obese subjects with type II diabetes mellitus when compared with controls. Cortisol had a significant positive association with plasma glucose, total cholesterol, triglycerides and LDL-cholesterol in obese subjects with type II diabetes mellitus while cortisol had a significant inverse relationship with HDL-cholesterol in both obese and non-obese subjects with type II diabetes mellitus.Conclusion: From this study, we conclude that elevated serum cortisol, a consequence of type II DM, accompanies dyslipidaemia in both obese and non-obese type II DM patients. It could therefore be inferred that ‘diabetic stress’ is the underlying factor of elevated cortisol in this group.


2000 ◽  
Vol 151 (1) ◽  
pp. 137
Author(s):  
D. Chan ◽  
G.F. Watts ◽  
P.H.R. Barrett ◽  
T. James ◽  
J. Mamo ◽  
...  

1994 ◽  
Vol 40 (12) ◽  
pp. 2240-2246 ◽  
Author(s):  
G F Watts ◽  
S Mandalia ◽  
B M Slavin ◽  
J N Brunt ◽  
D J Coltart ◽  
...  

Abstract We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a).


1986 ◽  
Vol 55 (02) ◽  
pp. 173-177 ◽  
Author(s):  
K Desai ◽  
J S Owen ◽  
D T Wilson ◽  
R A Hutton

SummaryPlatelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol: HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.


Author(s):  
В.В. Шерстнев ◽  
М.А. Грудень ◽  
В.П. Карлина ◽  
В.М. Рыжов ◽  
А.В. Кузнецова ◽  
...  

Цель - исследование взаимосвязи факторов риска сердечно-сосудистых заболеваний и развития предгипертонии. Методика. Проведен сравнительный и корреляционный анализы показателей модифицируемых и немодифицируемых факторов риска сердечно-сосудистых заболеваний у обследованных лиц в возрасте 30-60 лет с «оптимальным» артериальным давлением, (n = 63, АД <120/80 мм рт.ст.) и лиц с предгипертонией (n = 52, АД = 120-139/80-89 мм рт.ст.). Результаты. Показано, что лица с предгипертонией по сравнению с группой лиц, имеющих «оптимальное» артериальное давление характеризуются статистически значимо повышенным содержанием холестерина и холестерина липопротеидов низкой плотности, интеллектуальным характером трудовой деятельности, а также значимыми сочетаниями факторов риска: повышенный уровень холестерина липопротеидов низкой плотности с интеллектуальным характером трудовой деятельности; повышенное содержание креатинина с уровнем триглициридов; наследственная отягощенность по заболеваниям почек и интеллектуальным характером трудовой деятельности; наследственная отягощенность по сахарному диабету и гипертрофия левого желудочка сердца. У лиц с предгипертонией документированы перестройки структуры взаимосвязи (количество, направленность и сила корреляций) между показателями факторов риска в сравнении с лицами, имеющими «оптимальное» артериальное давление. Заключение. Выявленные особенности взаимосвязей факторов риска сердечно-сосудистых заболеваний при предгипертонии рассматриваются как проявление начальной стадии дизрегуляционной патологии и нарушения регуляции физиологических систем поддержания оптимального уровня артериального давления. The aim of the study was to investigate the relationship between risk factors for cardiovascular disease and development of prehypertension. Methods. Comparative and correlation analyses of modifiable and non-modifiable risk factors for cardiovascular disease were performed in subjects aged 30-60 with «optimal» blood pressure (n = 63, BP <120/80 mm Hg) and prehypertension (n = 52, BP = 120-139 / 80-89 mm Hg). Results. The group with prehypertension compared with the «optimal» blood pressure group had significantly increased serum levels of low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, sedentary/intellectual type of occupation, and significant combinations of risk factors. The risk factor combinations included an increased level of LDL cholesterol and a sedentary/intellectual occupation; increased serum levels of creatinine and triglycerides; hereditary burden of kidney disease and a sedentary/intellectual occupation; hereditary burden of diabetes mellitus and cardiac left ventricular hypotrophy. In subjects with prehypertension compared to subjects with «optimal» blood pressure, changes in correlations (correlation number, direction, and strength) between parameters of risk factors were documented. Conclusion. The features of interrelationships between risk factors for cardiovascular disease observed in prehypertension are considered a manifestation of early dysregulation pathology and disordered regulation of physiological systems, which maintain optimal blood pressure.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Oguri ◽  
K Kato ◽  
H Horibe ◽  
T Fujimaki ◽  
J Sakuma ◽  
...  

