Apolipoprotein B-48

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Gerald F. Watts - One of the best experts on this subject based on the ideXlab platform.

  • Effect of niacin on triglyceride-rich lipoprotein Apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.
    Diabetes obesity & metabolism, 2016
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Vijay S. Tenneti, Sandra J. Hamilton, P.h.r. Barrett
    Abstract:

    Aim To investigate the effects of extended-release (ER) niacin on Apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). Methods A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. Results In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). Conclusions ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

  • Abstract 10: Improving Postprandial Lipoprotein Apolipoprotein B-48 Metabolism in Statin-Treated Patients With Diabetes
    Arteriosclerosis Thrombosis and Vascular Biology, 2014
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Sandy Hamilton, Vijay S. Tenneti, Hugh Barrett
    Abstract:

    Background: Type 2 diabetics often have elevated plasma TG and Apolipoprotein B-48 (apoB-48) concentrations, particularly during the postprandial (PP) period. Evidence suggests that apoB-48 plays a central role in the development of atherosclerosis. Statins are frontline therapy to reduce CVD risk, however, residual risk still remains, suggesting that additional interventions are required to further reduce CVD risk. Aim: To compare PP apoB-48 kinetics in optimally statin-treated diabetic men with a group of normolipidemic healthy controls, and to investigate the effect of niacin on apoB-48 kinetics in these diabetic men. Methods: Twelve type 2 diabetic men and fourteen age-matched non-diabetic controls were recruited. Diabetics required a statin-treated LDL-C < 2.5 mmol/L to enter the trial: they were randomized to rosuvastatin or rosuvastatin plus niacin (titrated from 1 to 2 g daily) for 12 weeks and then crossed to the alternate therapy (3 week washout). PP metabolic studies were performed at the end of each treatment period, and on a single occasion in control subjects. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. Blood samples were collected over 24 h. ApoB-48 tracer/tracee ratios were measured using GCMS. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a compartmental model. Results: Fasting plasma TG (+112%, p

  • abstract p270 niacin lowers triglyceride rich lipoprotein Apolipoprotein b 48 secretion in statin treated type 2 diabetics
    Circulation, 2014
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Sandy Hamilton, Vijay S. Tenneti, Hugh Barrett
    Abstract:

    Background: Type 2 diabetic subjects often have hypertriglyceridemia and an increased concentration of Apolipoprotein B-48 (apoB-48) in circulation, particularly during the postprandial period. There is an accumulating body of evidence to suggest that apoB-48 plays a central role in the development of atherosclerosis. Statins are the frontline therapy to reduce cardiovascular risk, however, a large residual risk still remains. This residual risk suggests that additional therapeutic interventions may be required to further reduce CVD risk. Aim: To investigate the effect of niacin on the metabolism of triglyceride-rich lipoprotein (TRL) apoB-48 in men with type 2 diabetes on background statin therapy. Methods: Twelve type 2 diabetic men were recruited for this randomized, cross-over design study. Patients required a statin-treated low density lipoprotein (LDL) cholesterol of less than 2.5 mmol/L to enter the trial. Patients were then randomized to rosuvastatin alone or rosuvastatin plus niacin (titrated up from 1 to 2 g daily) for a period of 12 weeks and then were crossed over to the alternate therapy with a 3 week washout period in between. Metabolic studies were performed at the end of each treatment period. A bolus intravenous infusion of D3-leucine was administered as subjects consumed a standardised high-fat liquid meal. Blood samples were collected over 24 hours and TRL apoB-48 tracer/tracee ratios were measured using gas chromatography-mass spectrometry. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a multicompartmental model. Results: Niacin significantly reduced triglyceride, plasma cholesterol, LDL cholesterol and apoB (all p Conclusion: Niacin reduces TRL apoB-48 concentration by lowering basal and postprandial apoB-48 PR. This effect on apoB-48 metabolism may be beneficial for reducing atherogenic postprandial TRL particles and may provide CVD risk benefit to patients with type 2 diabetes.

  • plasma Apolipoprotein b 48 transport in obese men a new tracer kinetic study in the postprandial state
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Annette T Y Wong, Gerald F. Watts, Jing Pang, Dick C. Chan, Hugh P R Barrett
    Abstract:

    Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare Apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0–10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148%) and apoB-48 (+110%) concentrations as well as plasma total and incremental triglycerides (+184% and +185%, respectively) and apoB-48 (+182% and 224%, respectively) areas under the curve w...

  • Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment.
    Atherosclerosis, 2012
    Co-Authors: Dick C. Chan, Shizuya Yamashita, Annette T Y Wong, Gerald F. Watts
    Abstract:

    Abstract Objective Elevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment. Methods Plasma Apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique. Results In univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD ( r =−0.425 and −0.423, respectively, P P r =−0.644, P Conclusions Our findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.

Dick C. Chan - One of the best experts on this subject based on the ideXlab platform.

  • Effect of niacin on triglyceride-rich lipoprotein Apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.
    Diabetes obesity & metabolism, 2016
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Vijay S. Tenneti, Sandra J. Hamilton, P.h.r. Barrett
    Abstract:

    Aim To investigate the effects of extended-release (ER) niacin on Apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). Methods A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. Results In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). Conclusions ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

  • Abstract 10: Improving Postprandial Lipoprotein Apolipoprotein B-48 Metabolism in Statin-Treated Patients With Diabetes
    Arteriosclerosis Thrombosis and Vascular Biology, 2014
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Sandy Hamilton, Vijay S. Tenneti, Hugh Barrett
    Abstract:

    Background: Type 2 diabetics often have elevated plasma TG and Apolipoprotein B-48 (apoB-48) concentrations, particularly during the postprandial (PP) period. Evidence suggests that apoB-48 plays a central role in the development of atherosclerosis. Statins are frontline therapy to reduce CVD risk, however, residual risk still remains, suggesting that additional interventions are required to further reduce CVD risk. Aim: To compare PP apoB-48 kinetics in optimally statin-treated diabetic men with a group of normolipidemic healthy controls, and to investigate the effect of niacin on apoB-48 kinetics in these diabetic men. Methods: Twelve type 2 diabetic men and fourteen age-matched non-diabetic controls were recruited. Diabetics required a statin-treated LDL-C < 2.5 mmol/L to enter the trial: they were randomized to rosuvastatin or rosuvastatin plus niacin (titrated from 1 to 2 g daily) for 12 weeks and then crossed to the alternate therapy (3 week washout). PP metabolic studies were performed at the end of each treatment period, and on a single occasion in control subjects. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. Blood samples were collected over 24 h. ApoB-48 tracer/tracee ratios were measured using GCMS. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a compartmental model. Results: Fasting plasma TG (+112%, p

  • abstract p270 niacin lowers triglyceride rich lipoprotein Apolipoprotein b 48 secretion in statin treated type 2 diabetics
    Circulation, 2014
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Sandy Hamilton, Vijay S. Tenneti, Hugh Barrett
    Abstract:

    Background: Type 2 diabetic subjects often have hypertriglyceridemia and an increased concentration of Apolipoprotein B-48 (apoB-48) in circulation, particularly during the postprandial period. There is an accumulating body of evidence to suggest that apoB-48 plays a central role in the development of atherosclerosis. Statins are the frontline therapy to reduce cardiovascular risk, however, a large residual risk still remains. This residual risk suggests that additional therapeutic interventions may be required to further reduce CVD risk. Aim: To investigate the effect of niacin on the metabolism of triglyceride-rich lipoprotein (TRL) apoB-48 in men with type 2 diabetes on background statin therapy. Methods: Twelve type 2 diabetic men were recruited for this randomized, cross-over design study. Patients required a statin-treated low density lipoprotein (LDL) cholesterol of less than 2.5 mmol/L to enter the trial. Patients were then randomized to rosuvastatin alone or rosuvastatin plus niacin (titrated up from 1 to 2 g daily) for a period of 12 weeks and then were crossed over to the alternate therapy with a 3 week washout period in between. Metabolic studies were performed at the end of each treatment period. A bolus intravenous infusion of D3-leucine was administered as subjects consumed a standardised high-fat liquid meal. Blood samples were collected over 24 hours and TRL apoB-48 tracer/tracee ratios were measured using gas chromatography-mass spectrometry. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a multicompartmental model. Results: Niacin significantly reduced triglyceride, plasma cholesterol, LDL cholesterol and apoB (all p Conclusion: Niacin reduces TRL apoB-48 concentration by lowering basal and postprandial apoB-48 PR. This effect on apoB-48 metabolism may be beneficial for reducing atherogenic postprandial TRL particles and may provide CVD risk benefit to patients with type 2 diabetes.