Abstract Background The circulating concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, and low density lipoprotein (LDL)-cholesterol have a substantial genetic component. Although previous genome-wide association studies identified various genes and loci related to plasma lipid levels, those studies were conducted in a cross-sectional manner. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to hypertriglyceridemia, hypo-HDL-cholesterolemia, and hyper-LDL-cholesterolemia in Japanese. We have now performed longitudinal exome-wide association studies (EWASs) to identify novel loci for dyslipidemia by examining temporal changes in serum lipid profiles. Methods Longitudinal EWASs (mean follow-up period, 5 years) for hypertriglyceridemia (2056 case, 3966 controls), hypo-HDL-cholesterolemia (698 cases, 5324 controls), and hyper-LDL-cholesterolemia (2769 cases, 3251 controls) were performed with Illumina Human Exome arrays. The relation of genotypes of 24,691 single nucleotide polymorphisms (SNPs) that passed quality control to dyslipidemia-related traits was examined with the generalized estimating equation (GEE). To compensate for multiple comparisons of genotypes with each of the three conditions, we applied Bonferroni's correction for statistical significance of association. Replication studies with cross-sectional data were performed for hypertriglyceridemia (2685 cases, 4703 controls), hypo-HDL-cholesterolemia (1947 cases, 6146 controls), and hyper-LDL-cholesterolemia (1719 cases, 5833 controls). Results Longitudinal EWASs revealed that 30 SNPs were significantly (P&lt;2.03 × 10–6 by GEE) associated with hypertriglyceridemia, 46 SNPs with hypo-HDL-cholesterolemia, and 25 SNPs with hyper-LDL-cholesterolemia. After examination of the relation of identified SNPs to serum lipid profiles, linkage disequilibrium, and results of the previous genome-wide association studies, we newly identified rs74416240 of TCHP, rs925368 of GIT2, rs7969300 of ATXN2, and rs12231744 of NAA25 as a susceptibility loci for hypo-HDL-cholesterolemia; and rs34902660 of SLC17A3 and rs1042127 of CDSN for hyper-LDL-cholesterolemia. These SNPs were not in linkage disequilibrium with those previously reported to be associated with dyslipidemia, indicating independent effects of the SNPs identified in the present study on serum concentrations of HDL-cholesterol or LDL-cholesterol in Japanese. According to allele frequency data from the 1000 Genomes project database, five of the six identified SNPs were monomorphic or rare variants in European populations. In the replication study, all six SNPs were associated with dyslipidemia-related phenotypes. Conclusion We have thus identified six novel loci that confer susceptibility to hypo-HDL-cholesterolemia or hyper-LDL-cholesterolemia. Determination of genotypes for these SNPs at these loci may prove informative for assessment of the genetic risk for dyslipidemia in Japanese. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuang Li ◽  
Jingxun Chen ◽  
Siyue Wei ◽  
Mei Zhang ◽  
Yushun Chu ◽  
...  

Abstract Background The optimum lipid indexes, predicting the coronary lesion in postmenopausal women are not clear. Objective To evaluate the optimum lipid predicter for coronary lesion in routine and advanced lipid tests. Method 300 postmenopausal women were enrolled and assigned into coronary heart disease (CHD) Group (242), and non-CHD Group (58). Routine and advanced lipid indexes were measured with standard laboratory test and nuclear magnetic resonance (NMR) spectroscopy. The correlation and predictivities for CHD of routine and advanced lipid indexes were performed with Logistic regression, Spearman correlation analysis and receiver operating characteristic (ROC). Results Age (hazard ratio (HR) 2.58, 95% confidence interval (CI) 1.08–5.86, P = 0.03), apolipoprotein B (ApoB) (HR 1.35, 95% CI 1.15–1.59, P < 0.001), corrected particles of low-density lipoprotein (LDL-p-corr) (HR 1.05, 95% CI 1.03–1.06, P < 0.001) and corrected particles of non-high-density lipoprotein (non-HDL-p-corr) (HR 1.02, 95% CI 1.01–1.03, P < 0.001) were the risk factors of CHD. LDL cholesterol (LDL-C), LDL-p, LDL-p-corr, HDL cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C), non-HDL-p and non-HDL-p-corr were in linear correlation with Gensini score. Advanced lipid indexes LDL-p (area under curve (AUC) = 0.750, P = 0.02), LDL-p-corr (AUC = 0.759, P = 0.02), non-HDL-p (AUC = 0.693, P = 0.03) and non-HDL-p-corr (AUC = 0.699, P = 0.03) were more predictive for CHD than the routine ones (LDL-C and non-HDL-C). Conclusion In postmenopausal women, age, ApoB, LDL-p-corr and non-HDL-p-corr were risk factors of CHD. Compared with traditional lipid items, LDL-p, LDL-p-corr, non-HDL-p and non-HDL-p-corr may be better lipid indexes for CHD in postmenopausal women.


Author(s):  
Masato Karayama ◽  
Naoki Inui ◽  
Yusuke Inoue ◽  
Katsuhiro Yoshimura ◽  
Kazutaka Mori ◽  
...  

Abstract Background Lipids have immunomodulatory functions and the potential to affect cancer immunity. Methods The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. Results When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. Conclusions Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.


2011 ◽  
Vol 59 (4) ◽  
pp. 445-454 ◽  
Author(s):  
Ewa Skotnicka ◽  
Zbigniew Muszczyński ◽  
Maria Suska

Blood samples were taken from 12 goats during the periparturient period (4 and 1 weeks before and 2, 10 and 30 days after delivery), and from 10 nonpregnant goats. The following variables were determined: total lipids (TL), triacylglycerol (TG), total cholesterol (TCH) and high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol fractions. One week before delivery TL (2.32 ± 0.12 g/l, P ≤ 0.05), TG (0.32 ± 0.16 mmol/l, P ≤ 0.001) and TCH concentrations (1.65 ± 0.42 mmol/l, P ≤ 0.05) were significantly increased as compared to non-pregnant goats (2.08 ± 0.28 g/l, 0.15 ± 0.05 mmol/l, 1.38 ± 0.19 mmol/l, respectively). After delivery, the concentrations of TL, TG, TCH and HDL decreased significantly. The lowest TG concentration was observed 2 days after delivery (0.18 ± 0.02 mmol/l), while TL (1.73 ± 0.21 g/l), TCH (0.95 ± 0.21 mmol/l) and HDL (0.74 ± 0.16 mmol/l) reached the lowest level 10 days after delivery. Two days after delivery a significant increase of LDL concentration was observed (0.38 ± 0.04 mmol/l); however, ten days after delivery a threefold decrease was shown in the LDL concentration (0.12 ± 0.04 mmol/l). A month after delivery all the variables studied reached levels similar to those measured in non-pregnant goats.


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