  • plasma Apolipoprotein b 48 transport in obese men a new tracer kinetic study in the postprandial state
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Annette T Y Wong, Gerald F. Watts, Jing Pang, Dick C. Chan, Hugh P R Barrett
    Abstract:

    Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare Apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0–10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148%) and apoB-48 (+110%) concentrations as well as plasma total and incremental triglycerides (+184% and +185%, respectively) and apoB-48 (+182% and 224%, respectively) areas under the curve w...

  • Apolipoprotein B-48 as a determinant of endothelial function in obese subjects with type 2 diabetes mellitus: effect of fenofibrate treatment.
    Atherosclerosis, 2012
    Co-Authors: Dick C. Chan, Shizuya Yamashita, Annette T Y Wong, Gerald F. Watts
    Abstract:

    Abstract Objective Elevated triglyceride-rich lipoproteins may contribute to endothelial dysfunction in obese diabetic subjects. We investigated the association between plasma concentrations of chylomicron-related particles and endothelial function, and the corresponding responses to fenofibrate treatment. Methods Plasma Apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol concentrations were measured in 28 obese subjects with T2DM. Flow-mediated endothelium-dependent dilation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) in the brachial artery during reactive hyperaemia were examined by high-resolution ultrasound technique. Results In univariate analysis, plasma apoB-48 and RLP-cholesterol concentrations were inversely associated with brachial artery FMD ( r =−0.425 and −0.423, respectively, P P r =−0.644, P Conclusions Our findings demonstrate an association between changes in lipid metabolism and improvement in endothelial function in patients with diabetic dyslipidaemia treated with fenofibrate that may involve the effect of apoB-48 on endothelium-dependent vasodilator function.

Daisaku Masuda - One of the best experts on this subject based on the ideXlab platform.

  • abstract 14993 proteomic analysis of chylomicron remnants isolated by Apolipoprotein b 48 immunoprecipitation
    Circulation, 2014
    Co-Authors: Daisaku Masuda, Manabu Okubo, Tohru Ohama, Ryota Kawase, Hajime Nakaoka, Kazuhiro Nakatani, Takuya Kobayashi, Takeshi Okada, Masahiro Koseki, Hiroyuki Hanada
    Abstract:

    Introduction: Postprandial hypertriglyceridemia is caused by overproduction or impaired clearance of Apolipoprotein (apo)B-48-containing lipoproteins, chylomicrons (CMs) and CM remnants (CM-Rs). In vitro studies have suggested that CM-Rs may lead to the formation of atherosclerotic plaques. By our ELISA and CLEIA for measuring human serum apoB-48 concentrations, we reported fasting apoB-48 concentrations are significantly higher in patients with dyslipidemia, diabetes mellitus, metabolic syndrome and chronic kidney disease than in normal subjects, and correlated with the IMT of carotid arteries and the prevalence of coronary heart disease. However, it has been technically very difficult to isolate CM-Rs and to evaluate the atherogenicity of pure CM-Rs. Hypothesis: We tried to selectively isolate CM-Rs and analyze their lipoprotein and proteomics profiles and assessed their atherogenicity. Methods: Fractions containing CM-Rs and VLDL (d<1.01 mg/dL) were isolated from the postprandial sera of healthy volunteers by two-step ultracentrifugation. CM-Rs were selectively eluted and isolated by immunoprecipitation using anti-human apoB-48 monoclonal antibodies conjugated with magnetic beads. Mouse peritoneal macrophages were incubated with isolated CM-Rs and stained with Oil-red O. Lipoprotein profiles of isolated human CM-Rs and mouse CMs collected from the intestinal lymph were examined by high performance liquid chromatography and proteomic analyses were performed by mass spectrometry using Synapt G2 HDMS PRO. Results: Compared with the lipoprotein profile of postprandial serum, particle size of isolated lipoproteins varied in size from small chylomicrons to large LDL, which suggested CM-Rs. When incubated with isolated CM-Rs, foam cell formation of mouse peritoneal macrophages was observed. By proteomic analysis, isolated human CM-Rs and mouse CMs contained a variety of complements (C3, C4 and more), Apolipoproteins (apoB, apoA2, apoD and apoH), paraoxonase 1 (PON-1) and many serine protease inhibitors. Conclusions: The current study has demonstrated for the first time that human CM-Rs and CMs have an atherogenic nature and contain many types of complements, Apolipoproteins, PON-1 and serine protease inhibitors.

  • Abstract 14993: Proteomic Analysis of Chylomicron Remnants Isolated by Apolipoprotein B-48 Immunoprecipitation
    Circulation, 2014
    Co-Authors: Daisaku Masuda, Manabu Okubo, Tohru Ohama, Ryota Kawase, Hajime Nakaoka, Kazuhiro Nakatani, Takuya Kobayashi, Takeshi Okada, Masahiro Koseki, Hiroyuki Hanada
    Abstract:

    Introduction: Postprandial hypertriglyceridemia is caused by overproduction or impaired clearance of Apolipoprotein (apo)B-48-containing lipoproteins, chylomicrons (CMs) and CM remnants (CM-Rs). In vitro studies have suggested that CM-Rs may lead to the formation of atherosclerotic plaques. By our ELISA and CLEIA for measuring human serum apoB-48 concentrations, we reported fasting apoB-48 concentrations are significantly higher in patients with dyslipidemia, diabetes mellitus, metabolic syndrome and chronic kidney disease than in normal subjects, and correlated with the IMT of carotid arteries and the prevalence of coronary heart disease. However, it has been technically very difficult to isolate CM-Rs and to evaluate the atherogenicity of pure CM-Rs. Hypothesis: We tried to selectively isolate CM-Rs and analyze their lipoprotein and proteomics profiles and assessed their atherogenicity. Methods: Fractions containing CM-Rs and VLDL (d

  • Abstract 13452: Serum Apolipoprotein B-48 levels Are Significantly Correlated with Plaque Score of Carotid Arteries
    Circulation, 2014
    Co-Authors: Daisaku Masuda, Manabu Okubo, Hiroyuki Hanada, Yoh Hidaka, Yasushi Sakata, Masahiro Matsui, Shizuya Yamashita
    Abstract:

    Introduction: Fasting hypertriglyceridemia is a “residual risk” factor for atherosclerotic cardiovascular diseases and related to postprandial hypertriglyceridemia (PHTG). Intestine-derived lipoproteins such as chylomicrons and chylomicron remnants (CM-Rs), which contain one Apolipoprotein(apo) B-48 molecule per one particle, are accumulated in patients with PHTG. Basic studies showed that CM-R had an atherogenic nature and apoB-48 molecule was observed in atherosclerotic plaque twice as many as apoB-100 molecule histologically. We established a CLEIA for measuring serum apoB-48 concentrations and reported that high apoB-48 concentrations correlated with the prevalence of dyslipidemia, diabetes mellitus, metabolic syndrome, chronic kidney disease and coronary heart disease. Hypothesis: We investigated whether serum apoB-48 concentration correlated with subclinical carotid atherosclerosis. Methods: A total of 163 subjects who received ultrasonography of carotid arteries in Osaka University were enrolled. B...

  • Serum Apolipoprotein B-48 concentration is associated with a reduced estimated glomerular filtration rate and increased proteinuria.
    Journal of atherosclerosis and thrombosis, 2014
    Co-Authors: Manabu Okubo, Hiroyuki Hanada, Masahiko Matsui, Yoh Hidaka, Daisaku Masuda, Yasushi Sakata, Shizuya Yamashita
    Abstract:

    Aim Apolipoprotein B-48 (apoB-48) is a constituent of chylomicrons and their remnants (chylomicron remnants). A high concentration of serum apoB-48 is suspected to be a major risk factor for the development of atherosclerotic cardiovascular disease. Proteinuria and a reduced estimated glomerular filtration rate (eGFR) are independent risk factors for cardiovascular events and renal dysfunction. In the present study, we examined whether the serum apoB-48 concentration is associated with renal dysfunction. Methods A total of 264 patients was enrolled and classified into four groups according to the eGFR and level of proteinuria: a high eGFR (>60mL/min/1.73m(2)) without proteinuria (≥1+ by urine dipstick) (n=50); a high eGFR with proteinuria (n=75); a low eGFR (>60mL/min/1.73m(2)) without proteinuria (n=74); and a low eGFR with proteinuria (n=65). Biochemical markers of lipid metabolism, including the fasting serum apoB-48 concentration, were compared between the four groups. Results The serum log-apoB-48 and log-apoB-48/TG levels were significantly higher in the patients with a high eGFR with proteinuria, low eGFR with proteinuria and low eGFR without proteinuria than in those with a high eGFR without proteinuria, with the most significant differences for these parameters. The eGFR was found to be significantly correlated with the log-apoB-48 and log-apoB-48/TG levels, whereas urinary protein was found to be significantly correlated with the log-apoB-48 level only. A multiple regression analysis indicated that the log-apoB-48/TG level was a significant determinant of a reduced eGFR. Conclusions Both a low eGFR (<60) and proteinuria (≥1+) are independent determinants of a high apoB-48 concentration. Taken together, the present results suggest that an increased serum apoB-48 concentration contributes to an increased risk of cardiovascular events.

  • Reference interval for the Apolipoprotein B-48 concentration in healthy Japanese individuals.
    Journal of atherosclerosis and thrombosis, 2014
    Co-Authors: Daisaku Masuda, Hiroyuki Hanada, Makoto Nishida, Toshihiko Arai, Hiroshi Yoshida, Keiko Yamauchi-takihara, Toshiki Moriyama, Norio Tada, Shizuya Yamashita
    Abstract:

    AIM Small intestine-derived chylomicrons and chylomicron remnants, which are predominant in patients with postprandial hypertriglyceridemia, chylomicron syndrome and/or familial dyslipidemia, carry one molecule of Apolipoprotein B-48(apo B-48) per lipoprotein particle. We investigated the reference interval for the apo B-48 concentration. METHODS We studied 516 individuals who provided written informed consent and confirmed that they were not taking any medications. BMI, waist circumference, blood pressure and the fasting serum concentrations of LDL-C, triglyceride(TG), HDL-C and apo B-48 were measured. The Apo B-48 concentrations were compared according to sex, a pre- or postmenopausal status, dyslipidemia(LDL-C ≥140 mg/dL, TG ≥150 mg/dL, HDL-C <40 mg/dL), metabolic syndrome(MetS) and the number of risk factors. RESULTS The fasting apo B-48 concentrations(mean±SD) were significantly higher in men than in women(3.8±3.3 μg/mL vs 2.4±1.9 μg/mL, p<0.001), subjects with a BMI of ≥25 kg/m(2) versus a BMI of <25 kg/m(2) (4.4±3.7 μg/mL vs 2.8±2.4 μg/mL, p<0.001) and those with versus without MetS(6.5±4.3 μg/mL vs 3.0±2.6 μg/mL, p<0.001). High apo B-48 concentrations were also observed in correlation with the number of risk factors for the MetS. The upper reference limit of apo B-48 was estimated to be 5.7 μg/mL among the 332 patients with normolipidemia, excluding those exhibiting a mean value above ±2.58 standard deviations(SDs), as the mean and range of mean ±1.96 SD were calculated to be 2.04 μg/mL(reference value) and 0.74 to 5.65 μg/mL(reference interval), respectively. CONCLUSIONS Based on our study of normolipidemic patients, the upper reference limit for the fasting apo B-48 concentration is estimated to be 5.7 μg/mL.

Jing Pang - One of the best experts on this subject based on the ideXlab platform.

  • Effect of niacin on triglyceride-rich lipoprotein Apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.
    Diabetes obesity & metabolism, 2016
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Vijay S. Tenneti, Sandra J. Hamilton, P.h.r. Barrett
    Abstract:

    Aim To investigate the effects of extended-release (ER) niacin on Apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). Methods A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. Results In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). Conclusions ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

  • Abstract 10: Improving Postprandial Lipoprotein Apolipoprotein B-48 Metabolism in Statin-Treated Patients With Diabetes
    Arteriosclerosis Thrombosis and Vascular Biology, 2014
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Sandy Hamilton, Vijay S. Tenneti, Hugh Barrett
    Abstract:

    Background: Type 2 diabetics often have elevated plasma TG and Apolipoprotein B-48 (apoB-48) concentrations, particularly during the postprandial (PP) period. Evidence suggests that apoB-48 plays a central role in the development of atherosclerosis. Statins are frontline therapy to reduce CVD risk, however, residual risk still remains, suggesting that additional interventions are required to further reduce CVD risk. Aim: To compare PP apoB-48 kinetics in optimally statin-treated diabetic men with a group of normolipidemic healthy controls, and to investigate the effect of niacin on apoB-48 kinetics in these diabetic men. Methods: Twelve type 2 diabetic men and fourteen age-matched non-diabetic controls were recruited. Diabetics required a statin-treated LDL-C < 2.5 mmol/L to enter the trial: they were randomized to rosuvastatin or rosuvastatin plus niacin (titrated from 1 to 2 g daily) for 12 weeks and then crossed to the alternate therapy (3 week washout). PP metabolic studies were performed at the end of each treatment period, and on a single occasion in control subjects. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. Blood samples were collected over 24 h. ApoB-48 tracer/tracee ratios were measured using GCMS. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a compartmental model. Results: Fasting plasma TG (+112%, p

  • abstract p270 niacin lowers triglyceride rich lipoprotein Apolipoprotein b 48 secretion in statin treated type 2 diabetics
    Circulation, 2014
    Co-Authors: Jing Pang, Gerald F. Watts, Dick C. Chan, Sandy Hamilton, Vijay S. Tenneti, Hugh Barrett
    Abstract:

    Background: Type 2 diabetic subjects often have hypertriglyceridemia and an increased concentration of Apolipoprotein B-48 (apoB-48) in circulation, particularly during the postprandial period. There is an accumulating body of evidence to suggest that apoB-48 plays a central role in the development of atherosclerosis. Statins are the frontline therapy to reduce cardiovascular risk, however, a large residual risk still remains. This residual risk suggests that additional therapeutic interventions may be required to further reduce CVD risk. Aim: To investigate the effect of niacin on the metabolism of triglyceride-rich lipoprotein (TRL) apoB-48 in men with type 2 diabetes on background statin therapy. Methods: Twelve type 2 diabetic men were recruited for this randomized, cross-over design study. Patients required a statin-treated low density lipoprotein (LDL) cholesterol of less than 2.5 mmol/L to enter the trial. Patients were then randomized to rosuvastatin alone or rosuvastatin plus niacin (titrated up from 1 to 2 g daily) for a period of 12 weeks and then were crossed over to the alternate therapy with a 3 week washout period in between. Metabolic studies were performed at the end of each treatment period. A bolus intravenous infusion of D3-leucine was administered as subjects consumed a standardised high-fat liquid meal. Blood samples were collected over 24 hours and TRL apoB-48 tracer/tracee ratios were measured using gas chromatography-mass spectrometry. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a multicompartmental model. Results: Niacin significantly reduced triglyceride, plasma cholesterol, LDL cholesterol and apoB (all p Conclusion: Niacin reduces TRL apoB-48 concentration by lowering basal and postprandial apoB-48 PR. This effect on apoB-48 metabolism may be beneficial for reducing atherogenic postprandial TRL particles and may provide CVD risk benefit to patients with type 2 diabetes.

  • plasma Apolipoprotein b 48 transport in obese men a new tracer kinetic study in the postprandial state
    The Journal of Clinical Endocrinology and Metabolism, 2014
    Co-Authors: Annette T Y Wong, Gerald F. Watts, Jing Pang, Dick C. Chan, Hugh P R Barrett
    Abstract:

    Context: The mechanisms responsible for impaired chylomicron metabolism have not been adequately investigated in obese subjects. Objective: We aimed to compare Apolipoprotein (apo) B-48 kinetics in obese and lean men by developing a new model to describe the kinetics of apoB-48 particles in the postprandial state. Design, Setting, and Patients: Seven obese and 13 age-matched lean men were given an oral fat load. apoB-48 tracer to tracee ratios were measured after intravenous d3-leucine administration using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Outcomes Measures: Plasma total and incremental apoB-48 0–10 hour areas under the curve as well as apoB-48 secretion and fractional catabolic rate. Results: Compared with lean men, fasting plasma triglyceride (+148%) and apoB-48 (+110%) concentrations as well as plasma total and incremental triglycerides (+184% and +185%, respectively) and apoB-48 (+182% and 224%, respectively) areas under the curve w...

G. H. Tomkin - One of the best experts on this subject based on the ideXlab platform.

  • Improved metabolic control reduces the number of postprandial Apolipoprotein B-48-containing particles in type 2 diabetes.
    Atherosclerosis, 2000
    Co-Authors: Catherine M. Phillips, Daphne Owens, P. G. Collins, Alan H. Johnson, G Murugasu, G. H. Tomkin
    Abstract:

    Postprandial lipoproteins are raised in diabetes and there is increasing evidence for the atherogenicity of the chylomicron remnant. Increased postprandial cholesteryl ester transfer has also been demonstrated in diabetes and may contribute to the atherogenic lipoprotein profile. The present study examined the effect of improving metabolic control on postprandial lipoproteins in 13 Type 2 diabetic patients. Blood was taken fasting and at 2-h intervals following a high fat, 1100 kcal meal. Patients were brought into good control by intensified dietary advice and oral hyperglycaemic agents or insulin if blood glucose failed to respond. Fasting and postprandial cholesteryl ester transfer protein (CETP) and lecithin:cholesteryl acyltransferase (LCAT) were determined in six patients. Lipoproteins were isolated by sequential ultracentrifugation. Chylomicron and very low density lipoprotein (VLDL) Apolipoprotein B-48 and Apolipoprotein B-100 were isolated by polyacrylamide gradient gel electrophoresis and quantified by densitometric scanning. CETP and LCAT were determined by an endogenous method which determined cholesterol esterification and transfer between the patients’ lipoproteins. There was a significant reduction in postprandial chylomicron apo B-48 (PB0.005), apo B-100 (PB0.0005) and chylomicron cholesterol (PB 0.001) following improved diabetic control. The chylomicron lipid:apo B ratio increased with improved control (PB 0.01). Postprandial CETP and LCAT were significantly reduced in good control (PB0.01 and PB 0.05, respectively) and there were significant changes in HDL composition. The study shows that improvement in metabolic control in Type 2 diabetic patients leads to a reduction in postprandial chylomicron particles and less transfer of cholesterol to apo B-containing lipoproteins. © 2000 Elsevier Science Ireland Ltd. All rights reserved.

  • Elevated triglyceride-rich lipoproteins in diabetes. A study of Apolipoprotein B-48.
    Acta diabetologica, 1996
    Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. G. Collins, Alan H. Johnson, G. H. Tomkin
    Abstract:

    The role of the intestine in cholesterol metabolism in human diabetes in unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial Apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d

  • Elevated triglyceride-rich lipoproteins in diabetes
    Acta Diabetologica, 1996
    Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. Collins, A. Johnson, G. H. Tomkin
    Abstract:

    The role of the intestine in cholesterol metabolism in human diabetes in unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial Apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation ( d

  • Intestinally derived lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia
    Acta Diabetologica, 1995
    Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. Collins, A. Johnson, G. H. Tomkin
    Abstract:

    We have previously demonstrated alterations in Apolipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride 2.1 mmol 1^−1; HbA_1c 8.8%±0.9%); nondiabetic subjects with serum triglycerides 2.1 mmol l^−1). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation ( d

  • Alterations in Apolipoprotein B-48 in the postprandial state in NIDDM
    Diabetologia, 1994
    Co-Authors: A. Curtin, P. Deegan, Daphne Owens, P. G. Collins, Alan H. Johnson, G. H. Tomkin
    Abstract:

    The intestine is a major site of cholesterol synthesis and produces Apolipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in Apolipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (density