Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

PubMed

Ito, Matthew K

2015-10-01

Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hypertriglyceridemia during long-term interferon-alpha therapy: efficacy of diet and gemfibrosil treatment. A case report.

PubMed

Berruti, A; Gorzegno, G; Vitetta, G; Tampellini, M; Dogliotti, L

1992-10-31

Interferon-alpha might increase triglyceride serum levels through the enhancement of hepatic lipogenesis and/or inhibition of the peripheral lipoprotein lipase. Hypertriglyceridemia during interferon-alpha therapy has been only recently described, mostly in patients with previous abnormalities of lipid metabolism. The authors report here a case of a 65-year-old male bearing advanced colon carcinoma who developed hypertriglyceridemia during long-term interferon-alpha treatment in association with 5 fluorouracil administration. Hypertriglyceridemia was maintained within acceptable levels, without adjusting the treatment plan, by an appropriate diet and gemfibrosil administration.

Indicators of hypertriglyceridemia from anthropometric measures based on data mining.

PubMed

Lee, Bum Ju; Kim, Jong Yeol

2015-02-01

The best indicator for the prediction of hypertriglyceridemia derived from anthropometric measures of body shape remains a matter of debate. The objectives are to determine the strongest predictor of hypertriglyceridemia from anthropometric measures and to investigate whether a combination of measures can improve the prediction accuracy compared with individual measures. A total of 5517 subjects aged 20-90 years participated in this study. The numbers of normal and hypertriglyceridemia subjects were 3022 and 653 females, respectively, and 1306 and 536 males, respectively. We evaluated 33 anthropometric measures for the prediction of hypertriglyceridemia using statistical analysis and data mining. In the 20-90-year-old groups, age in women was the variable that exhibited the highest predictive power; however, this was not the case in men in all age groups. Of the anthropometric measures, the waist-to-height ratio (WHtR) was the best predictor of hypertriglyceridemia in women. In men, the rib-to-forehead circumference ratio (RFcR) was the strongest indicator. The use of a combination of measures provides better predictive power compared with individual measures in both women and men. However, in the subgroups of ages 20-50 and 51-90 years, the strongest indicators for hypertriglyceridemia were rib circumference in the 20-50-year-old group and WHtR in the 51-90-year-old group in women and RFcR in the 20-50-year-old group and BMI in the 51-90-year-old group in men. Our results demonstrated that the best predictor of hypertriglyceridemia may differ according to gender and age. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fruit and vegetable consumption and hypertriglyceridemia: Korean National Health and Nutrition Examination Surveys (KNHANES) 2007-2009.

PubMed

Yuan, C; Lee, H-J; Shin, H J; Stampfer, M J; Cho, E

2015-11-01

Limited research has been conducted on the association between intake of fruits and vegetables and hypertriglyceridemia, especially in Asian populations. This study aimed to investigate the association between total fruit and vegetable intake, as well as subgroups of fruit and vegetable intake, with hypertriglyceridemia among Korean adults. We conducted a cross-sectional study of 7934 adults aged 19-64 years from the fourth Korean Health and Nutrition Examination Survey. Fruit and vegetable intake was estimated from a food frequency questionnaire. Subgroups of fruits and vegetables included citrus, non-citrus and carotene-rich fruits and cruciferous, green leafy and carotene-rich vegetables. Hypertriglyceridemia (plasma triglyceride ⩾150 mg/dl) was diagnosed using a blood sample drawn after 12+ hours of fasting. There were 2001 (25.2%) cases of hypertriglyceridemia among the participants. Total fruit intake was significantly inversely associated with the prevalence of hypertriglyceridemia; the multivariate odds ratios (95% confidence intervals) of hypertriglyceridemia across increasing quintiles were 1.00 (ref), 0.76 (0.62, 0.92), 0.72 (0.58, 0.90), 0.68 (0.54, 0.85) and 0.64 (0.49, 0.82; Ptrend=0.001) after controlling for survey year, body mass index, waist circumference, smoking, alcohol drinking, physical activity, education and income. Similar inverse associations were found for all fruit subgroups. However, we found no significant association between intakes of total or subgroups of vegetable and hypertriglyceridemia; the odds ratio for top vs bottom quintile was 1.00 (0.81-1.24) for total vegetable intake. Our findings support a potential beneficial role of fruit consumption to reduce blood triglyceride levels in Asian populations.

Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice.

PubMed

Liu, Yun-Zi; Cheng, Xiaoyun; Zhang, Ting; Lee, Sojin; Yamauchi, Jun; Xiao, Xiangwei; Gittes, George; Qu, Shen; Jiang, Chun-Lei; Dong, H Henry

2016-07-08

Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of Hypertriglyceridemia on Beta Cell Mass and Function in ApoC3 Transgenic Mice*

PubMed Central

Liu, Yun-Zi; Cheng, Xiaoyun; Zhang, Ting; Lee, Sojin; Yamauchi, Jun; Xiao, Xiangwei; Gittes, George; Qu, Shen; Jiang, Chun-Lei; Dong, H. Henry

2016-01-01

Hypertriglyceridemia results from increased production and decreased clearance of triglyceride-rich very low-density lipoproteins, a pathological condition that accounts for heightened risk of ischemic vascular diseases in obesity and type 2 diabetes. Despite its intimate association with insulin resistance, whether hypertriglyceridemia constitutes an independent risk for beta cell dysfunction in diabetes is unknown. Answering this fundamental question is stymied by the fact that hypertriglyceridemia is intertwined with hyperglycemia and insulin resistance in obese and diabetic subjects. To circumvent this limitation, we took advantage of apolipoprotein C3 (ApoC3)-transgenic mice, a model with genetic predisposition to hypertriglyceridemia. We showed that ApoC3-transgenic mice, as opposed to age/sex-matched wild-type littermates, develop hypertriglyceridemia with concomitant elevations in plasma cholesterol and non-esterified fatty acid levels. Anti-insulin and anti-glucagon dual immunohistochemistry in combination with morphometric analysis revealed that ApoC3-transgenic and wild-type littermates had similar beta cell and alpha cell masses as well as islet size and architecture. These effects correlated with similar amplitudes of glucose-stimulated insulin secretion and similar degrees of postprandial glucose excursion in ApoC3-transgenic versus wild-type littermates. Oil Red O histology did not visualize lipid infiltration into islets, correlating with the lack of ectopic triglyceride and cholesterol depositions in the pancreata of ApoC3-transgenic versus wild-type littermates. ApoC3-transgenic mice, despite persistent hypertriglyceridemia, maintained euglycemia under both fed and fasting conditions without manifestation of insulin resistance and fasting hyperinsulinemia. Thus, hypertriglyceridemia per se is not an independent risk factor for beta cell dysfunction in ApoC3 transgenic mice. PMID:27226540

Role of Insulin in Endogenous Hypertriglyceridemia*

PubMed Central

Reaven, Gerald M.; Lerner, Roger L.; Stern, Michael P.; Farquhar, John W.

1967-01-01

Dietary carbohydrate accentuation of endogenous triglyceride production has been studied in 33 patients. A broad and relatively continuous spectrum of steady-state plasma triglyceride concentrations was produced in 31 of the 33 subjects during 3 wk of a high carbohydrate (fat-free) liquid formula diet. Two patients developed plasma triglyceride concentrations in excess of 2000 mg/100 ml, and these were the only patients we have studied in which carbohydrate induction of hypertriglyceridemia seemed to be associated with a defect in endogenous plasma triglyceride removal mechanisms. In the remaining 31 patients the degree of hypertriglyceridemia was highly correlated with the insulin response elicited by the ingestion of the high carbohydrate formula (P < 0.005). No significant correlation existed between fasting plasma triglyceride concentration and either plasma glucose or free fatty acid concentrations after the high carbohydrate diet, nor was the degree of hypertriglyceridemia related to degree of obesity. It is suggested that hypertriglyceridemia in most subjects results from an increase in hepatic triglyceride secretion rate secondary to exaggerated postprandial increases in plasma insulin concentration. Images PMID:6061748

Hypertriglyceridemia-induced pancreatitis: A case-based review

PubMed Central

Gan, S Ian; Edwards, Alun L; Symonds, Christopher J; Beck, Paul L

2006-01-01

Hypertriglyceridemia is an established cause of pancreatitis. In a case-based approach, we present a review of hypertriglyceridemia and how it can cause pancreatitis. We outline how to investigate and manage such patients. A 35 year old man presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. There was no history of alcohol consumption and biliary imaging was normal. The only relevant past medical history was that of mild hyperlipidemia, treated with diet alone. Physical exam revealed epigastric tenderness, right lateral rectus palsy, lipemia retinalis, bitemporal hemianopsia and a delay in the relaxation phase of his ankle reflexes. Subsequent laboratory investigation revealed marked hypertriglyceridemia and panhypopituarism. An enhanced CT scan of the head revealed a large suprasellar mass impinging on the optic chiasm and hypothalamus. The patient was treated supportively; thyroid replacement and lipid lowering agents were started. He underwent a successful resection of a craniopharyngioma. Post-operatively, the patient did well on hormone replacement therapy. He has had no further attacks of pancreatitis. This case highlights many of the factors involved in the regulation of triglyceride metabolism. We review the common causes of hypertriglyceridemia and the proposed mechanisms resulting in pancreatitis. The incidence and management of hypertriglyceridemia-induced pancreatitis are also discussed. PMID:17131487

Evaluation of hypertriglyceridemia using non-fasting health checkup data in a Japanese population.

PubMed

Takahara, Mitsuyoshi; Katakami, Naoto; Kaneto, Hideaki; Noguchi, Midori; Shimomura, Iichiro

2013-01-01

Some employees have difficulty undergoing health checkups in the workplace in a fasting state. However, hypertriglyceridemia is usually diagnosed based on fasting triglyceride (TG) measurements. The current study investigated the performance of non-fasting health checkup data for predicting hypertriglyceridemia in a Japanese population. We recruited a total of 1,959 Japanese employees who had their fasting TG levels reexamined after undergoing initial health checkups under either a fasting (the fasting population; n= 856) or non-fasting state (the non-fasting population; n= 1103). Hypertriglyceridemia was defined as a fasting TG level of ≥ 1.7 mmol/l. The area under the receiver operating characteristic (ROC) curve of the initial TG measurements for reexamination-detected hypertriglyceridemia was 0.85 in the fasting population and 0.83 in the non-fasting population. The area under the ROC curve of the initial TG measurements in the non-fasting population was not inferior to that of the multivariate model where other non-fasting health checkup data were added. The optimal non-fasting TG cutoff point was 2.0 mmol/l. The cutoff point was further lowered when the population was limited to patients undergoing health checkups four or more hours after their last meal and when the prevalence of hypertriglyceridemia in the population was simulated to be reduced. The non-fasting workplace TG measurements by themselves exhibited a tolerable performance for predicting hypertriglyceridemia. The optimal cutoff point in Japanese employees appears to be lower than 2.3 mmol/l, the recently proposed Western cutoff point.

Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic ketoacidosis.

PubMed

Pérez, Mayrim L; Kridel, Heather A; Gallagher, Alex; Sheppard, Barbara J; Reese, Shona; Kondo, Hirotaka; Alleman, Rick; Giger, Urs

2015-03-01

A 7-month-old, neutered male miniature schnauzer dog with a history of cryptorchidism and umbilical hernia was referred for diabetic ketoacidosis. Clinical evaluation revealed stunted growth, skeletal abnormalities, hypertriglyceridemia, diabetic ketoacidosis, and acute necrotizing pancreatitis. Further testing was diagnostic for mucopolysaccharidosis type VI causing the stunted growth and skeletal deformities, but no connection between mucopolysaccharidosis type VI, hypertriglyceridemia, and pancreatic diseases was found.

Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic ketoacidosis

PubMed Central

Pérez, Mayrim L.; Kridel, Heather A.; Gallagher, Alex; Sheppard, Barbara J.; Reese, Shona; Kondo, Hirotaka; Alleman, Rick; Giger, Urs

2015-01-01

A 7-month-old, neutered male miniature schnauzer dog with a history of cryptorchidism and umbilical hernia was referred for diabetic ketoacidosis. Clinical evaluation revealed stunted growth, skeletal abnormalities, hypertriglyceridemia, diabetic ketoacidosis, and acute necrotizing pancreatitis. Further testing was diagnostic for mucopolysaccharidosis type VI causing the stunted growth and skeletal deformities, but no connection between mucopolysaccharidosis type VI, hypertriglyceridemia, and pancreatic diseases was found. PMID:25750448

Severe Hypertriglyceridemia Possibly Masked Acute Pancreatitis and Led to a Difficult Diagnosis in an Obese Patient with Ketoacidosis-onset Type 2 Diabetes.

PubMed

Fujishiro, Midori; Horita, Akiko; Nakagawara, Hiroshi; Mawatari, Takayuki; Kishigami, Yoshifusa; Tominaga, Yoshiteru; Moriyama, Mitsuhiko; Ishihara, Hisamitsu

2017-10-01

A young obese man with ketoacidosis-onset type 2 diabetes mellitus, associated with severe hypertriglyceridemia, was admitted to a local hospital complaining of abdominal pain. Although the abdominal pain worsened, his serum amylase level remained normal with persistent severe hypertriglyceridemia until the second day of hospitalization. The next day, computed tomography showed severe acute pancreatitis (AP) with serum amylase elevation, while the patient's triglyceride level decreased to 558 mg/dL. He was transferred to our hospital and recovered after intensive care. AP accompanied by diabetic ketoacidosis is not rare but an early diagnosis can be difficult to make due to normal amylase levels in the presence of severe hypertriglyceridemia.

Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.

PubMed

Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Valenti, Vincenza; Ingrassia, Valeria; Giammanco, Antonina; Panno, Maria D; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

2015-12-01

Cyclic AMP responsive element-binding protein 3-like 3 (CREB3L3) is a novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which hypertriglyceridemia displayed an autosomal dominant pattern of inheritance. The proband was a 49-year-old woman with high plasma triglycerides (≤1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this family, we analyzed the candidate genes of recessive and dominant forms of primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3 gene, predicted to result in the formation of a truncated protein devoid of function (c.359delG-p.K120fsX20). Heterozygosity for the c.359delG mutation resulted in a severe phenotype occurring later in life in the proband and her brother and a good response to diet and a hypotriglyceridemic treatment. The same mutation was detected in a 13-year-old daughter who to date is normotriglyceridemic. We have identified a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance. © 2015 American Heart Association, Inc.

Genetic and environmental determinants of the susceptibility of Amerindian derived populations for having hypertriglyceridemia

PubMed Central

Aguilar-Salinas, Carlos A.; Tusie-Luna, Teresa; Pajukanta, Päivi

2014-01-01

Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explains the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia. PMID:24768220

Hypertriglyceridemia in Diabetes Mellitus: Implications for Pediatric Care.

PubMed

Hartz, Jacob C; de Ferranti, Sarah; Gidding, Samuel

2018-06-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). It is estimated that the risk of CVD in diabetes mellitus (DM) is 2 to 10 times higher than in the general population. Much of this increased risk is thought to be related to the development of an atherogenic lipid profile, in which hypertriglyceridemia is an essential component. Recent studies suggest that dyslipidemia may be present in children and adolescents with DM, particularly in T2DM and in association with poor control in T1DM. However, the role of hypertriglyceridemia in the development of future CVD in youth with DM is unclear, as data are scarce. In this review, we will evaluate the pathophysiology of atherogenic hypertriglyceridemia in DM, the evidence regarding an independent role of triglycerides in the development of CVD, and the treatment of hypertriglyceridemia in patients with DM, highlighting the potential relevance to children and the need for more data in children and adolescents to guide clinical practice.

Minimal contribution of severe hypertriglyceridemia in L-asparaginase-associated pancreatitis developed in a child with acute lymphocytic leukemia.

PubMed

Goto, Yoshinori; Nishimura, Ryosei; Nohara, Atsushi; Mase, Shintaro; Fujiki, Toshihiro; Irabu, Hitoshi; Kuroda, Rie; Araki, Raita; Ikawa, Yasuhiro; Maeba, Hideaki; Yachie, Akihiro

2016-08-01

A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable. Extremely large chylomicrons contribute directly to the onset of pancreatitis by causing blockage of small vessels. Although it is necessary to examine patients for dyslipidemia developing as a side effect of ASP, therapeutic intervention for hypertriglyceridemia is not considered to prevent the onset of ASP-associated pancreatitis.

Managing hypertriglyceridemia in children with systemic lupus erythematosus: Two sides of the same coin.

PubMed

Basu, Biswanath; Babu, Binu George; Bhattacharyya, Suman

Hypertriglyceridemia is common in children with systemic lupus erythematosus (SLE). A retrospective analysis of the baseline clinical-pathological presentation and treatment outcome (status of lipid profiles) was performed in two children with SLE, who presented with extreme hypertriglyceridemia over a follow-up period of four weeks. The children were treated with prednisolone, mycophenolate mofetil (MMF), hydroxychloroquine and hypolipidemic agents, depending on their disease status. On serial follow-up, the first child showed a significantly raised serum triglyceride level after receiving one week of oral prednisolone therapy. Anti-lipoprotein-lipase (LPL) autoantibody was absent. Lipid profile levels of this child gradually improved after replacing oral prednisolone with another immunosuppressant, namely MMF. The second child presented with extreme hypertriglyceridemia with positive anti-LPL autoantibody. She responded to plasmapheresis followed by increasing the dose of immunosuppressant. So, extreme hypertriglyceridemia in children with SLE may be steroid induced or due to presence of anti-LPL auto antibody. Management should be individualized depending on the etiology. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up.

PubMed

Mook-Kanamori, D O; Römisch-Margl, W; Kastenmüller, G; Prehn, C; Petersen, A K; Illig, T; Gieger, C; Wang-Sattler, R; Meisinger, C; Peters, A; Adamski, J; Suhre, K

2014-04-01

Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia (defined as having a fasting triglyceride level above 1.70 mmol/L) and diabetes at baseline, 755 subjects remained for analyses. Increased levels of leucine, arginine, valine, proline, phenylalanine, isoleucine and lysine were significantly associated with an increased risk of hypertriglyceridemia. These associations remained significant when restricting to those individuals who did not develop T2D in the 7-year follow-up. The increase per standard deviation of amino acid level was between 26 and 40 %. Seven amino acids were associated with an increased risk of developing hypertriglyceridemia after 7 years. Further studies are necessary to elucidate the complex role of these amino acids in the pathogenesis of metabolic disorders.

The Influence of Metabolic Syndrome on Prostate Cancer Progression and Risk of Recurrence in African American and European American Men

DTIC Science & Technology

2012-10-01

MetSyn: 1) abdominal obesity (waist circumference of> 102cm in men or> 88 em in women); 2) hypertriglyceridemia (<: 150mg/dl); 3)1ow high-density...em in men or >88 em in women), 2) hypertriglyceridemia (:0: 150 mg/dL), 3) low high-density lipoprotein (HDL) cholesterol (< 40 mg/dL in men and អ... hypertriglyceridemia and low HDL cholesterol), blacks and Asians present with hypertension whereas diabetes is diagnosed most often among Hispanics, Pacific Islanders

Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

PubMed

Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

2016-04-01

High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone. Georg Thieme Verlag KG Stuttgart · New York.

Plasmapheresis in the management of severe hypertriglyceridemia.

PubMed

Seda, Gilbert; Meyer, Jill M; Amundson, Dennis E; Daheshia, Massoud

2013-08-01

Plasmapheresis can benefit a variety of critically ill patients. A woman with diabetic ketoacidosis and severe hypertriglyceridemia was treated with plasmapheresis when conventional treatments did not markedly reduce her triglyceridemia. The patient was admitted to a medical intensive care unit because of diabetic ketoacidosis with severe lipemia. The lipemia-associated interference in laboratory studies made treatment of electrolyte abnormalities extremely difficult. The hypertriglyceridemia was initially treated with insulin, antilipidemic medications, and heparin, but the levels of triglycerides remained elevated, delaying results of needed laboratory studies for hours. After plasmapheresis, the serum level of triglycerides decreased by 77% in less than 24 hours. Severe lipemia interferes with photometric laboratory studies, yielding an underestimation of serum levels of electrolytes. Plasmapheresis is safe, rapid, and effective for emergent management of severe hypertriglyceridemia in critically ill patients. The impact of the procedure on critical care nursing is growing as nurses become involved in the treatment and follow-up care of patients who have plasmapheresis.

Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis

PubMed Central

Huang, Xie-Lin; Chen, Chao; Jin, Rong; Huang, Zhi-Ming; Zhou, Meng-Tao

2015-01-01

Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis. PMID:26079787

New Strategy to Reduce Hypertriglyceridemia During Parenteral Nutrition While Maintaining Energy Intake.

PubMed

Mateu-de Antonio, Javier; Florit-Sureda, Marta

2016-07-01

Hypertriglyceridemia is a frequent metabolic complication associated with fat administration in parenteral nutrition (PN). No clear guidelines have been published on how to proceed once hypertriglyceridemia has been detected. A new strategy could be to substitute the initial fat emulsion with another emulsion with faster clearance. Our objective was to determine the effectiveness in reducing triglyceridemia values, maintaining the caloric intake, and improving nutrition parameters in patients who had moderate hypertriglyceridemia during PN when an olive oil-based fat emulsion (OOFE) was substituted with a multiple-source oil fat emulsion (MOFE). We also assessed the safety of this substitution in hepatic and glycemic profiles. We performed a retrospective, observational study that included 38 adult patients to whom OOFE in PN was substituted with MOFE when moderate hypertriglyceridemia (≥250-400 mg/dL) was detected. Triglyceridemia values decreased in 36 (94.7%) patients. The mean reduction was 71 (88-22) mg/dL. Fat load was slightly reduced after substitution (-0.14 [-0.23 to 0] g/kg/d; P < .001), but total caloric intake increased from 22.5 (19.7-25.1) to 23.1 (19.8-26.8) kcal/kg/d (P = .053). After substitution, nutrition parameters improved, liver parameters remained unchanged, and insulin requirements increased. The substitution of OOFE with MOFE in patients with moderate hypertriglyceridemia during PN resulted in a reduction in triglyceridemia values of about 70 mg/dL. That allowed maintaining the caloric intake and improved nutrition parameters without affecting the hepatic profile. For some patients, insulin requirements increased moderately. © 2014 American Society for Parenteral and Enteral Nutrition.

Smoking, inflammatory patterns, and postprandial hypertriglyceridemia

USDA-ARS?s Scientific Manuscript database

Background: Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential "drivers" for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT. Methods: Men and women i...

Familial chylomicronemia syndrome and response to medium-chain triglyceride therapy in an infant with novel mutations in GPIHBP1.

PubMed

Ahmad, Zahid; Wilson, Don P

2014-01-01

Severe hypertriglyceridemia predisposes to attacks of acute pancreatitis, a serious condition complicated by multiorgan failure, pancreatic necrosis, and mortality rates up to 20% in adults and 6.5% in children. We describe an infant who suffered from an episode of acute pancreatitis from severe hypertriglyceridemia. Two major challenges complicate the case: identifying the etiology of severe hypertriglyceridemia and finding an efficacious treatment. A thorough history, physical examination, and laboratory workup failed to identify a clear etiology, prompting a genetic workup that identified compound heterozygous mutations in the glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) gene. This patient's hypertriglyceridemia responded to an infant formula rich in medium chain triglycerides (MCTs), and she remained free of pancreatitis 6 months later. This case highlights the need to pursue a genetic evaluation in the absence of secondary causes of severe hypertriglyceridemia in infants. Patients with mutations in GPIHBP1 fail to respond to currently available lipid-lowering agents so dietary management-specifically, an extremely low-fat diet and supplementation with MCT-remains the cornerstone of therapy. Treatment in infants should focus on dietary measures rather than pharmacologic agents. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Association of Serum Triglyceride Level and Gemfibrozil Consumption With Periodontal Status.

PubMed

Sayar, Ferena; Akhondi, Nasrin; Fallah, Soltanali; Moalemnia, Amir Abbas; Cheraghi, Azra

2017-05-01

Hyperlipidemia is a major risk factor for cardiovascular diseases. Considering the suggested association between periodontal and cardiovascular diseases, this study sought to assess the association, if any, between serum triglyceride (TG) levels and gemfibrozil consumption with periodontal parameters. This cross-sectional study was conducted on 90 participants, including 30 individuals with a normal lipid profile (group H), 30 patients with hypertriglyceridemia and not on medication (group N), and 30 patients with hypertriglyceridemia and taking gemfibrozil over a 3-month period (group M). Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index were measured at four sites of each tooth. Serum levels of total cholesterol (TC), TG, low-density lipoprotein, and high-density lipoprotein were measured. Mean values for PD and CAL in the two hypertriglyceridemic groups were significantly higher than those of the H group (P <0.001). After controlling for confounding variables, significant linear correlations were noted between PD and BOP, PD and TC, PD and TG, and CAL and TG in each group (P <0.01). Patients with hypertriglyceridemia had worse periodontal status than healthy controls. Patients with hypertriglyceridemia who were taking gemfibrozil did not show significant differences in CAL and PD compared with untreated patients with hypertriglyceridemia.

Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report.

PubMed

Kido, Kazuhiko; Evans, Rickey A; Gopinath, Anil; Flynn, Jeremy D

2018-02-01

Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis. The most recent triglyceride was down to 520 mg/dL 2 months after discontinuation of sirolimus. We estimate the probability of this reaction to sirolimus as probable based on a score of 5 points on the Naranjo scale. This is the first case report to our knowledge that highlights the sole use of oral lipid-lowering drug agents to treat severe hypertriglyceridemia secondary to sirolimus without the use of plasmapheresis. Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.

A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice.

PubMed

Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I

2017-07-01

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.

Association of NCOA3 polymorphisms with Dyslipidemia in the Chinese Han population.

PubMed

Yu, Mingxi; Gilbert, Siame; Li, Yong; Zhang, Huiping; Qiao, Yichun; Lu, Yuping; Tang, Yuan; Zhen, Qing; Cheng, Yi; Liu, Yawen

2015-10-09

Nuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Emerging evidence from previous studies using animal models suggests that the NCOA3 gene (NCOA3) plays a critical role in lipid metabolism as well as adipogenesis and obesity. The present study aims to investigate the association between NCOA3 SNPs and dyslipidemia in the Chinese Han population. Five hundred and twenty-nine (529) Chinese Han subjects were recruited. Four tag SNPs (rs2425955G > T, rs6066394T > C, rs10485463C > G, and rs6094753G > A) in NCOA3, selected from the HapMap website, were genotyped using MALDI-TOF mass spectrometry. Data analysis was performed using SPSS 16.0, SNPStats and haploview 4.2. Four SNPs (rs2425955, rs6066394, rs10485463, and rs6094753) were associated with triglyceride levels. Except for SNP rs10485463, genotype distributions and allele frequencies of the other three NCOA3 SNPs (rs2425955, rs6066394, and rs6094753) were significantly different between hypertriglyceridemia subjects and normal group. Significant differences were also observed in allele frequencies and genotype distributions of SNP rs10485463 between low-HDL cholesterolemia subjects and normal group. Carriers of rs2425955 T allele had a lower risk of hypertriglyceridemia compared to GG genotype. Similar results were observed from rs6094753. Subjects with rs6066394 CT genotype had a lower risk of hypertriglyceridemia than those with the TT genotype; however, CC and TT genotypes showed no significant difference in the risk of hypertriglyceridemia. Similar results were found in the association between rs6066394 and hypercholesterolemia. The variant alleles of rs2425955, rs6066394 and rs6094753 were associated with a lower risk of hypertriglyceridemia compared with the wild-type alleles. The G allele of rs10485463 was associated with an increased risk of low-HDL cholesterolemia. In the log-additive model the association between rs2425955 and hypertriglyceridemia remained significant after Bonferroni correction, and genotypes with variant alleles were associated with a lower risk of hypertriglyceridemia. In summary, this study demonstrated that variation in NCOA3 might influence the risk of dyslipidemia and serum lipid levels in Chinese Han population.

Hypertriglyceridemia: a too long unfairly neglected major cardiovascular risk factor.

PubMed

Tenenbaum, Alexander; Klempfner, Robert; Fisman, Enrique Z

2014-12-04

The existence of an independent association between elevated triglyceride (TG) levels, cardiovascular (CV) risk and mortality has been largely controversial. The main difficulty in isolating the effect of hypertriglyceridemia on CV risk is the fact that elevated triglyceride levels are commonly associated with concomitant changes in high density lipoprotein (HDL), low density lipoprotein (LDL) and other lipoproteins. As a result of this problem and in disregard of the real biological role of TG, its significance as a plausible therapeutic target was unfoundedly underestimated for many years. However, taking epidemiological data together, both moderate and severe hypertriglyceridaemia are associated with a substantially increased long term total mortality and CV risk. Plasma TG levels partially reflect the concentration of the triglyceride-carrying lipoproteins (TRL): very low density lipoprotein (VLDL), chylomicrons and their remnants. Furthermore, hypertriglyceridemia commonly leads to reduction in HDL and increase in atherogenic small dense LDL levels. TG may also stimulate atherogenesis by mechanisms, such excessive free fatty acids (FFA) release, production of proinflammatory cytokines, fibrinogen, coagulation factors and impairment of fibrinolysis. Genetic studies strongly support hypertriglyceridemia and high concentrations of TRL as causal risk factors for CV disease. The most common forms of hypertriglyceridemia are related to overweight and sedentary life style, which in turn lead to insulin resistance, metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Intensive lifestyle therapy is the main initial treatment of hypertriglyceridemia. Statins are a cornerstone of the modern lipids-modifying therapy. If the primary goal is to lower TG levels, fibrates (bezafibrate and fenofibrate for monotherapy, and in combination with statin; gemfibrozil only for monotherapy) could be the preferable drugs. Also ezetimibe has mild positive effects in lowering TG. Initial experience with en ezetimibe/fibrates combination seems promising. The recently released IMPROVE-IT Trial is the first to prove that adding a non-statin drug (ezetimibe) to a statin lowers the risk of future CV events. In conclusion, the classical clinical paradigm of lipids-modifying treatment should be changed and high TG should be recognized as an important target for therapy in their own right. Hypertriglyceridemia should be treated.

Hypertriglyceridemia thalassemia syndrome.

PubMed

Jain, Mili; Ali, Wahid; Singh, Brijendra Bahadur; Verma, Nishant; Kumar, Ashutosh

2018-06-14

Hypertriglyceridemia thalassemia syndrome is a rare entity with an unknown pathogenetic link. We report a case of an 8-month-old female with thalassemia major and increased triglyceride (TG) levels. The clinical features were as in classical thalassemia except for a white discoloration of the plasma. After exclusion of familial triglyceridemia and secondary causes (hypothyroidism, nephrotic syndrome, drugs etc.), a diagnosis of hypertriglyceridemia thalassemia syndrome was made. The high levels of TG in these patients are associated with oxidative stress and higher risk of acute pancreatitis and coronary diseases. An early recognition is thus essential. In our patient, the levels reduced after a transfusion therapy similar to previous reports.

Type V hypertriglyceridemia in children, a therapeutic challenge in pediatrics

PubMed Central

Mărginean, Cristina Oana; Meliţ, Lorena Elena; Dobreanu, Minodora; Mărginean, Maria Oana

2017-01-01

Abstract Rationale: Hypertriglyceridemia is defined as a level of triglycerides above 150 mg/dL. The complex causes and classification of hypertriglyceridemia lead to difficulties in the diagnosis and management of this condition. Patient concerns: We present the case of a 15 years and 6 months old female teenager, admitted in our clinic for the following complaints: severe abdominal pain predominantly in the lateral left quadrant, nausea, vomiting, and the lack of stools for 2 days. The clinical exam showed: impaired general status, painful abdomen at superficial and deep palpation in the left and upper abdominal quadrants, the absence of stools for 2 days. Diagnoses: The laboratory parameters revealed leukocytosis with neutrophilia, thrombocytopenia, high level of serum amylase and triglycerides, and increased inflammatory biomarkers. The imagistic investigations showed ascites and paralytic ileus. Interventions: The management was burdened by the side-effects of hypolipidemic drugs impairing the liver function and leading to rhabdomyolysis, but eventually the patient's outcome was good. Outcomes: Type V hyperlipoproteinemia is a rare condition accounting for approximately 5% of the cases. The risk for acute pancreatitis is well-known to be associated with hypertriglyceridemia, even though in rare cases. Lessons: The prognosis of hypertriglyceridemia is pediatrics is burdened not only by the long-term risk factors associated to the diseases itself, but also by the negative effects of long-term hypolipidemic treatment. PMID:29390422

Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia[S

PubMed Central

Mendoza-Barberá, Elena; Julve, Josep; Nilsson, Stefan K.; Lookene, Aivar; Martín-Campos, Jesús M.; Roig, Rosa; Lechuga-Sancho, Alfonso M.; Sloan, John H.; Fuentes-Prior, Pablo; Blanco-Vaca, Francisco

2013-01-01

During the diagnosis of three unrelated patients with severe hypertriglyceridemia, three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence of concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which APOA5 mutations result in severe hypertriglyceridemia remain poorly understood, and the functional impairment/s induced by these specific mutations was not obvious. Therefore, we performed a thorough structural and functional analysis that included follow-up of patients and their closest relatives, measurement of apoA-V serum concentrations, and sequencing of the APOA5 gene in 200 nonhyperlipidemic controls. Further, we cloned, overexpressed, and purified both wild-type and mutant apoA-V variants and characterized their capacity to activate LPL. The interactions of recombinant wild-type and mutated apoA-V variants with liposomes of different composition, heparin, LRP1, sortilin, and SorLA/LR11 were also analyzed. Finally, to explore the possible structural consequences of these mutations, we developed a three-dimensional model of full-length, lipid-free human apoA-V. A complex, wide array of impairments was found in each of the three mutants, suggesting that the specific residues affected are critical structural determinants for apoA-V function in lipoprotein metabolism and, therefore, that these APOA5 mutations are a direct cause of hypertriglyceridemia. PMID:23307945

Dyslipidemia in a Cohort of HIV-infected Latin American Children Receiving Highly Active Antiretroviral Therapy*

PubMed Central

Brewinski, Margaret; Megazzini, Karen; Freimanis Hance, Laura; Cruz, Miguel Cashat; Pavia-Ruz, Noris; Della Negra, Marinella; Ferreira, Flavia Gomes Faleiro; Marques, Heloisa

2011-01-01

In order to describe the prevalence of hypercholesterolemia and hypertriglyceridemia in a cohort of HIV-infected children and adolescents in Latin America and to determine associations with highly active antiretroviral therapy (HAART), we performed this cross-sectional analysis within the NICHD International Site Development Initiative pediatric cohort study. Eligible children had to be at least 2 years of age and be on HAART. Among the 477 eligible HIV-infected youth, 98 (20.5%) had hypercholesterolemia and 140 (29.4%) had hypertriglyceridemia. In multivariable analyses, children receiving protease inhibitor (PI)-containing HAART were at increased risk for hypercholesterolemia [adjusted odds ratio (AOR) = 2.7, 95% confidence interval (CI) 1.3–5.6] and hypertriglyceridemia (AOR = 3.5, 95% CI 1.9–6.4) compared with children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing HAART. In conclusion, HIV-infected youth receiving PI-containing HAART in this Latin American cohort were at increased risk for hypercholesterolemia and hypertriglyceridemia compared with those receiving NNRTI-containing HAART. PMID:20889625

Novel antipsychotics and severe hyperlipidemia.

PubMed

Meyer, J M

2001-08-01

Newer atypical antipsychotics demonstrate superior effectiveness, with a diminished incidence of extrapyramidal side effects compared with older typical antipsychotics, but they have been associated with the development of obesity and new-onset diabetes. A small number of reports documenting modest hypertriglyceridemia related to newer antipsychotics have implicated fluperlapine, clozapine, and, most recently, olanzapine. This study summarizes the results of 14 cases of severe hypertriglyceridemia (>600 mg/dL) associated with olanzapine and quetiapine therapy occurring among inpatients at Oregon State Hospital, including 7 patients whose serum triglyceride levels exceeded 1,000 mg/ dL. Four of these patients also developed new-onset diabetes. Nine cases occurred during the first 8 months of treatment, with three cases identified within 3 months of commencing olanzapine or quetiapine therapy. Weight gain in olanzapine and quetiapine groups was modest (12.3 lb and 8.5 lb, respectively) and did not correlate with the severity of hypertriglyceridemia. Biochemical causes for severe hypertriglyceridemia associated with novel antipsychotics are unclear, but clinical monitoring of serum lipids must be added to the concerns about the metabolic consequences of therapy with certain newer antipsychotic agents.

[Bezafibrate in an infant with congenital generalized lipodystrophy and severe hypertriglyceridemia].

PubMed

Araújo, Rogério Santiago; Ramos, André de Paula Silva; Borges, Máriton de Araújo Sousa

2013-11-01

Congenital generalized lipodystrophy (CGL) with severe hypertriglyceridemia in a children less than 1 year of age is associated with worse metabolic risk. We used data from patient records, as well as extensive literature research to write the manuscript. We report the case of an infant with typical phenotype of CGL and hypertriglyceridemia of 1,360 mg/dL who was treated with bezafibrate at a dose of 30 to 60 mg/day from age 11 months to 5.5 years old, with a measurement of nadir of triglycerides of 55 mg/dL. Clinical evolution and clinical laboratory tests before and after bezafibrate were carried out over 5 years and 6 months. Phenotype was classified as CGL type 2. Despite the efficient control of hypertriglyceridemia and absence of development of diabetes mellitus, the use of bezafibrate did not prevent the onset of hepatic steatosis during evolution. Hypolipidemic therapy with bezafibrate proved effective in maintaining the levels of triglycerides, cholesterol and its fractions at normal levels, and its use was not correlated with severe side effects during the described period.

The ddY mouse: a model of postprandial hypertriglyceridemia in response to dietary fat

PubMed Central

Yamazaki, Tomomi; Kishimoto, Kyoko; Ezaki, Osamu

2012-01-01

Postprandial hyperlipidemia (lipemia) is a risk factor for atherosclerosis. However, mouse models of postprandial hyperlipidemia have not been reported. Here, we report that ddY mice display marked postprandial hypertriglyceridemia in response to dietary fat. In ddY mice, the fasting serum total triacylglyceride (TG) concentration was 134 mg/dl, which increased to 571 mg/dl after an intragastric safflower oil load (0.4 ml/mouse). In C57BL/6J mice, these concentrations were 57 and 106 mg/dl, respectively. By lipoprotein analysis, ddY mice showed increases in chylomicron- and VLDL-sized TG fractions (remnants and VLDL) after fat load. In C57BL/6J mice, post-heparin plasma LPL activity after fat load was increased 4.8-fold relative to fasting. However, in ddY mice, the increase of LPL activity after fat load was very small (1.2-fold) and not significant. High fat feeding for 10 weeks led to obesity in ddY mice. A difference in LPL amino acid composition between C57BL/6J and ddY mice was detected but was deemed unlikely to cause hypertriglyceridemia because hypertriglyceridemia was not evident in other strains harboring the ddY-type LPL sequence. These findings indicate that postprandial hypertriglyceridemia in ddY mice is induced by decreased LPL activity after fat load and is associated with obesity induced by a high-fat diet. PMID:22735545

Type V hypertriglyceridemia in children, a therapeutic challenge in pediatrics: A case report and a review of the literature.

PubMed

Mărginean, Cristina Oana; Meliţ, Lorena Elena; Dobreanu, Minodora; Mărginean, Maria Oana

2017-12-01

Hypertriglyceridemia is defined as a level of triglycerides above 150 mg/dL. The complex causes and classification of hypertriglyceridemia lead to difficulties in the diagnosis and management of this condition. We present the case of a 15 years and 6 months old female teenager, admitted in our clinic for the following complaints: severe abdominal pain predominantly in the lateral left quadrant, nausea, vomiting, and the lack of stools for 2 days. The clinical exam showed: impaired general status, painful abdomen at superficial and deep palpation in the left and upper abdominal quadrants, the absence of stools for 2 days. The laboratory parameters revealed leukocytosis with neutrophilia, thrombocytopenia, high level of serum amylase and triglycerides, and increased inflammatory biomarkers. The imagistic investigations showed ascites and paralytic ileus. The management was burdened by the side-effects of hypolipidemic drugs impairing the liver function and leading to rhabdomyolysis, but eventually the patient's outcome was good. Type V hyperlipoproteinemia is a rare condition accounting for approximately 5% of the cases. The risk for acute pancreatitis is well-known to be associated with hypertriglyceridemia, even though in rare cases. The prognosis of hypertriglyceridemia is pediatrics is burdened not only by the long-term risk factors associated to the diseases itself, but also by the negative effects of long-term hypolipidemic treatment. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Laparoscopic bariatric surgery for the treatment of severe hypertriglyceridemia.

PubMed

Hsu, Sung-Yu; Lee, Wei-Jei; Chong, Keong; Ser, Kong-Han; Tsou, Jun-Jiun

2015-04-01

It is well established that severe hypertriglyceridemia can lead to pancreatitis. At present, medical treatment for patients with severe hypertriglyceridemia and repeat pancreatitis attacks is not adequate. The aim of this study was to assess the effectiveness of laparoscopic bariatric surgery in these patients. A review of 20 morbidly obese patients with severe hypertriglyceridemia (a triglyceride level of >1000 mg/dL) who received laparoscopic bariatric surgery was performed. The study population comprised 14 males and six females, with an average age of 35.0 years (range 24-52 years), and the mean body mass index was 38.2 kg/m(2) (range 25-53 kg/m(2)). The preoperative mean plasma triglyceride level was 1782.7 mg/dL (range 1043-3884 mg/dL). Four patients had a history of hypertriglyceridemic pancreatitis and 13 patients had associated diabetes. Of the 20 patients, 17 (85%) received gastric bypass, whereas three (15%) received restrictive-type surgery. Laparoscopic access was used in all of the patients. Hypertriglyceridemia in morbidly obese patients was more commonly associated with male sex and a poorly controlled diabetic state. The mean weight reduction was 25.5% 1 year after surgery, with a marked improvement in diabetes management. As early as 1 month following surgery, the plasma mean triglyceride levels had decreased to 254 mg/dL (range 153-519 mg/dL), and this was further reduced to mean levels of 192 mg/dL (range 73-385 mg/dL) 1 year after surgery. One patient developed acute pancreatitis during the perioperative period, but none of the patients suffered an episode of pancreatitis in the follow-up period (from 6 months to 13 years). Bariatric surgery can be successfully used as a metabolic surgery in severe hypertriglyceridemia patients at risk of acute pancreatitis. However, control of triglyceride levels prior to bariatric surgery is indicated. Copyright © 2014. Published by Elsevier Taiwan.

Characterization of hypertriglyceridemia and response to treatment with insulin in llamas and alpacas: 31 cases (1995-2005).

PubMed

Waitt, Laura H; Cebra, Christopher K

2008-05-01

To evaluate camelids with hypertriglyceridemia with regard to signalment, clinical features of disease, and response to treatment with insulin. Retrospective case series. 23 alpacas and 8 llamas with hypertriglyceridemia. For analysis of medical record data, 20 hypertriglyceridemic camelids with multiple recorded measurements of serum or plasma triglycerides concentration were classified as follows: those with an initial triglycerides concentration > 60 to > or = 500 mg/dL that were or were not treated with insulin (HT-I and HT-N camelids, respectively) and those with an initial triglycerides concentration > 500 mg/dL that were treated with insulin (lipemic [LIP-I] camelids). Only 1 recorded triglycerides concentration was available for an additional 11 hypertriglyceridemic camelids; data from those records were included in the characterization of signalment and clinical features of disease. Compared with the general population of hospitalized camelids, hypertriglyceridemic camelids did not differ significantly with respect to age or sex. Of 22 female camelids, only 7 were lactating or pregnant. Serum or plasma triglycerides concentrations in HT-N and HT-I camelids did not differ significantly at admission, but triglycerides concentrations in HT-I camelids decreased significantly after insulin treatment. Posttreatment triglycerides concentrations in HT-I camelids were significantly lower than those in HT-N camelids. During the period of hospitalization, triglycerides concentrations in HT-N camelids increased, whereas those in LIP-I camelids decreased significantly. Results indicated that hypertriglyceridemia affects llamas and alpacas of all ages and both sexes. Insulin treatment may reduce serum or plasma triglycerides concentrations in camelids with hypertriglyceridemia.

Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease: 20-year mortality follow-up of the BIP randomized control trial.

PubMed

Arbel, Yaron; Klempfner, Robert; Erez, Aharon; Goldenberg, Ilan; Benzekry, Sagit; Shlomo, Nir; Fisman, Enrique Z; Tenenbaum, Alexander

2016-01-22

Recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction. This study was designed to address the question of all-cause mortality during extended follow-up of the BIP trial in patients stratified by baseline triglyceride levels. In the BIP trial 3090 patients with proven coronary artery disease were randomized to bezafibrate 400 mg/day or placebo. All-cause mortality data after 20 years of follow-up, were obtained from the National Israeli Population Registry. Patients with hypertriglyceridemia (triglycerides ≥200 mg/dL, n = 458) were equally distributed among the study groups (15 % in both placebo and bezafibrate groups). During follow-up 1869 patients died (952 in placebo vs. 917 in bezafibrate group). Following multivariate adjustment allocation to bezafibrate was associated with small but significant 10 % mortality risk reduction (HR 0.90; 95 % CI 0.82-0.98, p = 0.026). Variables associated with significantly increased mortality risk were history of a past MI, NYHA class, diabetes, age, higher BMI and glucose level. In patients with hypertriglyceridemia multivariate analysis demonstrated a 25 % all-cause mortality risk reduction associated with allocation to bezafibrate (HR 0.75, CI 95 % 0.60-0.94; p = 0.012). In patients without hypertriglyceridemia bezafibrate had no significant effect on long-term mortality. During long-term follow-up bezafibrate-allocated patients experienced a modest but significant 10 % reduction in the adjusted risk of mortality. This effect of bezafibrate was more prominent among patients with baseline hypertriglyceridemia (25 % mortality risk reduction).

Serum Amino Acid Profiles in Childhood Predict Triglyceride Level in Adulthood: A 7-Year Longitudinal Study in Girls.

PubMed

Wiklund, Petri; Zhang, Xiaobo; Tan, Xiao; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

2016-05-01

Branched-chain and aromatic amino acids are associated with high risk of developing dyslipidemia and type II diabetes in adults. This study aimed to examine whether serum amino acid profiles associate with triglyceride concentrations during pubertal growth and predict hypertriglyceridemia in early adulthood. This was a 7.5-year longitudinal study. The study was conducted at the Health Science Laboratory, University of Jyväskylä. A total of 396 nondiabetic Finnish girls aged 11.2 ± 0.8 years at the baseline participated in the study. Body composition was assessed by dual-energy x-ray absorptiometry; serum concentrations of glucose, insulin, and triglyceride by enzymatic photometric methods; and amino acids by nuclear magnetic resonance spectroscopy. Serum leucine and isoleucine correlated significantly with future triglyceride, independent of baseline triglyceride level (P < .05 for all). In early adulthood (at the age of 18 years), these amino acids were significantly associated with hypertriglyceridemia, whereas fat mass and homeostasis model assessment of insulin resistance were not. Leucine was the strongest determinant discriminating subjects with hypertriglyceridemia from those with normal triglyceride level (area under the curve, 0.822; 95% confidence interval, 0.740-0.903; P = .000001). Serum leucine and isoleucine were associated with future serum triglyceride levels in girls during pubertal growth and predicted hypertriglyceridemia in early adulthood. Therefore, these amino acid indices may serve as biomarkers to identify individuals at high risk for developing hypertriglyceridemia and cardiovascular disease later in life. Further studies are needed to elucidate the role these amino acids play in the lipid metabolism.

[Multiple organ failure complicating a severe acute necrotising pancreatitis secondary of a severe hypertriglyceridemia: a case report].

PubMed

Degardin, J; Pons, B; Ardisson, F; Gallego, J-P; Thiery, G

2013-09-01

We report the case of a 42-year-old man admitted for a multi-organ failure with a coma, a hemodynamic instability, a respiratory distress syndrome, an acute renal failure and a thrombocytopenia. The blood samples highlighted a milky serum and allowed to diagnose an acute pancreatitis associated with a major dyslipidemia: hypertriglyceridemia 11,800 mg/dL and hypercholesterolemia 1195 mg/dL. The CT-scans do not reveal any cerebral abnormalities but highlighted pancreatic lesions without biliary obstruction. A multi-organ failure complicating a severe acute pancreatitis secondary of a major hypertriglyceridemia was mentioned. Despite the absence of clear guidelines, a session of plasma exchange was started in emergency. Symptomatic treatment with protective ventilation, vasopressors, continuous heparin and insulin was continued. The clinical and biological course was good in parallel of the normalization of lipid abnormalities. The patient was discharged at day 17 with a lipid-lowering therapy. We discuss the various treatments available for the management of acute pancreatitis complicating a severe hypertriglyceridemia and their actual relevance in the absence of clear recommendations. Copyright © 2013. Published by Elsevier SAS.

Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology?

PubMed

Carr, Rosalie A; Rejowski, Benjamin J; Cote, Gregory A; Pitt, Henry A; Zyromski, Nicholas J

2016-01-01

We sought to define the severity and natural history of hypertriglyceridemia induced acute pancreatitis (HTG-AP), specifically whether HTG-AP causes more severe AP than that caused by other etiologies. Systematic review of the English literature. Thirty-four studies (15 countries; 1972-2015) included 1340 HTG-AP patients (weighted mean prevalence of 9%). The median admission triglyceride concentration was 2622 mg/dl (range 1160-9769). Patients with HTG have a 14% weighted mean prevalence of AP. Plasmapheresis decreased circulating triglycerides, but did not conclusively affect AP mortality. Only 7 reports (n = 392 patients) compared severity of HTG-AP to that of AP from other etiologies. Of these, 2 studies found no difference in severity, while 5 suggested that HTG-AP patients may have increased severity compared to AP of other etiology. 1) hypertriglyceridemia is a relatively uncommon (9%) cause of acute pancreatitis; however, patients with hypertriglyceridemia have a high (14%) incidence of acute pancreatitis; 2) plasmapheresis may offer specific therapy unique to this patient population; and 3) data specifically comparing the severity of HTG-AP with AP caused by other etiologies are heterogeneous and scarce. Copyright © 2016. Published by Elsevier B.V.

Novel therapeutics in hypertriglyceridemia.

PubMed

Gryn, Steven E; Hegele, Robert A

2015-12-01

We provide an overview of recent advances in the therapy of hypertriglyceridemia, focusing on several new therapies with potential for treating of familial chylomicronemia, other forms of hypertriglyceridemia, and for triglyceride-lowering in patients with other lipid disorders. Newer triglyceride-lowering modalities under evaluation include gene therapy for lipoprotein lipase deficiency (alipogene tiparvovec), and antisense oligonucleotides against mRNA for apolipoproteins B (mipomersen) and C3 (volanesorsen, ISIS 304801). Other potential therapies include small molecule inhibitors of microsomal triglyceride transfer protein (lomitapide) and diacylglycerol acyltransferase-1 (pradigastat), and a monoclonal antibody against angiopoietin-like protein 3 (REGN1500). There is also renewed interest in omega-3 fatty acids, and in developing potent and selective agonists of peroxisome proliferator-activated receptors. Several promising triglyceride-lowering therapies are at various stages of development; a few are even available in some markets. Although existing data suggest good biochemical efficacy, data on long-term clinical outcomes are still limited. For some therapies, cost will be an important consideration, and use will likely be restricted to orphan indications, for example very severe cases of hypertriglyceridemia as seen in familial chylomicronemia syndrome, although some therapies could theoretically be more broadly used one day for cardiovascular disease prevention.

Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene.

PubMed

Soto, Angela Ganan; McIntyre, Adam; Agrawal, Sungeeta; Bialo, Shara R; Hegele, Robert A; Boney, Charlotte M

2015-09-04

Lipoprotein Lipase (LPL) deficiency is a rare autosomal recessive disorder with a heterogeneous clinical presentation. Several mutations in the LPL gene have been identified to cause decreased activity of the enzyme. An 11-week-old, exclusively breastfed male presented with coffee-ground emesis, melena, xanthomas, lipemia retinalis and chylomicronemia. Genomic DNA analysis identified lipoprotein lipase deficiency due to compound heterozygosity including a novel p.Q240H mutation in exon 5 of the lipoprotein lipase (LPL) gene. His severe hypertriglyceridemia, including xanthomas, resolved with dietary long-chain fat restriction. We describe a novel mutation of the LPL gene causing severe hypertriglyceridemia and report the response to treatment. A review of the current literature regarding LPL deficiency syndrome reveals a few potential new therapies under investigation.

Food Deprivation and Exercise in the Heat: Thermoregulatory and Metabolic Effects,

DTIC Science & Technology

resulted in severe hypoglycemia following exercise (P 0.01), and these decrements were accompanied by marked (p 0.01) reductions in circulating insulin...levels. Prolonged food deprivation (48 and 72h) resulted in significant (p 0.01) hypertriglyceridemia and hyperlactacidemia subsequent (p 0.01... hypertriglyceridemia and hyperlactacidemia subsequent to exercise. Levels of sodium, potassium, urea nitrogen, and creatine phosphokiinase were unaffected

Rare and common variants in LPL and APOA5 in Thai subjects with severe hypertriglyceridemia: A resequencing approach.

PubMed

Khovidhunkit, Weerapan; Charoen, Supannika; Kiateprungvej, Arunrat; Chartyingcharoen, Palm; Muanpetch, Suwanna; Plengpanich, Wanee

2016-01-01

Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors. Few data exist on the genetics of severe hypertriglyceridemia in Asian populations. To examine the genetic variants of 3 candidate genes known to influence triglyceride metabolism, LPL, APOC2, and APOA5, which encode lipoprotein lipase, apolipoprotein C-II, and apolipoprotein A-V, respectively, in a large group of Thai subjects with severe hypertriglyceridemia. We identified sequence variants of LPL, APOC2, and APOA5 by sequencing exons and exon-intron junctions in 101 subjects with triglyceride levels ≥ 10 mmol/L (886 mg/dL) and compared with those of 111 normotriglyceridemic subjects. Six different rare variants in LPL were found in 13 patients, 2 of which were novel (1 heterozygous missense variant: p.Arg270Gly and 1 frameshift variant: p.Asp308Glyfs*3). Four previously identified heterozygous missense variants in LPL were p.Ala98Thr, p.Leu279Val, p.Leu279Arg, and p.Arg432Thr. Collectively, these rare variants were found only in the hypertriglyceridemic group but not in the control group (13% vs 0%, P < .0001). One common variant in APOA5 (p.Gly185Cys, rs2075291) was found at a higher frequency in the hypertriglyceridemic group compared with the control group (25% vs 6%, respectively, P < .0005). Altogether, rare variants in LPL or APOA5 and/or the common APOA5 p.Gly185Cys variant were found in 37% of the hypertriglyceridemic group vs 6% in the controls (P = 3.1 × 10(-8)). No rare variant in APOC2 was identified. Rare variants in LPL and a common variant in APOA5 were more commonly found in Thai subjects with severe hypertriglyceridemia. A common p.Gly185Cys APOA5 variant, in particular, was quite prevalent and potentially contributed to hypertriglyceridemia in this group of patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

PubMed

Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

2004-07-01

Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to hypertriglyceridemia of nephrotic syndrome.

Effect of Andrographis paniculata Extract on Triglyceride Levels of the Patients with Hypertriglyceridemia: A Randomized Controlled Trial.

PubMed

Phunikhom, Kutcharin; Khampitak, Kovit; Aromdee, Chantana; Arkaravichien, Tarinee; Sattayasai, Jintana

2015-07-01

Hypertriglyceridemia is one of the risk factors for cardiovascular disease, and reduction oftriglyceride (TG) level is recommended in clinical practice guidelines for the treatment. Recently, andrographolide, a main active compound of Andrographispaniculata has been shown to possess hypolipidemic effects in animals. To investigate the TG-lowering effects of A. paniculata extract (APE) in patients with hypertriglyceridemia (TG ≥ 150 mg/dL) using gemfibrozil treatment as the reference. A randomized controlled clinical trial was carried out in sixty subjects with hypertriglyceridemia. They were divided into three groups and treated with low dose of APE (APE-L, andrographolide 71.64-72.36 mg/day), high dose of APE (APE-H, andrographolide 119.64-120.36 mg/day), and gemfibrozil 300 mg/day. The treatments were conducted for 8 weeks. Guidance on lifestyle modifications was provided. The primary endpoint was the mean difference ± SD (95% CI) in TG levels (baseline from the end of treatment), which were -3 ± 125.6 (-59.1, 58.5), 41.6 ± 86.3 (1.2, 82), and 57.1 ± 94.9 (12.7, 101.6) in the APE-L, APE-H, and gemfibrozil groups, respectively. APE-H 120 mg/day and gemfibrozil 300 mg/day caused a significant reduction of TG level (P = 0.0442 and 0.0145, respectively) when compared to the baseline. There was no notable difference in the safety or tolerability among the treatment groups. In patients with modest hypertriglyceridemia with lifestyle intervention, APE-H reduced the TG level comparable to the effect of gemfibrozil 300 mg/day. APE treatment was as tolerable as gemfibrozil treatment. Hence, Andrographis paniculata might be used as an alternative medicine in treating hypertriglyceridemic patients.

Acute Pancreatitis Complicated with Diabetic Ketoacidosis in a Young Adult without Hypertriglyceridemia: A Case Report.

PubMed

Kim, Jung Hyun; Oh, Myung Jin

2016-11-25

Systemic complications related to acute pancreatitis include acute respiratory distress syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation, hypocalcemia, hyperglycemia, and insulin dependent diabetes or diabetic ketoacidosis. In practice, the development of diabetic ketoacidosis induced by acute pancreatitis is rare and generally associated with hypertriglyceridemia. However, herein we report a case of a 34-year-old female without hypertriglyceridemia, who was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis. The patient was admitted with complaints of febrile sensation, back pain, and abdominal pain around the epigastric area. Levels of serum amylase and lipase were elevated to 663 U/L and 3,232 U/L. Contrast-enhanced abdominal CT showed pancreatic swelling, peri-pancreatic fat infiltration and fluid collection. The patient was initially diagnosed with simple acute pancreatitis. Though the symptoms were rapidly relieved after initiation of treatment, severe hyperglycemia (575 mg/dL), severe metabolic acidosis (pH 6.9), and ketonuria developed at four days after hospitalization. However, serum triglyceride levels remained within the normal range (134 mg/dL). Finally, the patient was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis unrelated to hypertriglyceridemia. She recovered through insulin and fluid therapy, and receives insulin therapy at the outpatient clinic.

Autoimmune severe hypertriglyceridemia induced by anti-apolipoprotein C-II antibody.

PubMed

Yamamoto, Hiroyasu; Tanaka, Minoru; Yoshiga, Satomi; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

2014-05-01

Among type V hyperlipoproteinemias, only one-fourth of the patients have genetic defects in lipoprotein lipase (LPL) or in its associated molecules; the exact mechanism in other patients is usually unknown. The aim of the study was to report a case of severe hypertriglyceridemia induced by anti-apolipoprotein (apo) C-II autoantibody and to clarify its pathogenesis. A 29-year-old Japanese woman presented with severe persistent hypertriglyceridemia since the age of 20 years. The past history was negative for acute pancreatitis, eruptive xanthomas, or lipemia retinalis. LPL mass and activities were normal. Plasma apo C-II levels were extremely low, but no mutation was observed in APOC2. Apo C-II protein was detected in the serum by immunoprecipitation and Western blotting. Large amounts of IgG and IgM were incorporated with apo C-II protein coimmunoprecipitated by anti-apo C-II antibody. IgG, but not IgM, purified from the serum prevented interaction of apo C-II with lipid substrate and diminished LPL hydrolysis activity. We identified anti-apo C-II antibody in a myeloma-unrelated severe hypertriglyceridemic patient. In vitro analysis confirmed that the autoantibody disrupted the interaction between apo C-II and lipid substrate, suggesting the etiological role of anti-apo C-II antibody in severe hypertriglyceridemia in this patient.

Role of omega-3 ethyl ester concentrate in reducing sudden cardiac death following myocardial infarction and in management of hypertriglyceridemia: An Indian consensus statement

PubMed Central

Dalal, J.J.; Kasliwal, R.R.; Dutta, A.L.; Sawhney, J.P.S.; Iyengar, S.S.; Dani, S.; Desai, N.; Sathyamurthy, I.; Rao, D.; Menon, A.; Dasbiswas, A.; Wander, G.S.; Chadha, M.; Hiremath, M.S.; Roy, D.G.; Gupta, V.; Shivakadaksham, N.

2012-01-01

Introduction Sudden cardiac death (SCD) is the most lethal manifestation of heart disease. In an Indian study the SCDs contribute about 10% of the total mortality and SCD post ST elevation myocardial infarction (MI) constitutes for about half of total deaths. Objective Given the limitations of existing therapy there is a need for an effective, easy to use, broadly applicable and affordable intervention to prevent SCD post MI. Leading cardiologists from all over India came together to discuss the potential role of n-3 acid ethyl esters (90%) of eicosapentaenoic acid (EPA) 460 mg & docosahexaenoic acid (DHA) 380 mg in the management of post MI patients and those with hypertriglyceridemia. Recommendations Highly purified & concentrated omega-3 ethyl esters (90%) of EPA (460 mg) & DHA (380 mg) has clinically proven benefits in improving post MI outcomes (significant 15% risk reduction for all-cause mortality, 20% risk reduction for CVD and 45% risk reduction in SCD in GISSI-Prevenzione trial) and in reducing hypertriglyceridemia, and hence, represent an interesting option adding to the treatment armamentarium in the secondary prevention after MI based on its anti-arrhythmogenic effects and also in reducing hypertriglyceridemia. PMID:23102390

Severe gestational hypertriglyceridemia: A practical approach for clinicians

PubMed Central

Wong, Bertha; Ooi, Teik C

2015-01-01

Severe gestational hypertriglyceridemia is a potentially life threatening and complex condition to manage, requiring attention to a delicate balance between maternal and fetal needs. During pregnancy, significant alterations to lipid homeostasis occur to ensure transfer of nutrients to the fetus. In women with an underlying genetic predisposition or a secondary exacerbating factor, severe gestational hypertriglyceridemia can arise, leading to devastating complications, including acute pancreatitis. Multidisciplinary care, implementation of a low-fat diet with nutritional support, and institution of a hierarchical therapeutic approach are all crucial to reduce maternal and fetal morbidity. To avoid maternal pancreatitis, close surveillance of triglycerides throughout pregnancy with elective hospitalization for refractory cases is recommended. Careful dietary planning is required to prevent neural and retinal complications from fetal essential fatty acid deficiency. Questions remain about the safety of fibrates and plasmapheresis in pregnancy as well as the optimal timing for induction and delivery of these women. PMID:27512474

[Rare cause for severe hypertriglyceridemia - case 9/2013].

PubMed

Kahl, Sabine; Roden, Michael; Mörike, Klaus; Müssig, Karsten

2013-11-01

We report on a 48-year-old female patient with recently developed severe hypertriglyceridemia. Medical history was remarkable for breast cancer with breast-preserving surgery and chemoradiotherapy. The patient has been treated with 20 mg tamoxifen per day for three months. Laboratory results showed hypertriglyeridemia, hypercholesterolemia and lowered HDL-cholesterol. Findings were consistent with a drug-induced hypertriglyceridemia caused by anti-estrogenic therapy with tamoxifen. After consulting the patient's gynaecologist, we discontinued tamoxifen treatment. Thereupon, triglyceride levels fell consistently. There were no signs of pancreatitis, serum amylase and lipase were in the normal range. Patients with pre-diagnosed metabolic disorders, especially dyslipidemia and type 2 diabetes, should undergo regular controls of serum triglycerides during tamoxifen treatment. Also, one should keep in mind that a subacute, severe rise in serum triglyceride levels may be caused, in rare cases, by tamoxifen treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of Age-Gene Correlation and the Association with Hypertriglyceridemia Using Adiponectin Receptor Single Nucleotide Polymorphism: A Potential Genetic Screening to Lower Risk of Vascular Disease in Young Asian Males

ERIC Educational Resources Information Center

Huang, William C. W.; Lin, Yi-MeiJoy; Chiu, Ching Che J.; Chiu, Chia-Huei; Chang, Fu-Sheng

2017-01-01

Purpose: This study was to investigate whether there is an age dependent effect on the association between ADIPPOR1 SNP and hypertriglyceridemia for each gender. Materials and Methods: 116 individuals aged 20 and above who claimed to be healthy were enrolled and grouped into male and female populations. Blood samples were taken to determine…

Lipoprotein marker for hypertriglyceridemia

DOEpatents

Cubicciotti, Roger S.; Karu, Alexander E.; Krauss, Ronald M.

1986-01-01

Methods and compositions are provided for the detection of a particular low density lipoprotein which has been found to be a marker for patients suffering from type IV hypertriglyceridemia. A monoclonal antibody capable of specifically binding to a characteristic epitopic site on this LDL subspecies can be utilized in a wide variety of immunoassays. Hybridoma cell line SPL.IVA5A1 was deposited at the American Type Culture Collection on Mar. 29, 1984, and granted accession no. HB 8535.

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative-nitrosative stress.

PubMed

Lupachyk, Sergey; Watcho, Pierre; Hasanova, Nailia; Julius, Ulrich; Obrosova, Irina G

2012-04-15

Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome before overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased nonesterified fatty acids (NEFA), and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative-nitrosative stress. Sixteen-week-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100 mg kg(-1) day(-1), 4 weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit and changes in behavioral measures of sensory function and corrected oxidative-nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative-nitrosative stress. Lipid-lowering agents and antioxidants may find a use in the management of this condition. Copyright © 2012 Elsevier Inc. All rights reserved.

LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

PubMed

Nocoń-Bohusz, Julita; Wikiera, Beata; Basiak, Aleksander; Śmigiel, Robert; Noczyńska, Anna

2016-02-18

Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed. © Polish Society for Pediatric Endocrinology and Diabetology.

Severe hypertriglyceridemia with pancreatitis: thirteen years' treatment with lomitapide.

PubMed

Sacks, Frank M; Stanesa, Maxine; Hegele, Robert A

2014-03-01

Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years. Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.

IL-10/STAT3 is reduced in childhood obesity with hypertriglyceridemia and is related to triglyceride level in diet-induced obese rats.

PubMed

Liu, Yuesheng; Xu, Dong; Yin, Chunyan; Wang, Sisi; Wang, Min; Xiao, Yanfeng

2018-06-13

The prevalence of childhood obesity and obesity-related metabolic disorder such as dyslipidemia has sharply increased in the past few decades. Chronic low-grade inflammation is associated with the development of comorbidities and poor prognosis in obesity. This study aims to evaluate interleukin-10 (IL-10) in childhood obesity with hypertriglyceridemia. We evaluated IL-10 and signal transducer and activator of transcription 3 (STAT3) mRNA expression in adipose tissue (AT) as well as serum IL-10 in 62 children of 3 groups and in high-fat diet (HFD) induced obese rat. Expression of IL-10 and STAT3 protein in AT of diet-induced obese rats were examined over feed period. Adipose IL-10 and STAT3 mRNA expression and serum IL-10 reduced in obese children with hypertriglyceridemia and in HFD obese rats. The protein expression of IL-10 and STAT3 decreased in AT of obese rats compared with the control rats at end time. Expression of IL-10 mRNA was negatively correlated to TG and LDL-C levels, and positively correlated to HDL-C, adiponectin and serum IL-10 levels. IL-10 expression and its downstream JAK-STAT pathway are down-regulated in obese children with hypertriglyceridemia and in HFD obese rats.

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized long-term (ORL) study.

PubMed

Tatsuno, Ichiro; Saito, Yasushi; Kudou, Kentarou; Ootake, Jun

2013-01-01

TAK-085 is an omega-3 preparation that contains eicosapentaenoic acid ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management of hypertriglyceridemia. The aim of the study was to evaluate the long-term safety (adverse events [AEs], laboratory parameters, vital signs, weight, and electrocardiograms) and effects on lipid profiles, especially triglyceride levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride levels ≥150 mg/dL and <750 mg/dL). In this multicenter, open-label, randomized study, adults with hypertriglyceridemia undergoing lifestyle modification received TAK-085 2 g (2 g once daily; n = 165) or 4 g (2 g twice daily; n = 171), or EPA-E 1.8 g (0.6 g three times daily; n = 167) for 52 weeks. Patients were stratified for co-administration of a statin. TAK-085 was well tolerated throughout the 52-week study. Overall, no substantial differences were found in the tolerability of TAK-085 2 g, TAK-085 4 g, and EPA-E 1.8 g with incidence rates for AEs of 83.6%, 86.0%, and 89.2%, respectively. Most AEs were mild or moderate in severity. Triglyceride levels decreased from baseline in all groups by week 4, and the decreases were maintained throughout the study. At week 52 the reduction in triglycerides with TAK-085 2 g (-13.9%) was similar to that with EPA-E 1.8 g (-12.1%), whereas the reduction seen with TAK-085 4 g (-25.5%) was greater than that with EPA-E 1.8 g, as assessed by point estimates and 95% confidence intervals. TAK-085 was safe and well tolerated for up to 52 weeks of treatment in Japanese patients with hypertriglyceridemia undergoing lifestyle modification. Reductions in triglyceride levels achieved after 4 weeks were maintained at 52 weeks. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

PubMed

Aye, Myint Myint; Kilpatrick, Eric S; Aburima, Ahmed; Wraith, Katie S; Magwenzi, Simbarashe; Spurgeon, B; Rigby, Alan S; Sandeman, Derek; Naseem, Khalid M; Atkin, Stephen L

2014-02-28

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814.

Acute Hypertriglyceridemia Induces Platelet Hyperactivity That is Not Attenuated by Insulin in Polycystic Ovary Syndrome

PubMed Central

Aye, Myint Myint; Kilpatrick, Eric S.; Aburima, Ahmed; Wraith, Katie S.; Magwenzi, Simbarashe; Spurgeon, B.; Rigby, Alan S.; Sandeman, Derek; Naseem, Khalid M.; Atkin, Stephen L.

2014-01-01

Background Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Methods and Results Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P‐selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg−1 min−1, P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg−1 min−1, P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid‐induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Conclusion Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero‐thrombotic risk. Clinical Trial Registration URL: www.isrctn.org. Unique Identifier: ISRCTN42448814. PMID:24584741

The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia.

PubMed

Backes, James; Anzalone, Deborah; Hilleman, Daniel; Catini, Julia

2016-07-22

Hypertriglyceridemia (triglycerides > 150 mg/dL) affects ~25 % of the United States (US) population and is associated with increased cardiovascular risk. Severe hypertriglyceridemia (≥ 500 mg/dL) is also a risk factor for pancreatitis. Three omega-3 fatty acid (OM3FA) prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia: (1) OM3FA ethyl esters (OM3EE), a mixture of OM3FA ethyl esters, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lovaza®, Omtryg™, and generics); (2) icosapent ethyl (IPE), EPA ethyl esters (Vascepa®); and (3) omega-3 carboxylic acids (OM3CA), a mixture of OM3FAs in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (Epanova®). At approved doses, all formulations substantially reduce triglyceride and very-low-density lipoprotein levels. DHA-containing formulations may also increase low-density lipoprotein cholesterol. However, this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk in this patient population. Proposed mechanisms of action of OM3FAs include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation. OM3CA bioavailability (area under the plasma concentration-time curve from zero to the last measurable concentration) is up to 4-fold greater than that of OM3FA ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis. All three formulations are well tolerated (the most common adverse events are gastrointestinal) and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs, such as statins and fibrates. OM3FAs appear to be an effective treatment option for patients with severe hypertriglyceridemia.

Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

PubMed Central

Weinstock, P H; Bisgaier, C L; Aalto-Setälä, K; Radner, H; Ramakrishnan, R; Levak-Frank, S; Essenburg, A D; Zechner, R; Breslow, J L

1995-01-01

Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups have threefold higher triglycerides and sevenfold higher VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient mice become pale, then cyanotic, and finally die at approximately 18 h of age. Before death, triglyceride levels are severely elevated (15,087 +/- 3,805 vs 188 +/- 71 mg/dl in controls). Capillaries in tissues of homozygous knockout mice are engorged with chylomicrons. This is especially significant in the lung where marginated chylomicrons prevent red cell contact with the endothelium, a phenomenon which is presumably the cause of cyanosis and death in these mice. Homozygous knockout mice also have diminished adipose tissue stores as well as decreased intracellular fat droplets. By crossbreeding with transgenic mice expressing human LPL driven by a muscle-specific promoter, mouse lines were generated that express LPL exclusively in muscle but not in any other tissue. This tissue-specific LPL expression rescued the LPL knockout mice and normalized their lipoprotein pattern. This supports the contention that hypertriglyceridemia caused the death of these mice and that LPL expression in a single tissue was sufficient for rescue. Heterozygous LPL knockout mice survive to adulthood and have mild hypertriglyceridemia, with 1.5-2-fold elevated triglyceride levels compared with controls in both the fed and fasted states on chow, Western-type, or 10% sucrose diets. In vivo turnover studies revealed that heterozygous knockout mice had impaired VLDL clearance (fractional catabolic rate) but no increase in transport rate. In summary, total LPL deficiency in the mouse prevents triglyceride removal from plasma, causing death in the neonatal period, and expression of LPL in a single tissue alleviates this problem. Furthermore, half-normal levels of LPL cause a decrease in VLDL fractional catabolic rate and mild hypertriglyceridemia, implying that partial LPL deficiency has physiological consequences. Images PMID:8675619

Icosapent ethyl: a review of its use in severe hypertriglyceridemia.

PubMed

Kim, Esther S; McCormack, Paul L

2014-12-01

Icosapent ethyl (Vascepa®) is a high-purity ethyl ester of eicosapentaenoic acid (EPA) that is de-esterified to EPA following oral administration. Both EPA and docosahexaenoic acid (DHA) are long-chain omega-3 fatty acids that have been associated with triglyceride (TG)-lowering. However, DHA has been associated with increased low-density lipoprotein cholesterol (LDL-C) levels. Icosapent ethyl contains ≥96 % of the EPA ethyl ester, does not contain DHA, and is approved in the USA for use as an adjunct to diet to lower TG levels in adult patients with severe (≥500 mg/dL [≥5.65 mmol/L]) hypertriglyceridemia. In a pivotal phase III trial, oral icosapent ethyl 4 g/day significantly decreased the placebo-corrected median TG levels by 33.1 %. It did not increase LDL-C, had favorable effects on other lipid parameters, and had a tolerability profile similar to that of placebo. Therefore, icosapent ethyl is an effective and well-tolerated agent for the treatment of severe hypertriglyceridemia in adults.

Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk.

PubMed

Thériault, Sébastien; Don-Wauchope, Andrew; Chong, Michael; Lali, Ricky; Morrison, Katherine M; Paré, Guillaume

2016-01-01

We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients*s⃞

PubMed Central

Pullinger, Clive R.; Aouizerat, Bradley E.; Movsesyan, Irina; Durlach, Vincent; Sijbrands, Eric J.; Nakajima, Katsuyuki; Poon, Annie; Dallinga-Thie, Geesje M.; Hattori, Hiroaki; Green, Lauri L.; Kwok, Pui-Yan; Havel, Richard J.; Frost, Philip H.; Malloy, Mary J.; Kane, John P.

2008-01-01

Apolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma TG levels in subjects of Chinese ancestry living in the United States and in a group of non-Chinese Asian ancestry. The frequency of the less common cysteine allele was 4-fold higher (15.1% vs. 3.7%) in Chinese high-TG subjects compared with a low-TG group (Chi-square = 20.2; P < 0.0001), corresponding with a 4.45 times higher risk of hypertriglyceridemia (95% confidence interval, 2.18–9.07; P < 0.001). These results were replicated in the non-Chinese Asians. Heterozygosity was associated, in the high-TG group, with a doubling of TG (P < 0.001), mainly VLDL TG (P = 0.014). All eleven TT homozygotes had severe hypertriglyceridemia, with mean TG of 2,292 ± 447 mg/dl. Compared with controls, carriers of the T allele had lower postheparin lipoprotein lipase activity but not hepatic lipase activity. In Asian populations, this common polymorphism can lead to profound adverse effects on lipoprotein profiles, with homozygosity accounting for a significant number of cases of severe hypertriglyceridemia. This specific apoA-V variant has a pronounced effect on TG metabolism, the mechanism of which remains to be elucidated. PMID:18441017

Association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals.

PubMed

Klafke, Jonatas Zeni; Porto, Fernando Garcez; Batista, Roselaine; Bochi, Guilherme Vargas; Moresco, Rafael Noal; da Luz, Protásio Lemos; Viecili, Paulo Ricardo Nazário

2015-08-25

Although hypercholesterolemia is a well-established risk factor for coronary heart disease, evidence suggests that increased triglyceride (TG) concentrations are also an independent risk factor. TG concentrations >150mg/dl are observed nearly twice as often in subjects with atherosclerosis. We assessed the association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals. We included 127 volunteers enrolled in Cruz Alta, RS, Brazil. The patients were stratified based on total cholesterol and TG concentrations for analysis of associations with inflammation (high-sensitivity C-reactive protein - hs-CRP), endothelial dysfunction (nitric oxide - NOx) and oxidative stress (advanced oxidation protein products - AOPPs; ischemia-modified albumin - IMA). Correlations between variables were determined and multiple regression analysis was employed to investigate whether some variables correlate with TG concentrations. Hypertriglyceridemia was related to oxidative stress and proinflammatory markers in individuals independent of total cholesterol concentrations. Moreover, the results indicate a stronger association of tested biomarkers with TG concentrations than with total cholesterol. The results indicate a positive correlation between oxidative stress and TG concentrations in the sera of hypercholesterolemia subjects. AOPPs and IMA concentrations were associated with the presence of hypertriglyceridemia in a manner that was independent of age, gender, hypertension and diabetes mellitus disease, smoking habits, sedentary lifestyle, BMI, waist circumference, LDL, HDL and total cholesterol concentrations. We speculate that TG concentrations can reflect the enhancement of protein oxidation and proinflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment by plasma exchange of a patient with hyperlipidemia and diabetic ketoacidosis with lesional pulmonary edema and acute pancreatitis.

PubMed

Gérard, A; Schooneman, F; Guine, J M; Roche, G; Canton, P; Dureux, J B; Janot, C; Streiff, F

1982-01-01

The authors report a case of severe hypertriglyceridemia (148.5 mmol/l) in a 27-year-old woman admitted for coma of unknown origin. Initial investigations revealed ketoacidosis, pancreatitis and noncardiogenic pulmonary edema. The diabetes was unknown. Ketoacidosis was rapidly controlled. The hypertriglyceridemia was corrected by one course of plasma exchange (4,400 ml) during which the patient returned to consciousness. The patient recovered without any sequelae. Only 2 similar cases, treated by plasma exchange, have been reported in the literature until now.

Severe hypertriglyceridemia in Puerto Rico blood donors: a population study 2009-2011.

PubMed

Morales-Borges, Raúl H; Merced, Carmen

2012-01-01

Puerto Rico blood donor issues has been identified in cases of severe hypertriglyceridemia presenting as turbid. Blood donations resulting in milky serum must be discarded. They are discarded because we cannot properly test the donation. This is the first report where we correlate turbidity and cardiovascular risk factors in the Puerto Rico population as well as blood types O and A, Rh (+) with dyslipidemia. Blood donors should be screened in more details regarding cardiovascular and metabolic risks to avoid problems with recruitment and retention strategies.

PPAR-α Agonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia

PubMed Central

Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Pan, Qingrong; Yao, Zhi; Yang, Ning; Liu, Jia; Xu, Yuan; Wang, Guang; Yang, Xinchun

2015-01-01

Irisin is related to insulin resistance and metabolic disorders. The physiologic effects of irisin are partially mediated through peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the effect of fenofibrate, a PPAR-α agonist, on serum irisin in type 2 diabetes patients with hypertriglyceridemia. This study evaluated cross-sectional and interventional studies of 25 type 2 diabetes patients with hypertriglyceridemia (group A) and 40 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum irisin and clinical characteristics were examined. Serum irisin was significantly higher in group A compared with group B (45.15 ± 10.48 versus 35.38 ± 9.97 ng/ml, P < 0.001) and correlated with body mass index (r = 0.314, P = 0.011), fasting blood glucose (r = 0.399, P = 0.001), total cholesterol (r = 0.256, P = 0.040), and high-density lipoprotein cholesterol (r = 0.247, P = 0.047). In multiple regression analysis after controlling for confounders, only fasting blood glucose (β = 5.615, P < 0.001) and high-density lipoprotein cholesterol (β = 19.483, P < 0.001) were independently related to serum irisin. After 8 weeks of fenofibrate treatment, serum irisin significantly decreased in group A compared with baseline (45.15 ± 10.48 versus 38.74 ± 12.54 ng/ml, P = 0.011). Conclusively, fenofibrate decreased serum irisin in type 2 diabetes patients with hypertriglyceridemia, indicating that PPAR-α agonists may protect against metabolic disorders by improving irisin resistance. PMID:26693220

Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low-Density Lipoprotein Cholesterol Levels.

PubMed

Kitagami, Masayuki; Yasuda, Ryuta; Toma, Naoki; Shiba, Masato; Nampei, Mai; Yamamoto, Yoko; Nakatsuka, Yoshinari; Sakaida, Hiroshi; Suzuki, Hidenori

2017-08-01

Dyslipidemia is a well-known risk factor for carotid stenosis progression, but triglycerides have attracted little attention. The aim of this study was to assess if serum triglycerides affect progression of carotid stenosis in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. This is a retrospective study in a single hospital consisting of 71 Japanese patients with internal carotid artery stenosis greater than or equal to 50% and normal serum LDL-C levels who underwent angiographic examination with or without the resultant carotid artery stenting or endarterectomy from 2007 to 2011, and were subsequently followed up for 4 years. Clinical factors including fasting serum triglyceride values were compared between the progression (≥10% increase in degree of carotid stenosis on ultrasonography) and the nonprogression groups. During 4 years, 15 patients (21.1%) had carotid stenosis progression on either side. Cox regression analysis demonstrated that symptomatic cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR, 6.228; P = .011) were associated with subsequent progression of carotid stenosis. Kaplan-Meier plots demonstrated that the progression-free survival rate was significantly higher in patients without hypertriglyceridemia and intracranial arteriosclerotic stenosis at baseline. Among patients with moderate to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an important risk factor for progression of carotid stenosis irrespective of surgical treatments. It would be worthwhile to test if triglyceride-lowering medications suppress carotid stenosis progression. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.

PubMed

Dussaillant, Catalina; Serrano, Valentina; Maiz, Alberto; Eyheramendy, Susana; Cataldo, Luis Rodrigo; Chavez, Matías; Smalley, Susan V; Fuentes, Marcela; Rigotti, Attilio; Rubio, Lorena; Lagos, Carlos F; Martinez, José Alfredo; Santos, José Luis

2012-11-15

Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

PubMed Central

2012-01-01

Background Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family. PMID:23151256

FoxO1 integrates insulin signaling to VLDL production

PubMed Central

Kamagate, Adama; Dong, H. Henry

2009-01-01

Very low-density lipoproteins (VLDL) are triglyceride-rich particles. VLDL is synthesized in hepatocytes and secreted from the liver in a pathway that is tightly regulated by insulin. Hepatic VLDL production is stimulated in response to reduced insulin action, resulting in increased release of VLDL into the blood under fasting conditions. Circulating VLDL serves as a vehicle for transporting lipids to peripheral tissues for energy homeostasis. Conversely, hepatic VLDL production is suppressed in response to increased insulin release after meals. This effect is critical for preventing prolonged excursion of postprandial plasma lipid profiles in normal individuals. In subjects with obesity and type 2 diabetes, the ability of insulin to regulate VLDL production becomes impaired due to insulin resistance in the liver, resulting in excessive VLDL secretion and accumulation of triglyceride-rich particles in the blood. Such abnormality in lipid metabolism characterizes the pathogenesis of hypertriglyceridemia and accounts for increased risk of coronary artery disease in obesity and type 2 diabetes. Nevertheless, the molecular basis that links insulin resistance to VLDL overproduction remains poorly understood. Our recent studies illustrate that the forkhead transcription factor FoxO1 acts in the liver to integrate hepatic insulin action to VLDL production. Augmented FoxO1 activity in insulin resistant livers promotes hepatic VLDL overproduction and predisposes to the development of hypertriglyceridemia. These new findings raise an important question: Is FoxO1 a therapeutic target for ameliorating hypertriglyceridemia? Here we discuss this question in the context of recent advances toward our understanding of the pathophysiology of hypertriglyceridemia. PMID:18927507

Higher rates and clustering of abnormal lipids, obesity, and diabetes mellitus in psoriatic arthritis compared with rheumatoid arthritis.

PubMed

Labitigan, Monalyn; Bahče-Altuntas, Asena; Kremer, Joel M; Reed, George; Greenberg, Jeff D; Jordan, Nicole; Putterman, Chaim; Broder, Anna

2014-04-01

We compared the prevalence and the clustering of the metabolic syndrome (MetS) components (obese body mass index [BMI; ≥30 kg/m(2) ], hypertriglyceridemia, low high-density lipids, hypertension, and diabetes mellitus) in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. We included CORRONA participants with a rheumatologist-confirmed clinical diagnosis of PsA or RA with complete data. We used a modified definition of MetS that did not include insulin resistance, waist circumference, or blood pressure measurements. Logistic regression models were adjusted for age, sex, and race. In the overall CORRONA population, the rates of diabetes mellitus and obesity were significantly higher in PsA compared with RA. In 294 PsA and 1,162 RA participants who had lipids measured, the overall prevalence of MetS in PsA versus RA was 27% versus 19%. The odds ratio (OR) of MetS in PsA versus RA was 1.44 (95% confidence interval [95% CI] 1.05-1.96, P = 0.02). The prevalence of hypertriglyceridemia was higher in PsA compared with RA (38% versus 28%; OR 1.51 [95% CI 1.15-1.98], P = 0.003). The prevalence of type 2 diabetes mellitus was also higher in PsA compared with RA (15% versus 11%; OR 1.56 [95% CI 1.07-2.28], P = 0.02) in the adjusted model. Similarly, higher rates of hypertriglyceridemia and diabetes mellitus were observed in the subgroup of PsA and RA patients with obese BMI. Compared with RA, PsA is associated with higher rates of obesity, diabetes mellitus, and hypertriglyceridemia. Copyright © 2014 by the American College of Rheumatology.

Elevated depressive symptoms are associated with hypertriglyceridemia in Japanese male workers.

PubMed

Kamezaki, Fumihiko; Sonoda, Shinjo; Nakata, Sei; Okazaki, Masahiro; Tamura, Masahito; Abe, Haruhiko; Takeuchi, Masaaki; Otsuji, Yutaka

2011-01-01

The aim of this study was to determine whether elevated depressive symptoms are associated with metabolic syndrome and its components in the Japanese population. Out of 1,386 male workers who underwent measurements of variables of metabolic syndrome components in their health checkup, 1,186 subjects (44.5 ± 9.6 years) completed the Zung self-rating depression scale (ZSDS) (response rate 85.6%). In this study, metabolic syndrome was defined according to the joint scientific statement proposed by 6 major organizations, including the International Diabetes Federation. The overall frequency of elevated depressive symptoms (ZSDS scores ≥40) was 42.1% (n=499). The incidence of metabolic syndrome was significantly higher in subjects with elevated depressive symptoms than in those without (13.2% vs. 8.9%, p<0.05). Of all the metabolic syndrome components, mean triglyceride levels were significantly higher in subjects with elevated depressive symptoms than in those without [124.7 (95% confidence interval (CI): 117.8-131.7) mg/dL vs. 111.5 (95% CI: 107.2-115.9) mg/dL, p<0.05]. Consequently, hypertriglyceridemia (28.9% vs. 21.0%, p<0.01) was the main component correlated with the between-group difference of metabolic syndrome incidence. In the logistic regression analysis after adjustment for potential confounders, the odds ratio of the total ZSDS scores for the diagnosis of hypertriglyceridemia was 1.52 (95% CI: 1.13-2.04; p<0.01), and the major depressive symptom was psychomotor agitation (odds ratio: 1.47; 95% CI: 1.10-1.94; p<0.01). This study showed that elevated depressive symptoms were associated with hypertriglyceridemia in Japanese male workers, which affected the clinical diagnosis of metabolic syndrome.

Clinical characteristics of Japanese patients with severe hypertriglyceridemia.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Nakahashi, Takuya; Yagi, Kunimasa; Chujo, Daisuke; Ohbatake, Azusa; Mori, Yukiko; Mori, Shunsuke; Kometani, Mitsuhiro; Fujii, Hiroshi; Nohara, Atsushi; Inazu, Akihiro; Mabuchi, Hiroshi; Yamagishi, Masakazu; Hayashi, Kenshi

2015-01-01

Although of interest, few data exist on the clinical characteristics of Japanese patients with an extremely high triglyceride level (≥ 1000 mg/dL). We assessed the clinical characteristics of Japanese patients with an extremely high triglyceride level. We investigated the presence of coronary artery disease, history of pancreatitis, the presence of fatty liver, and the potential causes of elevated triglyceride in Japanese subjects with an extremely high level of fasting triglyceride (≥ 1000 mg/dL) among 70,368 subjects whose serum triglyceride was measured for any reason at Kanazawa University Hospital from April 2004 to March 2014. We identified 215 (0.31%) subjects (mean age, 46 years; male, 170, mean body mass index, 25 kg/m(2)) with severe hypertriglyceridemia. Among them, 4 (1.9%) subjects were classified as type I, 97 (45.1%) subjects were type IV, and 114 (53.0%) subjects were type V hyperlipidemia, according to Fredrickson's classification. Among 215 subjects, 116 subjects (54.0%) drank alcohol, 58 (27.0%) showed heavy intake (≥ 60 g/d), and 64 (29.8%) subjects had diabetes. In total, 59 (27.4%) subjects had transient severe hypertriglyceridemia caused by corticosteroids (N = 19), antidepressant (N = 18), l-asparaginase and steroids for acute lymphoid leukemia (N = 15), hormone replacement therapy for breast cancer (N = 9), β-blocker (N = 5), hypothyroidism (N = 4), pregnancy (N = 4), and panhypopituitarism (N = 2). As many as 119 (55.3%) subjects exhibited fatty liver. Moreover, 12 (5.6%) and 17 (7.9%) subjects had a history of pancreatitis and coronary artery disease, respectively. A variety of situations can cause severe hypertriglyceridemia. We suggest that potential secondary causes should be carefully assessed for such patients. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

PubMed

Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

2013-05-01

During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan.

PubMed

Kuwabara, Masanari; Borghi, Claudio; Cicero, Arrigo F G; Hisatome, Ichiro; Niwa, Koichiro; Ohno, Minoru; Johnson, Richard J; Lanaspa, Miguel A

2018-06-15

High serum uric acid (SUA) is associated with the dyslipidemia, but whether hyperuricemia predicts an increase in serum low-density lipoprotein (LDL) cholesterol is unknown. This study is to evaluate whether an elevated SUA predicts the development of high LDL cholesterol as well as hypertriglyceridemia. This is a retrospective 5-year cohort study of 6476 healthy Japanese adults (age, 45.7 ± 10.1 years; 2.243 men) who underwent health examinations at 2004 and were reevaluated in 2009 at St. Luke's International Hospital, Tokyo, Japan. Subjects were included if at their baseline examination they did not have hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, or if they were on medication for hyperuricemia and/or gout. The analysis was adjusted for age, body mass index (BMI), smoking and drinking habits, baseline estimated glomerular filtration rate (eGFR), baseline SUA and SUA change over the 5 years. High baseline SUA was an independent risk for developing high LDL cholesterol both in men (OR: 1.159 per 1 mg/dL increase, 95% CI:1.009-1.331) and women (OR: 1.215, 95% CI:1.061-1.390). Other risk factors included a higher baseline LDL cholesterol, higher BMI, and higher baseline eGFR (the latter two in women only). Increased SUA over 5 years were also independent risks for developing high LDL cholesterol and hypertriglyceridemia, but not for low high-density lipoprotein (HDL) cholesterol. This is the first study to report that an elevated SUA increases the risk for developing high LDL cholesterol, as well as hypertriglyceridemia. This may shed light into the role of SUA in cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Organophosphorus Flame Retardants Inhibit Specific Liver Carboxylesterases and Cause Serum Hypertriglyceridemia

PubMed Central

2015-01-01

Humans are prevalently exposed to organophosphorus flame retardants (OPFRs) contained in consumer products and electronics, though their toxicological effects and mechanisms remain poorly understood. We show here that OPFRs inhibit specific liver carboxylesterases (Ces) and cause altered hepatic lipid metabolism. Ablation of the OPFR target Ces1g has been previously linked to dyslipidemia in mice. Consistent with OPFR inhibition of Ces1g, we also observe OPFR-induced serum hypertriglyceridemia in mice. Our findings suggest novel toxicities that may arise from OPFR exposure and highlight the utility of chemoproteomic and metabolomic platforms in the toxicological characterization of environmental chemicals. PMID:24597639

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine.

PubMed

Hiel, Sophie; Neyrinck, Audrey M; Rodriguez, Julie; Pachikian, Barbara D; Bouzin, Caroline; Thissen, Jean-Paul; Cani, Patrice D; Bindels, Laure B; Delzenne, Nathalie M

2018-04-25

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 ( Apoc3 , inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.

Inulin Improves Postprandial Hypertriglyceridemia by Modulating Gene Expression in the Small Intestine

PubMed Central

Hiel, Sophie; Rodriguez, Julie; Pachikian, Barbara D.; Thissen, Jean-Paul; Delzenne, Nathalie M.

2018-01-01

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk. PMID:29693598

Secondary hypertriglyceridemia in children and adolescents.

PubMed

Blackett, Piers R; Wilson, Don P; McNeal, Catherine J

2015-01-01

Secondary dyslipidemia with predominant hypertriglyceridemia may occur as a consequence of both common and rare causes. After accounting for obesity and associated insulin resistance, clinicians should carefully consider other contributing factors and conditions. Genetic background and causative factors prevail during gestation, infancy, and childhood and continue in adults. Elevations in triglyceride (TG) are associated with transfer of TG to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) resulting in lipolysis, HDL degradation, and formation of atherogenic LDL particles. Defining and treating the underlying cause is the first step toward restoring the lipids and lipoproteins to normal, especially in cases with severe hypertriglyceridemia, who are at risk for acute pancreatitis. Disorders involving the liver, kidney, endocrine, and immune systems and medications need to be considered. Rare diseases such as lipodystrophy and glycogen storage disease are particularly challenging, and there have been promising new developments. Treatment depends on the severity; prevention of acute pancreatitis being a priority in severe cases and lifestyle modification being a foundation for general management followed by targeting TG and predictors of coronary artery disease such as LDL cholesterol and non-HDL cholesterol, when they exceed cutpoints. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Whole-Exome Sequencing Reveals GPIHBP1 Mutations in Infantile Colitis With Severe Hypertriglyceridemia

PubMed Central

Gonzaga-Jauregui, Claudia; Mir, Sabina; Penney, Samantha; Jhangiani, Shalini; Midgen, Craig; Finegold, Milton; Muzny, Donna M.; Wang, Min; Bacino, Carlos A.; Gibbs, Richard A.; Lupski, James R.; Kellermayer, Richard; Hanchard, Neil A.

2014-01-01

Severe congenital hypertriglyceridemia (HTG) is a rare disorder caused by mutations in genes affecting lipoprotein lipase (LPL) activity. Here we report a 5-week-old Hispanic girl with severe HTG (12,031 mg/dL, normal limit 150 mg/dL) who presented with the unusual combination of lower gastrointestinal bleeding and milky plasma. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. After negative sequencing of the LPL gene, whole-exome sequencing revealed novel compound heterozygous mutations in GPIHBP1. Our study broadens the phenotype of GPIHBP1-associated HTG, reinforces the effectiveness of whole-exome sequencing in Mendelian diagnoses, and implicates triglycer-ides in gastrointestinal mucosal injury. PMID:24614124

Whole-exome sequencing reveals GPIHBP1 mutations in infantile colitis with severe hypertriglyceridemia.

PubMed

Gonzaga-Jauregui, Claudia; Mir, Sabina; Penney, Samantha; Jhangiani, Shalini; Midgen, Craig; Finegold, Milton; Muzny, Donna M; Wang, Min; Bacino, Carlos A; Gibbs, Richard A; Lupski, James R; Kellermayer, Richard; Hanchard, Neil A

2014-07-01

Severe congenital hypertriglyceridemia (HTG) is a rare disorder caused by mutations in genes affecting lipoprotein lipase (LPL) activity. Here we report a 5-week-old Hispanic girl with severe HTG (12,031 mg/dL, normal limit 150 mg/dL) who presented with the unusual combination of lower gastrointestinal bleeding and milky plasma. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. After negative sequencing of the LPL gene, whole-exome sequencing revealed novel compound heterozygous mutations in GPIHBP1. Our study broadens the phenotype of GPIHBP1-associated HTG, reinforces the effectiveness of whole-exome sequencing in Mendelian diagnoses, and implicates triglycerides in gastrointestinal mucosal injury.

A novel APOC2 gene mutation identified in a Chinese patient with severe hypertriglyceridemia and recurrent pancreatitis.

PubMed

Jiang, Jingjing; Wang, Yuhui; Ling, Yan; Kayoumu, Abudurexiti; Liu, George; Gao, Xin

2016-01-16

The severe forms of hypertriglyceridemia are usually caused by genetic defects. In this study, we described a Chinese female with severe hypertriglyceridemia caused by a novel homozygous mutation in the APOC2 gene. Lipid profiles of the pedigree were studied in detail. LPL and HL activity were also measured. The coding regions of 5 candidate genes (namely LPL, APOC2, APOA5, LMF1, and GPIHBP1) were sequenced using genomic DNA from peripheral leucocytes. The ApoE gene was also genotyped. Serum triglyceride level was extremely high in the proband, compared with other family members. Plasma LPL activity was also significantly reduced in the proband. Serum ApoCII was very low in the proband as well as in the heterozygous mutation carriers. A novel mutation (c.86A > CC) was identified on exon 3 [corrected] of the APOC2 gene, which converted the Asp [corrected] codon at position 29 into Ala, followed by a termination codon (TGA). This study presented the first case of ApoCII deficiency in the Chinese population, with a novel mutation c.86A > CC in the APOC2 gene identified. Serum ApoCII protein might be a useful screening test for identifying mutation carriers.

[Severe hypertriglyceridemia : Diagnostics and new treatment principles].

PubMed

Kassner, U; Dippel, M; Steinhagen-Thiessen, E

2017-08-01

Severe hypertriglyceridemia is defined at a plasma triglyceride (TG) concentration of >885 mg/dl and may result - in particular when clinical symptoms appear before the age of 40 - from "large variant" mutations in genes which influence the function of the lipoprotein lipase (LPL). For diagnosis, secondary factors have to be excluded and treated before further genetic tests are considered. Typical symptoms in almost all patients are recurrent, sometimes severe abdominal pain attacks, which can result in acute pancreatitis, the most important, sometimes life-threatening complication. To minimize the risk of severe pancreatitis, the aim is to maintain the plasma TG concentration <1000 mg/dl. Other clinical manifestations which can occur and are reversible are eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, dyspnea syndrome, and impaired neurocognitive function. The hyperviscosity syndrome caused by chylomicronemia is seen as the underlying reason for some of the symptoms. Patients with mild-to-moderate hypertriglyceridemia have an increased cardiovascular risk. To lower this is the primary treatment goal here. Treatment mainly consists of a life-long, strict fat- and carbohydrate-restricted diet and the abstention from alcohol. Omega‑3-Fatty acids and fibrates can be used to lower plasma TG levels. Recently, new gene therapy approaches for LPL-deficient patients have become available in Germany.

Genomic interval engineering of mice identified a novel modulator of triglyceride production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Y.; Jong, M.C.; Frazer, K.A.

1999-10-01

To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepaticmore » very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.« less

Medical nutrition therapy is the essential cornerstone for effective treatment of "refractory" severe hypertriglyceridemia regardless of pharmaceutical treatment: Evidence from a Lipid Management Program.

PubMed

Rhodes, Katherine S; Weintraub, Martha; Marchlewicz, Elizabeth H; Rubenfire, Melvyn; Brook, Robert D

2015-01-01

Patients with refractory severe hypertriglyceridemia are at risk of pancreatitis and cardiovascular disease. The role of individualized nutrition therapy in these patients independent of pharmaceutical treatment has not been documented. To document the effect of nutrition intervention on severe hypertriglyceridemia regardless of medication status or prior nutrition counseling. Outcomes of new patients with triglycerides ≥ 500 mg/dL presenting to a Lipid Management Program over a 6-year period were tracked. Patients received comprehensive laboratory assessment, nutrition assessment, and initiation of an individualized diet intervention before seeing the lipidologist. Clinical and behavioral outcomes were recorded. In all, 168 patients (117 men; mean age, 49.03 ± 11.22 years; body mass index, 32.61 ± 5.85 kg/m(2); 110 (65.5%) on lipid-lowering medications) returned for assessment of nutrition intervention. Triglycerides were reduced from median (interquartile range) 961.5 (611.5-1785.3) to 493.0 (337-736.3) mg/dL (P < .0001 for log transformation of triglycerides). There was no difference in median percentage reduction in triglycerides after nutrition intervention between those not on lipid-lowering medication, on a fibric acid derivative, on other lipid-lowering medication, or on a combination of lipid-lowering medications (P = .376) in a median (interquartile range) of 5 (3-7) weeks. Effect was independent of prior nutrition counseling (P = .260). Reported percentage fat in the diet at second visit correlated with log-transformed triglycerides achieved, independent of initial triglycerides level (r = 0.290; P = .001). Individualized nutrition therapy results in changes in eating behavior and reductions in triglyceride levels in patients with refractory severe hypertriglyceridemia independent of lipid-lowering medication(s) and prior nutrition counseling. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Inhibition of ERK1/2 and activation of LXR synergistically reduce atherosclerotic lesions in ApoE-deficient mice.

PubMed

Chen, Yuanli; Duan, Yajun; Yang, Xiaoxiao; Sun, Lei; Liu, Mengyang; Wang, Qixue; Ma, Xingzhe; Zhang, Wenwen; Li, Xiaoju; Hu, Wenquan; Miao, Robert Q; Xiang, Rong; Hajjar, David P; Han, Jihong

2015-04-01

Activation of liver X receptor (LXR) inhibits atherosclerosis but induces hypertriglyceridemia. In vitro, it has been shown that mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor synergizes LXR ligand-induced macrophage ABCA1 expression and cholesterol efflux. In this study, we determined whether MEK1/2 (U0126) and LXR ligand (T0901317) can have a synergistic effect on the reduction of atherosclerosis while eliminating LXR ligand-induced fatty livers and hypertriglyceridemia. We also set out to identify the cellular mechanisms of the actions. Wild-type mice were used to determine the effect of U0126 on a high-fat diet or high-fat diet plus T0901317-induced transient dyslipidemia and liver injury. ApoE deficient (apoE(-/-)) mice or mice with advanced lesions were used to determine the effect of the combination of T0901317 and U0126 on atherosclerosis and hypertriglyceridemia. We found that U0126 protected animals against T0901317-induced transient or long-term hepatic lipid accumulation, liver injury, and hypertriglyceridemia. Meanwhile, the combination of T0901317 and U0126 inhibited the development of atherosclerosis in a synergistic manner and reduced advanced lesions. Mechanistically, in addition to synergistic induction of macrophage ABCA1 expression, the combination of U0126 and T0901317 maintained arterial wall integrity, inhibited macrophage accumulation in aortas and formation of macrophages/foam cells, and activated reverse cholesterol transport. The inhibition of T0901317-induced lipid accumulation by the combined U0126 might be attributed to inactivation of lipogenesis and activation of lipolysis/fatty acid oxidation pathways. Our study suggests that the combination of mitogen-activated protein kinase kinase 1/2 inhibitor and LXR ligand can function as a novel therapy to synergistically reduce atherosclerosis while eliminating LXR-induced deleterious effects. © 2015 American Heart Association, Inc.

The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study.

PubMed

Kwon, Yu Hyun; Kim, Seul Ki; Cho, Jung Hwan; Kwon, Hyemi; Park, Se Eun; Oh, Hyung Geun; Park, Cheol Young; Lee, Won Young; Oh, Ki Won; Park, Sung Woo; Rhee, Eun Jung

2018-03-01

Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time. A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014. Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80). In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI. Copyright © 2018 Korean Endocrine Society.

The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study

PubMed Central

Kwon, Yu Hyun; Kim, Seul-Ki; Cho, Jung Hwan; Kwon, Hyemi; Park, Se Eun; Oh, Hyung-Geun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo

2018-01-01

Background Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time. Methods A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014. Results Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80). Conclusion In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI. PMID:29388400

Acute starvation ketoacidosis in pregnancy with severe hypertriglyceridemia: A case report.

PubMed

Hui, Li; Shuying, Li

2018-05-01

Pregnant women are more prone to ketosis due to the relative insulin resistance, accelerated lipolysis and increased free fatty acids. We report a pregnant woman with hyperlipidemia, who experienced severe metabolic acidosis after a short period of starvation. Based on her clinical symptoms, exclusion diagnosis and therapeutic diagnosis, her condition was diagnosed as starvation ketoacidosis. An emergency caesarean section under general anesthesia was implemented 2 hours after her admission. The metabolic acidosis was treated with fluid resuscitation using compound sodium lactate, bicarbonate, and 5% dextrose together with insulin 6U. Both mother and baby were discharged clinically well. Starvation ketoacidosis may happen in special patient who was in pregnancy and with severe hypertriglyceridemia, after just one day fasting and vomiting.

Medications not intended for treatment of dyslipidemias and with a variable effect on lipids.

PubMed

Whayne, Thomas F; Mukherjee, Debabrata

2014-01-01

Many therapeutically active medications have significant side effects, some of which can compromise the intended therapeutic goal. The development of plasma lipid abnormalities or a dyslipidemia as the result of a medication intended for an unrelated effect has been reported. Human immunodeficiency virus (HIV) infection can cause dyslipidemia as can the medications used to treat this infection. Such dyslipidemia can be a significant problem made more relevant by the already increased risk of cardiovascular (CV) disease faced by these patients. Some hypoglycemic medications used to treat diabetes can also be associated with dyslipidemia, most notably rosiglitazone. Antihypertensive medications are intended to decrease CV risk but are not free of dyslipidemia problems with thiazides able to cause hypertriglyceridemia and older beta-blockers without an alpha-blocking effect associated with moderate plasma lipid abnormalities and altered glucose metabolism. Estrogen administered orally can be associated with a severe hypertriglyceridemia. Currently-used antipsychotic medications have a significant association with hypertriglyceridemia. Clinicians must be aware of the dyslipidemias caused by these medications and know how to manage them, even treating a secondary dyslipidemia with another medication as in the case of HIV infection rather than trying to switch treatment of the infection in many cases. Mention is also made of lipid lowering effects of medications intended for other purposes (e.g. angiotensin receptor blockers and orlistat).

Successful treatment of severe hypertriglyceridemia with a formula diet rich in omega-3 fatty acids and medium-chain triglycerides.

PubMed

Hauenschild, Annette; Bretzel, Reinhard G; Schnell-Kretschmer, Henning; Kloer, Hans-Ulrich; Hardt, Philip D; Ewald, Nils

2010-01-01

Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears to be a fast but expensive method to reduce triglyceride levels. In this study we describe the use of a new omega-3 fatty acid and medium-chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma triglyceride levels fast and effectively. Thirty-two patients with severe hypertriglyceridemia were treated with the especially composed formula diet for a period of 7 days. Within this period of time, plasma triglycerides decreased from 1,601 (402-4,555) to 554 (142-2,382) mg/dl (p < 0.05). Total cholesterol levels were reduced from 417 (211-841) to 287 (165-457) mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (-8%; -12%). The formula diet as a 1-week treatment was well tolerated and accepted by the patients. This diet was successfully used as an acute treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and safely lowering plasma triglyceride levels. (c) 2010 S. Karger AG, Basel.

Incidence of hypertriglyceridemia in critically ill neonates receiving lipid injectable emulsions in glass versus plastic containers: a retrospective analysis.

PubMed

Martin, Camilia R; Dumas, Gregory J; Shoaie, Claire; Zheng, Zheng; Mackinnon, Brenda; Al-Aweel, Issa; Bistrian, Bruce R; Pursley, DeWayne M; Driscoll, David F

2008-02-01

To evaluate plasma clearance of lipid injectable emulsions packaged in either glass or plastic containers in neonates from 2 7-month periods, 1 year apart. Clinical records from June 1 to December 31, 2003 (glass [G] period) and the same months in 2004 (plastic [P] period) were assessed. Neonates who received lipid injectable emulsions were studied. Lipid container (glass vs plastic) was the independent variable. Of the 197 patients studied, 122 (G, 50/81; P, 72/116) had evaluable triglyceride (TG) levels, for an overall rate of 62%. Only birth weight (G, 1.09 +/- 0.32 kg vs P, 1.23 +/- .45 kg) and birth length (G, 36.4 +/- 3.5 cm vs P, 37.9 +/- 3.5 cm) were significantly different between the 2 groups (P = .047 and .028, respectively). There were no differences in the day of life on which lipid injection was started, the lipid dose, or the timing of TG measurements. The incidence of hypertriglyceridemia was significantly higher in the P period (G, 3/50 vs P, 19/72; P = .004). Administration of the same lipid formulation in plastic bags compared with glass containers is associated with higher rates of hypertriglyceridemia. The poorer clearance of lipids could be due to a higher proportion of large-diameter fat globules in plastic bags compared with those in glass containers.

Association of STAT3 Common Variations with Obesity and Hypertriglyceridemia: Protective and Contributive Effects

PubMed Central

Ma, Zuliang; Wang, Guanghai; Chen, Xuejiao; Ou, Zejin; Zou, Fei

2014-01-01

Signal transducer and activator of transcription 3 (STAT3) plays an important role in energy metabolism. Here we explore whether STAT3 common variations influence risks of obesity and other metabolic disorders in a Chinese Han population. Two tagging single nucleotide polymorphisms (tagSNPs), rs1053005 and rs957970, were used to capture the common variations of STAT3. Relationships between genotypes and obesity, body mass index, plasma triglyceride and other metabolic diseases related parameters were analyzed for association study in 1742 subjects. Generalized linear model and logistic regression model were used for quantitative data analysis and case-control study, respectively. rs1053005 was significantly associated with body mass index and waist circumference (p = 0.013 and p = 0.02, respectively). rs957970 was significantly associated with plasma level of triglyceride (p = 0.007). GG genotype at rs1053005 had lower risks of both general obesity and central obesity (OR = 0.40, p = 0.034; OR = 0.42, p = 0.007, respectively) compared with AA genotype. CT genotype at rs957970 had a higher risk of hypertriglyceridemia (OR = 1.43, p = 0.015) compared with TT genotype. Neither of the two SNPs was associated with othermetabolic diseases related parameters. Our observations indicated that common variations of STAT3 could significantly affect the risk of obesity and hypertriglyceridemia in Chinese Han population. PMID:25014397

Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants.

PubMed

Kassner, Ursula; Salewsky, Bastian; Wühle-Demuth, Marion; Szijarto, Istvan Andras; Grenkowitz, Thomas; Binner, Priska; März, Winfried; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

2015-09-01

Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families.

Double Filtration Plasma Apheresis Shortens Hospital Admission Duration of Patients With Severe Hypertriglyceridemia-Associated Acute Pancreatitis.

PubMed

Chang, Chiz-Tzung; Tsai, Tsung-Yu; Liao, Hsin-Yi; Chang, Chia-Ming; Jheng, Jyun-Shan; Huang, Wen-Hsin; Chou, Che-Yi; Chen, Chao-Jung

2016-04-01

The treatment effectiveness of double filtration plasma apheresis (DFPP) on severe hypertriglyceridemia-associated acute pancreatitis (STAP) has been questioned because the currently defined serum triglyceride level--1000 mg/dL--is too low for STAP. Given this, we aimed to investigate DFPP effectiveness when we elevated STAP definition to 5000 mg/dL serum triglyceride. We performed nested case-control studies for STAP patients and divided them into groups "with" or "without" DFPP. We further recruited outpatient asymptomatic hypertriglyceridemia patients with STAP history, then divided them into groups "with" or "without" prophylactic DFPP once every 3 to 6 months for 2 years. We observed hospitalization duration and STAP recurrence between patients with and patients without DFPP. Twelve STAP patients receiving DFPP had a median hospitalization of 5 days, whereas 24 patients without DFPP had 10 days (P = 0.009). Six outpatient referrals with STAP history receiving prophylactic DFPP showed no STAP recurrences whereas 6 without DFPP showed 3 recurrences (P = 0.046). For the 25 patients whose serum triglyceride exceeded 5000 mg/dL, 11 receiving DFPP had median hospitalization of 5 days while 14 without DFPP had 11 days (P = 0.012). When applied to serum triglyceride in excess of 5000 mg/dL, DFPP removes oxidized and inflammatory lipoproteins, shortens hospitalization duration, and minimizes STAP recurrence.

Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants

PubMed Central

Kassner, Ursula; Salewsky, Bastian; Wühle-Demuth, Marion; Szijarto, Istvan Andras; Grenkowitz, Thomas; Binner, Priska; März, Winfried; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

2015-01-01

Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families. PMID:25585702

[Diet in disordered lipid metabolism. A culinary balance act].

PubMed

Richter, W O

2003-08-07

When LDL cholesterol is elevated, HDL cholesterol is low or triglycerides are raised, dietary changes form the basis of treatment. Such changes are most important in the case of hypertriglyceridemia. Some 3 to 4 hours after a meal, triglycerides increase to an extent determined by the composition of the meal. Hypertriglyceridemia cannot be successfully treated unless alcohol is banished and rapidly assimilatable carbohydrates are restricted. In patients with elevated LDL cholesterol, a change in eating habits can have an appreciable effect (on average 10-15%). Since this measure can save the use or reduce the dose of medications, its value is obvious, and it must not be neglected. The measures aimed at elevating HDL cholesterol have only a moderate effect, so that more importance should be attached to lowering the LDL fraction.

Acute pancreatitis in pregnancy: an overview.

PubMed

Papadakis, Efstathios P; Sarigianni, Maria; Mikhailidis, Dimitri P; Mamopoulos, Apostolos; Karagiannis, Vasilios

2011-12-01

Acute pancreatitis is rare in pregnancy but it is associated with increased incidence of maternal and fetal mortality. It should be considered in the differential diagnosis of upper quadrant abdominal pain with or without nausea and vomiting. The commonest identified causes of acute pancreatitis in pregnancy are gallstones, alcohol and hypertriglyceridemia. The main laboratory finding is increased amylase activity. Appropriate investigations include ultrasound of the right upper quadrant and measurement of serum triglycerides and ionized calcium. Management of gallstone pancreatitis is controversial, although laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) are often used and may be associated with lower complication rates. In hypertriglyceridemia-induced acute pancreatitis ω-3 fatty acids and even therapeutic plasma exchange can be used. We also discuss preventive measures. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Familial hypertriglyceridemia

MedlinePlus

The goal of treatment is to control conditions that can raise triglyceride levels. These include obesity , hypothyroidism , and diabetes . Your provider may tell you not to drink alcohol. Certain birth control pills can raise triglyceride levels. ...

Efficacy and safety of TAK-085 compared with eicosapentaenoic acid in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: the omega-3 fatty acids randomized double-blind (ORD) study.

PubMed

Tatsuno, Ichiro; Saito, Yasushi; Kudou, Kentarou; Ootake, Jun

2013-01-01

Hypertriglyceridemia is a risk factor for cardiovascular disease, and clinical practice guidelines advocate treatment to reduce triglyceride (TG) levels. In Japan, an EPA-E (eicosapentaenoic acid-ethyl ester) product has been used clinically for treating dyslipidemia. We investigated the TG-lowering effects of TAK-085 (EPA-E + docosahexaenoic acid-ethyl ester) in comparison with EPA-E in Japanese patients with hypertriglyceridemia (TG ≥150 mg/dL and <750 mg/dL). In this multicenter, 12-week, double-blind study, subjects were stratified for coadministration of a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor then randomized to TAK-085 2 g once daily (n = 205), TAK-085 2 g twice daily (n = 210), or EPA-E 0.6 g three times daily (n = 195). Each one gram of fatty acid in TAK-085 contains approximately 465 mg of EPA plus 375 mg of docosahexaenoic acid-ethyl as ethyl esters. Guidance on lifestyle modifications was provided throughout. The primary end point was the percent change in TG levels (baseline from end of treatment), which was -10.8 ± 22.6, -22.9 ± 23.1, and -11.2 ± 25.7 in the TAK-085 2 g/day, TAK-085 4 g/day, and EPA-E 1.8 g/day groups, respectively. TAK-085 4 g/day produced a significantly greater reduction in TG than EPA-E 1.8 g/day (P < .0001), whereas TAK-085 2 g/day was not inferior to EPA-E 1.8 g/day. Changes in other lipid parameters were relatively modest. There were no notable safety or tolerability differences between the groups. In Japanese patients with modest hypertriglyceridemia who also underwent lifestyle intervention, TAK-085 4 g/day reduced TG more than EPA-E 1.8 g/day. TAK-085 2 g/day had similar effects on TG as EPA-E 1.8 g/day. TAK-085 was well-tolerated. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Risk factors increasing health hazards after air dives.

PubMed

Kaczerska, Dorota; Pleskacz, Katarzyna; Siermontowski, Piotr; Olszański, Romuald; Krefft, Karolina

2015-01-01

The aim of the present study was to determine the effect of postprandial hypertriglyceridemia on the risk of decompression stress following hyperbaric air exposures. The study involved 55 male individuals aged 20-48 years (31.47 ± 5.49 years), body mass index 20.3-33.2 kg/m2 (25.5 ± 2.58 kg/m2). Blood was sampled two hours after a meal each participant had in accordance with individual dietary preferences to determine the following parameters: blood cell counts, activity of aspartate aminotransferase (AST) and alanine ammotransterase (ALT), concentrations of total cholesterol and triglycerides. After each hyperbaric exposure, the presence and intensity of decompression stress were assessed using the Doppler method. Decompression stress was found in 30 individuals. Postprandial hypertriglyceridemia and hypercholesterolemia increased the risk of decompression stress after hyperbaric air exposures.

Association of early maternal hypertriglyceridemia with pregnancy-induced hypertension.

PubMed

Chandi, Anadeep; Sirohiwal, Daya; Malik, Roopa

2015-11-01

Hypertensive diseases are directly responsible for 24 % of maternal deaths in India. A screening method is yet to be discovered to reduce the morbidity and mortality related to it. Serum triglyceride (TG) levels are reported to increase in hypertensive pregnant women. To predict pregnancy-induced hypertension (PIH) by serum triglyceride values. This study is a prospective cohort study that was conducted over three hundred normotensive, primigravida women with singleton pregnancy at 14-20 weeks of gestation. These were divided into two groups on the basis of their TG concentration estimated at 14-20 weeks of gestation. The pregnancy was then followed till delivery and, signs and symptoms of PIH were noted in both the groups. Out of 300 women, 210 women completed the study. Fifty-nine women developed PIH and 151 women remained normotensive. Among 59 women, 45 women had raised TG values i.e., ≥160 mg/dL and 14 women were with normal TG levels i.e., <160 mg/dL. A significant positive correlation was found between serum TG concentration and systolic and diastolic blood pressure. It was observed that a cutoff of 162.50 mg/dL for TG could reliably predict PIH with sensitivity of 76 % and specificity of 85 %. Also, the mothers with hypertriglyceridemia were found to be at higher risk of developing early-onset PIH. Our study supports the evidence that early pregnancy hypertriglyceridemia is associated with an increased risk of PIH.

Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bagby, G.J.; Corll, C.B.; Martinez, R.R.

1987-07-01

Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionallymore » hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.« less

Pentoxifylline Treatment in Acute Pancreatitis (AP)

ClinicalTrials.gov

2018-02-21

Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles.

PubMed Central

Aalto-Setälä, K; Fisher, E A; Chen, X; Chajek-Shaul, T; Hayek, T; Zechner, R; Walsh, A; Ramakrishnan, R; Ginsberg, H N; Breslow, J L

1992-01-01

Hypertriglyceridemia is common in the general population, but its mechanism is largely unknown. In previous work human apo CIII transgenic (HuCIIITg) mice were found to have elevated triglyceride levels. In this report, the mechanism for the hypertriglyceridemia was studied. Two different HuCIIITg mouse lines were used: a low expressor line with serum triglycerides of approximately 280 mg/dl, and a high expressor line with serum triglycerides of approximately 1,000 mg/dl. Elevated triglycerides were mainly in VLDL. VLDL particles were 1.5 times more triglyceride-rich in high expressor mice than in controls. The total amount of apo CIII (human and mouse) per VLDL particle was 2 and 2.5 times the normal amount in low and high expressors, respectively. Mouse apo E was decreased by 35 and 77% in low and high expressor mice, respectively. Under electron microscopy, VLDL particles from low and high expressor mice were found to have a larger mean diameter, 55.2 +/- 16.6 and 58.2 +/- 17.8 nm, respectively, compared with 51.0 +/- 13.4 nm from control mice. In in vivo studies, radiolabeled VLDL fractional catabolic rate (FCR) was reduced in low and high expressor mice to 2.58 and 0.77 pools/h, respectively, compared with 7.67 pools/h in controls, with no significant differences in the VLDL production rates. In an attempt to explain the reduced VLDL FCR in transgenic mice, tissue lipoprotein lipase (LPL) activity was determined in control and high expressor mice and no differences were observed. Also, VLDLs obtained from control and high expressor mice were found to be equally good substrates for purified LPL. Thus excess apo CIII in HuCIIITg mice does not cause reduced VLDL FCR by suppressing the amount of extractable LPL in tissues or making HuCIIITg VLDL a bad substrate for LPL. Tissue uptake of VLDL was studied in hepatoma cell cultures, and VLDL from transgenic mice was found to be taken up much more slowly than control VLDL (P < 0.0001), indicating that HuCIIITg VLDL is not well recognized by lipoprotein receptors. Additional in vivo studies with Triton-treated mice showed increased VLDL triglyceride, but not apo B, production in the HuCIIITg mice compared with controls. Tissue culture studies with primary hepatocytes showed a modest increase in triglyceride, but not apo B or total protein, secretion in high expressor mice compared with controls. In summary, hypertriglyceridemia in HuCIIITg mice appears to result primarily from decreased tissue uptake of triglyceride-rich particles from the circulation, which is most likely due to increased apo CIII and decreased apo E on VLDL particles. the HuCIIITg mouse appears to be a suitable animal model of primary familial hypertriglyceridemia, and these studies suggest a possible mechanism for this common lipoprotein disorder. Images PMID:1430212

Marked hypertriglyceridemia in a woman receiving metoprolol succinate.

PubMed

Kim, Yeunjung; Miller, Michael

2014-01-01

β-blockers are commonly used therapies after acute myocardial infarction and in the management of congestive heart failure and hypertension. We report a case of a middle-aged woman with a history of mild hypertension who was placed on metoprolol succinate. Before initiation of the β-blocker, her triglyceride level was in the borderline-high range (150-199 mg/dL). On treatment, her triglyceride levels exceeded 1000 mg/dL. She developed fatigue and mild abdominal discomfort but without biochemical evidence of pancreatitis. After discontinuation of metoprolol succinate, her triglyceride levels receded. This case illustrates an uncommon side effect with a very commonly used therapy in clinical practice. Clinicians should closely evaluate medications and/or other therapies in patients presenting with new-onset hypertriglyceridemia especially when levels are sufficiently elevated to pose increased risk of pancreatitis. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Treatment options for hypertriglyceridemia: from risk reduction to pancreatitis

PubMed Central

Berglund, Lars; Brunzell, John D.; Goldberg, Anne C.; Goldberg, Ira J.; Stalenhoef, Anton

2013-01-01

While there has been considerable focus on the role and treatment of LDL cholesterol levels, a definitive role of triglycerides in the management of cardiovascular disease has been uncertain. Notably, with increasing triglyceride levels, there is a parallel increase in cholesterol levels carried by triglyceride-rich lipoproteins, which has prompted interest in the use of non-HDL cholesterol levels as a tool guiding interventions. Recent studies have provided evidence for an independent role of triglyceride levels as a cardiovascular risk factor, and recently, an Endocrine Society guideline was published for treatment of hypertriglyceridemia. In contrast to the relative uncertainty regarding triglycerides and cardiovascular disease, a role of very high triglyceride levels as a risk factor for pancreatitis has been well known. The present paper summarizes the underlying evidence for a risk role for triglyceride levels in cardiovascular disease and pancreatitis, current treatment recommendations and areas of future research. PMID:24840268

PPAR delta: a dagger in the heart of the metabolic syndrome.

PubMed

Barish, Grant D; Narkar, Vihang A; Evans, Ronald M

2006-03-01

Obesity is a growing threat to global health by virtue of its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X. The nuclear receptors PPARalpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the less-described PPAR isotype PPARdelta has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARdelta in the treatment of metabolic disease. PPARdelta enhances fatty acid catabolism and energy uncoupling in adipose tissue and muscle, and it suppresses macrophage-derived inflammation. Its combined activities in these and other tissues make it a multifaceted therapeutic target for the metabolic syndrome with the potential to control weight gain, enhance physical endurance, improve insulin sensitivity, and ameliorate atherosclerosis.

Relationships among Smoking Habits, Airflow Limitations, and Metabolic Abnormalities in School Workers

PubMed Central

Horie, Masafumi; Noguchi, Satoshi; Tanaka, Wakae; Goto, Yasushi; Yoshihara, Hisanao; Kawakami, Masaki; Suzuki, Masaru; Sakamoto, Yoshio

2013-01-01

Background Chronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality. Objective We evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities. Methods Between 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history. Results Airflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012–1.018; p<0.0001) and low high-density-lipoprotein cholesterolemia (1.013; 1.010–1.016; p<0.0001) in men. Length of smoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975–0.994; p = 0.007). Conclusions Habitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities. PMID:24312268

Relationships among smoking habits, airflow limitations, and metabolic abnormalities in school workers.

PubMed

Horie, Masafumi; Noguchi, Satoshi; Tanaka, Wakae; Goto, Yasushi; Yoshihara, Hisanao; Kawakami, Masaki; Suzuki, Masaru; Sakamoto, Yoshio

2013-01-01

Chronic obstructive pulmonary disease is caused mainly by habitual smoking and is common among elderly individuals. It involves not only airflow limitation but also metabolic disorders, leading to increased cardiovascular morbidity and mortality. We evaluated relationships among smoking habits, airflow limitation, and metabolic abnormalities. Between 2001 and 2008, 15,324 school workers (9700 males, 5624 females; age: ≥ 30 years) underwent medical checkups, including blood tests and spirometry. They also responded to a questionnaire on smoking habits and medical history. Airflow limitation was more prevalent in current smokers than in ex-smokers and never-smokers in men and women. The frequency of hypertriglyceridemia was higher in current smokers in all age groups, and those of low high-density-lipoprotein cholesterolemia and diabetes mellitus were higher in current smokers in age groups ≥ 40 s in men, but not in women. There were significant differences in the frequencies of metabolic abnormalities between subjects with airflow limitations and those without in women, but not in men. Smoking index was an independent factor associated with increased frequencies of hypertriglyceridemia (OR 1.015; 95% CI: 1.012-1.018; p<0.0001) and low high-density-lipoprotein cholesterolemia (1.013; 1.010-1.016; p<0.0001) in men. Length of smoking cessation was an independent factor associated with a decreased frequency of hypertriglyceridemia (0.984; 0.975-0.994; p = 0.007). Habitual smoking causes high incidences of airflow limitation and metabolic abnormalities. Women, but not men, with airflow limitation had higher frequencies of metabolic abnormalities.

Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways.

PubMed

Uebanso, Takashi; Taketani, Yutaka; Fukaya, Makiko; Sato, Kazusa; Takei, Yuichiro; Sato, Tadatoshi; Sawada, Naoki; Amo, Kikuko; Harada, Nagakatsu; Arai, Hidekazu; Yamamoto, Hironori; Takeda, Eiji

2009-07-01

The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation.

Soy isoflavones (Glycine max) ameliorate hypertriglyceridemia and hepatic steatosis in high fat-fed ovariectomized Wistar rats (an experimental model of postmenopausal obesity).

PubMed

Panneerselvam, Sankar; Packirisamy, Rajaa Muthu; Bobby, Zachariah; Elizabeth Jacob, Sajini; Sridhar, Magadi Gopalakrishna

2016-12-01

Obesity emerged as the major risk factor for metabolic syndrome. Postmenopausal women are more prone to develop obesity than premenopausal women. The absence of safe and effective conventional treatments for postmenopausal obesity has changed the focus to natural products as alternative remedy. We investigated the molecular basis of the effect of soy isoflavones (SIFs) on hypertriglyceridemia and hepatic steatosis in an animal model of postmenopausal obesity. Ovariectomized (OVX) and sham-operated Wistar rats were fed with high-fat diet (HFD) and normal diet for 8 weeks with and without SIF extract (150mg/kg body weight/day). Both OVX and HFD per se and when combined caused hypertriglyceridemia, hypercholesterolemia and atherogenic lipid profile. Proteomic studies revealed that both OVX and HFD caused overexpression of hepatic lipogenic proteins, such as LXR, SREBP1, PPARγ, ACC and FAS, in association with reduced expression of lipolytic proteins, such as FXR, PPARα, insig2 and SHP. Histological analysis showed fat accumulation and morphological abnormalities in the liver of OVX and HFD rats. All these metabolic derangements were further augmented when OVX was followed by HFD. In conclusion, these findings suggest that there was a synergism in the development of deranged lipid metabolism with the coexistence of postmenopausal state and the intake of fat-rich diet. SIF extract markedly alleviated the derangement of lipid metabolism suggesting the use of this natural phytoestrogen as a strategy for relieving dyslipidemia and hepatic steatosis associated with the postmenopausal women. Copyright © 2016 Elsevier Inc. All rights reserved.

Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia.

PubMed

Blair, Hannah A; Dhillon, Sohita

2014-10-01

Omega-3 carboxylic acids (Epanova) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥ 500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.

High-risk drinking is associated with dyslipidemia in a different way, based on the 2010-2012 KNHANES.

PubMed

Kwon, Yu-Jin; Kim, Sung-Eun; Park, Byoung-Jin; Bae, Jang-Whan; Kang, Hee-Taik

2016-05-01

The Alcohol Use Disorders Identification Test (AUDIT) questionnaire is a simple and useful method for the early detection of hazardous and harmful drinking. In this study, we examined the association between alcohol drinking pattern and dyslipidemia in Korean adults. This cross-sectional study included 14,308 participants who took part in the 2010-2012 Korean National Health and Nutrition Examination Survey. We categorized alcohol drinking patterns into three groups. We classified dyslipidemia into hypercholesterolemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia, and hyper-non-HDL-cholesterolemia. Of those who participated, 25.1% of men and 4.8% of women were high-risk drinkers. Compared with the low-risk group, Odd Ratios for hypercholesterolemia and hypertriglyceridemia in the high-risk group were 1.198 (1.001-1.434) and 1.979 (1.622-2.413) for men. Odd Ratios for hypo-HDL-cholesterolemia in the high-risk group was 0.351 (0.279-0.441) in men and 0.413 (0.291-0.586) in women. Compared with the low-risk participants, the high-risk group was associated with higher prevalence and increased risk for hyper-LDL-cholesterolemia in both sexes (1.541 [1.467-1.913] for men and 1.631 [1.034-2.575] for women). High-risk drinking was associated with higher risk for hypertriglyceridemia and hyper-LDL-cholesterolemia in both sexes and hypercholesterolemia in men but lower risk for hypo-HDL-cholesterolemia in both sexes. Copyright © 2016 Elsevier B.V. All rights reserved.

Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion

PubMed Central

Butler, Judy A.; Hagen, Tory M.; Moreau, Régis

2009-01-01

Elevated blood triacylglycerol (TG) is a significant contributing factor to the current epidemic of obesity-related health disorders, including type-2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The observation that mice lacking the enzyme sn-glycerol-3-phosphate acyltransferase are protected from insulin resistance suggests the possibility that the regulation of TG synthesis be a target for therapy. Five-week old Zucker Diabetic Fatty (ZDF) rats were fed a diet containing (R)-α-lipoic acid (LA, ~200 mg/kg body weight per day) for 5 weeks. LA offset the rise in blood and liver TG by inhibiting liver lipogenic gene expression (e.g. sn-glycerol-3-phosphate acyltransferase-1 and diacylglycerol O-acyltransferase-2), lowering hepatic TG secretion, and stimulating clearance of TG-rich lipoproteins. LA-induced TG lowering was not due to the anorectic properties of LA, as pair-fed rats developed hypertriglyceridemia. Livers from LA-treated rats exhibited elevated glycogen content, suggesting dietary carbohydrates were stored as glycogen rather than becoming lipogenic substrate. Although AMP-activated protein kinase (AMPK) reportedly mediates the metabolic effects of LA in rodents, no change in AMPK activity was observed, suggesting LA acted independently of this kinase. The hepatic expression of peroxisome proliferator activated receptor α (PPARα) target genes involved in fatty acid β-oxidation was either unchanged or decreased with LA, indicating a different mode of action than for fibrate drugs. Given its strong safety record, LA may have potential clinical applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia. PMID:19232511

ApoCIII as a Cardiovascular Risk Factor and Modulation by the Novel Lipid-Lowering Agent Volanesorsen.

PubMed

Rocha, Natalia A; East, Cara; Zhang, Jun; McCullough, Peter A

2017-11-09

Apolipoprotein CIII (ApoCIII) is now recognized as a key regulator in severe hypertriglyceridemia, chylomicronemia, and conditions of triglyceride-rich lipoprotein (TRL) remnant excess due to its inhibition of lipoprotein lipase (LPL) and hepatic lipase, leading to decreased hepatic reuptake of TRLs, as well as enhanced synthesis and secretion of VLDL from the liver. ApoCIII gain-of-function mutations are associated with atherosclerosis and coronary heart disease (CHD), and contribute to the development of cardiometabolic syndrome, hypertriglyceridemia, and type 2 diabetes mellitus. Conversely, loss-of-function mutations in ApoCIII are associated with lower levels of plasma triglycerides (TG), attenuation of vascular inflammatory processes such as monocyte adhesion and endothelial dysfunction, and potentially, a reduction in the incidence and progression of atherosclerosis and cardioprotection. Evidence is now emerging that volanesorsen, a second-generation antisense oligonucleotide drug targeting ApoCIII messenger RNA resulting in decreases in TG in patients with familial chylomicronemia syndrome, severe hypertriglyceridemia, and metabolic dyslipidemia with type 2 diabetes giving support to the hypothesis that ApoCIII is a powerful inhibitor of LPL, and when reduced, endogenous clearance of TRLs can result in substantial reductions in TG levels. Discovery of the ApoCIII inhibitor volanesorsen opens a new era of lipid-lowering drugs for reduction in TG and potentially for reduction in LDL-C. Herein, this review will provide an update on the pathophysiology of ApoCIII-linked atherosclerosis and the development of the first drug to target ApoCIII, volanesorsen, as a promising lipid-lowering agent.

Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)

MedlinePlus

... day because of the risk of liver damage. • Omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and ... high triglycerides. You can get high doses of omega-3 fatty acids in a fish oil supplement or ...

[PPARβ/δ Activation prevents hypertriglyceridemia caused by a high fat diet. Involvement of AMPK and PGC-1α-Lipin1-PPARα pathway].

PubMed

Barroso, Emma; Astudillo, Alma M; Balsinde, Jesús; Vázquez-Carrera, Manuel

2013-01-01

Excessive consume of hypercaloric and high in saturated fat food causes an atherogenic dyslipidemia. In this study we analyzed the effects of PPARβ/δ activator GW501516 on the hypertriglyceridemia induced by a high-fat diet. Male mice were randomized in three groups: control (standard chow), high fat diet (HFD, 35% fat by weight, 58% Kcal from fat) and high fat diet plus GW501516 (3mg/Kg/day). Treatment duration was three weeks. HFD-induced hypertriglyceridemia was accompanied by a reduction in hepatic levels of phospho-AMPK and in PGC-1α and Lipin1 mRNA levels. All these effects were reversed by GW501516 treatment. The lack of changes in phospho-AMPK levels after GW501516 treatment in HFD-fed animals could be the result of an increase in the AMP/ATP ratio. GW501516 treatment also increased Lipin1 protein levels in the nucleus, led to the amplification of the PGC-1α-PPARα pathway and increased PPARα DNA-binding activity, as well as the expression of PPARα-target genes involved in fatty acid oxidation. GW501516 also increased β-hydroxibutirate plasmatic levels, a hepatic β-oxidation end product. Finally, GW501516 increased the hepatic levels of the PPARα endogenous ligand 16:0/18:1-PC and the expression of the VLDL receptor. These data indicate that the hypotriglyceridemic effect of GW501516 in mice subjected to HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-Lipin1-PPARα pathway. Copyright © 2012 Elsevier España, S.L. and SEA. All rights reserved.

APOC3 Protein Is Not a Predisposing Factor for Fat-induced Nonalcoholic Fatty Liver Disease in Mice.

PubMed

Cheng, Xiaoyun; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Gong, Zhenwei; Muzumdar, Radhika; Qu, Shen; Dong, H Henry

2017-03-03

Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in liver, is prevalent in obesity. Genetic factors that link obesity to NAFLD remain obscure. Apolipoprotein C3 (APOC3) is a lipid-binding protein with a pivotal role in triglyceride metabolism. Humans with APOC3 gain-of-function mutations and mice with APOC3 overproduction are associated with hypertriglyceridemia. Nonetheless, it remains controversial whether APOC3 is culpable for diet-induced NAFLD. To address this fundamental issue, we fed APOC3-transgenic and wild-type littermates a high fructose diet or high fat diet, followed by determination of the effect of APOC3 on hepatic lipid metabolism and inflammation and the progression of NAFLD. To gain mechanistic insight into NAFLD, we determined the impact of APOC3 on hepatic triglyceride synthesis and secretion versus fatty acid oxidation. APOC3-transgenic mice were hypertriglyceridemic, culminating in marked elevation of triglycerides, cholesterols, and non-esterified fatty acids in plasma. Despite the prevailing hypertriglyceridemia, APOC3-transgenic mice, relative to wild-type littermates, had similar weight gain and hepatic lipid content without alterations in hepatic expression of key genes involved in triglyceride synthesis and secretion and fatty acid oxidation. APOC3-transgenic and wild-type mice had similar Kupffer cell content without alterations in hepatic expression of pro- and anti-inflammatory cytokines. APOC3 neither exacerbated diet-induced adiposity nor aggravated the degree of steatosis in high fructose or high fat-fed APOC3-transgenic mice. These effects ensued independently of weight gain even after 10-month high fat feeding. We concluded that APOC3, whose dysregulation is liable for hypertriglyceridemia, is not a predisposing factor for linking overnutrition to NAFLD in obesity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Association of APOA5 -1131T>C polymorphism and serum lipid levels in patients with type 2 diabetes.

PubMed

Celap, Ivana; Simundic, Ana-Maria; Nikolac, Nora; Kackov, Sanja; Katalinic, Darko

2013-10-01

Significant abnormalities in lipid metabolism are frequently present in patients with type 2 diabetes mellitus (T2DM). Hypertriglyceridemia, a highly proatherogenic state, is associated with increased risk of coronary artery disease. Genetic polymorphism APOA5 -1131T>C has been recognized as a significant contributor to hypertriglyceridemia in both healthy and diabetic populations. The aim of the study was to investigate the association of APOA5 -1131T>C polymorphism with the serum levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in patients with T2DM. In total, 234 DNA samples from patients with T2DM were genotyped using the PCR-RFLP method. Serum lipid levels were measured using standard laboratory methods. Obtained APOA5 -1131T>C genotype frequencies were 89% (T/T) and 11% (T/C+C/C). There was no significant association between APOA5 -1131T>C genotypes and triglyceride levels (1.90 mM [1.32-2.74] vs. 1.78 mM [1.54-3.05] for T/T vs. T/C+C/C genotype; p=0.553), HDL cholesterol levels (1.30 mM [1.10-1.40] vs. 1.30 mM [1.05-1.40] for T/T vs. T/C+C/C; p=0.534), and LDL cholesterol levels (3.1 mM [2.3-3.8] vs. 3.0 mM [2.2-3.5] for T/T vs. T/C+C/C; p=0.313). Our results suggest that hypertriglyceridemia in patients with T2DM is not likely to be associated with the APOA5 -1131T>C polymorphism.

Associations between a common variant near the MC4R gene and serum triglyceride levels in an obese pediatric cohort.

PubMed

Fernandes, Ariana Ester; de Melo, Maria Edna; Fujiwara, Clarissa Tamie Hiwatashi; Pioltine, Marina Brosso; Matioli, Sergio Russo; Santos, Aritânia; Cercato, Cintia; Halpern, Alfredo; Mancini, Marcio C

2015-08-01

Polymorphisms near the MC4R gene may be related to an increased risk for obesity, but studies of variations in this gene and its relation to cardiometabolic profiles and food intake are scarce and controversial. The aim of this study is to evaluate the influence of the variants rs12970134 and rs17782313 near the MC4R gene in food intake, binge eating (BE) behavior, anthropometric parameters, body composition, metabolic profile, and cardiometabolic risk factors in obese children and adolescents. This is a cross-sectional study that included obese children and adolescents. We evaluated anthropometric, metabolic parameters and cardiometabolic risk factors, including hypertension, impaired fasting glucose, hypertriglyceridemia, and low HDL-cholesterol. BE was assessed through the BE scale, and a 24-h recall was used to evaluate total caloric intake and percentage of macronutrients and types of dietary fat. The MC4R variants rs12970134 and rs17782313 were genotyped using TaqMan assay. To assess the magnitude of risk, a logistic regression adjusted for Z-BMI, age, and gender was performed, adopting the significance level of 0.05. The study included 518 subjects (52.1 % girls, 12.7 ± 2.7 years old, Z-BMI = 3.24 ± 0.57). Carriers of the variant rs17782313 exhibit increased triglyceride levels (108 ± 48 vs. 119 ± 54, p = 0.034) and an increased risk of hypertriglyceridemia (OR 1.985, 95 % CI 1.288-3.057, p = 0.002). There was no association of the SNP rs12970134 with clinical, metabolic, or nutritional parameters. The variant rs12970134 and rs17782313 did not influence food intake or the presence of BE. The variant rs17782313 is associated with an increased risk of hypertriglyceridemia in obese children and adolescents.

Prevalence of Suspected Nonalcoholic Fatty Liver Disease In Lean Adolescents In The United States.

PubMed

Selvakumar, Praveen Kumar Conjeevaram; Kabbany, Mohammad Nasser; Lopez, Rocio; Rayas, Maria S; Lynch, Jane L; Alkhouri, Naim

2018-03-21

Nonalcoholic fatty liver disease (NAFLD) can develop in lean subjects referred to as lean NAFLD. We aim to evaluate the prevalence and risk factors of NAFLD in lean adolescents in the United States (US). Cross sectional data from 1482 lean subjects (body mass index < 85 percentile) aged between 12 and 18 years, who were enrolled in the National Health and Examination Survey during the 2005-2014 cycles were included. We defined suspected NAFLD as alanine aminotransferase > 25.8 U/L for boys and > 22.1 U/L for girls; hypertriglyceridemia as triglycerides ≥ 150 mg/dL; low HDL as HDL < 40 mg/dL and insulin resistance (IR) as homeostatic model assessment of IR ≥ 3. The mean weighted prevalence of suspected NAFLD among lean adolescents during 2005-2014 cycles was 8% (95% CI: 6.2, 9.9). Lean subjects with suspected NAFLD were significantly older compared to lean non-NAFLD subjects (15.5 vs. 15 years, p-value < 0.05). Low HDL (15.5% vs. 6.8%; p-value 0.016) and hypertriglyceridemia (10% vs. 3.9%; p-value 0.028) were also found to be more common among lean NAFLD subjects compared to their non-NAFLD counterparts. Presence of IR increased the risk of having suspected NAFLD by 4-fold among lean adolescents. Non-Hispanic black lean adolescents were less likely to have suspected NAFLD compared to non-Hispanic white lean adolescents. The estimated prevalence of suspected NAFLD among lean adolescents in the US was found to be 8% with evidence of metabolic derangements such as low HDL, hypertriglyceridemia and IR.

Association of postprandial serum triglyceride concentration and serum canine pancreatic lipase immunoreactivity in overweight and obese dogs.

PubMed

Verkest, K R; Fleeman, L M; Morton, J M; Groen, S J; Suchodolski, J S; Steiner, J M; Rand, J S

2012-01-01

Hypertriglyceridemia has been proposed to contribute to the risk of developing pancreatitis in dogs. To determine associations between postprandial serum triglyceride concentrations and canine pancreatic lipase immunoreactivity (cPLI) concentrations or pancreatic disease. Thirty-five client-owned overweight (n = 25) or obese (n = 10) dogs weighing >10 kg. Healthy dogs were prospectively recruited for a cross-sectional study. Serum triglyceride concentrations were measured before and hourly for 12 hours after a meal. Fasting cPLI and canine trypsin-like immunoreactivity (cTLI) concentrations were assayed. Cut-off values for hypertriglyceridemia were set a priori for fasting (≥ 88, ≥ 177, ≥ 354, ≥ 885 mg/dL) and peak postprandial (≥ 133, ≥ 442, ≥ 885 mg/dL) triglyceride concentrations. The association between hypertriglyceridemia and high cPLI concentrations was assessed by exact logistic regression. Follow-up was performed 4 years later to determine the incidence of pancreatic disease. Eight dogs had peak postprandial triglycerides >442 mg/dL and 3 dogs had fasting serum cPLI concentrations ≥ 400 μg/L. Odds of high cPLI concentrations were 16.7 times higher in dogs with peak postprandial triglyceride concentrations ≥ 442 mg/dL relative to other dogs (P < .001). Fasting triglyceride concentration was not significantly associated with cPLI concentrations. None of the dogs with high triglyceride concentrations and one of the dogs with low fasting and peak postprandial triglyceride concentrations developed clinically important pancreatic disease. Overweight and obese dogs with peak serum postprandial triglyceride concentrations ≥ 442 mg/dL after a standard meal are more likely to have serum cPLI concentrations ≥ 400 μg/L, but did not develop clinically important pancreatic disease. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states.

PubMed

Perez-Martinez, Pablo; Corella, Dolores; Shen, Jian; Arnett, Donna K; Yiannakouris, Nikos; Tai, E Syong; Orho-Melander, Marju; Tucker, Katherine L; Tsai, Michael; Straka, Robert J; Province, Michael; Kai, Chew Suok; Perez-Jimenez, Francisco; Lai, Chao-Qiang; Lopez-Miranda, Jose; Guillen, Marisa; Parnell, Laurence D; Borecki, Ingrid; Kathiresan, Sekar; Ordovas, Jose M

2009-01-01

Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. We investigated the combined effects of the GCKR rs780094C-->T, APOA5 -1131T-->C, and APOA5 56C-->G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7,730 men and women) and 2 intervention studies in US whites (n = 1,061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001). SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment.

Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

PubMed

Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

2014-10-20

Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.

PubMed

Arthur, Rhonda; Møller, Henrik; Garmo, Hans; Holmberg, Lars; Stattin, Pår; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Robinson, David; Jungner, Ingmar; Hemelrijck, Mieke Van

2016-06-01

Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The Association Between Obesity and Cognitive Function in Older Persons: How Much Is Mediated by Inflammation, Fasting Plasma Glucose, and Hypertriglyceridemia?

PubMed

Gunathilake, Roshan; Oldmeadow, Christopher; McEvoy, Mark; Inder, Kerry J; Schofield, Peter W; Nair, Balakrishnan R; Attia, John

2016-12-01

The aim of the study was to determine how much of the association between obesity, measured by body mass index (BMI), and cognition in older persons is mediated through inflammation, fasting plasma glucose, and hypertriglyceridemia. Anthropometrics, high-sensitivity C-reactive protein (CRP), fasting plasma glucose, and serum triglycerides were measured in 3,256 community-dwelling individuals aged 55-85 years residing in Newcastle, New South Wales, Australia. Audio recorded cognitive screen (ARCS) was used to assess multiple cognitive domains. Mediation analyses showed very modest but significant direct mediation effects, whereby obesity was associated with better cognitive function after adjusting for potential confounders (controlled direct effect ≈ 1/500 point increase in the total ARCS score per 1.0-kg/m 2 increase in BMI). There were significant indirect negative mediation effects from BMI to cognition mediated through CRP, that is, increased BMI was associated with increased CRP which was associated with decreased cognition (natural indirect effect -0.20 unit; 95% confidence interval [CI] -0.39, -0.02), and through fasting plasma glucose, that is, increased BMI was associated with increased fasting plasma glucose which was associated with decreased cognition (natural indirect effect -0.12 unit; 95% CI -0.24, -0.01], but not through serum triglycerides. There is a weak positive association between obesity and cognitive performance in older persons, which is partially antagonized by inflammation and elevated fasting plasma glucose, but not hypertriglyceridemia. Further studies are needed to elucidate whether this is due to selection bias, or truly reflects biologically complex and counter balancing pathways involved in obesity. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states123

PubMed Central

Perez-Martinez, Pablo; Corella, Dolores; Shen, Jian; Arnett, Donna K; Yiannakouris, Nikos; Tai, E Syong; Orho-Melander, Marju; Tucker, Katherine L; Tsai, Michael; Straka, Robert J; Province, Michael; Kai, Chew Suok; Perez-Jimenez, Francisco; Lai, Chao-Qiang; Lopez-Miranda, Jose; Guillen, Marisa; Parnell, Laurence D; Borecki, Ingrid; Kathiresan, Sekar; Ordovas, Jose M

2009-01-01

Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C→T, APOA5 −1131T→C, and APOA5 56C→G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies in US whites (n = 1061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). Results: Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001). Conclusions: SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment. PMID:19056598

APOC3 Protein Is Not a Predisposing Factor for Fat-induced Nonalcoholic Fatty Liver Disease in Mice*

PubMed Central

Cheng, Xiaoyun; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Gong, Zhenwei; Muzumdar, Radhika; Qu, Shen; Dong, H. Henry

2017-01-01

Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in liver, is prevalent in obesity. Genetic factors that link obesity to NAFLD remain obscure. Apolipoprotein C3 (APOC3) is a lipid-binding protein with a pivotal role in triglyceride metabolism. Humans with APOC3 gain-of-function mutations and mice with APOC3 overproduction are associated with hypertriglyceridemia. Nonetheless, it remains controversial whether APOC3 is culpable for diet-induced NAFLD. To address this fundamental issue, we fed APOC3-transgenic and wild-type littermates a high fructose diet or high fat diet, followed by determination of the effect of APOC3 on hepatic lipid metabolism and inflammation and the progression of NAFLD. To gain mechanistic insight into NAFLD, we determined the impact of APOC3 on hepatic triglyceride synthesis and secretion versus fatty acid oxidation. APOC3-transgenic mice were hypertriglyceridemic, culminating in marked elevation of triglycerides, cholesterols, and non-esterified fatty acids in plasma. Despite the prevailing hypertriglyceridemia, APOC3-transgenic mice, relative to wild-type littermates, had similar weight gain and hepatic lipid content without alterations in hepatic expression of key genes involved in triglyceride synthesis and secretion and fatty acid oxidation. APOC3-transgenic and wild-type mice had similar Kupffer cell content without alterations in hepatic expression of pro- and anti-inflammatory cytokines. APOC3 neither exacerbated diet-induced adiposity nor aggravated the degree of steatosis in high fructose or high fat-fed APOC3-transgenic mice. These effects ensued independently of weight gain even after 10-month high fat feeding. We concluded that APOC3, whose dysregulation is liable for hypertriglyceridemia, is not a predisposing factor for linking overnutrition to NAFLD in obesity. PMID:28115523

Severe hypertriglyceridemia due to two novel loss-of-function lipoprotein lipase gene mutations (C310R/E396V) in a Chinese family associated with recurrent acute pancreatitis.

PubMed

Lun, Yu; Sun, Xiaofang; Wang, Ping; Chi, Jingwei; Hou, Xu; Wang, Yangang

2017-07-18

Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c.T928C mutation also carried a novel missense mutation c.A1187T (p.E396V) in exon 8 of the LPL gene. Furthermore, COS-1 cells were transfected with lentiviruses containing the mutant LPL genes. While C310R markedly reduced the overall LPL protein level, COS-1 cells carrying E396V or double mutations contained similar overall LPL protein levels to the wild-type. The specific activity of the LPL mutants remained at comparable magnitude to the wild-type. However, few LPL were detected in the culture medium for the mutants, suggesting that both mutations caused aberrant triglyceride catabolism. More specifically, E396V and double mutations dampened the transport of LPL to the cell surface, while for the C310R mutation, reducing LPL protein level might be involved. By characterizing these two novel LPL mutations, this study has expanded our understanding on the pathogenesis of familial hypertriglyceridemia (FHTG).

Extreme hypertriglyceridemia, pseudohyponatremia, and pseudoacidosis in a neonate with lipoprotein lipase deficiency due to segmental uniparental disomy.

PubMed

Ashraf, Ambika P; Hurst, Anna C E; Garg, Abhimanyu

Extreme hypertriglyceridemia is rare in the neonatal period. We report a neonate with lipoprotein lipase (LPL) deficiency who presented with diagnostic and management conundrum. A full-term 36-day-old female was noted to have "Pepto-Bismol like" blood when repeating a newborn screening. The initial plasma triglyceride level was 24,318 mg/dL. The laboratory tests revealed serum bicarbonate level of <5 mmol/L, sodium of 127 mmol/L, and severe anemia. There were no signs of acute distress. The point of care capillary blood testing, however, demonstrated normal serum pH (7.2), bicarbonate (25.4 mmol/L), and sodium (139 mmol/L). The patient had mild elevation of serum lactic acid and no ketonuria. A diagnosis of type I hyperlipoproteinemia was made. Oral feeding was stopped, and the infant received intravenous fluids for the next 7 days resulting in lowering of serum triglyceride levels to 1016 mg/dL. Oral feeding was initiated with an amino acid-rich formula to which medium chain triglycerides were slowly added, while maintaining the total fat content to <15% of total daily energy. Sequencing of the LPL gene revealed a homozygous c.644G>A, p.(Gly215Glu) mutation. Subsequent analysis of the parental samples revealed that only the father, but not the mother, was a heterozygous carrier of the same mutation. Analysis of 18 informative microsatellite markers on chromosome 8 revealed paternal segmental uniparental disomy with partial absence of the maternal chromosome 8p, confirmed by single-nucleotide polymorphism microarray. We conclude that besides pseudohyponatremia, extreme hypertriglyceridemia can rarely present as pseudoacidosis and uniparental disomy can be an underlying mechanism for autosomal recessive diseases such as LPL deficiency. Published by Elsevier Inc.

Different Patterns of Walking and Postprandial Triglycerides in Older Women

PubMed Central

KASHIWABARA, KYOKO; KIDOKORO, TETSUHIRO; YANAOKA, TAKUMA; BURNS, STEPHEN F.; STENSEL, DAVID J.; MIYASHITA, MASASHI

2018-01-01

ABSTRACT Purpose Although a single bout of continuous exercise (≥30 min) reduces postprandial triglyceride (TG), little evidence is available regarding the effect of multiple short (≤10 min) bouts of exercise on postprandial TG in individuals at increased risk for cardiovascular diseases. This study compared the effects of different patterns of walking on postprandial TG in postmenopausal, older women with hypertriglyceridemia. Methods Twelve inactive women (mean age ± SD, 71 ± 5 yr) with hypertriglyceridemia (fasting TG ≥1.70 mmol·L−1) completed three, 1-d laboratory-based trials in a random order: 1) control, 2) continuous walking, and 3) multiple short bouts of walking. On the control trial, participants sat in a chair for 8 h. For the walking trials, participants walked briskly in either one 30-min bout in the morning (0900–0930 h) or twenty 90-s bouts over 8 h. Except for walking, both exercise trials mimicked the control trial. In each trial, participants consumed a standardized breakfast (0800 h) and lunch (1100 h). Venous blood samples were collected in the fasted state and at 2, 4, 6, and 8 h after breakfast. Results The serum TG incremental area under the curve was 35% and 33% lower on the continuous and multiple short bouts of walking trials than that on the control trial (8.2 ± 3.1 vs 8.5 ± 5.4 vs 12.7 ± 5.8 mmol per 8 h·L−1, respectively; main effect of trial: effect size = 0.459, P = 0.001). Conclusions Accumulating walking in short bouts limits postprandial TG in at-risk, inactive older women with fasting hypertriglyceridemia. PMID:28857839

Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. Reversal by cholic acid feeding.

PubMed

Repa, J J; Lund, E G; Horton, J D; Leitersdorf, E; Russell, D W; Dietschy, J M; Turley, S D

2000-12-15

Sterol 27-hydroxylase (CYP27) participates in the conversion of cholesterol to bile acids. We examined lipid metabolism in mice lacking the Cyp27 gene. On normal rodent chow, Cyp27(-/-) mice have 40% larger livers, 45% larger adrenals, 2-fold higher hepatic and plasma triacylglycerol concentrations, a 70% higher rate of hepatic fatty acid synthesis, and a 70% increase in the ratio of oleic to stearic acid in the liver versus Cyp27(+/+) controls. In Cyp27(-/-) mice, cholesterol 7alpha-hydroxylase activity is increased 5-fold, but bile acid synthesis and pool size are 47 and 27%, respectively, of those in Cyp27(+/+) mice. Intestinal cholesterol absorption decreases from 54 to 4% in knockout mice, while fecal neutral sterol excretion increases 2.5-fold. A compensatory 2.5-fold increase in whole body cholesterol synthesis occurs in Cyp27(-/-) mice, principally in liver, adrenal, small intestine, lung, and spleen. The mRNA for the cholesterogenic transcription factor sterol regulatory element-binding protein-2 (SREBP-2) and mRNAs for SREBP-2-regulated cholesterol biosynthetic genes are elevated in livers of mutant mice. In addition, the mRNAs encoding the lipogenic transcription factor SREBP-1 and SREBP-1-regulated monounsaturated fatty acid biosynthetic enzymes are also increased. Hepatic synthesis of fatty acids and accumulation of triacylglycerols increases in Cyp27(-/-) mice and is associated with hypertriglyceridemia. Cholic acid feeding reverses hepatomegaly and hypertriglyceridemia but not adrenomegaly in Cyp27(-/-) mice. These studies confirm the importance of CYP27 in bile acid synthesis and they reveal an unexpected function of the enzyme in triacylglycerol metabolism.

Cardiovascular and Thermoregulatory Effects of Niacin

DTIC Science & Technology

1989-05-01

to recover. Mean arterial pressure was decreased~by 1.6 kPa during niacin treatment (two subjects). In several subjects, weating rate increased...proportionally. Clinical doses (1-7 g) of niacin are used in the treatment of hyperlipoproteinemia and hypertriglyceridemia , and it has been suggested’ that

Severe hypertriglyceridemia and colchicine intoxication following suicide attempt.

PubMed

Lev, Shaul; Snyder, David; Azran, Carmil; Zolotarsky, Victor; Dahan, Arik

2017-01-01

Colchicine overdose is uncommon but potentially life threatening. Due to its serious adverse systemic effects, overdose must be recognized and treated. We report a case of an 18-year-old female who ingested 18 mg (~0.4 mg/kg) of colchicine in a suicide attempt. The patient's clinical manifestations included abdominal cramps, vomiting, pancytopenia, hypocholesterolemia, and rhabdomyolysis. Two unique manifestations of toxicity in this patient were profound and persistent, severe hypertriglyceridemia and electrolyte imbalance, mainly hypophosphatemia, with no other evident cause except the colchicine intoxication. Following intensive supportive treatment, including ventilator support, N-acetylcysteine, granulocyte colony stimulating factor, electrolyte repletion, and zinc supplementation, the patient made a complete recovery. Colchicine intoxication is a severe, life-threatening situation that should be followed closely in intensive care units. Severe changes in body functions can rapidly develop, as previously described in the literature. To our knowledge, this extremely elevated triglyceride level has never been reported without the administration of propofol, and requires further evaluation.

Severe hypertriglyceridemia at new onset type 1 diabetes mellitus.

PubMed

Fick, Tyler; Jack, Julie; Pyle-Eilola, Amy L; Henry, Rohan K

2017-08-28

Severe hypertriglyceridemia (HTG) as well as diabetic ketoacidosis (DKA) are complications of type 1 diabetes (T1DM). HTG is an exceedingly rare complication in the pediatric population and herein we report a case of HTG at new-onset T1DM in DKA and discuss management and potential complications. An 11-year-old previously well patient with a history of fatigue and weight loss presented with: glucose >600 mg/dL, venous blood gas: pH 7.26, pCO2 20 mmHg, PO2 101 mmHg and base deficit 13 with triglyceride level 3573 mg/dL. An insulin drip was continued past criteria for discontinuation to facilitate lipoprotein lipase-based triglyceride metabolism. Lipemia secondary to severe HTG, though exceedingly rare, may exist in new onset T1DM with DKA. Complicating the diagnosis is the possibility of an analytical error from lipemia causing incongruence in diagnostic criteria. Clinicians should rely on clinical criteria for management and should consider HTG if laboratory data is inconsistent with the clinical picture.

Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.

PubMed

Zeitler, Heike; Balta, Zeynep; Klein, Burkhard; Strassburg, Christian P

2015-08-01

Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia-induced pancreatitis (HTGP). The rationale behind this approach is the depletion of triglycerides and the reduction of inflammatory cytokines. The time span between onset of clinical symptoms and start of plasmapheresis might have an important impact on mortality. Hyperviscosity of patients' plasma represents another special challenge for the applied separation technology. The procedures can be performed either by centrifugal device (CFD) or membrane based (MBS) units. The present study reports the outcome of 10 patients suffering from HTG. The expected mortality of the collective was 25%. Plasmapheresis was started after an average 16.3 h (SD ± 6.7 h) after onset of symptoms. No mortality occurred. Apheresis was statistically equally effective with both devices. A median of 3 sessions reduced the TG level to normal and correlated with patients' improvement. During follow up, three patients developed a pancreatic pseudocyst requiring surgical intervention without further complication. © 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.

Application of an in vivo hepatic triacylglycerol production method in the setting of a high fat diet in mice

USDA-ARS?s Scientific Manuscript database

High fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Changes in TAG metabolism contribute to the development of hepatic steatosis including changes in production rate from de novo lipogenes...

IRF-1 and miRNA126 modulate inflammatory VCAM-1 expression in response to a high fat meal

USDA-ARS?s Scientific Manuscript database

Rationale: High-fat diets accompanied by hypertriglyceridemia increase an individual’s risk for developing atherosclerosis. An early event in this process is monocyte recruitment through binding to VCAM-1 on inflamed arterial endothelium. Diets high in polyunsaturated fatty acids (PUFAs) may provide...

Polyradiculopathy secondary to severe hypertriglyceridemia.

PubMed

Nesbitt, Cassie; Wong, Daniel; Batchelor, Peter

2015-05-08

A 74-year-old man presented with a subacute severe thoracic polyradiculopathy affecting the T4-T8 dermatomes bilaterally. Extensive investigation demonstrated markedly raised triglyceride levels of 44 mmol/L (<1.7). The patient's unique presentation is discussed alongside a review of triglyceride-induced neurotoxicity and therapeutic management. 2015 BMJ Publishing Group Ltd.

A genome-wide study of lipid response to fenofibrate in Caucasians: a combined analysis of the GOLDN and ACCORD studies

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Fibrates are commonly prescribed for hypertriglyceridemia, but they also lower LDL cholesterol and increase HDL cholesterol. Large interindividual variations in lipid response suggest that some patients may benefit more than others and genetic studies could help identify such patients. M...

[Assessment of an intervention on cardiovascular risk factors in patients with rheumatoid arthritis].

PubMed

Zacarías, Andrea; Narváez, Javier; Rodríguez Moreno, Jesús; Jordana, Montserrat; Nolla, Joan M; Gómez Vaquero, Carmen

2016-08-05

To evaluate the effectiveness of an intervention on cardiovascular risk factors (CVRF) in patients with rheumatoid arthritis. After determining their CVRF and cardiovascular risk (CVR) by modified SCORE, we gave the patients a letter for their general practitioners in which they were requested for their cooperation in controlling CVRF and where the therapeutic goal for LDL cholesterol was specified. Three months later, any therapeutic intervention was recorded as well as the results. We included 211 patients, 29% with a high CVR. There were new diagnoses of CVRF in 100 patients (47%). The general practitioner changed the treatment in 2/12 diabetes, 30/84 HBP, 74/167 with elevation of LDL cholesterol and 21/51 with hypertriglyceridemia. The percentage of patients with good control over CVRF was: a) in HBP, 25 to 73%; b) elevation of LDL cholesterol from 10 to 17%; and c) in hypertriglyceridemia, 25 to 38%. Through this intervention, a new CVRF was diagnosed in nearly half of the patients. The effectiveness of the intervention on CVRF was low. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

[Severely increased serum lipid levels in diabetic ketoacidosis - case report].

PubMed

Stefansson, Hrafnkell; Sigvaldason, Kristinn; Kjartansson, Hilmar; Sigurjonsdottir, Helga Águsta

2017-01-01

Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

High prevalence of cardiometabolic risk factors in young employees of Information Technology industry.

PubMed

Limaye, Tejas Y; Kulkarni, Ravindra L; Deokar, Manisha R; Kumaran, Kalyanaraman

2016-01-01

We assessed the burden of cardiometabolic risk factors in Information Technology (IT) employees as they are exposed to adverse lifestyle. In this cross-sectional study, health records were obtained from two IT industries in Pune. Prevalence of cardiometabolic risk factors [hyperglycemia, high blood pressure (BP), hypertriglyceridemia, high low-density lipoprotein (LDL)-cholesterol, low high-density lipoprotein (HDL)-cholesterol, and overweight/obesity] was determined using standard cutoffs. We also examined clustering of risk factors (≥two risk factors). Data were available on 1,350 of 5,800 employees (mean age: 33 ± 6 years, 78% men). Prevalence of diabetes and hypertension was 2.5% and 13.5%, respectively. Prevalence of prediabetes, borderline high BP, hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, and overweight/obesity was 6.5%, 20.3%, 21%, 22.1%, 70.1%, and 51.4%, respectively. Risk factor clustering was observed in 63.5% that increased with age (P < 0.001). Given the high burden of risk factors at relatively young age, spreading awareness and promoting healthy lifestyle through workplace interventions are warranted.

[Obesity or overweight and metabolic syndrome in Mexico City teenagers].

PubMed

Cardoso-Saldaña, Guillermo C; Yamamoto-Kimura, Liria; Medina-Urrutia, Aida; Posadas-Sánchez, Rosalinda; Caracas-Portilla, Nacú A; Posadas-Romero, Carlos

2010-01-01

aim: To know the metabolic syndrome and its components prevalence in Mexico City adolescents sample. A cross-sectional survey was conducted in 772 men and 1078 women, 12 to 16 years old, from 8 randomly selected public junior high schools in Mexico City. Anthropometric variables, lipids, lipoproteins, Apo AI and B, glucose and insulin were determined. Prevalence of metabolic syndrome was 12.5%, 11.15% in men and 13.5% en women (p ns). The most frequently metabolic syndrome component found in México City adolescents was low HDL-C levels (38%), followed by hypertriglyceridemia (25.5%), hypertension (19.2%), central obesity (11.8%) and elevated fasting glucose (1.7). Except by the hypertriglyceridemia, higher in woman than in men, 28.2% vs. 21.6%, p < 0.001, the prevalence of metabolic syndrome components was similar between males and females. The high prevalence of biochemical and physiological factors of metabolic syndrome, associated with overweight and obesity in Mexico City adolescents, increases the risk of premature development of coronary atherosclerosis and diabetes mellitus in this population.

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus.

PubMed

Lampman, R M; Schteingart, D E

1991-06-01

Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

Fenofibrate monotherapy-induced rhabdomyolysis in a patient with hypothyroidism: A rare case report and literature review.

PubMed

Wang, Dawei; Wang, Yanqiu

2018-04-01

Fenofibrate is a fibric acid derivative indicated for use in hypertriglyceridemia and mixed dyslipidemia treatment among adults. Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle contents into the systemic circulation, which is the most serious and fatal side effect of fenofibrate. The objective of this paper is to discuss fatal side effect of fenofibrate and keep safe medication. A patient with hypothyroidism who presented with rhabdomyolysis during fenofibrate monotherapy for hypertriglyceridemia was reported. Fenofibrate Monotherapy Induced Rhabdomyolysis. Fenofibrate was stopped. Adequate fluid resuscitation, mannitol diuresis, myocardium protection, hepatoprotection and urine alkalinization with sodium bicarbonate were performed. Blood tests were normal and the patient was good and discharged 2 weeks later. 13 cases associated with fenofibrate monotherapy-induced rhabdomyolysis were reviewed, which had been published in the English literature. The severity of fenofibrate muscle toxicity may be the result of the combination of two rhabdomyolysis enhancers, such as hypothyroidism and female gender. To avoid it, strict clinical and laboratory monitoring should be maintained, particularly hypothyroidism. Patients should be informed of possible potentially irreversible effects after taking fibrates.

Management of severe hypertriglyceridemia in the hospital: a review.

PubMed

Schaefer, Eric W; Leung, Alicia; Kravarusic, Jelena; Stone, Neil J

2012-01-01

For hospitalists, hypertriglyceridemia (HTG) is more than cardiovascular risk. Severe HTG occurs when serum triglycerides rise above 1000 mg/dL, and it carries a risk of abdominal pain and pancreatitis. The etiology of severe HTG is usually a combination of genetic and secondary factors. A detailed history with attention to family history, medications, and alcohol consumption can often lead to the cause. Physical examination findings may stretch across multiple organ systems. Patients with severe HTG should be admitted to the hospital for aggressive medical therapy if they develop symptoms such as abdominal pain or pancreatitis. Asymptomatic patients with severe HTG who have significant short-term risk for developing symptoms require urgent consultation that may lead to a brief hospitalization to address exacerbating factors. Treatment of severe HTG includes a combination of pharmacologic agents and a restriction on dietary triglyceride intake. If oral medications fail to adequately lower triglyceride levels, intravenous insulin and in rare cases therapeutic plasma exchange may be required. To prevent recurrent severe HTG, the patient should be counseled about adherence to long-term medications and lifestyle changes. Copyright © 2011 Society of Hospital Medicine.

A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis

PubMed Central

2014-01-01

Background Alterations or mutations in the lipoprotein lipase (LPL) gene contribute to severe hypertriglyceridemia (HTG). This study reported on two patients in a Chinese family with LPL gene mutations and severe HTG and acute pancreatitis. Methods Two patients with other five family members were included in this study for DNA-sequences of hyperlipidemia-related genes (such as LPL, APOC2, APOA5, LMF1, and GPIHBP1) and 43 healthy individuals and 70 HTG subjects were included for the screening of LPL gene mutations. Results Both patients were found to have a compound heterozygote for a novel LPL gene mutation (L279V) and a known mutation (A98T). Furthermore, one HTG subject out of 70 was found to carry this novel LPL L279V mutation. Conclusions The data from this study showed that compound heterozygote mutations of A98T and L279V inactivate lipoprotein lipase enzymatic activity and contribute to severe HTG and acute pancreatitis in two Chinese patients. Further study will investigate how these LPL gene mutations genetically inactivate the LPL enzyme. PMID:24646025

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older.

PubMed

Majerczyk, M; Kocełak, P; Choręza, P; Arabzada, H; Owczarek, A J; Bożentowicz-Wikarek, M; Brzozowska, A; Szybalska, A; Puzianowska-Kuźnicka, M; Grodzicki, T; Więcek, A; Olszanecka-Glinianowicz, M; Chudek, J

2018-03-09

Elevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older. The study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured. Nutritional status (BMI/waist circumference) and treatment with statins and fibrates were evaluated. Glomerular filtration rate (eGFR), de Ritis ratio, and fatty liver index (FLI), as well as HOMA-IR were calculated. Our study revealed a strong relationship between components of MS and RBP4 in both sexes: plasma RBP4 levels were increased in men by at least 3×, and in women by at least 4×. Hypertriglyceridemia was most strongly associated with elevated plasma RBP4 levels. Multivariate, sex-adjusted regression analysis demonstrated that chronic kidney disease [OR 1.86 (95% CI 1.78-1.94)], hypertriglyceridemia [OR 1.52 (1.24-1.87)], hypertension [OR 1.15 (1.12-1.19)], low serum HDL cholesterol [OR 0.94 (0.92-0.97)], and age > 80 years [OR 0.86 (0.81-0.90)] were each independently associated with RBP4 concentration (all p < 0.001). In Caucasians 65 years and older, RBP4 serum levels are associated with a number of components of MS, independent of sex and kidney function. Hypertriglyceridemia as a component of MS is most significantly related to RBP4 concentration.

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study)

PubMed Central

Aguilar-Salinas, Carlos A; Assis-Luores-Vale, Andréia; Stockins, Benjamín; Rengifo, Hector Mario; Filho, José Dondici; Neto, Abrahão Afiune; Rabelo, Lísia Marcílio; Torres, Kerginaldo Paulo; Oliveira, José Egídio Paulo de; Machado, Carlos Alberto; Reyes, Eliana; Saavedra, Victor; Florenzano, Fernando; Hernández, Ma Victoria; Jiménez, Sergio Hernandez; Ramírez, Erika; Vazquez, Cuauhtémoc; Salinas, Saul; Hernández, Ismael; Medel, Octavio; Moreno, Ricardo; Lugo, Paula; Alvarado, Ricardo; Mehta, Roopa; Gutierrez, Victor; Gómez Pérez, Francisco J

2004-01-01

Background Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. Methods Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6–3.9 mM/l and HDL cholesterol ≤ 1.05 mM/l for women and ≤ 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. Results After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m2) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs -10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. Conclusions Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated. PMID:15272932

A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge.

PubMed

Lopez, Sergio; Bermudez, Beatriz; Montserrat-de la Paz, Sergio; Abia, Rocio; Muriana, Francisco J G

2018-07-01

The postprandial hypertriglyceridemia is an important and largely silent disturbance involved in the genesis of numerous pathological conditions. Exaggerated and prolonged states of postprandial hypertriglyceridemia are frequently related to the ingestion of meals enriched in saturated fatty acids (SFAs). MicroRNAs are noncoding RNAs that function as gene regulators and play significant roles in both health and disease. However, differential miRNA expression between fasting and postprandial states has never been elucidated. Here, we studied the impact of a high-saturated-fat meal, mainly rich in palmitic acid, on the miRNA signature in peripheral blood mononuclear cells (PBMCs) of nine male healthy individuals in the postprandial period by using a two-step analysis: miRNA array and validation through quantitative real-time polymerase chain reaction. Compared with miRNA expression signature in PBMCs at fasting, 36 miRNAs were down-regulated and 43 miRNAs were up-regulated in PBMCs at postprandial hypertriglyceridemic peak. Six chromosomes (3, 7, 8, 12, 14 and 19) had nearly half (48.1%) of dysregulated miRNA-gene-containing regions. Down-regulated miR-300 and miR-369-3p and up-regulated miR-495-3p, miR-129-5p and miR-7-2-3p had the highest number of target genes. The differentially expressed miRNAs and their predicted target genes involved pathways in cancer, MAPK signaling pathway, endocytosis and axon guidance. Only down-regulated miRNAs notably targeted PI3K-Akt signaling pathways, whereas only up-regulated miRNAs targeted focal adhesion, Wnt signaling pathway, transcriptional misregulation in cancer and ubiquitin-mediated proteolysis. This is the first study of miRNA expression analysis of human PBMCs during postprandial hypertriglyceridemia and offers insight into new potential mechanisms by which dietary SFAs influence health or disease. Copyright © 2018 Elsevier Inc. All rights reserved.

A Snack Dietary Pattern Increases the Risk of Hypercholesterolemia in Northern Chinese Adults: A Prospective Cohort Study

PubMed Central

Na, Lixin; Han, Tianshu; Zhang, Wei; Wu, Xiaoyan; Na, Guanqiong; Du, Shanshan; Li, Ying; Sun, Changhao

2015-01-01

The evidence about the effect of dietary patterns on blood cholesterol from cohort studies was very scarce. The study was to identify the association of dietary patterns with lipid profile, especially cholesterol, in a cohort in north China. Using a 1-year food frequency questionnaire, we assessed the dietary intake of 4515 adults from the Harbin People’s Health Study in 2008, aged 20-74 years. Principle component analysis was used to identify dietary patterns. The follow-up was completed in 2012. Fasting blood samples were collected for the determination of blood lipid concentrations. Logistic regression models were used to evaluate the association of dietary patterns with the incidence of hypercholesterolemia, hypertriglyceridemia, and low-HDL cholesterolemia. Five dietary patterns were identified (“staple food”, “vegetable, fruit and milk”, “potato, soybean and egg”, “snack”, and “meat”). The relative risk (RR) between the extreme tertiles of the snack dietary pattern scores was 1.72 (95% CI = 1.14, 2.59, P = 0.004) for hypercholesterolemia, 1.39 (1.13, 1.75, P = 0.036) for hypertriglyceridemia, after adjustment for age, sex, education, body mass index, smoking, alcohol consumption, energy intake, exercise and baseline lipid concentrations. There was a significant positive association between the snack dietary pattern scores and fasting serum total cholesterol (SRC (standardized regression coefficient) = 0.262, P = 0.025), LDL-c (SRC = 0.324, P = 0.002) and triglycerides (SRC = 0.253, P = 0.035), after adjustment for the multiple variables above. Moreover, the adjusted RR of hypertriglyceridemia between the extreme tertiles was 0.73 (0.56, 0.94, P = 0.025) for the vegetable, fruit and milk dietary pattern, and 1.86 (1.33, 2.41, P = 0.005) for the meat dietary pattern. The snack dietary pattern was a newly emerged dietary pattern in northern Chinese adults. It appears conceivable that the risk of hypercholesterolemia can be reduced by changing the snack dietary pattern. PMID:26244510

Risk factors for benign prostatic enlargement: The role of lifestyle habits at younger age. The #Controllati2017 initiative study group.

PubMed

Mirone, Vincenzo; Carrieri, Giuseppe; Morgia, Giuseppe; Carmignani, Luca; Vespasiani, Giuseppe; Parazzini, Fabio; Artibani, Walter

2017-12-31

The risk factors for benign prostatic enlargement (BPE) are not well understood and particularly few data are available from Italian population. This was an observational cross sectional study aimed to examine the association between several risk factors and BPE. During the "#Controllati2017" initiative, men aged 18 years or more were invited to attend participating urologic centers for a free of charge visit for counseling about urologic or andrologic conditions. Each participating man underwent a physical examination including digital rectal examination (DRE). Further he was asked about his medical history, urologic symptoms, sexual activity and related problems. Diagnosis of BPE was made by the urologist after DRE. Out of the 1902 [mean age 54 years (SD 12, range 18-92)] considered men, a total of 603 subjects (31.7%) had diagnosis of BPE. The diagnosis of BPE increased from 9.3% in men aged < = 50 years, to 34.1% in those aged 51-60 years and to 58.7% among men aged > 60 years. A history of hypertension, diabetes, heart diseases, hypercholesterolemia and hypertriglyceridemia were all significantly associated with an increased risk of BPE in the total series and, although not always in a statistically significant way, in strata of age. Physical activity (PA) was significantly associated with a decreased risk of BPE. We have further analyzed the risk of BPE in men with one or more of the identified risk factors (i.e. hypertension, diabetes, heart disease, hypercholesterolemia, hypertriglyceridemia and low PA): the risk of BPE increased with number of risk factors reported by the subjects. The estimated risk were higher among younger men. In our study a history of hypertension, diabetes, heart disease, hypercholesterolemia and hypertriglyceridemia increased the risk and physical activity lowered the risk of BPE. This risk profile was observed also in men aged < 50 years.

A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients.

PubMed

Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Lee, Eunji; Chae, Jey Sook; Lee, Sang-Hyun; Lee, Jong Ho

2017-01-01

Hypertriglyceridemia is recognized as an independent risk factor for coronary artery disease. The apolipoprotein A5 gene (APOA5) is a key regulator of triglyceride levels. We aimed to evaluate the associations of single nucleotide polymorphisms (SNPs) in APOA5, including -1131T>C and c.553G>T, with hypertriglyceridemia, apoA5 concentrations, atherogenic LDL cholesterol levels, and arterial stiffness in hypertriglyceridemic patients. The study population included 599 hypertriglyceridemic patients (case) and 1,549 untreated normotriglyceridemic subjects (control). We genotyped two APOA5 variants, -1131T>C (rs662799) and c.553G>T (rs2075291). The frequencies of the CC genotype of -1131T>C (0.165) and the T allele of c.553G>T (0.119) were significantly higher in hypertriglyceridemic patients than in normotriglyceridemic subjects (0.061 and 0.070, respectively; all p<0.001). In the control and case groups, both the -1131T>C and c.553G>T variants were associated with higher triglyceride and lower HDL cholesterol levels. Controls with the -1131CC variant had lower apoA5 concentrations than controls with the -1131TT variant. Similar effects of the -1131T>C variant on apoA5 were observed in the cases. In the hypertriglyceridemic group, the -1131T>C variant was associated with a smaller LDL particle size, higher levels of oxidized LDL and malondialdehyde, and higher brachial-ankle pulse wave velocity. The -1131T>C and c.553G>T polymorphisms were associated with hypertriglyceridemia in the study population, but only the -1131T>C polymorphism directly affected apoA5 concentrations. Hypertriglyceridemic patients carrying the APOA5 -1131T>C polymorphism exhibited increased atherogenic LDL levels and arterial stiffness, probably due to an effect of the -1131T>C polymorphism on apoA5 concentrations.

Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy.

PubMed

Chung, Yoo-Ri; Park, Sung Wook; Choi, Shin-Young; Kim, Seung Woo; Moon, Ka Young; Kim, Jeong Hun; Lee, Kihwang

2017-01-07

To investigate the effects of dyslipidemia and statin therapy on progression of diabetic retinopathy and diabetic macular edema in patients with type 2 diabetes. The medical records of 110 patients with type 2 diabetes (70 statin users and 40 non-users) were retrospectively reviewed. The two outcome measures were progression of diabetic retinopathy by two or more steps on the early treatment diabetic retinopathy study scale and diabetic macular edema based on optical coherence tomography. Serum lipid profiles were analyzed from 6 months prior to diagnosis of diabetic macular edema. Diabetic retinopathy progressed in 23% of statin users and 18% of non-users (p = 0.506), but diabetic macular edema was present in 23% of statin users and 48% of non-users (p = 0.008). Statins reduced low-density lipoprotein cholesterol levels in patients with and without diabetic macular edema (p = 0.043 and p = 0.031, respectively). Among statin users, patients with diabetic macular edema had higher levels of triglycerides (p = 0.004) and lower levels of high-density lipoprotein cholesterol (p = 0.033) than those without diabetic macular edema. Logistic regression analysis showed that statin use significantly lowered the risk of diabetic macular edema [odds ratio (OR): 0.33, 95% confidence interval (CI) 0.12-0.91, p = 0.032]. Hypertriglyceridemia at 6 months prior to development of macular edema was significantly associated with central retinal thickness (OR: 1.52; 95% CI 1.14-2.02, p = 0.005). Lipid lowering therapy with statins protected against the development of diabetic macular edema and progression of diabetic retinopathy in patients with type 2 diabetes. Hypertriglyceridemia could be used as a surrogate marker for diabetic macular edema.

A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

PubMed Central

Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

2015-01-01

Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

PubMed Central

Toth, Peter P

2016-01-01

Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available epidemiological, clinical, and genetic evidence relating to the atherogenicity of TRLs and their role in the progression of CVD. PMID:27226718

Frequency of rare mutations and common genetic variations in severe hypertriglyceridemia in the general population of Spain.

PubMed

Lamiquiz-Moneo, Itziar; Blanco-Torrecilla, Cristian; Bea, Ana M; Mateo-Gallego, Rocío; Pérez-Calahorra, Sofía; Baila-Rueda, Lucía; Cenarro, Ana; Civeira, Fernando; de Castro-Orós, Isabel

2016-04-23

Hypertriglyceridemia (HTG) is a common complex metabolic trait that results of the accumulation of relatively common genetic variants in combination with other modifier genes and environmental factors resulting in increased plasma triglyceride (TG) levels. The majority of severe primary hypertriglyceridemias is diagnosed in adulthood and their molecular bases have not been fully defined yet. The prevalence of HTG is highly variable among populations, possibly caused by differences in environmental factors and genetic background. However, the prevalence of very high TG and the frequency of rare mutations causing HTG in a whole non-selected population have not been previously studied. The total of 23,310 subjects over 18 years from a primary care-district in a middle-class area of Zaragoza (Spain) with TG >500 mg/dL were selected to establish HTG prevalence. Those affected of primary HTG were considered for further genetic analysis. The promoters, coding regions and exon-intron boundaries of LPL, LMF1, APOC2, APOA5, APOE and GPIHBP1 genes were sequenced. The frequency of rare variants identified was studied in 90 controls. One hundred ninety-four subjects (1.04%) had HTG and 90 subjects (46.4%) met the inclusion criteria for primary HTG. In this subgroup, nine patients (12.3%) were carriers of 7 rare variants in LPL, LMF1, APOA5, GPIHBP1 or APOE genes. Three of these mutations are described for the first time in this work. The presence of a rare pathogenic mutation did not confer a differential phenotype or a higher family history of HTG. The prevalence of rare mutations in candidate genes in subjects with primary HTG is low. The low frequency of rare mutations, the absence of a more severe phenotype or the dominant transmission of the HTG would not suggest the use of genetic analysis in the clinical practice in this population.

A Snack Dietary Pattern Increases the Risk of Hypercholesterolemia in Northern Chinese Adults: A Prospective Cohort Study.

PubMed

Na, Lixin; Han, Tianshu; Zhang, Wei; Wu, Xiaoyan; Na, Guanqiong; Du, Shanshan; Li, Ying; Sun, Changhao

2015-01-01

The evidence about the effect of dietary patterns on blood cholesterol from cohort studies was very scarce. The study was to identify the association of dietary patterns with lipid profile, especially cholesterol, in a cohort in north China. Using a 1-year food frequency questionnaire, we assessed the dietary intake of 4515 adults from the Harbin People's Health Study in 2008, aged 20-74 years. Principle component analysis was used to identify dietary patterns. The follow-up was completed in 2012. Fasting blood samples were collected for the determination of blood lipid concentrations. Logistic regression models were used to evaluate the association of dietary patterns with the incidence of hypercholesterolemia, hypertriglyceridemia, and low-HDL cholesterolemia. Five dietary patterns were identified ("staple food", "vegetable, fruit and milk", "potato, soybean and egg", "snack", and "meat"). The relative risk (RR) between the extreme tertiles of the snack dietary pattern scores was 1.72 (95% CI = 1.14, 2.59, P = 0.004) for hypercholesterolemia, 1.39 (1.13, 1.75, P = 0.036) for hypertriglyceridemia, after adjustment for age, sex, education, body mass index, smoking, alcohol consumption, energy intake, exercise and baseline lipid concentrations. There was a significant positive association between the snack dietary pattern scores and fasting serum total cholesterol (SRC (standardized regression coefficient) = 0.262, P = 0.025), LDL-c (SRC = 0.324, P = 0.002) and triglycerides (SRC = 0.253, P = 0.035), after adjustment for the multiple variables above. Moreover, the adjusted RR of hypertriglyceridemia between the extreme tertiles was 0.73 (0.56, 0.94, P = 0.025) for the vegetable, fruit and milk dietary pattern, and 1.86 (1.33, 2.41, P = 0.005) for the meat dietary pattern. The snack dietary pattern was a newly emerged dietary pattern in northern Chinese adults. It appears conceivable that the risk of hypercholesterolemia can be reduced by changing the snack dietary pattern.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

PubMed Central

2010-01-01

Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. Conclusion Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ε4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia. PMID:20429872

Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism

USDA-ARS?s Scientific Manuscript database

Interleukin 1b (IL1B or IL-1ß), is a key modulator of the immune response which exerts its functions mainly via interleukin 6 (IL6) regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susc...

Thirteen Week Oral Toxicity Study of WR242511 in Rats. Volume 1

DTIC Science & Technology

1994-01-14

hypercholesterolemia and hypertriglyceridemia seen in high dose females, as previously discussed. Heptatobiliary changes were suggested by significant elevations in...lung (alveolar histiocytosis) lesions. Severe thymic lymphocyte depletion was also observed in these animals where the thymus could be identified...this animal, but it was attributed to the severe and diffuse chronic-active inflammation. As indicated above, treatment-related histopathologic

A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

PubMed

Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

2015-08-13

Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.

Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Tieqiang; Guo Jun; Li Hui

2006-03-24

Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopymore » demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.« less

Regulation of Hepatic ApoC3 Expression by PGC-1β Mediates Hypolipidemic Effect of Nicotinic Acid

PubMed Central

Hernandez, Carlos; Molusky, Matthew; Li, Yaqiang; Li, Siming; Lin, Jiandie D.

2010-01-01

SUMMARY Peroxisome-proliferator activated receptor (PPAR) γ coactivator-1β (PGC-1β) is a transcriptional coactivator that induces hypertriglyceridemia in response to dietary fats through activating hepatic lipogenesis and lipoprotein secretion. The expression of PGC-1β is regulated by free fatty acids. Here we show that PGC-1β regulates plasma triglyceride metabolism through stimulating apolipoprotein C3 (APOC3) expression and elevating APOC3 levels in circulation. Remarkably, liver-specific knockdown of APOC3 significantly ameliorates PGC-1β-induced hypertriglyceridemia in mice. Hepatic expression of PGC-1β and APOC3 is reduced in response to acute and chronic treatments with nicotinic acid, a widely prescribed drug for lowering plasma triglycerides. Adenoviral-mediated knockdown of PGC-1β or APOC3 in the liver recapitulates the hypolipidemic effect of nicotinic acid. Proteomic analysis of hepatic PGC-1β transcriptional complex indicates that it stimulates APOC3 expression through coactivating orphan nuclear receptor ERRα and recruiting chromatin-remodeling cofactors. Together, these studies identify PGC-1β as an important regulator of the APOC3 gene cluster and reveal a mechanism through which nicotinic acid achieves its therapeutic effects. PMID:20889132

Regulation of hepatic ApoC3 expression by PGC-1β mediates hypolipidemic effect of nicotinic acid.

PubMed

Hernandez, Carlos; Molusky, Matthew; Li, Yaqiang; Li, Siming; Lin, Jiandie D

2010-10-06

Peroxisome proliferator-activated receptor (PPAR) γ coactivator-1β (PGC-1β) is a transcriptional coactivator that induces hypertriglyceridemia in response to dietary fats through activating hepatic lipogenesis and lipoprotein secretion. The expression of PGC-1β is regulated by free fatty acids. Here we show that PGC-1β regulates plasma triglyceride metabolism through stimulating apolipoprotein C3 (APOC3) expression and elevating APOC3 levels in circulation. Remarkably, liver-specific knockdown of APOC3 significantly ameliorates PGC-1β-induced hypertriglyceridemia in mice. Hepatic expression of PGC-1β and APOC3 is reduced in response to acute and chronic treatments with nicotinic acid, a widely prescribed drug for lowering plasma triglycerides. Adenoviral-mediated knockdown of PGC-1β or APOC3 in the liver recapitulates the hypolipidemic effect of nicotinic acid. Proteomic analysis of hepatic PGC-1β transcriptional complex indicates that it stimulates APOC3 expression through coactivating orphan nuclear receptor ERRα and recruiting chromatin-remodeling cofactors. Together, these studies identify PGC-1β as an important regulator of the APOC3 gene cluster and reveal a mechanism through which nicotinic acid achieves its therapeutic effects. Copyright © 2010 Elsevier Inc. All rights reserved.

Therapeutic silencing of FSP27 reduces the progression of atherosclerosis in Ldlr-/- mice.

PubMed

Rajamoorthi, Ananthi; Lee, Richard G; Baldán, Ángel

2018-05-24

Obesity, hepatosteatosis, and hypertriglyceridemia are components of the metabolic syndrome and independent risk factors for cardiovascular disease. The lipid droplet-associated protein CIDEC (cell death-inducing DFFA-like effector C), known in mice as FSP27 (fat-specific protein 27), plays a key role in maintaining triacylglyceride (TAG) homeostasis in adipose tissue and liver, and controls circulating TAG levels in mice. Importantly, mutations and SNPs in CIDEC are associated with dyslipidemia and altered metabolic function in humans. Here we tested whether systemic silencing of Fsp27 using antisense oligonucleotides (ASOs) was atheroprotective in LDL receptor knock-out (Ldlr -/- ) mice. Atheroprone Ldlr -/- mice were fed a high-fat, high-cholesterol diet for 12 weeks while simultaneously dosed with saline, ASO-ctrl, or ASO-Fsp27. Data show that, compared to control treatments, silencing Fsp27 significantly reduced body weight gain and visceral adiposity, prevented diet-induced hypertriglyceridemia, and reduced atherosclerotic lesion size both in en face aortas and in the aortic root. Our findings suggest that therapeutic silencing of Fsp27 with ASOs may be beneficial in the prevention and management of atherogenic disease in patients with metabolic syndrome. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A 1H-NMR based metabolomics study of the intervention effect of mangiferin on hyperlipidemia hamsters induced by a high-fat diet.

PubMed

Guo, Fuchuan; Zi, Tianqi; Liu, Liyan; Feng, Rennan; Sun, Changhao

2017-07-19

It has been demonstrated that mangiferin can ameliorate hypertriglyceridemia by modulating the expression levels of genes involved in lipid metabolism in animal experiments, but its effects on the serum metabolic fingerprinting of hyperlipidemia animal models have not been reported. Thus, a NMR-based metabolomics approach was conducted to explore the effects of mangiferin on hyperlipidemia hamsters and to gain a better understanding of the involved metabolic pathways. Hamsters fed with a high-fat diet were orally administered with mangiferin 150 mg per kg BW once a day for 8 weeks. Serum samples were analysed by 1 H NMR, and multivariate statistical analysis was applied to the data to identify potential biomarkers. In total, 20 discriminating metabolites were identified. It turned out that mangiferin administration can partly reverse the metabolism disorders induced by a high-fat diet and exerted a good anti-hypertriglyceridemia effect. Mangiferin ameliorated hyperlipidemia by intervening in some major metabolic pathways, involving glycolysis, the TCA cycle, synthesis of ketone bodies, and BCAAs as well as choline and lipid metabolism. These findings provided new essential information on the effects of mangiferin and demonstrated the great potential of this nutrimetabolomics approach.

PEG-asparaginase induced severe hypertriglyceridemia.

PubMed

Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

2016-04-01

Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

Lipolysis, and not hepatic lipogenesis, is the primary modulator of triglyceride levels in streptozotocin-induced diabetic mice

PubMed Central

Willecke, Florian; Scerbo, Diego; Nagareddy, Prabhakara; Obunike, Joseph C; Barrett, Tessa J; Abdillahi, Mariane L.; Trent, Chad M.; Huggins, Lesley Ann; Fisher, Edward A; Drosatos, Konstantinos; Goldberg, Ira J.

2014-01-01

Objective Diabetic hypertriglyceridemia is thought to be primarily driven by increased hepatic de novo lipogenesis. However, experiments in animal models indicated that insulin deficiency should decrease hepatic de novo lipogenesis and reduce plasma triglyceride levels. Approach and Results To address the discrepancy between human data and genetically altered mouse models, we investigated whether insulin deficient diabetic mice had triglyceride changes that resemble those in diabetic humans. Streptozotocin (STZ)–induced insulin deficiency increased plasma triglyceride levels in mice. Contrary to the mouse models with impaired hepatic insulin receptor signalling, insulin deficiency did not reduce hepatic triglyceride secretion and de novo lipogenesis-related gene expression. Diabetic mice had a marked decrease in postprandial TG clearance, which was associated with decreased lipoprotein lipase (LpL) and PPARα mRNA levels in peripheral tissues and decreased LpL activity in skeletal muscle, heart and brown adipose tissue. Diabetic heterozygous LpL knockout mice had markedly elevated fasting plasma triglyceride levels and prolonged postprandial TG clearance. Conclusion Insulin deficiency causes hypertriglyceridemia by decreasing peripheral lipolysis and not by an increase in hepatic TG production and secretion. PMID:25395613

A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial).

PubMed

Maki, Kevin C; Orloff, David G; Nicholls, Stephen J; Dunbar, Richard L; Roth, Eli M; Curcio, Danielle; Johnson, Judith; Kling, Douglas; Davidson, Michael H

2013-09-01

A novel omega-3 formulation in free fatty acid form (OM3-FFA) has as much as 4-fold greater bioavailability than ethyl ester forms and reduces triglyceride (TG) levels in patients with severe hypertriglyceridemia. This study was designed to evaluate the efficacy of adding OM3-FFA (2 or 4 g/d) to statin therapy for lowering non-HDL-C and TG levels in subjects with persistent hypertriglyceridemia and at high risk for cardiovascular disease. In this double-blind, parallel-group study, 647 diet-stable patients with fasting TG levels ≥ 200 mg/dL and <500 mg/dL (treated with a maximally tolerated dose of statin or statin with ezetimibe) and at high risk for cardiovascular disease were randomized to 6 weeks of treatment with capsules of control (olive oil [OO]) 4 g/d, OM3-FFA 2 g/d (plus 2 g/d OO), or OM3-FFA 4 g/d. Assessments included fasting serum levels of lipids and apolipoproteins (apo); plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and arachidonic acid; and laboratory safety values and adverse events. In the 627 subjects in the intention to treat sample, non-HDL-C levels were reduced with OM3-FFA 2 g/d and OM3-FFA 4 g/d (-3.9% and -6.9%, respectively) compared with OO (-0.9%) (both, P < 0.05), as were TG levels (-14.6% and -20.6%, respectively, vs -5.9%; both, P < 0.001). LDL-C levels increased with OM3-FFA 2 g/d (4.6%) compared with OO (1.1%) (P = 0.025) but not with OM3-FFA 4 g/d (1.3%). Total cholesterol and VLDL-C concentrations were reduced compared with OO with both OM3-FFA dosages, and the total cholesterol/HDL-C ratio and apo AI and apo B levels were significantly lowered with OM3-FFA 4 g/d only (all at least P < 0.05). Percent changes from baseline in HDL-C did not differ between OO and either OM3-FFA group. Plasma concentrations of docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid were significantly increased and arachidonic acid was significantly reduced in both OM3-FFA treatment groups compared with the OO responses (all, P < 0.001). Withdrawals related to treatment-emergent adverse events ranged from 0.9% with OO to 3.2% with OM3-FFA 4 g/d. OM3-FFA was well tolerated and lowered non-HDL-C and TG levels at both 2- and 4-g/d dosages in patients with persistent hypertriglyceridemia taking a statin, with the 4-g/d dosage providing incremental improvements compared with 2 g/d. © 2013 Elsevier HS Journals, Inc. All rights reserved.

Food Deprivation and Exercise in the Heat: Thermoregulatory and Metabolic Effects,

DTIC Science & Technology

1984-12-05

deprivation. Food deprivation resulted in severe hypoglycemia following exercise (P .01), and these decrements were acccmpanied by marked (P .01...reductions in circula- ting insulin levels. Prolonged food deprivation (48 and 72h) resulted in significant (P .01) hypertriglyceridemia and...intervals. We have concluded frac these studies that while several thermoregulatory and metabolic responses to exercise in the heat can be significantly

Evaluation and Management of Dyslipidemia in Patients with HIV Infection

PubMed Central

Green, Michael L

2002-01-01

OBJECTIVE Persons with HIV infection develop metabolic abnormalities related to their antiretroviral therapy and HIV infection itself. The objective of this study was to summarize the emerging evidence for the incidence, etiology, health risks, and treatment of dyslipidemias in HIV disease. DESIGN Systematic review of original research with quantitative synthesis. MAIN RESULTS Dyslipidemia is common in persons with HIV infection on highly active antiretroviral therapy (HAART), but methodologic differences between studies preclude precise estimates of prevalence and incidence. The typical pattern includes elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides, which may be markedly elevated. The dyslipidemia may be associated with lipodystrophy, insulin resistance, and, rarely, frank diabetes mellitus. Exposure to protease inhibitors (PIs) is associated with this entire range of metabolic abnormalities. PI-naïve patients on nucleoside reverse transcriptase inhibitors (NRTIs) may develop lipodystrophy, insulin resistance, hypercholesterolemia, and possibly modest elevations in triglycerides but not severe hypertriglyceridemia, which appears to be linked to PIs alone. Most studies have not found an association between CD4 lymphocyte count or HIV viral load and lipid abnormalities. The pathogenesis is incompletely understood and appears to be multifactorial. There are insufficient data to definitively support an increased coronary heart disease risk in patients with HIV-related dyslipidemia. However, some of the same metabolic abnormalities remain firmly established risk factors in other populations. Patients on HAART with severe hypertriglyceridemia may develop pancreatitis or other manifestations of the chylomicronemia syndrome. Some of the metabolic derangements (particularly hypertriglyceridemia) may improve upon replacing a PI with a non-nucleoside reverse transcriptase inhibitor. The limited experience suggests that fibrates, pravastatin, and atorvastatin can safely treat lipid abnormalities in HIV-infected patients. CONCLUSIONS Patients with HIV infection on HAART should be screened for lipid disorders, given their incidence, potential for morbidity, and possible long-term cardiovascular risk. Treatment decisions are complex and must include assessments of cardiac risk, HIV infection status, reversibility of the dyslipidemia, and the effectiveness and toxicities of lipid-lowering medications. The multiple potential drug interactions with antiretroviral or other HIV-related medications should be considered in lipid-lowering drug selection and monitoring. PMID:12390557

The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus and associated risk factors among adults living in a rural Koladiba town, northwest Ethiopia.

PubMed

Worede, Abebaw; Alemu, Shitaye; Gelaw, Yalemzewod Assefa; Abebe, Molla

2017-07-06

Diabetes mellitus is becoming a big public health challenge, particularly in developing countries like Ethiopia. It is a manageable disease if early screening and follow up is made. However, as studies in Ethiopia are limited and unorganized, determining the magnitude of prediabetes and diabetes and identifying associated risk factors is quite essential. A community-based, cross-sectional study was conducted from February to April 2015 among adults (aged ≥20 years) in a rural Koladiba town. A multistage sampling technique was used to select a total of 392 study participants. Data were collected after a fully informed written consent was obtained from each participant. Demographic, behavioral, and clinical data were collected using a well-structured questionnaire. Multivariable logistic regression models were fitted to control the effect of confounders. Adjusted odds ratios (AOR) with their 95% confidence intervals (95% CI) were computed to measure associations. A p value of <0.05 was considered as statistically significant. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus were 12% (95% CI 9-16) and 2.3% (95% CI 1.1-4), respectively, in Koladiba. Overweight (AOR: 4.257, 95% CI 1.345-13.476), obesity (AOR: 5.26, 95% CI 1.138-24.316), hypertriglyceridemia (AOR: 2.83, 95% CI 1.451-5.521), and systolic hypertension (AOR: 3.858, 95% CI 1.62-9.189) were found to be independently associated with impaired fasting glucose. Positive family history of diabetes also showed a marginal association with impaired fasting glucose (p = 0.057). Male sex (p = 0.012) and hypertriglyceridemia (p = 0.030) were associated with undiagnosed diabetes mellitus. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus are found to be significant. Obesity, hypertriglyceridemia, and systolic hypertension are independently associated with impaired fasting glucose among adults. We recommend that the community be aware of healthy life style, early screening, and maintain continuous follow up.

APOA5-1131T>C genotype effects on apolipoprotein A5 and triglyceride levels in response to dietary intervention and regular exercise (DIRE) in hypertriglyceridemic subjects.

PubMed

Jang, Yangsoo; Chae, Jey Sook; Kim, Oh Yoen; Park, Hey Jun; Kim, Ji Young; Paik, Jean Kyung; Lee, Sang-Hyun; Lee, Jong Ho

2010-08-01

We aimed to determine the influence of apolipoprotein A5 gene (APOA5)-1131T>C single nucleotide polymorphism on the effects of dietary intervention and regular exercise (DIRE) targeting ApoA5 and triglyceride (TG) concentrations. Hypertriglyceridemia patients (TG, 150-500mg/dL, n=283) undertook a 12-week DIRE (replacing 1/3 of refined rice in their diets with legumes, increasing vegetable intake, and regular walking). Pre-treatment, no genotype-related differences were detected in ApoA5, TG, or HDL cholesterol levels; however, post-treatment, subjects homozygous (T/T) for the T allele had lower serum TG (P=0.009) and higher HDL cholesterol (P=0.036) than other subjects. In T/T subjects, after adjustments for age, sex and weight changes (r1) or initial TG levels (r2), changes in ApoA5 levels negatively correlated with TG changes (r1=-0.29, P=0.05, r2=-0.28, P<0.1) and positively correlated with changes in HDL cholesterol (r1=0.30, P<0.05, r2=0.32, P<0.05) and free fatty acid (r1=0.38, P<0.01, r2=0.40, P<0.01). In those with moderate hypertriglyceridemia (TG, 200-500mg/dL, n=130), APOA5-1131T/T carriers achieved significantly lower TG (P=0.007) and higher HDL cholesterol (P<0.001) than -1131C allele carriers. Additionally, statistically significant interactions between the -1131T>C and the compliance of DIRE were found for the change in TG (P=0.002) and HDL cholesterol (P=0.039). In good compliance group, T/T subjects showed greater reduction of TG and higher increase of HDL cholesterol than other subjects. On the other hand, non-good compliance group had no significant improvement in these variables. APOA5-1131T/T carriers may benefit more from the DIRE than C allele carriers. These effects were remarkable in patients with moderate hypertriglyceridemia and the individuals with good compliance. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

PubMed

Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

2015-02-10

Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. Dengue patients with diabetes tended to have more severe thrombocytopenia and were more likely to have DHF/DSS. Older age, hypoalbuminemia, and hypertriglyceridemia were independently associated with more severe thrombocytopenia in dengue patients.

Effects of dietary carbohydrates on glucose and lipid metabolism in golden Syrian hamsters.

PubMed

Kasim-Karakas, S E; Vriend, H; Almario, R; Chow, L C; Goodman, M N

1996-08-01

Frequent coexistence of insulin resistance, central obesity, and hypertriglyceridemia in the same individual suggests an underlying common pathogenesis. Insulin resistance and hypertriglyceridemia can be induced by carbohydrate feeding in rats. Golden Syrian hamsters are believed to be resistant to the metabolic effects of dietary carbohydrates. We investigated the effects of diets containing 60% fructose or sucrose on glucose and lipid metabolism in hamsters, both in the fasting state and during an intravenous glucose tolerance test. Fructose caused obesity (weight after treatment: 131 +/- 7 gm in the control group, 155 +/- 5 gm in the fructose group, 136 +/- 7 gm in sucrose group, p < 0.04). Fructose also reduced glucose disappearance rate (KG: 2.69% +/- 0.39% in the control group, 1.45% +/- 0.18% in the fructose group, p < 0.02). Sucrose caused a marginal decrease in glucose disappearance (KG: 1.93% +/- 0.21%, p = 0.08 vs the control group). Only fructose feeding increased fasting plasma nonesterified fatty acids (0.645 +/- 0.087 mEq/L in the control group, 1.035 +/- 0.083 mEq/L in the fructose group, 0.606 +/- 0.061 mEq/L in the sucrose group, p < 0.002), plasma triglycerides (84 +/- 6 mg/dl in the control group, 270 +/- 65 mg/dl in the fructose group, 94 +/- 16 mg/dl in the sucrose group, p < 0.0002), and liver triglycerides (1.88 +/- 0.38 mg/gm liver weight in the control group, 2.35 =/- 0.24 mg/gm in the fructose group, 1.41 +/- 0.13 mg/gm in the sucrose group, p < 0.04). Previous studies in the rat have suggested that dietary carbohydrates induce insulin resistance by increasing plasma nonesterified fatty acids and triglycerides, which are preferentially used by the muscles. The present report shows that sucrose also can cause some decrease in glucose disappearance in the hamster without causing hypertriglyceridemia or increasing plasma nonesterified fatty acids. Thus other mechanisms may also contribute to the insulin resistance in the hamster. These findings suggest that hamsters provide a good model for investigation of hormonal and nutritional regulation of glucose and lipid metabolism.

Nutrition and the brain.

PubMed

Morley, John E

2010-02-01

Severe nutritional deficiencies, such as protein energy malnutrition and deficiency of nicotinamide, vitamin B(12), folate, and thiamine, have long been recognized to cause severe confusion. Lesser vitamin deficiencies have been linked to the pathogenesis of delirium. Hypo- and hyperglycemia and hypertriglyceridemia can cause cognitive deficits. Epidemiologic and animal studies have linked several other nutrients (omega-3 fatty acids, lutein, alpha-lipoic acid, and the Mediterranean diet) to cognitive performance and the prevention of dementia.

Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations.

PubMed

Lopez, Sergio; Bermudez, Beatriz; Ortega, Almudena; Varela, Lourdes M; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G

2011-03-01

The nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis. The objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations. Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis. The high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs. MUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

Interleukin-1beta gene polymorphisms in Taiwanese patients with gout.

PubMed

Chen, Man-Ling; Huang, Chung-Ming; Tsai, Chang-Hai; Tsai, Fuu-Jen

2005-04-01

The purpose of this study was to examine whether interleukin-1 beta (IL-1beta) promoter and exon 5 gene polymorphisms are markers of susceptibility or clinical manifestations in Taiwanese patients with gout. The study included 196 patients in addition to 103 unrelated healthy control subjects living in central Taiwan. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and IL-1beta exon 5 were typed. Allelic frequencies were compared between the two groups, and the relationship between allelic frequencies and clinical manifestations of gout was evaluated. No significant differences were observed in the allelic frequencies of the IL-1beta promoter between patients with gout and healthy control subjects. Additionally, we did not detect any association of the IL-1beta promoter genotype with the clinical and laboratory profiles of gout patients. However, there was a significant difference between the two groups in terms of hypertriglyceridemia (P=0.0004, chi(2)=12.52, OR 7.14, 95%CI 0.012-0.22). There was also a significant difference in the genotype of IL-1beta exon 5 polymorphism between patients with and without hypertriglyceridemia. Results of the present study suggest that polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are not related to gout patients in central Taiwan.

Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verreth, Wim; Verhamme, Peter; Pelat, Michael

2003-09-01

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and ofmore » key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.« less

Association of SNP3 polymorphism in the apolipoprotein A-V gene with plasma triglyceride level in Tunisian type 2 diabetes

PubMed Central

Chaaba, Raja; Attia, Nebil; Hammami, Sonia; Smaoui, Maha; Mahjoub, Sylvia; Hammami, Mohamed; Masmoudi, Ahmed Slaheddine

2005-01-01

Background Apolipoprotein A-V (Apo A-V) gene has recently been identified as a new apolipoprotein involved in triglyceride metabolism. A single nucleotide polymorphism (SNP3) located in the gene promoter (-1131) was associated with triglyceride variation in healthy subjects. In type 2 diabetes the triglyceride level increased compared to healthy subjects. Hypertriglyceridemia is a risk factor for coronary artery disease. We aimed to examine the interaction between SNP3 and lipid profile and coronary artery disease (CAD) in Tunisian type 2 diabetic patients. Results The genotype frequencies of T/T, T/C and C/C were 0.74, 0.23 and 0.03 respectively in non diabetic subjects, 0.71, 0.25 and 0.04 respectively in type 2 diabetic patients. Triglyceride level was higher in heterozygous genotype (-1131 T/C) of apo A-V (p = 0.024). Heterozygous genotype is more frequent in high triglyceride group (40.9%) than in low triglyceride group (18.8%) ; p = 0.011. Despite the relation between CAD and hypertriglyceridemia the SNP 3 was not associated with CAD. Conclusion In type 2 diabetic patients SNP3 is associated with triglyceride level, however there was no association between SNP3 and coronary artery disease. PMID:15636639

Efficient lowering of triglyceride levels in mice by human apoAV protein variants associated with hypertriglyceridemia.

PubMed

Vaessen, Stefan F C; Sierts, Jeroen A; Kuivenhoven, Jan Albert; Schaap, Frank G

2009-02-06

Variation in the apolipoprotein A5 (APOA5) gene has consistently been associated with increased plasma triglyceride (TG) levels in epidemiological studies. In vivo functionality of these variations, however, has thus far not been tested. Using adenoviral over-expression, we evaluated plasma expression levels and TG-lowering efficacies of wild-type human apoAV, two human apoAV variants associated with increased TG (S19W, G185C) and one variant (Q341H) that is predicted to have altered protein function. Injection of mice with adenovirus encoding wild-type or mutant apoAV resulted in an identical dose-dependent elevation of human apoAV levels in plasma. The increase in apoAV levels resulted in pronounced lowering of plasma TG levels at two viral dosages. Unexpectedly, the TG-lowering efficacy of all three apoAV variants was similar to wild-type apoAV. In addition, no effect on TG-hydrolysis-related plasma parameters (free fatty acids, glycerol and post-heparin lipoprotein lipase activity) was apparent upon expression of all apoAV variants. In conclusion, our data indicate that despite their association with hypertriglyceridemia and/or predicted protein dysfunction, the 19W, 185C and 341H apoAV variants are equally effective in reducing plasma TG levels in mice.

Eicosanoids in Metabolic Syndrome

PubMed Central

Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

2013-01-01

Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

Hemophagocytic lymphohistiocytosis in acute African swine fever clinic.

PubMed

Karalyan, Z R; Ter-Pogossyan, Z R; Karalyan, N Yu; Semerjyan, Z B; Tatoyan, M R; Karapetyan, S A; Karalova, E M

2017-05-01

Hemophagocytic lymphohistiocytosis (HLH) usually has been defined as the combination of a proliferation of cytologically benign, actively phagocytic macrophages in bone marrow, spleen, lymph nodes, etc. in association with fever, cytopenia, splenomegaly, and hypertriglyceridemia. HLH is often triggered by viral infection. The aim of this study was to ascertain the features of HLH involvement in African swine fever virus (ASFV) (genotype II) pathogenesis. The serum levels of macrophage colony-stimulating factor (MCSF) and granulocyte-macrophage colony-stimulating factor (GMCSF), as well as the histological constitution (for hemophagocytic macrophages detection) of various organs of pigs infected with ASFV genotype II were investigated. The diagnosis of HLH was made according to universally accepted human criteria. The association of fever, cytopenias, splenomegaly, and hemophagocytosis was present in 87.5% of the infected pigs (absence of hyperthermia in one of eight pigs). Marked hypertriglyceridemia was observed at 3-4days post infection. Previously it was shown that ASFV induced a significant decrease in the level of fibrinogen from day 5 till the end of experiment. Progression of the HLH coincided with a temporary increase in the serum levels of MCSF levels (early stage of disease) and GMCSF levels (2-3 pays post infection). Hemophagocytic syndrome should be suspected in ASFV (genotypeII) infected pigs. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of diabetes and cardiovascular risk factors in middle-class urban participants in India.

PubMed

Gupta, Arvind; Gupta, Rajeev; Sharma, Krishna Kumar; Lodha, Sailesh; Achari, Vijay; Asirvatham, Arthur J; Bhansali, Anil; Gupta, Balkishan; Gupta, Sunil; Jali, Mallikarjuna V; Mahanta, Tulika G; Maheshwari, Anuj; Saboo, Banshi; Singh, Jitendra; Deedwania, Prakash C

2014-01-01

To determine the prevalence of diabetes and awareness, treatment and control of cardiovascular risk factors in population-based participants in India. A study was conducted in 11 cities in different regions of India using cluster sampling. Participants were evaluated for demographic, biophysical, and biochemical risk factors. 6198 participants were recruited, and in 5359 participants (86.4%, men 55%), details of diabetes (known or fasting glucose >126 mg/dL), hypertension (known or blood pressure >140/>90 mm Hg), hypercholesterolemia (cholesterol >200 mg/dL), low high-density lipoprotein (HDL) cholesterol (men <40, women <50 mg/dL), hypertriglyceridemia (>150 mg/dL), and smoking/tobacco use were available. Details of awareness, treatment, and control of hypertension and hypercholesterolemia were also obtained. The age-adjusted prevalence (%) of diabetes was 15.7 (95% CI 14.8 to 16.6; men 16.7, women 14.4) and that of impaired fasting glucose was 17.8 (16.8 to 18.7; men 17.7, women 18.0). In participants with diabetes, 27.6% were undiagnosed, drug treatment was in 54.1% and control (fasting glucose ≤130 mg/dL) in 39.6%. Among participants with diabetes versus those without, prevalence of hypertension was 73.1 (67.2 to 75.0) vs 26.5 (25.2 to 27.8), hypercholesterolemia 41.4 (38.3 to 44.5) vs 14.7 (13.7 to 15.7), hypertriglyceridemia 71.0 (68.1 to 73.8) vs 30.2 (28.8 to 31.5), low HDL cholesterol 78.5 (75.9 to 80.1) vs 37.1 (35.7 to 38.5), and smoking/smokeless tobacco use in 26.6 (23.8 to 29.4) vs 14.4 (13.4 to 15.4; p<0.001). Awareness, treatment, and control, respectively, of hypertension were 79.9%, 48.7%, and 40.7% and those of hypercholesterolemia were 61.0%, 19.1%, and 45.9%, respectively. In the urban Indian middle class, more than a quarter of patients with diabetes are undiagnosed and the status of control is low. Cardiovascular risk factors-hypertension, hypercholesterolemia, low HDL cholesterol, hypertriglyceridemia, and smoking/smokeless tobacco use-are highly prevalent. There is low awareness, treatment, and control of hypertension and hypercholesterolemia in patients with diabetes.

Effects of betel nut on cardiovascular risk factors in a rat model

PubMed Central

2012-01-01

Background Areca nut (commonly known as betel nut) chewing has been shown to be associated with metabolic syndrome and cardiovascular disease (CVD). The mechanism by which betel nut ingestion could lead to development of CVD is not precisely known; however, dyslipidemia, hyperhomocysteinemia, hypertriglyceridemia and inflammation could be some of the potential risk factors. This study was undertaken to investigate the effects of two dosages of betel nut on homocysteinemia, inflammation and some of the components of metabolic syndrome, such as hypertriglyceridemia, low HDL-cholesterol, obesity and fasting hyperglycemia in a rat model. Methods Thirty-six adult female Sprague Dawley rats, aged 10–12 weeks were divided into three equal groups. Group-1 served as the control group (n = 12) and received water, whereas groups 2 and 3 were given water suspension of betel nut orally in two dosages, 30 mg and 60 mg, respectively for a period of 5 weeks. At the end of the fifth week, the animals were weighed and sacrificed, blood was collected and liver, kidney, spleen and stomach were removed for histological examination. Plasma/serum was analyzed for glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, homocysteine, folate, vitamin B12 and N-acetyl-β-D-glucosaminidase (NAG) – a marker of inflammation. Results When the mean concentration values of 3 groups were compared using one way ANOVA followed by Tukey’s HSD-test, there was a significant increase in the concentration of total cholesterol (p = 0.04) in the group receiving 30 mg/day betel nut compared to the control group. However, administration of a higher dose of betel nut (60 mg/day) had no significant effect on the serum concentrations of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and NAG. Histological examination of spleen revealed a dose-dependent extramedullary hematopoiesis. No other remarkable change in the tissues (liver, kidney and stomach) was observed. Mean serum/plasma levels of folate, vitamin B12 and homocysteine were not found to be significantly different in all the groups. Betel nut ingestion had no effect on the mean body weights of rats. Conclusions Low dosage of betel nut is found to be associated with hypercholesterolemia. However, betel nut ingestion is not associated with hyperhomocysteinemia, hypertriglyceridemia, hyperglycemia, inflammation and increase in body weight in a rat model. PMID:23095290

Effects of betel nut on cardiovascular risk factors in a rat model.

PubMed

Iqbal, Mohammad Perwaiz; Mehboobali, Naseema; Haider, Ghulam; Pervez, Shahid; Azam, Iqbal

2012-10-24

Areca nut (commonly known as betel nut) chewing has been shown to be associated with metabolic syndrome and cardiovascular disease (CVD). The mechanism by which betel nut ingestion could lead to development of CVD is not precisely known; however, dyslipidemia, hyperhomocysteinemia, hypertriglyceridemia and inflammation could be some of the potential risk factors. This study was undertaken to investigate the effects of two dosages of betel nut on homocysteinemia, inflammation and some of the components of metabolic syndrome, such as hypertriglyceridemia, low HDL-cholesterol, obesity and fasting hyperglycemia in a rat model. Thirty-six adult female Sprague Dawley rats, aged 10-12 weeks were divided into three equal groups. Group-1 served as the control group (n = 12) and received water, whereas groups 2 and 3 were given water suspension of betel nut orally in two dosages, 30 mg and 60 mg, respectively for a period of 5 weeks. At the end of the fifth week, the animals were weighed and sacrificed, blood was collected and liver, kidney, spleen and stomach were removed for histological examination.Plasma/serum was analyzed for glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, homocysteine, folate, vitamin B12 and N-acetyl-β-D-glucosaminidase (NAG) - a marker of inflammation. When the mean concentration values of 3 groups were compared using one way ANOVA followed by Tukey's HSD-test, there was a significant increase in the concentration of total cholesterol (p = 0.04) in the group receiving 30 mg/day betel nut compared to the control group. However, administration of a higher dose of betel nut (60 mg/day) had no significant effect on the serum concentrations of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and NAG. Histological examination of spleen revealed a dose-dependent extramedullary hematopoiesis. No other remarkable change in the tissues (liver, kidney and stomach) was observed.Mean serum/plasma levels of folate, vitamin B12 and homocysteine were not found to be significantly different in all the groups. Betel nut ingestion had no effect on the mean body weights of rats. Low dosage of betel nut is found to be associated with hypercholesterolemia. However, betel nut ingestion is not associated with hyperhomocysteinemia, hypertriglyceridemia, hyperglycemia, inflammation and increase in body weight in a rat model.

Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice.

PubMed

Stewart, Taryn P; Kim, Hyoung Yon; Saxton, Arnold M; Kim, Jung Han

2010-12-19

Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. In order to determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and F2 mice were phenotyped at 8, 12, 16, 20, and 24 weeks of age for 4-hour fasting plasma triglyceride, cholesterol, insulin, and glucose levels and body, fat pad and carcass weights. The F2 mice were genotyped genome-wide and used for quantitative trait locus (QTL) mapping. We also applied a genetical genomic approach using a subset of the F2 mice to seek candidate genes underlying the QTLs. Major QTLs were detected on chromosomes (Chrs) 1, 11, 4, and 8 for hypertriglyceridemia, 1 and 3 for hypercholesterolemia, 4 for hyperglycemia, 11 and 1 for body weight, 1 for fat pad weight, and 11 and 14 for carcass weight. Most alleles, except for Chr 3 and 14 QTLs, increased phenotypic values when contributed by the TH strain. Fourteen pairs of interacting loci were detected, none of which overlapped the major QTLs. The QTL interval linked to hypercholesterolemia and hypertriglyceridemia on distal Chr 1 contains Apoa2 gene. Sequencing analysis revealed polymorphisms of Apoa2 in TH mice, suggesting Apoa2 as the candidate gene for the hyperlipidemia QTL. Gene expression analysis added novel information and aided in selection of candidates underlying the QTLs. We identified several genetic loci that affect the quantitative variations of plasma lipid and glucose levels and obesity traits in a TH × B6 intercross. Polymorphisms in Apoa2 gene are suggested to be responsible for the Chr 1 QTL linked to hypercholesterolemia and hypertriglyceridemia. Further, genetical genomic analysis led to potential candidate genes for the QTLs.

Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice

PubMed Central

2010-01-01

Background Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. Results In order to determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and F2 mice were phenotyped at 8, 12, 16, 20, and 24 weeks of age for 4-hour fasting plasma triglyceride, cholesterol, insulin, and glucose levels and body, fat pad and carcass weights. The F2 mice were genotyped genome-wide and used for quantitative trait locus (QTL) mapping. We also applied a genetical genomic approach using a subset of the F2 mice to seek candidate genes underlying the QTLs. Major QTLs were detected on chromosomes (Chrs) 1, 11, 4, and 8 for hypertriglyceridemia, 1 and 3 for hypercholesterolemia, 4 for hyperglycemia, 11 and 1 for body weight, 1 for fat pad weight, and 11 and 14 for carcass weight. Most alleles, except for Chr 3 and 14 QTLs, increased phenotypic values when contributed by the TH strain. Fourteen pairs of interacting loci were detected, none of which overlapped the major QTLs. The QTL interval linked to hypercholesterolemia and hypertriglyceridemia on distal Chr 1 contains Apoa2 gene. Sequencing analysis revealed polymorphisms of Apoa2 in TH mice, suggesting Apoa2 as the candidate gene for the hyperlipidemia QTL. Gene expression analysis added novel information and aided in selection of candidates underlying the QTLs. Conclusions We identified several genetic loci that affect the quantitative variations of plasma lipid and glucose levels and obesity traits in a TH × B6 intercross. Polymorphisms in Apoa2 gene are suggested to be responsible for the Chr 1 QTL linked to hypercholesterolemia and hypertriglyceridemia. Further, genetical genomic analysis led to potential candidate genes for the QTLs. PMID:21167066

Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin.

PubMed

He, Liang; Hao, Lili; Fu, Xin; Huang, Mingshu; Li, Rui

2015-04-11

Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important complement to existing diabetic models for pathophysiological studies in early acute and chronic kidney disease, especially hyperlipidemia. These data suggest that both severe hypertriglyceridemia and hypercholesterolemia can accelerate renal injury in the early development of T1DM.

The Dynamics of the Human Infant Gut Microbiome in Development and in Progression Toward Type1 Diabetes

DTIC Science & Technology

2016-09-09

5Research Program Unit, Diabetes and Obesity , University of Helsinki, 00290 Helsinki, Finland 6Department of Information and Computer Science, Aalto...Figure 6C). Altered levels of serum triglycerides are a common feature of obesity and type 2 diabetes, and hypertriglyceridemia is (B) Shown is the...composition that may contribute to childhood disease, we must first investigate the normal dynamics of the community in the developing infant. Here

Identifying Blood Biomarkers and Physiological Processes That Distinguish Humans with Superior Performance under Psychological Stress

DTIC Science & Technology

2009-12-18

338 (Pt2): 281–287. 27. Berbee JF, van der Hoogt CC, Sundararaman D, Havekes LM, Rensen PC (2005) Severe hypertriglyceridemia in human APOC1 transgenic...plasma lipid regulation. Each of these processes is discussed in detail. Innate Immunity Several innate immune response pathways were differentially...response to infection, injury or stress resulting in the increased or decreased plasma concentration of several proteins called acute phase proteins (APP

Cardiovascular Risk Factors in Primary Relatives of Sudden Cardiac Death Victims

DTIC Science & Technology

1991-01-01

hypertriglyceridemia and hypertension as risk factors in relatives of sudden death victims. The sample for both studies will be the same. 5 Chapter II The...provided most of the research information on SCD. Pathology of Sudden Cardiac Death There appear to be several different pathologic scenarios which render a...had severe two or three vessel disease. By comparison, 100 age matched controls who died of other causes, had a combined 27% incidence of two and

Anthropometric and metabolic indices in assessment of type and severity of dyslipidemia.

PubMed

Zaid, Muhammad; Ameer, Fatima; Munir, Rimsha; Rashid, Rida; Farooq, Nimrah; Hasnain, Shahida; Zaidi, Nousheen

2017-02-28

It has been shown that obesity is associated with increased rates of dyslipidemia. The present work revisits the association between plasma lipid levels and classical indicators of obesity including body mass index (BMI). The significance of various anthropometric/metabolic variables in clinical assessment of type and severity of dyslipidemia was also determined. Recently described body indices, a body shape index (ABSI) and body roundness index (BRI), were also assessed in this context. For the present cross-sectional analytical study, the participants (n = 275) were recruited from the patients visiting different health camps. Participants were anthropometrically measured and interviewed, and their fasting intravenous blood was collected. Plasma lipid levels were accordingly determined. The values for different anthropometric parameters are significantly different between dyslipidemic and non-dyslipidemic participants. Receiver operating characteristics curve analyses revealed that all the tested variables gave the highest area under the curve (AUC) values for predicting hypertriglyceridemia in comparison to other plasma lipid abnormalities. BRI gave slightly higher AUC values in predicting different forms of dyslipidemia in comparison to BMI, whereas ABSI gave very low values. Several anthropometric/metabolic indices display increased predictive capabilities for detecting hypertriglyceridemia in comparison to any other form of plasma lipid disorders. The capacity of BRI to predict dyslipidemia was comparable but not superior to the classical indicators of obesity, whereas ABSI could not detect dyslipidemia.

[High frequency of dyslipidemia in children and adolescents with Down Syndrome].

PubMed

de la Piedra, María J; Alberti, Gigliola; Cerda, Jaime; Cárdenas, Antonia; Paul, María A; Lizama, Macarena

2017-01-01

Down Syndrome (DS) shows an increased risk of chronic diseases, associated to higher morbidity and mortality for cardiovascular disease. Some studies have shown a worse lipid profile in children with DS, however, until now there is no recommendation for screening for dyslipidemia in these subjects. To describe the frequency of dyslipidemia in a population of Chilean children and adolescents with DS. Retrospective study, including patients with DS, aged 2 to 18 years, who participated in a special health care program for people with DS in Health Net UC CHRISTUS, between 2007 and 2015. Patients who had a lipid profile between their routine laboratory tests were included. Clinical characteristics, relevant comorbidities, malformations, medications, nutritional status and pubertal development were obtained from medical records. Diagnosis of dyslipidemia was considered according to the criteria of the NHLBI 2011. The medical records of 218 children with DS were revised, 58,3% had some type of dyslipidemia. The most frequent single dyslipidemias were low HDL Chol (15,1%) and hypertriglyceridemia (12,8%). Atherogenic dyslipidemia (low HDL plus hypertriglyceridemia) was the most frequent combined dyslipidemia (13,3%). The occurrence of atherogenic dyslipidemia was not associated with overnutrition and obesity. A high frequency of dyslipidemia was found in Chilean children and adolescents with DS. Our results make us suggest that lipid profile should be performed early in all patients with DS, independent of the presence of risk factors for dyslipidemia.

SstI Polymorphism of the Apolipoprotein CIII Gene in Iranian Hyperlipidemic Patients: A Study in Semnan Province

PubMed Central

Bandegi, Ahmad Reza; Firoozrai, Mohsen; Akbari Eidgahi, Mohammad Reza; Kokhaei, Parviz

2011-01-01

Objective(s) The Sst-I polymorphic site on the 3' untranslated region of the apo CIII gene, has been previously reported to be associated with hypertriglyceridemia. The aim of the present study was to explore the association between Sst-I polymorphism with plasma lipid and lipoprotein levels in hyperlipidemic (HLP) patients from Semnan province, Iran. Materials and Methods Genomic DNA was prepared from 76 patients with HLP and 75 matched healthy subjects. DNA samples were amplified by polymerase chain reaction. The samples were analyzed by restriction fragment length polymorphism (RFLP) method using SstI enzyme. Results The genotype and allelic frequencies for this polymorphism were significantly different between HLP and normolipidemic groups (P< 0.002). Plasma triglyceride (TG) level was higher in both groups, in S2S2 genotype was more than in the S1S1and S1S2 genotypes, however, there was no significant difference in comparison with the control group. Subjects with S1S2 + S2S2 genotypes in compare to S1S1 genotype had odd ratio of 2.8 (95% CI: 1.41-5.56, P< 0.003) for developing hypertriglyceridemia. Conclusion The results showed that the presence of rare S2 allele was associated with change in TG level in the selected population. PMID:23493241

Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia.

PubMed

Whitney, M S; Boon, G D; Rebar, A H; Story, J A; Bottoms, G D

1993-01-01

To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen MS were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic MS was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic MS had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic MS and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic MS were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB; those of diabetic lipemic MS resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low density lipoproteins.

Abdominal obesity modifies the risk of hypertriglyceridemia for all-cause and cardiovascular mortality in hemodialysis patients.

PubMed

Postorino, Maurizio; Marino, Carmen; Tripepi, Giovanni; Zoccali, Carmine

2011-04-01

Hypertriglyceridemia is the most prevalent lipid alteration in end-stage renal disease, and we studied the relationship between serum triglycerides and all-cause and cardiovascular death in these patients. Since abdominal fat modifies the effect of lipids on atherosclerosis, we analyzed the interaction between serum lipids and waist circumference (WC) as a metric of abdominal obesity. In a cohort of 537 hemodialysis patients, 182 died, 113 from cardiovascular causes, over an average follow-up of 29 months. In Cox models that included traditional and nontraditional risk factors, there were significant strong interactions between triglycerides and WC to both all-cause and cardiovascular death. A fixed (50 mg/dl) excess in triglycerides was associated with a progressive lower risk of all-cause and cardiovascular mortality in patients with threshold WC <95 cm but with a progressive increased risk in those above this threshold. A significant interaction between cholesterol and WC with all-cause and cardiovascular death emerged only in models excluding the triglycerides-WC interaction. Neither high-density lipoprotein (HDL) nor non-HDL cholesterol or their interaction terms with WC were associated with study outcomes. Thus, the predictive value of triglycerides and cholesterol for survival and atherosclerotic complications in hemodialysis patients is critically dependent on WC. Hence, intervention studies in end-stage renal disease should specifically target patients with abdominal obesity and hyperlipidemia.

[Investigation of glucocorticoid-induced side effects in patients with autoimmune diseases].

PubMed

Nakajima, Aya; Doki, Kosuke; Homma, Masato; Sagae, Terumi; Saito, Reiko; Ito, Satoshi; Sumida, Takayuki; Kohda, Yukinao

2009-04-01

High dose glucocorticoids (GC) are commonly used for the treatment of autoimmune diseases. The frequencies, occurrence day and dose-dependency for side effects may be different among the events such as diabetes mellitus, hyperlipidemia, infectious disease, osteoporosis, and peptic ulcer. We investigated GC-induced side effects in 68 patients treated with GC for autoimmune diseases. Initial dose of GC (prednisolone equivalent) was 0.67+/-0.35 mg/kg/d. Hypercholesterolemia (66%), hypertension (62%), insomnia (50%), hypertriglyceridemia (44%), excessive appetite (38%), hyperglycemia (18%), digestive symptom (16%), moon-shaped face (13%) and oral candidiasis (12%) were observed in 63 patients treated with GC. Hypercholesterolemia, excessive appetite, digestive symptom, moon-shaped face, and oral candidiasis were associated with the initial dose of prednisolone greater than 0.80 mg/kg/d. Insomnia [median 6 days (range 1-88)], excessive appetite [7 days (2-57)], hypertension [8 days (1-37)], digestive symptom [15 days (1-87)] and hypercholesterolemia [19 days (3-77)] were observed early after 6-19 days starting GC. On the other hand, hypertriglyceridemia [33 days (2-131)], oral candidiasis [35 days (7-52)] and hyperglycemia [60 days (4-134)] were developed after 33-60 days starting GC. Since the frequencies, dose-dependency and occurrence day were different among the side effects of GC, medical staffs including physicians and pharmacists should pay attention such features of the events in the treatment of autoimmune diseases.

Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.

PubMed

Troina, A A; Figueiredo, M S; Passos, M C F; Reis, A M; Oliveira, E; Lisboa, P C; Moura, E G

2012-07-01

We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil+SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40 mg of SDG/100g diet (SDG) or diet added 40 mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14th day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-β estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lipoprotein lipase activity in surgical patients: influence of trauma and infection.

PubMed

Robin, A P; Askanazi, J; Greenwood, M R; Carpentier, Y A; Gump, F E; Kinney, J M

1981-08-01

Hypertriglyceridemia commonly accompanies clinical sepsis and may be caused by increased hepatic production or decreased clearance of triglyceride from the bloodstream. In contrast, enhanced lipid clearing capacity is usually seen after uncomplicated trauma. The purpose of the study was to determine the role of lipoprotein lipase (LPL) in effecting the above changes. Enzyme activity was assayed in skeletal muscle and adipose tissue biopsy samples from 11 normal subjects and from 17 injured and 11 infected surgical patients. Normal subjects after 4 days of 5% dextrose infusion (D5) showed a significant decrease in adipose tissue LPL activity but no change in skeletal muscle activity. Trauma patients after several days of D5 had higher activity in adipose tissue and higher plasma insulin levels than diet-matched control subjects but showed no change in skeletal muscle activity. Infected patients with high plasma triglyceride levels had significantly decreased LPL activity in both tissues. A linear relationship was found between insulin concentration and adipose tissue LPL activity in normal subjects. We conclude that: (1) low tissue LPL activity in sepsis may result in diminished lipid clearance and contribute to hypertriglyceridemia, (2) after trauma, changes in tissue LPL activity as well as other factors such as altered hemodynamics play a role in determining in vivo lipid clearance, and (3) adipose tissue LPL activity is related to the plasma insulin concentration in normal subjects.

Effect of green tea extract microencapsulation on hypertriglyceridemia and cardiovascular tissues in high fructose-fed rats

PubMed Central

Jung, Moon Hee; Seong, Pil Nam; Kim, Myung Hwan; Myong, Na-Hye

2013-01-01

The application of polyphenols has attracted great interest in the field of functional foods and nutraceuticals due to their potential health benefits in humans. However, the effectiveness of polyphenols depends on their bioactivity and bioavailability. In the present study, the bioactive component from green tea extract (GTE) was administrated orally (50 mg/kg body weight/day) as free or in a microencapsulated form with maltodextrin in rats fed a high fructose diet. High fructose diet induced features of metabolic syndrome including hypertriglyceridemia, hyperuricemia, increased serum total cholesterol, and retroperitoneal obesity. In addition, myocardial fibrosis was increased. In rats receiving high fructose diet, the lowering of blood triglycerides, total cholesterol, non esterified fatty acid (NEFA) and uric acid, as well as the reduction in final body weight and retroperitoneal fat weight associated with the administration of GTE, led to a reversal of the features of metabolic syndrome (P < 0.05). In particular, the administration of microencapsulated GTE decreased myocardial fibrosis and increased liver catalase activity consistent with a further alleviation of serum NEFA, and hyperuricemia compared to administration of GTE. Taken together, our results suggest that microencapsulation of the bioactive components of GTE might have a protective effect on cardiovasucular system by attenuating the adverse features of myocardial fibrosis, decreasing uric acid levels and increasing hepatic catalase activity effectively by protecting their bioactivities. PMID:24133615

Two novel rare variants of APOA5 gene found in subjects with severe hypertriglyceridemia.

PubMed

Pisciotta, Livia; Fresa, Raffaele; Bellocchio, Antonella; Guido, Virgilia; Priore Oliva, Claudio; Calandra, Sebastiano; Bertolini, Stefano

2011-11-20

Common variants of APOA5 gene affect plasma triglyceride (TG) in the population and a number of rare variants APOA5 have been reported in individuals with hypertriglyceridemia (HTG). APOA5 was analysed in 98 HTG individuals (plasma TG >9 mmol/L) in whom no mutations in LPL and APOC2 had been found. Two patients were found to be heterozygous for two novel APOA5 variants. The first variant (p.L253P) was identified in an obese male who consumed a diet rich in fat and simple sugars. He was also a carrier in trans of the common TG-raising p.S19W SNP (5*3 haplotype). The second variant (c.295-297 del GAG, p.E99 del) was found in a lean male with no life style or metabolic factors known to affect plasma TG. He was a carrier in trans of the TG-raising 5*2 haplotype and was homozygous for the rare c.1337T allele of a SNP of GCKR gene. No mutations in other genes affecting plasma TG (LMF1 and GPIHBP1) were found in these patients. These APOA5 variants, resulted to be deleterious in silico, were not found in 350 control subjects. These novel APOA5 variants predispose to HTG in combination with other genetic or nutritional factors. Copyright © 2011 Elsevier B.V. All rights reserved.

All-Cause and Acute Pancreatitis Health Care Costs in Patients With Severe Hypertriglyceridemia.

PubMed

Rashid, Nazia; Sharma, Puza P; Scott, Ronald D; Lin, Kathy J; Toth, Peter P

2017-01-01

The aim of this study was to assess health care utilization and costs related to acute pancreatitis (AP) in patients with severe hypertriglyceridemia (sHTG) levels. Patients with sHTG levels 1000 mg/dL or higher were identified from January 1, 2007, to June 30, 2013. The first identified incident triglyceride level was labeled as index date. All-cause, AP-related health care visits, and mean total all-cause costs in patients with and without AP were compared during 12 months postindex. A generalized linear model regression was used to compare costs while controlling for patient characteristics and comorbidities. Five thousand five hundred fifty sHTG patients were identified, and 5.4% of these patients developed AP during postindex. Patients with AP had significantly (P < 0.05) more all-cause outpatient visits, hospitalizations, longer length of stays during the hospital visits, and emergency department visits versus patients without AP. Mean (SD) unadjusted all-cause health care costs in the 12 months postindex were $25,343 ($33,139) for patients with AP compared with $15,195 ($24,040) for patients with no AP. The regression showed annual all-cause costs were 49.9% higher (P < 0.01) for patients with AP versus without AP. Patients who developed AP were associated with higher costs; managing patients with sHTG at risk of developing AP may help reduce unnecessary costs.

Severe hypertriglyceridemia in Norway: prevalence, clinical and genetic characteristics.

PubMed

Retterstøl, Kjetil; Narverud, Ingunn; Selmer, Randi; Berge, Knut E; Osnes, Ingvild V; Ulven, Stine M; Halvorsen, Bente; Aukrust, Pål; Holven, Kirsten B; Iversen, Per O

2017-06-12

There is a lack of comprehensive patient-datasets regarding prevalence of severe hypertriglyceridemia (sHTG; triglycerides ≥10 mmol/L), frequency of co-morbidities, gene mutations, and gene characterization in sHTG. Using large surveys combined with detailed analysis of sub-cohorts of sHTG patients, we here sought to address these issues. We used data from several large Norwegian surveys that included 681,990 subjects, to estimate the prevalence. Sixty-five sHTG patients were investigated to obtain clinical profiles and candidate disease genes. We obtained peripheral blood mononuclear cells (PBMC) from six male patients and nine healthy controls and examined expression of mRNAs involved in lipid metabolism. The prevalence of sHTG was 0.13 (95% CI 0.12-0.14)%, and highest in men aged 40-49 years and in women 60-69 years. Among the 65 sHTG patients, a possible genetic cause was found in four and 11 had experienced acute pancreatitis. The mRNA expression levels of carnitine palmitoyltransferase (CPT)-1A, CPT2, and hormone-sensitive lipase, were significantly higher in patients compared to controls, whereas those of ATP-binding cassette, sub-family G, member 1 were significantly lower. In Norway, sHTG is present in 0.1%, carries considerable co-morbidity and is associated with an imbalance of genes involved in lipid metabolism, all potentially contributing to increased cardiovascular morbidity in sHTG.

Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies.

PubMed

Bays, Harold E; Ballantyne, Christie M; Doyle, Ralph T; Juliano, Rebecca A; Philip, Sephy

2016-09-01

Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The relationship of body fat to metabolic disease: influence of sex and ethnicity.

PubMed

Sumner, Anne E

2008-12-01

Clinical investigations designed to determine risk profiles for the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually performed in homogenous populations and often focus on body mass index (BMI), waist circumference (WC), and fasting triglyceride (TG) levels. However, there are major ethnic differences in the relationship of these risk factors to outcomes. For example, the BMI risk threshold may be higher in blacks than in whites and higher in women than in men. Furthermore, a WC that predicts an obese BMI in white women only predicts a BMI in the overweight category in black women. In addition, overweight black men have a greater risk of developing type 2 DM than do overweight black women. Although TG levels are excellent predictors of insulin resistance in whites, they are not effective markers of insulin resistance in blacks. Among the criteria sets currently available to predict the development of CVD and type 2 DM, the most well known is the metabolic syndrome. The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be present. For central obesity and low HDL, the metabolic syndrome guidelines are sex specific. Diagnostic guidelines should also take ethnic differences into account, particularly in the diagnosis of central obesity and hypertriglyceridemia.

The triglycerides and glucose index is associated with cardiovascular risk factors in normal-weight children and adolescents.

PubMed

Simental-Mendía, Luis E; Hernández-Ronquillo, Gabriela; Gómez-Díaz, Rita; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

2017-12-01

BackgroundGiven the usefulness of the product of triglycerides and glucose (TyG) to recognize individuals at high risk for developing cardiovascular events, the aim of this study was to determine whether the TyG index is associated with the presence of cardiovascular risk factors in apparently healthy normal-weight children and adolescents.MethodsApparently healthy children and adolescents with normal weight, aged 6-15 years, were enrolled in a population-based cross-sectional study. The children were allocated into groups with and without cardiovascular risk factors. Cardiovascular risk factors were considered as the occurrence of at least one of the following: elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), or hyperglycemia.ResultsA total of 2,117 children and adolescents were enrolled in the study; of them, 1,078 (50.9%) participants exhibited cardiovascular risk. The adjusted logistic regression analysis showed that elevated TyG index was significantly associated with hypertriglyceridemia (odds ratio (OR)=96.45, 95% confidence interval (CI): 48.44-192.04), low HDL-C (OR=2.07, 95% CI: 1.46-2.92), and hyperglycemia (OR=3.11, 95% CI: 2.05-4.72), but not with elevated blood pressure (OR=1.39, 95% CI: 0.89-2.16).ConclusionThe elevated TyG index is associated with the presence of cardiovascular risk factors in healthy normal-weight children and adolescents.

Hemophagocytic Lymphohistiocytosis in a Young Child.

PubMed

Saikia, Uma Nahar; Gupta, Anju; Vignesh, Pandiarajan; Suri, Deepti; Singh, Mini P

2016-06-08

Hemophagocytic lymphohistiocytosis (HLH) is a multisystem disorder mediated by cytokine storm and is characterized by fever, pancytopenia and organomegaly coupled with laboratory features like hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia and transaminitis. Etiology can be genetic or acquired such as infections, malignancy and autoimmune disorders. Diagnosis, identification of underlying etiology and management of HLH remain tough clinical puzzles to sort out for the managing physician. We report a clinico-pathological conference of a three-year-old boy who had such a presentation and succumbed during the hospital stay.

Burn after feeding. An old uncoupler of oxidative phosphorylation is redesigned for the treatment of nonalcoholic fatty liver disease.

PubMed

Fromenty, B

2014-10-01

Uncoupling of oxidative phosphorylation (OXPHOS) in brown adipose tissue can be used by hibernating animals to produce heat at the expense of their fat mass. In a recent work, Dr Shulman et al. generated a liver-targeted derivative of the prototypical OXPHOS uncoupler 2,4-dinitrophenol that alleviated steatosis, hypertriglyceridemia and insulin resistance in several models of nonalcoholic fatty liver disease and type 2 diabetes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Metabolic syndrome correlates poorly with cognitive performance in stroke-free community-dwelling older adults: a population-based, cross-sectional study in rural Ecuador.

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Zambrano, Mauricio

2016-04-01

Studies investigating a possible correlation between metabolic syndrome and cognitive decline have been inconsistent. To determine whether metabolic syndrome or each of its components correlate with cognitive performance in community-dwelling older adults in rural Ecuador. Stroke-free Atahualpa residents aged ≥60 years were identified during a door-to-door survey. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Cognition was evaluated by the use of the Montreal Cognitive Assessment (MoCA). Multivariate logistic regression models estimated the association between metabolic syndrome and each of its components with cognitive performance. A total of 212 persons (mean age: 69.2 ± 7.2 years, 64 % women) were enrolled. Of these, 120 (57 %) had metabolic syndrome. Mean scores in the MoCA were 18.2 ± 4.6 for persons with and 19 ± 4.7 for those without metabolic syndrome. In fully adjusted logistic models, MoCA scores were not associated with metabolic syndrome (p = 0.101). After testing individual components of metabolic syndrome with the MoCA score, we found that only hypertriglyceridemia was independently associated with the MoCA score (p = 0.009). This population-based study showed a poor correlation of metabolic syndrome with cognitive performance after adjusting for relevant confounders. Of the individual components of metabolic syndrome, only hypertriglyceridemia correlated with worse cognitive performance.

Saroglitazar for the treatment of dyslipidemia in diabetic patients.

PubMed

Joshi, Shashank R

2015-03-01

Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects. Saroglitazar , a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters. This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events. Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.

Loss of LCAT activity in the golden Syrian hamster elicits pro-atherogenic dyslipidemia and enhanced atherosclerosis.

PubMed

Dong, Zhao; Shi, Haozhe; Zhao, Mingming; Zhang, Xin; Huang, Wei; Wang, Yuhui; Zheng, Lemin; Xian, Xunde; Liu, George

2018-06-01

Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis. CRISPR/CAS9 gene editing system was employed to generate mutant LCAT hamsters. The characteristics of lipid metabolism and the development of atherosclerosis in the mutant hamsters were investigated using various conventional methods in comparison with wild type control animals. Hamsters lacking LCAT activity exhibited pro-atherogenic dyslipidemia as diminished high density lipoprotein (HDL) and ApoAI, hypertriglyceridemia, Chylomicron/VLDL accumulation and significantly increased ApoB100/48. Mechanistic study for hypertriglyceridemia revealed impaired LPL-mediated lipolysis and increased very low density lipoprotein (VLDL) secretion, with upregulation of hepatic genes involved in lipid synthesis and transport. The pro-atherogenic dyslipidemia in mutant hamsters was exacerbated after high fat diet feeding, ultimately leading to near a 3- and 5-fold increase in atherosclerotic lesions by aortic en face and sinus lesion quantitation, respectively. Our findings demonstrate that LCAT deficiency in hamsters develops pro-atherogenic dyslipidemia and promotes atherosclerotic lesion formation. Published by Elsevier Inc.

Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

PubMed

Sánchez-Corona, J; Flores-Martínez, S E; Machorro-Lazo, M V; Galaviz-Hernández, C; Morán-Moguel, M C; Perea, F J; Mújica-López, K I; Vargas-Ancona, L; Laviada-Molina, H A; Fernández, V; Pardío, J; Arroyo, P; Barrera, H; Hanson, R L

2004-01-01

The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

Pilot Study on the Safety and Tolerability of Extended Release Niacin for HIV-infected Patients with Hypertriglyceridemia

PubMed Central

Souza, Scott A; Walsh, Erica J; Shippey, Ford; Shikuma, Cecilia

2010-01-01

Background To determine the safety and tolerability of extended release niacin (ERN) in HIV-infected patients. Methods This was a pilot, open-label, 36 week study evaluating the safety and tolerability of ERN in HIV-infected patients with hypertriglyceridemia. Subjects with cardiovascular disease, diabetes or liver disease were excluded. Subjects with persistent elevation of triglyceride (TG) >200 after 8 weeks on American Heart Association Step One and Two Diets were started on ERN 500mg once daily, with continuation of the diet and exercise recommendations until the end of the study. ERN was increased by 500mg every 4 weeks, to a maximum of 1500mg/day, depending on subject tolerability. Safety and tolerability of ERN were assessed. Results Ten subjects enrolled received ERN. Dose titration and maintenance to 1500mg/day were achieved in all 10 subjects. No subject required dose adjustment. Mild flushing was experienced in 8 subjects. Asymptomatic hypophosphotemia was noted in 4 subjects; all resolved with oral phosphate supplementation. Median TG was reduced by 254 mg/dL (p<0.05). Non-significant changes were noted in liver enzymes, HDL, LDL, and total cholesterol. Fasting insulin and glucose levels did not change with treatment. Conclusion In this pilot study, ERN was well-tolerated and resulted in reduction of TG. Although the results of this study are promising, the study is limited in the small number of subjects. Further investigation is warranted. PMID:20533755

A novel frameshift mutation in the lipoprotein lipase gene is rescued by alternative messenger RNA splicing.

PubMed

Laurie, Andrew D; Kyle, Campbell V

Type I hyperlipoproteinemia, manifesting as chylomicronemia and severe hypertriglyceridemia, is a rare autosomal recessive disorder usually caused by mutations in the lipoprotein lipase gene (LPL). We sought to determine whether mutations in LPL could explain the clinical indications of a patient presenting with pancreatitis and hypertriglyceridemia. Coding regions of LPL were amplified by polymerase chain reaction and analyzed by nucleotide sequencing. The LPL messenger RNA transcript was also analyzed to investigate whether alternative splicing was occurring. The patient was homozygous for the mutation c.767_768insTAAATATT in exon 5 of the LPL gene. This mutation is predicted to result in either a truncated nonfunctional LPL, or alternatively a new 5' donor splice site may be used, resulting in a full-length LPL with an in-frame deletion of 3 amino acids. Analysis of messenger RNA from the patient showed that the new splice site is used in vivo. Homozygosity for a mutation in the LPL gene was consistent with the clinical findings. Use of the new splice site created by the insertion mutation rescues an otherwise damaging frameshift mutation, resulting in expression of an almost full-length LPL that is predicted to be partially functional. The patient therefore has a less severe form of type I hyperlipoproteinemia than would be expected if she lacked any functional LPL. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Nuts in the prevention and treatment of metabolic syndrome.

PubMed

Salas-Salvadó, Jordi; Guasch-Ferré, Marta; Bulló, Mònica; Sabaté, Joan

2014-07-01

Nuts are rich in many bioactive compounds that can exert beneficial effects on cardiovascular health. We reviewed the evidence relating nut consumption and the metabolic syndrome (MetS) and its components. Nuts reduce the postprandial glycemic response; however, long-term trials of nuts on insulin resistance and glycemic control in diabetic individuals are inconsistent. Epidemiologic studies have shown that nuts may lower the risk of diabetes incidence in women. Few studies have assessed the association between nuts and abdominal obesity, although an inverse association with body mass index and general obesity has been observed. Limited evidence suggests that nuts have a protective effect on blood pressure and endothelial function. Nuts have a cholesterol-lowering effect, but the relation between nuts and hypertriglyceridemia and high-density lipoprotein cholesterol is not well established. A recent pooled analysis of clinical trials showed that nuts are inversely related to triglyceride concentrations only in subjects with hypertriglyceridemia. An inverse association was found between the frequency of nut consumption and the prevalence and the incidence of MetS. Several trials evaluated the effect of nuts on subjects with MetS and found that they may have benefits in some components. Compared with a low-fat diet, a Mediterranean diet enriched with nuts could be beneficial for MetS management. The protective effects on metabolism could be explained by the modulation of inflammation and oxidation. Further trials are needed to clarify the role of nuts in MetS prevention and treatment. © 2014 American Society for Nutrition.

Proteinuria and lipoprotein lipase activity in Miniature schnauzer dogs with and without hypertriglyceridemia

PubMed Central

Furrow, E.; Jaeger, J.Q.; Parker, V.J.; Hinchcliff, K.W.; Johnson, S.E.; Murdoch, S.J.; de Boer, I.H.; Sherding, R.G.; Brunzell, J.D.

2016-01-01

Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature shnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77–0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. PMID:27256031

Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia.

PubMed

Furrow, E; Jaeger, J Q; Parker, V J; Hinchcliff, K W; Johnson, S E; Murdoch, S J; de Boer, I H; Sherding, R G; Brunzell, J D

2016-06-01

Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC ≥ 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic screening of the lipoprotein lipase gene for mutations in Chinese subjects with or without hypertriglyceridemia.

PubMed

Yang, Yuhong; Mu, Yunxiang; Zhao, Yu; Liu, Xinyu; Zhao, Lili; Wang, Junmei; Xie, Yonghong

2007-05-01

To investigate the association between the mutations in lipoprotein lipase gene and hypertriglyceridemia (HTG). The lipoprotein lipase (LPL) gene was screened for mutations in 386 Chinese subjects with (108 cases in the HTG group) or without HTG (278 cases in the control group), by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. One novel silent mutation L103L, one missense mutation P207L, three splicing mutations Int3/3'-ass/C(-6) --> T, and the common S447X polymorphism has been identified in the whole coding region and exon-intron junctions of the LPL gene were examined. Heterozygous P207L found in the HTG group was the first case reported in Asia and subsequently another P207L heterozygote was found in the proband's family, all of which suggested that P207L was one of the causes of familial combined hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'-ass/C(-6) --> T was found in both groups in the present study although it was regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial polymorphism S447X, there was also some supportive evidence that the levels of triglycerides (TG) in S447X carriers were significantly lower than noncarriers in the subjects without HTG. The association between the LPL variants and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale screening should be necessary and justifiable.

Fast Food Intake Increases the Incidence of Metabolic Syndrome in Children and Adolescents: Tehran Lipid and Glucose Study.

PubMed

Asghari, Golaleh; Yuzbashian, Emad; Mirmiran, Parvin; Mahmoodi, Behnaz; Azizi, Fereidoun

2015-01-01

The aim of the study was to evaluate the association between fast food consumption and incidence of metabolic syndrome (MetS) and its components among children and adolescents over a 3.6 year follow-up. Dietary data of 424 healthy subjects, aged 6-18 years, was collected using a valid and reliable food frequency questionnaire. Metabolic syndrome was defined according to the Cook et al criteria. Consumption of fast foods including hamburgers, sausages, bologna (beef), and fried potatoes was calculated and further categorized to quartiles. Multiple logistic regression models were used to estimate the incidence of MetS and its components in each quartile of fast food intake. The incidence of MetS was 11.3% after a 3.6 year follow up. In the fully adjusted model, compared to the lowest quartile of fast food intake, individuals in the highest had odds ratios of 2.96 (95% CI: 1.02-8.63; P for trend<0.001), 2.82 (95% CI: 1.01-7.87; P for trend = 0.037), and 2.58 (95% CI: 1.01-6.61; P for trend = 0.009) for incidence of MetS, hypertriglyceridemia, and abdominal obesity, respectively. No significant association was found between fast food intakes and other components of MetS. Fast food consumption is associated with the incidence of MetS, abdominal obesity, and hypertriglyceridemia in Tehranian children and adolescents.

Effects of melatonin on biochemical factors and food and water consumption in diabetic rats

PubMed Central

Bibak, Bahram; Khalili, Monavareh; Rajaei, Ziba; Soukhtanloo, Mohammad; Hadjzadeh, Mousa-Al-Reza; Hayatdavoudi, Parichehr

2014-01-01

Background: Diabetic neuropathy is one of the serious problems due to microvessel vasculopathy in diabetes. It has been reported that hyperglycemia and hypertriglyceridemia are the underlying mechanisms in inducing and progression of diabetic neuropathy. The aim of the present study was to investigate the effects of melatonin on serum glucose and lipid levels, as well as food consumption and water intake in streptozotocin-induced diabetic rats. Materials and Methods: Eighty male Wistar rats were randomly assigned to six groups including; normal control group, diabetic control group and 4 diabetic experimental groups that received melatonin intraperitoneally at doses of 2.5, 5, 10, and 20 mg/kg at the end of sixth week after verification of neuropathy by means of evaluation of sciatic nerve conduction velocity (MNCV), for two weeks. Blood glucose and lipid levels, body weight, the amounts of food consumption, and water intake were determined in all groups at weeks 0 (before diabetes induction), 3, 6, and at the end of eighth week. Results: Treatment with melatonin reduced significantly the serum glucose (P < 0.001) and triglyceride (P < 0.05) levels, food consumption (P < 0.001), and water intake (P < 0.001) in diabetic rats at the end of eighth week. However, melatonin had no significant effect on body weight of diabetic animals. Conclusions: Treatment with melatonin could improve several signs of diabetes, including hyperglycemia, hypertriglyceridemia, polyphagia, and polydipsia. Therefore, melatonin may be used as an adjunct therapy in the treatment of diabetes. PMID:25250287

[Subclinical hypothyroidism and cardiovascular risk].

PubMed

López Rubio, María Antonia; Tárraga López, Pedro Juan; Rodríguez Montes, José Antonio; Frías López, María del Carmen; Solera Albero, Juan; Bermejo López, Pablo

2015-05-01

To assess whether subclinical hypothyroidism can behave as a cardiovascular risk factor or a modifier thereof, identifying epidemiological variables and estimated in a sample of patients diagnosed in the province of Albacete (Spain) cardiovascular risk. Observational, descriptive study was carried out in Albacete during the first half of January 2012 in patients of both genders with subclinical hypothyroidism. The following variables were analyzed: Fasting glucose , total cholesterol , HDL cholesterol, LDL cholesterol , triglycerides , TSH , T4 , weight, height, Body Mass Index , blood pressure, a history of cardiovascular disease , cardiovascular risk factors and estimated cardiovascular risk. 326 patients younger than 65 years at 78% without cardiovascular risk factors in 48.61 %, with female predominance (79.2 %). The prevalence of cardiovascular risk factors was identified: smoking (33.2 %), diabetes mellitus (24.9%), hypertension (23.4 %), lipid abnormalities (28.9%) and atrial fibrillation (4,9%). No association between subclinical hypothyroidism and most lipid profile parameters that determine a pro- atherogenic profile, except with hypertriglyceridemia was found. Likewise, neither association with increased cardiovascular risk was found. The profile of patients with subclinical hypothyroidism is a middle-aged woman with no cardiovascular risk factors in half of cases. It has been found relationship between subclinical hypothyroidism and hypertriglyceridemia, but not with the other parameters of lipid profile, other cardiovascular risk factors or with increased risk. However, 25% of diabetics and 22% of non-diabetics are at moderate to high cardiovascular risk. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde

2004-02-15

The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment withmore » insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.« less

Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.

PubMed

Tarr, Philip E; Taffé, Patrick; Bleiber, Gabriela; Furrer, Hansjakob; Rotger, Margalida; Martinez, Raquel; Hirschel, Bernard; Battegay, Manuel; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Rickenbach, Martin; Ledergerber, Bruno; Telenti, Amalio

2005-05-01

Single-nucleotide polymorphisms in genes involved in lipoprotein and adipocyte metabolism may explain why dyslipidemia and lipoatrophy occur in some but not all antiretroviral therapy (ART)-treated individuals. We evaluated the contribution of APOC3 -482C-->T, -455T-->C, and 3238C-->G; epsilon 2 and epsilon 4 alleles of APOE; and TNF -238G-->A to dyslipidemia and lipoatrophy by longitudinally modeling >2600 lipid determinations and 2328 lipoatrophy assessments in 329 ART-treated patients during a median follow-up period of 3.4 years. In human immunodeficiency virus (HIV)-infected individuals, the effects of variant alleles of APOE on plasma cholesterol and triglyceride levels and of APOC3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOC3 and [corrected] APOE were at risk of extreme hypertriglyceridemia. They had median plasma triglyceride levels of 7.33 mmol/L, compared with 3.08 mmol/L in the absence of ART. The net effect of the APOE*APOC3*ritonavir interaction was an increase in plasma triglyceride levels of 2.23 mmol/L. No association between TNF -238G-->A and lipoatrophy was observed. Variant alleles of APOE and APOC3 contribute to an unfavorable lipid profile in patients with HIV. Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia.

Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis.

PubMed

Ariza, María José; Martínez-Hernández, Pedro Luis; Ibarretxe, Daiana; Rabacchi, Claudio; Rioja, José; Grande-Aragón, Cristina; Plana, Nuria; Tarugi, Patrizia; Olivecrona, Gunilla; Calandra, Sebastiano; Valdivielso, Pedro

2016-01-01

Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) has been demonstrated to be essential for the in vivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations of GPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients. Two unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1. The 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile). In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[Biological disturbances during the lupus-associated pancreatitis: case report].

PubMed

Sayagh, Sanae; Benchekroun, Leila; Bouabdellah, Mounya; Jaouhar, Nezha; El Aoufi, Farida; El Oufir, Fatiha; Alaoui, Meryem; Adnaoui, Mohammed; Chabraoui, Layachi

2015-01-01

We report in this paper the case of female patient, hypertriglyceridemia associated with milky serum and hyperglycemia have been the alarm signal of a lupus-associated pancreatitis, the confirmation of this entity was done with elevated rate of serum lipase activity. It is about a 33 years age female. She has as unique antecedent a lupus diagnosed on January of the same. The patient was admitted on august 2013 for another episode of lupus associated to the lower lamb edema with a rate of C3 at 0.4 g/L (0.82-1,93) and C4 at 0.05 g/L (0.15-0.57). One day after the beginning of the corticotherapy, the patient presented hyperthermia, ataxis and behavior troubles, epigastric and articular pains and vomiting. Biochemical tests found hyperglycemia at 38.9 mmol/L (3.9-6.1), dyslipidemia with hypertriglyceridemia at 15.7 mmol/L (0.3-1.7) and total cholesterol rate at 5.2 mmol/L (<5.2) associated with milky serum. Haematological tests objective normocytic normochromic anemia with 81 g/L of hemoglobin, lymphopenia at 0.88 G/L and normal platelet rate. Lupus associated pancreatitis was suggested and confirmed biologically with an hyperlipasemia at 180 UI/L (8-78) and radiologicaly with the image of focal hepatic steatosis. We conclude that on the presence of lupus, gastrointestinal and/or biological signs must motivate the measurement of the serum lipase activity as quickly as possible to assess the diagnosis of lupus-associated pancreatitis.

Prevalence of Atherogenic Dyslipidemia in Spanish Hypertensive Patients and Its Relationship With Blood Pressure Control and Silent Organ Damage.

PubMed

de la Sierra, Alejandro; Gorostidi, Manuel; Aranda, Pedro; Corbella, Emili; Pintó, Xavier

2015-07-01

To assess the prevalence of atherogenic dyslipidemia in hypertensive patients and its relationship with risk profile and blood pressure control. The study included 24 351 hypertensive patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. Atherogenic dyslipidemia was defined as the presence of hypertriglyceridemia (> 150mg/dL) and low levels of high-density lipoprotein cholesterol (< 40mg/dL in men and < 46mg/dL in women). Blood pressure control was assessed by office and ambulatory monitoring. Atherogenic dyslipidemia was present in 2705 patients (11.1%). Of these, 30% had hypertriglyceridemia and 21.7% had low levels of high-density lipoprotein cholesterol. Compared with patients without these risk factors, the former group were more often male (60% vs 52%), younger (57 years vs 59 years), had other risk factors and organ damage (microalbuminuria, reduced estimated glomerular filtration rate, and left ventricular hypertrophy), worse office, diurnal, and nocturnal blood pressure values (odds ratio 1.09, 1.06, and 1.10, respectively), and the lowest nocturnal blood pressure reduction (odds ratio=1.07), despite the greater use of antihypertensive drugs. Atherogenic dyslipidemia is present in more than 10% of hypertensive patients and is associated with other risk factors, organ damage, and poorer blood pressure control. Greater therapeutic effort is needed to reduce overall risk in these patients. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Hypertriglyceridemia

PubMed Central

Brahm, Amanda; Hegele, Robert A.

2013-01-01

Hypertriglyceridemia (HTG) is commonly encountered in lipid and cardiology clinics. Severe HTG warrants treatment because of the associated increased risk of acute pancreatitis. However, the need to treat, and the correct treatment approach for patients with mild to moderate HTG are issues for ongoing evaluation. In the past, it was felt that triglyceride does not directly contribute to development of atherosclerotic plaques. However, this view is evolving, especially for triglyceride-related fractions and variables measured in the non-fasting state. Our understanding of the etiology, genetics and classification of HTG states is also evolving. Previously, HTG was considered to be a dominant disorder associated with variation within a single gene. The old nomenclature includes the term “familial” in the names of several hyperlipoproteinemia (HLP) phenotypes that included HTG as part of their profile, including combined hyperlipidemia (HLP type 2B), dysbetalipoproteinemia (HLP type 3), simple HTG (HLP type 4) and mixed hyperlipidemia (HLP type 5). This old thinking has given way to the idea that genetic susceptibility to HTG results from cumulative effects of multiple genetic variants acting in concert. HTG most is often a “polygenic” or “multigenic” trait. However, a few rare autosomal recessive forms of severe HTG have been defined. Treatment depends on the overall clinical context, including severity of HTG, concomitant presence of other lipid disturbances, and the patient's global risk of cardiovascular disease. Therapeutic strategies include dietary counselling, lifestyle management, control of secondary factors, use of omega-3 preparations and selective use of pharmaceutical agents. PMID:23525082

Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.

PubMed

Chen, Yong; Liu, Ping; Qi, Rong; Wang, Yu-Hui; Liu, George; Wang, Chun

2016-05-15

Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. Copyright © 2016 Elsevier B.V. All rights reserved.

A young infant with transient severe hypertriglyceridemia temporarily associated with meropenem administration: A case report and review of the literature.

PubMed

Esposito, Susanna; Pinzani, Raffaella; Raffaeli, Genny; Lucchi, Tiziano; Agostoni, Carlo; Principi, Nicola

2016-09-01

Slight changes in the lipid profile can be observed over the acute phase of infectious diseases. Moreover, some anti-infective drugs can modify serum lipid concentrations, although antibiotics do not seem to have a relevant, direct, or acute effect on the lipid profile. A 75-day-old breastfed Caucasian female, born at term after a regular pregnancy, was hospitalized for osteomyelitis. She was immediately treated with intravenous meropenem and vancomycin. Therapy was effective, but after 22 days of treatment, her blood was found to be viscous with a purple shade. A fasting blood sample showed serum triglycerides of 966 mg/dL, total cholesterol of 258 mg/dL, and high-density lipoprotein cholesterol of 15 mg/dL. Secondary causes of hyperlipidemia and primary hereditary disorders were ruled out. Thereafter, the possibility that antibiotics may have had a role in the hypertriglyceridemia was considered, and meropenem was discontinued. After 72 hours of meropenem discontinuation, a sharp modification of lipid variables was observed, and further testing showed a complete normalization of the lipid profile. In this child with osteomyelitis, the increase in serum triglycerides appeared suddenly after 3 weeks of meropenem treatment and resolved quickly after meropenem discontinuation, thus highlighting the possible association between meropenem and lipid profile alterations. Monitoring the lipid profile should be considered in cases of long-term treatment with meropenem, and further studies on meropenem safety should include evaluation of the lipid profile.

Fast Food Intake Increases the Incidence of Metabolic Syndrome in Children and Adolescents: Tehran Lipid and Glucose Study

PubMed Central

Asghari, Golaleh; Yuzbashian, Emad; Mirmiran, Parvin; Mahmoodi, Behnaz; Azizi, Fereidoun

2015-01-01

The aim of the study was to evaluate the association between fast food consumption and incidence of metabolic syndrome (MetS) and its components among children and adolescents over a 3.6 year follow-up. Dietary data of 424 healthy subjects, aged 6–18 years, was collected using a valid and reliable food frequency questionnaire. Metabolic syndrome was defined according to the Cook et al criteria. Consumption of fast foods including hamburgers, sausages, bologna (beef), and fried potatoes was calculated and further categorized to quartiles. Multiple logistic regression models were used to estimate the incidence of MetS and its components in each quartile of fast food intake. The incidence of MetS was 11.3% after a 3.6 year follow up. In the fully adjusted model, compared to the lowest quartile of fast food intake, individuals in the highest had odds ratios of 2.96 (95% CI: 1.02–8.63; P for trend<0.001), 2.82 (95% CI: 1.01–7.87; P for trend = 0.037), and 2.58 (95% CI: 1.01–6.61; P for trend = 0.009) for incidence of MetS, hypertriglyceridemia, and abdominal obesity, respectively. No significant association was found between fast food intakes and other components of MetS. Fast food consumption is associated with the incidence of MetS, abdominal obesity, and hypertriglyceridemia in Tehranian children and adolescents. PMID:26447855

Metabolic syndrome in Tunisian bipolar I patients.

PubMed

Ezzaher, A; Haj, Mouhamed D; Mechri, A; Neffati, F; Douki, W; Gaha, L; Najjar, M F

2011-09-01

The metabolic syndrome is a growing global public health problem which is frequently associated with psychiatric illness. To evaluate the prevalence of metabolic syndrome and to study its profile in Tunisian bipolar I patients. Our study included 130 patients with bipolar I disorder diagnosed according to the DSM-IV and assessed for metabolic syndrome according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III modified criteria. The mean age was 37.9 ± 12.1 years, 45 were women (mean age 37.5 ± 13.4 years) and 85 were men (mean age 38.1 ± 11.4 years). The prevalence of metabolic syndrome was 26.1%.The highest prevalence of this syndrome was obtained by association between obesity, low c-HDL and hypertriglyceridemia (44.1%). In the total sample, 59.2% met the criteria for low c-HDL, 53.1% for hypertriglyceridemia, 33.8% for obesity, 16.1% for high fasting glucose and 5.4% for hypertension. Gender, age, illness episode and treatment were not significantly associated with metabolic syndrome, while patients under lithium had higher prevalence of metabolic syndrome than those under valproic acid, carbamazepine or antipsychotics. Patients with metabolic syndrome had significant higher levels of HOMA-IR and uric acid than metabolic syndrome free patients (p< 0.001). Bipolar patients have high prevalence of metabolic syndrome which is associated with insulin resistance and an increase of uric acid values that raise the risk of cardiovascular disease.

Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial.

PubMed

Kastelein, John J P; Maki, Kevin C; Susekov, Andrey; Ezhov, Marat; Nordestgaard, Borge G; Machielse, Ben N; Kling, Douglas; Davidson, Michael H

2014-01-01

Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms. The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid. This was a multinational, double-blind, randomized, out-patient study. Men and women with triglycerides (TGs) ≥ 500 mg/dL, but <2000 mg/dL, took control (olive oil [OO] 4 g/d; n = 99), OM3-FFA 2 g/d (plus OO 2 g/d; n = 100), OM3-FFA 3 g/d (plus OO 1 g/d; n = 101), or OM3-FFA 4 g/d (n = 99) capsules for 12 weeks in combination with the National Cholesterol Education Program Therapeutic Lifestyle Changes diet. Fasting serum TGs changed from baseline by -25.9% (P < .01 vs OO), -25.5% (P < .01 vs OO), and -30.9% (P < .001 vs OO) with 2, 3, and 4 g/d OM3-FFA, respectively, compared with -4.3% with OO. Non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol-to-HDL-C ratio, very low-density lipoprotein cholesterol, remnant-like particle cholesterol, apolipoprotein CIII, lipoprotein-associated phospholipase A2, and arachidonic acid were significantly lowered (P < .05 at each OM3-FFA dosage vs OO); and plasma eicosapentaenoic acid and docosahexaenoic acid were significantly elevated (P < .001 at each OM3-FFA dosage vs OO). With OM3-FFA 2 and 4 g/d (but not 3 g/d), low-density lipoprotein cholesterol was significantly increased compared with OO (P < .05 vs OO). High-sensitivity C-reactive protein responses with OM3-FFA did not differ significantly from the OO response at any dosage. Fewer subjects reported any adverse event with OO vs OM3-FFA, but frequencies across dosage groups were similar. Discontinuation due to adverse event, primarily gastrointestinal, ranged from 5% to 7% across OM3-FFA dosage groups vs 0% for OO. OM3-FFA achieved the primary end point for TG lowering and secondary end point of non-HDL-C lowering at 2, 3, and 4 g/d in persons with severe hypertriglyceridemia. This trial was registered at www.clinicaltrials.gov as NCT01242527. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Aseptic necrosis of the femoral head after pregnancy: a case report.

PubMed

Nassar, Kawtar; Rachidi, Wafae; Janani, Saadia; Mkinsi, Ouafa

2016-01-01

A documented case of beginning aseptic necrosis of the femoral head associated with pregnancy together with a review of the literature about this rare complication of pregnancy is presented. The known risk factors of osteonecrosis are; steroid use, alcoholism, organ transplantation, especially after kidney transplant or bone marrow transplantation bone, systemic lupus erythematosus, dyslipidemia especially hypertriglyceridemia, dysbaric decompression sickness, drepanocytosis and Gaucher's disease. Among the less established factors, we mention procoagulations abnormalities, HIV infection, chemotherapy. We report a case of osteonecrosis of femoral head after pregnancy.

Hypertension, dyslipidemia, and insulin resistance: links in a chain or spokes on a wheel?

PubMed

Hopkins, P N; Hunt, S C; Wu, L L; Williams, G H; Williams, R R

1996-08-01

Rather than a link in a causal chain leading to hypertension, insulin resistance and resultant hyperinsulinemia may be 'spokes on a wheel', with central or visceral obesity as the postulated hub of the wheel. Hypertension, hypertriglyceridemia and high density lipoprotein cholesterol are depicted as other spokes. Newly identified metabolic pathways in adipose tissue or the modulating effects of various predisposing genes may lead to variable expression of various components of the multiple metabolic syndrome in individuals with a predisposition to the collection of visceral fat.

Prevalence of Dyslipidemia and Associated Factors in Obese Children and Adolescents.

PubMed

Elmaoğulları, Selin; Tepe, Derya; Uçaktürk, Seyit Ahmet; Karaca Kara, Fatma; Demirel, Fatma

2015-09-01

Childhood-onset obesity is associated with increased mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. Dyslipidemia has a fundamental role in the pathogenesis of CVD. This study aimed to evaluate the prevalence of dyslipidemia and related factors among obese children and adolescents. Obese patients aged between 2 and 18 years were included in the study. Serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), fasting glucose levels, insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver ultrasound findings were evaluated retrospectively. Among 823 obese patients, 353 (42.9%) met the dyslipidemia criteria: 21.7% had hypertriglyceridemia, 19.7% had low levels of HDL-C, 18.6% had hypercholesterolemia, and 13.7% had high levels of LDL-C. Older age and/or high body mass index (BMI) were related to increased prevalence of dyslipidemia. Hepatosteatosis was more common among dyslipidemic patients. The frequency of insulin resistance (IR) and of higher levels of ALT and TSH were also detected in dyslipidemic patients. Patients with both dyslipidemia and grade 2-3 hepatosteatosis had higher levels of ALT, AST and TSH and lower levels of fT4. Prevalence of dyslipidemia is high in obese children, and hypertriglyceridemia is in the foreground. Higher levels of IR and more apparent abnormal liver function test results are observed in the context of dyslipidemia and hepatosteatosis coexistence. Metabolic and hormonal alterations related with thyroid functions may also be associated with dyslipidemia and hepatosteatosis in obese patients.

[Atherogenic dyslipidemia in patients with type 1 diabetes mellitus].

PubMed

Chillarón, Juan J; Sales, María P; Flores Le-Roux, Juana A; Castells, Ignasi; Benaiges, David; Sagarra, Enric; Pedro-Botet, Juan

2013-12-07

To assess the prevalence of lipid abnormalities, with special emphasis on atherogenic dyslipidemia and its relationship with chronic complications in patients with type 1 diabetes mellitus (T1DM). Cross-sectional study including all patients aged 18 and over, diagnosed of T1DM attending the outpatient clinic at Hospital del Mar and Hospital de Granollers, in Barcelona, during 2008. Of the 291 enrolled patients, 17.2 and 7.9% had high density lipoproteins (HDL) cholesterol<40 mg/dL (men) or<50mg/dL (women) and triglycerides>150 mg/dL, respectively. Hypoalphalipoproteinemic patients had a higher prevalence of peripheral neuropathy (28 vs. 7.1%, P<.001), macroalbuminuria (14 vs. 2.5%, P<.001) and higher concentrations of triglycerides (107.5 [55.8] vs. 82.7 [36] mg/dL, P<.0001) compared with those with normal/high HDL cholesterol levels. Hypertriglyceridemia was associated with increasing age (43.6 [11.2] vs. 37.6 [11.8] yr, P<.02), higher prevalence of hypertension (47.8 vs. 22.8%, P<.008), metabolic syndrome (82.6 vs. 22%, P<.001) and microangiopathic complications, lower insulin sensitivity (6.75 [2.1] vs. 8.54 [2.6] mg/Kg(-1)/min(-1), P<.004) compared with the normotriglyceridemic group. One in 5 patients with T1DM has hypoalphalipoproteinemia or hypertriglyceridemia and these conditions are associated with 3 fold-increase microangiopathy. Thus, in these patients glycemic and blood pressure but also lipid profile control must be optimum. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Prevalence and Risk Factors Associated with Dyslipidemia in Chongqing, China.

PubMed

Qi, Li; Ding, Xianbin; Tang, Wenge; Li, Qin; Mao, Deqiang; Wang, Yulin

2015-10-26

The increasing prevalence of dyslipidemia has become a worldwide public health problem, and the prevalence varies widely according to socioeconomic, cultural and ethnic characteristics. Chongqing has experienced rapid economic development and is now the economic center of Southwestern China. There are scant data on serum lipid profile of residents in Chongqing, the largest municipality directly under the Central Government in China. We conducted a cross-sectional study in a representative sample of 5375 residents of Chongqing, aged ≥18 years, and estimated the prevalence of dyslipidemia and its associated risk factors. According to the National Cholesterol Education Program-Adult Treatment Panel III criteria, the age-standardized prevalence of dyslipidemia was 35.5% (34.4% among men and 37.6% among women). Among the 2009 patients with dyslipidemia, 44.2% had isolated hypertriglyceridemia, 14.7% had isolated hypercholesterolemia, 13.2% had mixed hyperlipidemia, and 28.0% had isolated low high-density lipoprotein cholesterol. The peak prevalence of dyslipidemia in men was between 30 and 39 years (48.2%), and then declined gradually; in women, the prevalence of dyslipidemia increased with age, with the peak prevalence occurring after age 60 (46.3%). Multivariable logistic regression analysis revealed that dyslipidemia was associated with age, education level, physical activity, obesity and central obesity for both men and women. In conclusion, the results indicated dyslipidemia, particularly hypertriglyceridemia and low high-density lipoprotein cholesterol, are very common in Chongqing. To prevent dyslipidemia, it is essential to conduct appropriate intervention programs aimed at risk factor reduction and implement routine screening programs for blood lipid levels in Chongqing, China.

Prevalence and Risk Factors Associated with Dyslipidemia in Chongqing, China

PubMed Central

Qi, Li; Ding, Xianbin; Tang, Wenge; Li, Qin; Mao, Deqiang; Wang, Yulin

2015-01-01

The increasing prevalence of dyslipidemia has become a worldwide public health problem, and the prevalence varies widely according to socioeconomic, cultural and ethnic characteristics. Chongqing has experienced rapid economic development and is now the economic center of Southwestern China. There are scant data on serum lipid profile of residents in Chongqing, the largest municipality directly under the Central Government in China. We conducted a cross-sectional study in a representative sample of 5375 residents of Chongqing, aged ≥18 years, and estimated the prevalence of dyslipidemia and its associated risk factors. According to the National Cholesterol Education Program-Adult Treatment Panel III criteria, the age-standardized prevalence of dyslipidemia was 35.5% (34.4% among men and 37.6% among women). Among the 2009 patients with dyslipidemia, 44.2% had isolated hypertriglyceridemia, 14.7% had isolated hypercholesterolemia, 13.2% had mixed hyperlipidemia, and 28.0% had isolated low high-density lipoprotein cholesterol. The peak prevalence of dyslipidemia in men was between 30 and 39 years (48.2%), and then declined gradually; in women, the prevalence of dyslipidemia increased with age, with the peak prevalence occurring after age 60 (46.3%). Multivariable logistic regression analysis revealed that dyslipidemia was associated with age, education level, physical activity, obesity and central obesity for both men and women. In conclusion, the results indicated dyslipidemia, particularly hypertriglyceridemia and low high-density lipoprotein cholesterol, are very common in Chongqing. To prevent dyslipidemia, it is essential to conduct appropriate intervention programs aimed at risk factor reduction and implement routine screening programs for blood lipid levels in Chongqing, China. PMID:26516874

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

PubMed

Ortega-Gómez, Almudena; Varela, Lourdes M; López, Sergio; Montserrat de la Paz, Sergio; Sánchez, Rosario; Muriana, Francisco J G; Bermúdez, Beatriz; Abia, Rocío

2017-09-01

Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe -/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population.

PubMed

Wan, W; Xu, X; Zhao, D B; Pang, Y F; Wang, Y X

2015-03-30

In this study, we analyzed single nucleotide polymorphisms (SNP) in urate transporter genes to examine the pathogenesis of gout. We conducted a 1:1-matched case-control study that included 110 patients with acute gout attacks as the patient group and 110 healthy age- and gender-matched subjects as the control group. Clinical parameters were recorded and blood biochemistry tests were conducted for both groups. Multivariate logistic regression analysis was used to analyze the data. Hyperuricemia, hypercholesterolemia, and hypertriglyceridemia were found to be the main risk factors for the onset of gout, with relative risks of 29.2 (P < 0.001), 25.5 (P = 0.003), and 11.2 (P < 0.001). For all detected SNP, rs2231142, located in ABCG2, showed the largest frequency differences for the G/G, G/T, and T/T genotypes between groups: the distribution of these genotypes in the case group was 22, 49, and 26 individuals, respectively, and was 54, 38, and 9 individuals, respectively, in the control group. There was a statistically significant difference between the 2 groups (P < 0.001) and the odds ratio was 7.091 (95% confidence interval = 2.867-17.541). Other SNPs (rs1165196, rs1165205, rs1183201, rs17300741, rs2078267, rs2242206, rs3733591, and rs9358856) showed no significant difference between the groups (P > 0.05). The risk factors of gout were hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and the T/T genotype of the rs2231142 locus in the ABCG2 gene; expression of the G/G genotype may be a protective factor against gout development.

Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186.

PubMed

Gerber, John G; Kitch, Douglas W; Fichtenbaum, Carl J; Zackin, Robert A; Charles, Stéphannie; Hogg, Evelyn; Acosta, Edward P; Connick, Elizabeth; Wohl, David; Kojic, E Milu; Benson, Constance A; Aberg, Judith A

2008-04-01

Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels < or =200 mg/dL with either agent alone. One hundred subjects on highly active antiretroviral therapy with serum TG concentrations > or =400 mg/dL and low-density lipoprotein cholesterol < or =160 mg/dL were randomized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks. Subjects with a fasting TG level >200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18. Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group (P = not significant). Fish oil reduced TG levels by a median of 283 mg/dL (46%), fenofibrate reduced them by 367 mg/dL (58%), and combination therapy reduced them by 65.5%. Combination therapy achieved TG levels of < or =200 mg/dL in 22.7% subjects. Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir. Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia.

Fish Oil and Fenofibrate for the Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy

PubMed Central

Gerber, John G.; Kitch, Douglas W.; Fichtenbaum, Carl J.; Zackin, Robert A.; Charles, Stéphannie; Hogg, Evelyn; Acosta, Edward P.; Connick, Elizabeth; Wohl, David; Kojic, E. Milu; Benson, Constance A.; Aberg, Judith A.

2009-01-01

Introduction Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute to increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy of fish oil plus fenofibrate in subjects not achieving serum TG levels ≤200 mg/dL with either agent alone. Methods One hundred subjects on highly active antiretroviral therapy with serum TG concentrations ≥400 mg/dL and low-density lipoprotein cholesterol ≤160 mg/dL were randomized to 3 g of fish oil twice daily or 160 mg of fenofibrate daily for 8 weeks. Subjects with a fasting TG level >200 mg/dL at week 8 received a combination of fish oil and fenofibrate in the same doses from week 10 to week 18. Results Median baseline TG was 662 mg/dL in the fish oil group and 694 mg/dL in the fenofibrate group (P = not significant). Fish oil reduced TG levels by a median of 283 mg/dL (46%), fenofibrate reduced them by 367 mg/dL (58%), and combination therapy reduced them by 65.5%. Combination therapy achieved TG levels of ≤200 mg/dL in 22.7% subjects. Fish oil had no measurable effect on immunologic parameters or the pharmacokinetics of lopinavir. Conclusions Fish oil was safe when administered alone or combined with fenofibrate and significantly reduced TG levels in HIV-infected subjects with hypertriglyceridemia. PMID:17971707

Evaluation of metabolic syndrome prevalence in semi-rural areas of Central Anatolia, Turkey.

PubMed

Arikan, Inci; Metintas, Selma; Kalyoncu, Cemalettin; Colak, Omer; Arikan, Ufuk

2009-08-01

To assess the prevalence and clustering of components of metabolic syndrome (MetS) in semi-rural areas of Central Anatolia, Turkey. This study was conducted between January and August 2008 on a randomly selected sample of participants from semi-rural settlement areas of the Eskisehir province, Central Anatolia, Turkey. The MetS was diagnosed as the presence of 3, or more risk factors according to the National Cholesterol Education Program-Expert Panel Adult Treatment Panel III (NCEP ATP III) criteria. The MetS prevalence was standardized according to age, and logistic regression was used to determine the risk factors affecting prevalence. The study group composed of 2,766 people (40.4% male, 59.6% female). The corrected MetS prevalence according to age was 27.6%, with values of 19.4% in males, and 33.2% in females. The prevalence increased with increasing age in both genders. Groups engaged in heavy physical exercise, and smoking showed decreased odds of having MetS, while MetS risk was lower in men who consumed proper amounts of red meat, fruits, and vegetables. In the MetS group, central obesity risk was higher for women, whereas hypertriglyceridemia risk was higher for men. In the non-MetS group, hypertension, and central obesity risks were higher for women, whereas hypertriglyceridemia risk was higher for men. It was concluded that MetS is a major problem in the Eskisehir province, and it is imperative that changes in lifestyle be made within this population to reduce the risk factors for the condition.

The Frequency of Prediabetes and Contributing Factors in Patients with Chronic Kidney Disease

PubMed Central

Razeghi, Effat; Heydarian, Peimaneh; Heydari, Mahshid

2011-01-01

AIMS: Uremia is a prediabetic state, but abnormal glucose metabolism and relative risk factors in non-diabetic chronic kidney disease (CKD) patients are not studied extensively. This study aimed to evaluate prediabetes and contributing factors in patients with CKD. METHODS: We studied the frequency of prediabetes (defined as fasting plasma glucose 100-125 mg/dl and 2-h plasma glucose 140-199 mg/dl) and contributing risk factors in 91 (34 women and 57 men) non-diabetic CKD (GFR < 60) patients who were referred to Sina Hospital between November 2010 and November 2011. Impaired fasting glucose and impaired glucose tolerance were regarded as prediabetic state. RESULTS: Thirty-eight patients (41.8%), 28 male and 10 female, with mean age of 57.4 ± 17.1 yr, had prediabetes. Among these, 18.7% had impaired fasting glucose, 7.7% impaired glucose tolerance, and 15.4% combined impaired fasting glucose and impaired glucose tolerance. CKD patients with impaired glucose tolerance had more frequently hypertriglyceridemia (85.7% vs. 42.0%, p = 0.001), hypertension (66.6% vs. 31.4%, p = 0.004), and metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III (52.3% vs. 25.7%, p = 0.02). Also, mean systolic blood pressure (134.2 ± 13.9 vs. 124.5 ± 20.0, p = 0.004) was higher in CKD patients with impaired glucose tolerance compared to CKD patients with normal glucose. CONCLUSIONS: Prediabetes is a frequent condition in CKD patients. Also, hypertriglyceridemia and hypertension are more prevalent in prediabetic CKD patients than in non-diabetic CKD patients. PMID:22189551

Cardiorenal Involvement in Metabolic Syndrome Induced by Cola Drinking in Rats: Proinflammatory Cytokines and Impaired Antioxidative Protection.

PubMed

Otero-Losada, Matilde; Gómez Llambí, Hernán; Ottaviano, Graciela; Cao, Gabriel; Müller, Angélica; Azzato, Francisco; Ambrosio, Giuseppe; Milei, José

2016-01-01

We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drank ad libitum regular cola (C, n = 12) or tap water (W, n = 12). Measures. Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%, p < 0.05), hyperglycemia (+11%, p < 0.05), hypertriglyceridemia (2-fold, p < 0.001), higher AIP (2-fold, p < 0.01), and lower Q10 level (-55%, p < 0.05); (II) increased LV diastolic diameter (+9%, p < 0.05) and volume (systolic +24%, p < 0.05), posterior wall thinning (-8%, p < 0.05), and larger cardiac output (+24%, p < 0.05); (III) glomerulosclerosis (+21%, p < 0.05), histopathology (+13%, p < 0.05), higher tubular expression of IL-6 (7-fold, p < 0.001), and TNFα (4-fold, p < 0.001). (IV) Correlations were found for LV dimensions with IL-6 (74%, p < 0.001) and TNFα (52%, p < 0.001) and fully abolished after TG and Q10 control. Chronic cola drinking induced cardiac remodeling associated with increase in proinflammatory cytokines and renal damage. Hypertriglyceridemia and oxidative stress were key factors. Hypertriglyceridemic lipotoxicity in the context of defective antioxidant/anti-inflammatory protection due to low Q10 level might play a key role in cardiorenal disorder induced by chronic cola drinking in rats.

Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis.

PubMed

Vázquez-Bourgon, Javier; Pérez-Iglesias, Rocío; Ortiz-García de la Foz, Víctor; Suárez Pinilla, Paula; Díaz Martínez, Álvaro; Crespo-Facorro, Benedicto

2018-01-01

The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment. One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment. After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment. We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.

Overview of Omega-3 Fatty Acid Therapies

PubMed Central

Bradberry, J. Chris; Hilleman, Daniel E.

2013-01-01

The triglyceride (TG)-lowering benefits of the very-long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are well documented. Available as prescription formulations and dietary supplements, EPA and DHA are recommended by the American Heart Association for patients with coronary heart disease and hypertriglyceridemia. Dietary supplements are not subject to the same government regulatory standards for safety, efficacy, and purity as prescription drugs are; moreover, supplements may contain variable concentrations of EPA and DHA and possibly other contaminants. Reducing low-density lipoprotein-cholesterol (LDL-C) levels remains the primary treatment goal in the management of dyslipidemia. Dietary supplements and prescription formulations that contain both EPA and DHA may lower TG levels, but they may also increase LDL-C levels. Two prescription formulations of long-chain omega-3 fatty acids are available in the U.S. Although prescription omega-3 acid ethyl esters (OM-3-A EEs, Lovaza) contain high-purity EPA and DHA, prescription icosapent ethyl (IPE, Vascepa) is a high-purity EPA agent. In clinical trials of statin-treated and non–statin-treated patients with hypertriglyceridemia, both OM-3-A EE and IPE lowered TG levels and other atherogenic markers; however, IPE did not increase LDL-C levels. Results of recent outcomes trials of long-chain omega-3 fatty acids, fibrates, and niacin have been disappointing, failing to show additional reductions in adverse cardiovascular events when combined with statins. Therefore, the REDUCE–IT study is being conducted to evaluate the effect of the combination of IPE and statins on cardiovascular outcomes in high-risk patients. The results of this trial are eagerly anticipated. PMID:24391388

Impairment of Novel Object Recognition Memory and Brain Insulin Signaling in Fructose- but Not Glucose-Drinking Female Rats.

PubMed

Sangüesa, Gemma; Cascales, Mar; Griñán, Christian; Sánchez, Rosa María; Roglans, Núria; Pallàs, Mercè; Laguna, Juan Carlos; Alegret, Marta

2018-01-26

Excessive sugar intake has been related to cognitive alterations, but it remains unclear whether these effects are related exclusively to increased energy intake, and the molecular mechanisms involved are not fully understood. We supplemented Sprague-Dawley female rats with 10% w/v fructose in drinking water or with isocaloric glucose solution for 7 months. Cognitive function was assessed through the Morris water maze (MWM) and the novel object recognition (NOR) tests. Plasma parameters and protein/mRNA expression in the frontal cortex and hippocampus were determined. Results showed that only fructose-supplemented rats displayed postprandial and fasting hypertriglyceridemia (1.4 and 1.9-fold, p < 0.05) and a significant reduction in the discrimination index in the NOR test, whereas the results of the MWM test showed no differences between groups. Fructose-drinking rats displayed an abnormal glucose tolerance test and impaired insulin signaling in the frontal cortex, as revealed by significant reductions in insulin receptor substrate-2 protein levels (0.77-fold, p < 0.05) and Akt phosphorylation (0.72-fold, p < 0.05), and increased insulin-degrading enzyme levels (1.86-fold, p < 0.001). Fructose supplementation reduced the expression of antioxidant enzymes and altered the amount of proteins involved in mitochondrial fusion/fission in the frontal cortex. In conclusion, cognitive deficits induced by chronic liquid fructose consumption are not exclusively related to increased caloric intake and are correlated with hypertriglyceridemia, impaired insulin signaling, increased oxidative stress and altered mitochondrial dynamics, especially in the frontal cortex.

Apolipoprotein C3 (-455T>C) polymorphism confers susceptibility to nonalcoholic fatty liver disease in the Southern Han Chinese population

PubMed Central

Li, Min-Rui; Zhang, Sheng-Hong; Chao, Kang; Liao, Xian-Hua; Yao, Jia-Yan; Chen, Min-Hu; Zhong, Bi-Hui

2014-01-01

AIM: To investigate the relationship between Apolipoprotein C3 (APOC3) (-455T>C) polymorphism and nonalcoholic fatty liver disease (NAFLD) in the Southern Chinese Han population. METHODS: In this prospective case-control study, we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese Han population at The First Affiliated Hospital, Sun Yat-sen University, from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3 (-455T>C) variants. RESULTS: After adjusting for age, gender, and body-mass index, TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype, with adjusted odds ratios (ORs) of 1.77 (95%CI: 1.16-2.72) and 2.80 (95%CI: 1.64-4.79), respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance (IR) than those of the TT genotype, with an OR of 3.24 (95%CI: 1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL) (P < 0.05). No association was found between the APOC3 (-455T>C) polymorphism and obesity, impaired glucose tolerance, hyperuricemia, hypercholesterolemia, or high levels of low-density lipoprotein cholesterol (LDL) (P > 0.05). CONCLUSION: APOC3 (-455T>C) genetic variation is involved in the susceptibility to developing NAFLD, IR, hypertension, hypertriglyceridemia, and low HDL in the Southern Chinese Han population. PMID:25320541

Hospital Management of Severe Hypertriglyceridemia in Children.

PubMed

Valaiyapathi, Badhma; Ashraf, Ambika P

2017-01-01

Severe Hypertriglyceridemia (HTG), i.e., plasma triglyceride levels exceeding 1000 mg/dL, is one of the established causes of acute pancreatitis and severe abdominal pain. There are no established pediatric guidelines regarding treatment of children and adolescents with severe HTG. To review the pathophysiology and etiology of severe HTG in the pediatric age group, and to discuss management options. Severe HTG is usually due to deficient or absent Lipoprotein Lipase (LPL) activity, which can be due to primary genetic etiology or secondary causes triggering HTG in those with underlying genetic susceptibility. Hospitalization is indicated for patients with severe HTG who are symptomatic with abdominal pain or pancreatitis, in those with uncontrolled diabetes requiring insulin, or, in those with substantial elevations of plasma TG. Fasting followed by fat free diet until plasma TG declines to <1000mg/dL is essential. Subsequently, stringent fat restriction followed by slowly increasing the dietary fat while maintaining the plasma TG concentration at a targeted level is recommended. Insulin infusions are helpful in patients who have some LPL activity, especially in those with diabetes. Plasmapheresis may be considered in those with severe pancreatitis, shock or multi-organ failure. Medications such as fibrates and omega-3 fatty acids are not effective if LPL activity is absent or when plasma TG is >1800 mg/dL. Medications only have an adjunct role in the management. Low fat diet, lifestyle changes, weight loss, control of secondary causes, and patient education form the mainstay of management once the patient is discharged. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A causal role for uric acid in fructose-induced metabolic syndrome.

PubMed

Nakagawa, Takahiko; Hu, Hanbo; Zharikov, Sergey; Tuttle, Katherine R; Short, Robert A; Glushakova, Olena; Ouyang, Xiaosen; Feig, Daniel I; Block, Edward R; Herrera-Acosta, Jaime; Patel, Jawaharlal M; Johnson, Richard J

2006-03-01

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.

Cardiorenal Involvement in Metabolic Syndrome Induced by Cola Drinking in Rats: Proinflammatory Cytokines and Impaired Antioxidative Protection

PubMed Central

Otero-Losada, Matilde; Gómez Llambí, Hernán; Ottaviano, Graciela; Cao, Gabriel; Müller, Angélica; Azzato, Francisco; Ambrosio, Giuseppe; Milei, José

2016-01-01

We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drank ad libitum regular cola (C, n = 12) or tap water (W, n = 12). Measures. Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%, p < 0.05), hyperglycemia (+11%, p < 0.05), hypertriglyceridemia (2-fold, p < 0.001), higher AIP (2-fold, p < 0.01), and lower Q10 level (−55%, p < 0.05); (II) increased LV diastolic diameter (+9%, p < 0.05) and volume (systolic +24%, p < 0.05), posterior wall thinning (−8%, p < 0.05), and larger cardiac output (+24%, p < 0.05); (III) glomerulosclerosis (+21%, p < 0.05), histopathology (+13%, p < 0.05), higher tubular expression of IL-6 (7-fold, p < 0.001), and TNFα (4-fold, p < 0.001). (IV) Correlations were found for LV dimensions with IL-6 (74%, p < 0.001) and TNFα (52%, p < 0.001) and fully abolished after TG and Q10 control. Chronic cola drinking induced cardiac remodeling associated with increase in proinflammatory cytokines and renal damage. Hypertriglyceridemia and oxidative stress were key factors. Hypertriglyceridemic lipotoxicity in the context of defective antioxidant/anti-inflammatory protection due to low Q10 level might play a key role in cardiorenal disorder induced by chronic cola drinking in rats. PMID:27340342

Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

PubMed Central

Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

2013-01-01

Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and 13C-NEFA over 6 h compared with controls. AUC6 h of plasma 13C-triglyceride and 13C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in 13C-triolein oxidation rate, which suggests lower 13C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT 3H-lipid following a 4 h incubation of women's WAT with synthetic 3H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower 3H-TRL hydrolysis and 3H-NEFA storage. Treatment of women's WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated 3H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo. PMID:23417739

Geography of Food Consumption Patterns between South and North China.

PubMed

Song, Fangfang; Cho, Mi Sook

2017-05-05

The geographical environment, food culture, and dietary habits are substantially different between the southern and northern regions in China. We investigated the associations with dietary patterns and metabolic syndrome between Chinese adult from the southern and northern regions (North: 1249; South: 1849) using data from the Chinese Health and Nutrition 2009 survey. Respectively, four dietary patterns were identified by factor analysis in each of the two regions. Using factor analysis, each dietary pattern of factor score was calculated for three groups by tertile (T1 < T2 < T3). In the northern region, the association between the Alcohol and Western pattern and the risk of abdominal obesity (OR: 1.31; 95%: 1.01, 1.68) (OR: Odds Ratio), hypertriglyceridemia (OR: 1.35; 95%: 1.05, 1.74), high fasting blood glucose (OR: 1.37; 95%: 1.05, 1.80), and hypertension (OR: 1.55; 95%: 1.45, 1.99) was increased compared T1 to T3. In the southern region, the Convenience Food pattern was positively associated with hypertriglyceridemia (OR: 1.53; 95%: 1.03, 2.26), low high density lipoprotein (HDL)-cholesterol (OR: 1.96; 95%: 1.12, 3.43), and metabolic syndrome (OR: 1.79; 95%: 1.03, 3.11). The Alcohol dietary pattern was positively associated with high fasting blood glucose (OR: 1.83, 95%: 1.13, 2.97). There are some dietary pattern differences in the two regions. It is necessary to consider the factors of food culture and food intake habits in order to provide nutrition education to Chinese individuals from different regions in the future.

Gemfibrozil hepatotoxicity: a case report.

PubMed

Domínguez Tordera, Patricia; Comellas Alabern, José Francisco; Ronda Rivero, Félix

2011-10-01

A 55-year-old woman was admitted to our hospital for management of thoracic trauma and bone fractures. One month after admission she started to receive gemfibrozil for hypertriglyceridemia. In the second month of admission, the patient complained of nausea and malaise. Laboratory value showed an acute hepatitis with raised AST, ALT. The abdominal ultrasound scan was normal, and viral serologic tests were negative. Gemfibrozil was discontinued and in a few days AST and ALT levels returned to normal. Gemfibrozil-induced hepatitis is a rare event but should be considered in the differential diagnoses of hepatitis in which no other obvious alternative cause is found.

Ethnic differences in the ability of triglyceride levels to identify insulin resistance.

PubMed

Sumner, Anne E; Cowie, Catherine C

2008-02-01

The Metabolic Syndrome is used to predict the onset of coronary artery disease and Type 2 diabetes. As the predictive value of the Metabolic Syndrome has been challenged, alternative syndromes have been developed. All of these syndromes were developed in populations that were predominantly non-Hispanic white (NHW). They include the Enlarged Waist Elevated Triglyceride Syndrome, the Overweight-Lipid Syndrome and the Hypertriglyceridemic Waist Syndrome. The first applies to postmenopausal women, the second to overweight individuals (BMI> or =25 kg/m(2)), and the third to men. Each syndrome uses hypertriglyceridemia as a criterion. However, the definition of hypertriglyceridemia varies by syndrome i.e. TG> or =128 mg/dL for the Enlarged Waist Elevated Triglyceride Syndrome, TG> or =130 mg/dL for the Overweight-Lipid Syndrome, > or =150 mg/dL for the Metabolic Syndrome, and TG> or =176 mg/dL for the Hypertriglyceridemic Waist Syndrome. Insulin resistance and hypertriglyceridemia are highly correlated. But as insulin resistant non-Hispanic blacks (NHB) often have triglyceride (TG) levels below the thresholds set by these syndromes, the ability of either TG or these syndromes to identify high risk NHB is unknown. Using the National Health and Nutrition Examination Survey (NHANES) 1999-2002, our goals were to determine by ethnicity: (1) the prevalence of each of these syndromes; (2) the ability of fasting TG concentrations to identify insulin resistance at cut-off levels established by these syndromes, specifically 130, 150 and 176 mg/dL. Participants were 2804 adults from NHANES 1999-2002. The cohort was divided into tertiles of homeostasis model assessment. Insulin resistance was defined as the upper tertile (> or =2.73). The prevalence of each syndrome was lower in NHB than NHW or Mexican Americans (MA) (all P<0.05). Mean TG levels in NHB, non-Hispanic Whites (NHW) and Mexican Americans (MA) were: 99, 140 and 144mg/dL, respectively. The mean percents of insulin-resistant NHB, NHW and MA with TG<130mg/dL were: 64, 31 and 36. The percents of insulin-resistant NHB, NHW and MA with TG<150mg/dL were: 75, 46 and 47. The percents of insulin-resistant NHB, NHW and MA with TG<176 mg/dL were: 81, 58 and 59. Significance was P<0.001 for each comparison to NHB. In conclusion, the prevalence of syndromes that use TG as a diagnostic criterion is lower in NHB than NHW or MA. NHB are more likely than NHW or MA to be insulin-resistant and have TG levels below threshold values. As syndromes are formulated to identify individuals at high risk for conditions such as cardiovascular disease and Type 2 diabetes, ethnic differences in TG levels should be considered.

Effects of Weight Reduction on Obesity STUDIES OF LIPID AND CARBOHYDRATE METABOLISM IN NORMAL AND HYPERLIPOPROTEINEMIC SUBJECTS

PubMed Central

Olefsky, Jerrold; Reaven, Gerald M.; Farquhar, John W.

1974-01-01

Considerable controversy exists over the purported role of obesity in causing hyperglycemia, hyperlipemia, hyperinsulinemia, and insulin resistance; and the potential beneficial effects of weight reduction remain incompletely defined. Hypertriglyceridemia is one of the metabolic abnormalities proposed to accompany obesity, and in order to help explain the mechanisms leading to this abnormality we have proposed the following sequential hypothesis: insulin resistance → hyperinsulinemia → accelerated hepatic triglyceride(TG) production → elevated plasma TG concentrations. To test this hypothesis and to gain insight into both the possible role of obesity in causing the above metabolic abnormalities and the potential benefit of weight reduction we studied the effects of weight loss on various aspects of carbohydrate and lipid metabolism in a group of 36 normal and hyperlipoproteinemic subjects. Only weak to absent correlations (r = 0.03 — 0.46) were noted between obesity and the metabolic variables measured. This points out that in our study group obesity cannot be the sole, or even the major, cause of these abnormalities in the first place. Further, we have observed marked decreases after weight reduction in fasting plasma TG (mean value: pre-weight reduction, 319 mg/100 ml; post-weight reduction, 180 mg/100 ml) and cholesterol (mean values: pre-weight reduction, 282 mg/100 ml; post-weight reduction, 223 mg/100 ml) levels, with a direct relationship between the magnitude of the fall in plasma lipid values and the height of the initial plasma TG level. We have also noted significant decreases after weight reduction in the insulin and glucose responses during the oral glucose tolerance test (37% decrease and 12% decrease, respectively). Insulin and glucose responses to liquid food before and after weight reduction were also measured and the overall post-weight reduction decrease in insulin response was 48% while the glucose response was relatively unchanged. In a subgroup of patients we studied both the degree of cellular insulin resistance and the rate of hepatic very low density (VLDL) TG production before and after weight reduction. These subjects demonstrated significant decreases after weight reduction in both degree of insulin resistance (33% decrease) and VLDL-TG production rates (40% decrease). Thus, weight reduction has lowered each of the antecedent variables (insulin resistance, hyperinsulinemia, and VLDL-TG production) that according to the above hypothesis lead to hypertriglyceridemia, and we believe the overall scheme is greatly strengthened. Furthermore, the consistent decreases in plasma TG and cholesterol levels seen in all subjects lead us to conclude that weight reduction is an important therapeutic modality for patients with endogenous hypertriglyceridemia. Images PMID:4357617

The prevalence of diabetes and associated coronary risk factors in urban and rural older Mexican populations.

PubMed

Lerman, I G; Villa, A R; Martinez, C L; Cervantes Turrubiatez, L; Aguilar Salinas, C A; Wong, B; Gómez Pérez, F J; Gutierrez Robledo, L M

1998-11-01

To determine the prevalence of diabetes and examine its association with food intake, anthropometric and metabolic variables, and other coronary risk factors in urban and rural older Mexican populations. A cross-sectional study. Three Mexican communities (urban areas of medium and low income and a rural area). A total of 121 men and 223 women aged 60 years and older and 93 men and 180 women aged 35 to 59 years were selected randomly for inclusion in the survey, which was derived from the CRONOS study (Cross-Cultural Research on Nutrition in the Older Adult Study Group) promoted by the European Economic Community. A personal interview assessed demographic information, personal medical history, and functional status, and a 24-hour diet recall was obtained. A physical examination included anthropometric and blood pressure measurements. A fasting blood sample was obtained for measurements of lipids, insulin, and glucose. Diabetes prevalence was higher in men than in women for all age groups: 16.7% versus 9.5% in younger adults and 30.8% versus 22.8% in older adults. For all age groups, diabetes was more highly prevalent in urban communities. Using a multivariate stepwise logistic regression, variables associated independently with diabetes in older individuals were: gender (male sex: OR = 2.1; P < .009); diminished carbohydrate intake in the diet (OR = 0.77; P < .03); central distribution of adiposity (OR = 1.9; P < .03); and functional disability (OR = 2.3; P < .01). This relationship was not observed with living area, income, education, fiber and alcohol intake, body mass index, or age. Individuals 80 years and older had a diminished atherogenic risk profile. Diabetes in older people was associated significantly with hypertriglyceridemia, impaired functional status, and an increased prevalence of ischemic heart disease; in younger adults diabetes was associated with low density lipoprotein (LDL) hypercholesterolemia, hypertriglyceridemia, and a proportionally higher fat intake. This survey confirms the high prevalence of diabetes in the older Mexican population - particularly in men and in individuals living in urban areas - associated with an increased prevalence of other coronary risk factors. Diabetes was associated with higher fat, low carbohydrate, low fiber diets and increased prevalence of central distribution of adiposity. In the older subjects, diabetes was associated significantly with hypertriglyceridemia, impaired functional status, and increased prevalence of ischemic heart disease. A bias produced by early mortality and a survivorship effect must be considered in studies of older individuals. The health situation in the older Mexican population presents a complex problem that needs correct diagnosis and better strategies to benefit those segments of the population at increased risk.

Appropriate Body Mass Index and Waist Circumference Cutoffs for Categorization of Overweight and Central Adiposity among Uighur Adults in Xinjiang

PubMed Central

Ma, Yi-Tong; Liu, Fen; Yang, Yi-Ning; Ma, Xiang; Fu, Zhen-Yan; Li, Xiao-Mei; Xie, Xiang; Chen, You; Chen, Bangdang; He, Chun-Hui

2013-01-01

Objective The current overweight and central adiposity guidelines based on Western populations were not consistent with many studied based on the Asian populations. Uighur people live in Xinjiang Uighur Autonomous Region which is located in the center of Asia. Their overweight and central cutoffs were largely unknown. We aimed to identify cutoffs for body mass index (BMI; in kg/m2) and waist circumference (WC; in cm) for categorization of overweight and central adiposity among Uighur adults in Xinjiang. Methods 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS) which was carried out from October 2007 to March 2010. The age of the participants were from 35 to 101 years old with the mean age of 50.09 years. Anthropometric data, blood pressure, serum concentration of serum total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) and fasting glucose were documented. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each BMI and waist circumference values were calculated. Results The prevalence of hypertension, hypercholesterolemia and hypertriglyceridemia were higher with higher BMI for both men and women. The prevalence of hypertension and hypercholesterolemia were higher with higher waist circumference for both men and women. In women, the prevalence of hypertriglyceridemia was noticed to increase as the waist circumference increased. The shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥ 2 of these risk factors suggested a BMI cutoff of 26 and a waist circumference cutoff of 90 cm for both men and women. Conclusions Higher cutoffs for BMI and waist circumference are needed in the identification of Uighur patients at high risk of cardiovascular disease. PMID:24244645

Frequency of cardiovascular risk factors before and 6 and 12 months after bariatric surgery.

PubMed

Silva, Maria Alayde Mendonça da; Rivera, Ivan Romero; Barbosa, Emília Maria Wanderley de Gusmão; Crispim, Maria Angélica Correia; Farias, Guilherme Costa; Fontan, Alberto Jorge Albuquerque; Bezerra, Rodrigo Azavedo; Sá, Larissa Gabriella de Souza

2013-01-01

To compare the frequency of cardiovascular risk factors (CVRFs) in obese patients of the Brazilian Unified Health System (Sistema Único de Saúde - SUS) with indication of bariatric surgery during the preoperative period and after the sixth month and the first year of the procedure. An observational, longitudinal, prospective, and analytical study was performed, with consecutive selection of obese patients with indication for surgery referred to preoperative cardiac evaluation. The protocol consisted of: medical history, physical examination, electrocardiogram, echocardiogram, and biochemical analysis. This study analyzed the following variables: weight, body mass index (BMI), waist circumference (WC), systemic arterial hypertension (SAH), diabetes mellitus type 2(DM), dyslipidemia (high LDL cholesterol; low HDL cholesterol; hypertriglyceridemia), and metabolic syndrome (MS). The chi-squared test and the Tukey-Kramer method were used for statistical analysis. The sample was composed of 96 obese people, among which 86 were women, aged between 18 and 58 years old (median 35 years old). At the end of six months, significant reductions of 88%, 95%, 71%, 89%, and 80% in the frequency of SAH, high LDL cholesterol, hypertriglyceridemia, DM, and MS could already be observed. A significant and small reduction in the frequency of low HDL cholesterol (24%) and abnormal WC (31%) was observed only at the end of 12 months. After six months and one year, weight and BMI experienced reductions of 33.4kg and 44.3kg, and 13.1kg/m(2) and 17.2kg/m(2), respectively. The positive impact on weight loss and the reduction in BMI, WC, and in the frequency of CVRFs are already extremely significant after six months and remain so one year after bariatric surgery. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Association of obesity with hypertension and dyslipidemia in type 2 diabetes mellitus subjects.

PubMed

Anari, Razieh; Amani, Reza; Latifi, Seyed Mahmoud; Veissi, Masoud; Shahbazian, Hajieh

Obesity and diabetes are contributed to cardiovascular disease risk. The current study was performed to evaluate the association of central and general obesity and cardio-metabolic risk factors, including dyslipidemia and hypertension in T2DM patients. This was a cross-sectional study in T2DM adults. Body mass index (BMI) was used to identify general obesity and waist circumference (WC) was measured to define abdominal obesity (based on ATP III). Biochemical analyses, and anthropometric and blood pressure measurements were done for all participants. Participants with central obesity showed significantly higher systolic (132.5mmHg vs. 125.4mmHg, p=0.024) and diastolic blood pressures (84.9mmHg vs. 80mmHg, p=0.007) than participants without obesity. Dyslipidemia was more prevalent in all participants either by BMI (98.3% vs. 97%, 95% CI: 0.18-17.53) or by WC (97.2% vs. 98%, 95% CI: 0.07-7.19). Abdominal adiposity in diabetic subjects showed significant reverse association with high level of physical activity (OR=0.22, 95% CI: 0.06-0.85). Hypertriglyceridemia rate was increased with both central (OR=2.11; p=0.040) and general obesity (OR=2.68; p=0.021). After adjustment for energy intake and age, females had higher risk of general (OR=4.57, 95% CI=1.88-11.11) and central obesity (OR=7.93, 95% CI=3.48-18.08). Females were more susceptible to obesity. Hypertension was associated with both obesity measures. Dyslipidemia, except for hypertriglyceridemia, was correlated to neither abdominal nor general obesity. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Higher BNP levels within physiological range correlate with beneficial nonfasting lipid profiles in the elderly: a cross-sectional study.

PubMed

He, Wen-Tao; Mori, Masayuki; Yu, Xue-Feng; Kanda, Tsugiyasu

2016-01-05

Emerging studies indicate that B-type natriuretic peptide (BNP), a well-known biomarker for heart failure, also plays pivotal roles in metabolic control. Circulating BNP levels progressively increase as ages grow older. However, the association between BNP levels and lipid metabolism in the elderly remains unknown. A total of 680 eligible volunteers (male/female: 334/346) aged between 60 and 80 years old without overt heart failure (BNP <100 pg/ml) were enrolled. Random nonfasting venous samples were obtained for biochemical analysis. The subjects were stratified based on BNP quartiles: BNP Q1 (range: 2.2-9.0 pg/ml), Q2 (9.1-20.4 pg/ml), Q3 (20.5-44.4 pg/ml) and Q4 (44.6-99.7 pg/ml). Difference of metabolic parameters was compared among the subjects grouped by BNP quartiles. Univariate correlation and multiple linear regression were performed to analyze the association between BNP levels and metabolic parameters. The odds ratios (OR) and 95 % confidence intervals (CI) for dyslipidemia in subjects within BNP Q1-3 relative to subjects within BNP Q4 were calculated. Circulating BNP levels positively correlated with age, while negatively correlated with body mass index (BMI), eGFR and non-HDL. Subjects with lower BNP quartiles had significantly elevated prevalence of dyslipidemia, including hypertriglyceridemia, hyper-LDL-emia and hypercholesterolemia. The OR of hypertriglyceridemia and hypercholesterolemia for subjects within BNP Q1-2 significantly increased relative to BNP Q4. The elderly people with higher BNP levels have significantly reduced risks for nonfasting dyslipidemia. Verification of the cause-effect relationship between BNP and dyslipidemia may bring therapeutic implications.

Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

PubMed Central

Ramos-Lopez, Omar; Panduro, Arturo; Martinez-Lopez, Erika; Roman, Sonia

2016-01-01

Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively). Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively). In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG. PMID:26907331

The PPARβ/δ activator GW501516 prevents the down-regulation of AMPK caused by a high-fat diet in liver and amplifies the PGC-1α-Lipin 1-PPARα pathway leading to increased fatty acid oxidation.

PubMed

Barroso, Emma; Rodríguez-Calvo, Ricardo; Serrano-Marco, Lucía; Astudillo, Alma M; Balsinde, Jesús; Palomer, Xavier; Vázquez-Carrera, Manuel

2011-05-01

Metabolic syndrome-associated dyslipidemia is mainly initiated by hepatic overproduction of the plasma lipoproteins carrying triglycerides. Here we examined the effects of the peroxisome proliferator-activated receptors (PPAR)-β/δ activator GW501516 on high-fat diet (HFD)-induced hypertriglyceridemia and hepatic fatty acid oxidation. Exposure to the HFD caused hypertriglyceridemia that was accompanied by reduced hepatic mRNA levels of PPAR-γ coactivator 1 (PGC-1)-α and lipin 1, and these effects were prevented by GW501516 treatment. GW501516 treatment also increased nuclear lipin 1 protein levels, leading to amplification in the PGC-1α-PPARα signaling system, as demonstrated by the increase in PPARα levels and PPARα-DNA binding activity and the increased expression of PPARα-target genes involved in fatty acid oxidation. These effects of GW501516 were accompanied by an increase in plasma β-hydroxybutyrate levels, demonstrating enhanced hepatic fatty acid oxidation. Moreover, GW501516 increased the levels of the hepatic endogenous ligand for PPARα, 16:0/18:1-phosphatidilcholine and markedly enhanced the expression of the hepatic Vldl receptor. Interestingly, GW501516 prevented the reduction in AMP-activated protein kinase (AMPK) phosphorylation and the increase in phosphorylated levels of ERK1/2 caused by HFD. In addition, our data indicate that the activation of AMPK after GW501516 treatment in mice fed HFD might be the result of an increase in the AMP to ATP ratio in hepatocytes. These findings indicate that the hypotriglyceridemic effect of GW501516 in HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-lipin 1-PPARα pathway.

Appropriate body mass index and waist circumference cutoffs for categorization of overweight and central adiposity among Uighur adults in Xinjiang.

PubMed

Pan, Shuo; Yu, Zi-Xiang; Ma, Yi-Tong; Liu, Fen; Yang, Yi-Ning; Ma, Xiang; Fu, Zhen-Yan; Li, Xiao-Mei; Xie, Xiang; Chen, You; Chen, Bangdang; He, Chun-Hui

2013-01-01

The current overweight and central adiposity guidelines based on Western populations were not consistent with many studied based on the Asian populations. Uighur people live in Xinjiang Uighur Autonomous Region which is located in the center of Asia. Their overweight and central cutoffs were largely unknown. We aimed to identify cutoffs for body mass index (BMI; in kg/m(2)) and waist circumference (WC; in cm) for categorization of overweight and central adiposity among Uighur adults in Xinjiang. 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS) which was carried out from October 2007 to March 2010. The age of the participants were from 35 to 101 years old with the mean age of 50.09 years. Anthropometric data, blood pressure, serum concentration of serum total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) and fasting glucose were documented. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each BMI and waist circumference values were calculated. The prevalence of hypertension, hypercholesterolemia and hypertriglyceridemia were higher with higher BMI for both men and women. The prevalence of hypertension and hypercholesterolemia were higher with higher waist circumference for both men and women. In women, the prevalence of hypertriglyceridemia was noticed to increase as the waist circumference increased. The shortest distance in the receiver operating characteristic curves for hypertension, dyslipidemia, diabetes, or ≥ 2 of these risk factors suggested a BMI cutoff of 26 and a waist circumference cutoff of 90 cm for both men and women. Higher cutoffs for BMI and waist circumference are needed in the identification of Uighur patients at high risk of cardiovascular disease.

Altered Plasma Lysophosphatidylcholines and Amides in Non-Obese and Non-Diabetic Subjects with Borderline-To-Moderate Hypertriglyceridemia: A Case-Control Study

PubMed Central

Jung, Saem; Lee, Sang-Hyun; Lee, Jong Ho

2015-01-01

Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (CVD). We investigated alterations in plasma metabolites associated with borderline-to-moderate HTG (triglycerides (TG) 150-500 mg/dL). Using UPLC-LTQ-Orbitrap mass spectrometry analysis, the metabolomics profiles of 111 non-diabetic and non-obese individuals with borderline-to-moderate HTG were compared with those of 111 age- and sex-matched controls with normotriglyceridemia (NTG, TG <150 mg/dL). When compared to the NTG control group, the HTG group exhibited higher plasma levels of lysophosphatidylcholines (lysoPCs), including C14:0 (q = 0.001) and C16:0 (q = 1.8E-05), and several amides, including N-ethyldodecanamide (q = 2.9E-05), N-propyldodecanamide (q = 3.5E-05), palmitoleamide (q = 2.9E-06), and palmitic amide (q = 0.019). The metabolomic profiles of the HTG group also exhibited lower plasma levels of cis-4-octenedioic acid (q<1.0E-9) and docosanamide (q = 0.002) compared with those of the NTG controls. LysoPC 16:0 and palmitoleamide emerged as the primary metabolites able to discriminate the HTG group from the NTG group in a partial least-squares discriminant analysis and were positively associated with the fasting triglyceride levels. We identified alterations in lysoPCs, amides, and cis-4-octenedioic acid among non-diabetic and non-obese individuals with borderline-to-moderate HTG. These results provide novel insights into the metabolic alterations that occur in the early metabolic stages of HTG. This information may facilitate the design of early interventions to prevent disease progression. PMID:25856314

A randomized, placebo-controlled, double-blind study on the effects of (-)-epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects.

PubMed

Gutiérrez-Salmeán, Gabriela; Meaney, Eduardo; Lanaspa, Miguel A; Cicerchi, Christina; Johnson, Richard J; Dugar, Sundeep; Taub, Pam; Ramírez-Sánchez, Israel; Villarreal, Francisco; Schreiner, George; Ceballos, Guillermo

2016-11-15

Cardiometabolic disruptions such as insulin resistance, obesity, high blood pressure, hyperglycemia, and dyslipidemias, are known to increase the risk for cardiovascular and metabolic diseases such as type 2 diabetes mellitus and atherosclerosis. Several screening tools for assessing cardiometabolic risk have been developed including the TG/HDLc ratio, which has been, demonstrated to possess a strong association with insulin resistance and coronary disease. Dietary modifications, together with regular moderate exercise have proven to be effective in attenuating cardiometabolic disruptions. However, they often exhibit poor long-term patient compliance. Nutraceutics, including (-)-epicatechin (EPI), have gained increasing interest as coadjuvant effective and safe therapies that are able to attenuate hypertension, hyperglycemia, hyperinsulinemia, hypertriglyceridemia and hypoalphalipoproteinemia. The aims of this study were: 1) to compare the in vitro effect of EPI vs. (+)-catechin on fructose induced triglyceride accumulation and mitochondrial function in Hep2 cells in culture, 2) to evaluate the efficacy of EPI treatment in reducing fasting blood triglycerides and improving the TG/HDLc ratio in hypertriglyceridemic patients with a total daily dose of 100mg of EPI. Secondary clinical variables included total cholesterol, LDLc, fructosamine, glucose, insulin, and high sensitivity C-reactive protein blood levels. Our results provide preliminary evidence as to favorable effects of EPI on glycemia homeostasis, lipid profile and systemic inflammation such bioactive actions are not class-effects (i.e. limited to their antioxidant potential) but instead, may result from the specific activation of associated downstream signaling pathways since catechin has no effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease.

PubMed

Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Sarfati, Gilles; Nubret, Esther; Kapel, Nathalie; Waligora-Dupriet, Anne-Judith; Bergheim, Ina; Cynober, Luc; De-Bandt, Jean-Pascal

2016-02-01

Fructose diets have been shown to induce insulin resistance and to alter liver metabolism and gut barrier function, ultimately leading to non-alcoholic fatty liver disease. Citrulline, Glutamine and Arginine may improve insulin sensitivity and have beneficial effects on gut trophicity. Our aim was to evaluate their effects on liver and gut functions in a rat model of fructose-induced non-alcoholic fatty liver disease. Male Sprague-Dawley rats (n = 58) received a 4-week fructose (60%) diet or standard chow with or without Citrulline (0.15 g/d) or an isomolar amount of Arginine or Glutamine. All diets were made isonitrogenous by addition of non-essential amino acids. At week 4, nutritional and metabolic status (plasma glucose, insulin, cholesterol, triglycerides and amino acids, net intestinal absorption) was determined; steatosis (hepatic triglycerides content, histological examination) and hepatic function (plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin) were assessed; and gut barrier integrity (myeloperoxidase activity, portal endotoxemia, tight junction protein expression and localization) and intestinal and hepatic inflammation were evaluated. We also assessed diets effects on caecal microbiota. In these experimental isonitrogenous fructose diet conditions, fructose led to steatosis with dyslipidemia but without altering glucose homeostasis, liver function or gut permeability. Fructose significantly decreased Bifidobacterium and Lactobacillus and tended to increase endotoxemia. Arginine and Glutamine supplements were ineffective but Citrulline supplementation prevented hypertriglyceridemia and attenuated liver fat accumulation. While nitrogen supply alone can attenuate fructose-induced non-alcoholic fatty liver disease, Citrulline appears to act directly on hepatic lipid metabolism by partially preventing hypertriglyceridemia and steatosis. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Correlation of metabolic syndrome with urinary stone composition.

PubMed

Cho, Sung Tae; Jung, Seung Il; Myung, Soon Chul; Kim, Tae Hyoung

2013-02-01

To determine the correlation between metabolic syndrome and the distribution of stone components in patients with urolithiasis. Between January 2007 and December 2010, renal or ureteral stones were collected from 712 patients (432 males, 280 females) who underwent surgical intervention at three hospitals in South Korea. Metabolic syndrome was defined according to the latest definition of the International Diabetes Federation, using ethnicity- and sex-specific cut-off values for central obesity. Patients were assessed by factors used in metabolic syndrome. All urinary stones were analyzed using infrared spectrophotometry and categorized according to their main component. The patients' mean age was 55.9 years (range 19-93 years). Of the 712 patients, 347 (48.7%; 205 males, 142 females) had a diagnosis of metabolic syndrome. Calcium oxalate (71.5%), uric acid (15.3%), carbonate apatite (8.0%) and struvite (4.1%) calculi were found as the main stone components. Overall, the proportion of uric acid calculi was markedly higher in patients with rather than without metabolic syndrome (19.6 vs 11.2%; P=0.002). However, the proportion of calcium oxalate, carbonate apatite and struvite calculi did not differ between the two groups. The multivariable-adjusted odds ratio for uric acid calculi according to the metabolic syndrome components indicated that the presence of metabolic syndrome was associated with a 93% increased odds ratio of uric acid calculi compared with the absence of metabolic syndrome. Impaired fasting glucose and hypertriglyceridemia were independent risk factors for uric acid calculi. Metabolic syndrome is associated with a significantly increased risk of uric acid calculi development, especially those with impaired fasting glucose and hypertriglyceridemia. © 2012 The Japanese Urological Association.

Chronic cola drinking induces metabolic and cardiac alterations in rats.

PubMed

Milei, José; Otero Losada, Matilde; Gómez Llambí, Hernán; Grana, Daniel R; Suárez, Daniel; Azzato, Francisco; Ambrosio, Giuseppe

2011-04-26

To investigate the effects of chronic drinking of cola beverages on metabolic and echocardiographic parameters in rats. Forty-eight male Wistar rats were divided in 3 groups and allowed to drink regular cola (C), diet cola (L), or tap water (W) ad libitum during 6 mo. After this period, 50% of the animals in each group were euthanized. The remaining rats drank tap water ad libitum for an additional 6 mo and were then sacrificed. Rat weight, food, and beverage consumption were measured regularly. Biochemical, echocardiographic and systolic blood pressure data were obtained at baseline, and at 6 mo (treatment) and 12 mo (washout). A complete histopathology study was performed after sacrifice. After 6 mo, C rats had increased body weight (+7%, P < 0.01), increased liquid consumption (+69%, P < 0.001), and decreased food intake (-31%, P < 0.001). C rats showed mild hyperglycemia and hypertriglyceridemia. Normoglycemia (+69%, P < 0.01) and sustained hypertriglyceridemia (+69%, P < 0.01) were observed in C after washout. Both cola beverages induced an increase in left ventricular diastolic diameter (C: +9%, L: +7%, P < 0.05 vs W) and volumes (diastolic C: +26%, L: +22%, P < 0.01 vs W; systolic C: +24%, L: +24%, P < 0.05 vs W) and reduction of relative posterior wall thickness (C: -8%, L: -10%, P < 0.05 vs W). Cardiac output tended to increase (C: +25%, P < 0.05 vs W; L: +17%, not significant vs W). Heart rate was not affected. Pathology findings were scarce, related to aging rather than treatment. This experimental model may prove useful to investigate the consequences of high consumption of soft drinks.

High Prevalence of Obesity, Hypertension, Hyperlipidemia, and Diabetes Mellitus in Japanese Outpatients with Schizophrenia: A Nationwide Survey

PubMed Central

Sugai, Takuro; Suzuki, Yutaro; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Ozeki, Yuji; Matsuda, Hiroshi; Sugawara, Norio; Yasui-Furukori, Norio; Minami, Yoshitake; Okamoto, Kurefu; Sagae, Toyoaki; Someya, Toshiyuki

2016-01-01

Background Patients with schizophrenia have significantly shorter life expectancy than the general population, and a problem they commonly face is an unhealthy lifestyle, which can lead to obesity and metabolic syndrome. There is a very clear need to determine the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus which are components of metabolic syndrome in patients with schizophrenia, but there has been a paucity of large-scale studies examining this situation in Japan. The aim of our study was to address this need. Setting & Participants We conducted a large-scale investigation of the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus using a questionnaire in 520 outpatient facilities and 247 inpatient facilities of the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7,655 outpatients and 15,461 inpatients with schizophrenia. Results The outpatients had significantly higher prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus than the inpatients. The prevalence of hypo-HDL cholesterolemia was higher in inpatients than outpatients. Age-specific analysis showed the prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus among outpatients to be 2- to 3-fold higher than among inpatients. In individuals aged ≥60 years, the prevalence of obesity and DM among outpatients was about 3-fold higher than among inpatients. Conclusion Japanese outpatients with schizophrenia were more likely to have physical risk such as obesity, hypertension, hyperlipidemia, and diabetes mellitus than inpatients. The physical risk to patients with schizophrenia may be affected by environmental parameters, such as type of care. The physical risk to Japanese patients with schizophrenia demands greater attention. PMID:27855222

Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents.

PubMed

Goedeke, Leigh; Bates, Jamie; Vatner, Daniel F; Perry, Rachel J; Wang, Ting; Ramirez, Ricardo; Li, Li; Ellis, Matthew W; Zhang, Dongyan; Wong, Kari E; Beysen, Carine; Cline, Gary W; Ray, Adrian S; Shulman, Gerald I

2018-05-23

Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet (HFSD)-induced hepatic steatosis, PKCε activation and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (∼30 to 130%, depending on length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to a ∼15% increase in hepatic VLDL production and ∼20% reduction in triglyceride clearance by lipoprotein lipase (LPL) (P ≤ 0.05). At the molecular level, these changes were associated with increases in LXR/SREBP1 and decreases in PPARα target activation and could be reversed with fenofibrate co-treatment in a high-fat diet mouse model. Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Aripiprazole-Induced Hyperlipidemia: An Update.

PubMed

Tarraf, Caroline; Naja, Wadih J

2016-08-25

To review the literature on the metabolic side effects of aripiprazole. Three cases of aripiprazole-induced hypertriglyceridemia are also presented. A search was conducted of English-language articles and abstracts (meta-analyses, randomized controlled trials, clinical trials, naturalistic open-label trials, reviews, and case reports) published up to August 31, 2014, in electronic databases (PubMed, MEDLINE). Free-text and MeSH search keywords included aripiprazole, cholesterol, triglyceride, lipid profile, hyperlipidemia, and hypercholesterolemia and their differing terminations and combinations. The search was supplemented by a manual review of reference lists from the identified publications. Pediatric studies were excluded. Twenty-two articles were found and 3 aspects of the metabolic side effects of aripiprazole were reviewed: (1) the prevalence of the metabolic syndrome in mentally ill patients prior to any antipsychotic use to highlight the initial predisposition of this group of patients to develop the metabolic syndrome, (2) the prevalence of metabolic changes depending on the choice of antipsychotic (aripiprazole compared to other antipsychotics), and (3) metabolic changes reported after switching from an antipsychotic to aripiprazole. Patients with mental disorders are at high risk for developing dyslipidemia, diabetes, and the full criteria of the metabolic syndrome. Antipsychotic use exacerbates this risk, thus increasing the mortality in this population. Nevertheless, it seems that the risk for these side effects varies with each antipsychotic. Although by and large the literature supports the supposition that aripiprazole causes less metabolic effects than other antipsychotics, we report 3 cases of serious aripiprazole-related dyslipidemia in young subjects. On the basis of these 3 cases, aripiprazole can cause hypertriglyceridemia. Triglyceride levels should be carefully monitored in patients with mental disorders taking aripiprazole. © Copyright 2016 Physicians Postgraduate Press, Inc.

Dysregulation of hepatic fatty acid metabolism in chronic kidney disease.

PubMed

Jin, Kyubok; Norris, Keith; Vaziri, Nosratola D

2013-02-01

Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here. Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined. Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue. Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride.

The Association between Symptoms of Dry Eye Syndrome and Metabolic Outcome in a General Population in Korea.

PubMed

Park, Hye Won; Park, Jong Woon

2016-07-01

Dry eye syndrome (DES) is recognized as a public health concern. One of the pathophysiologies in the development of DES is inflammation, and metabolic syndrome (MetS), which is highly prevalent in the general population, is a well-known chronic and systemic inflammatory condition. Despite the increasing interest regarding a relationship between DES and MetS, information is lacking on the association between DES and MetS and its individual components. We investigated the association between DES symptoms and MetS and its components among adults aged ≥ 19 years using population-based data from the Korea National Health and Nutrition Examination Survey V. A sample group of 15,294 adults (42.67% men and 57.33% women) completed household interviews in which they provided blood (for high-density lipoprotein cholesterol, triglyceride, and glucose) and anthropometric measurements (including waist circumference, weight, and height) to define MetS. We also collected information regarding sociodemographic and behavioral risk factors. The survey results showed that 11.50% of men and 22.35% of women experienced DES and 5.30% of patients had both DES and diagnosis of MetS, including 204 men and 606 women. Thus, no significant difference was observed between DES and the diagnosis of MetS according to sex (P = 0.4008 in men; P = 0.0804 in women); however, a significant association was observed between DES and hypertriglyceridemia in women (OR, 1.13; 95% CI, 1.01-1.29). Therefore, hypertriglyceridemia might be an important factor in the association between DES and MetS. Further longitudinal research is needed to evaluate this relationship.

Differences in Severity and Outcomes Between Hypertriglyceridemia and Alcohol-Induced Pancreatitis

PubMed Central

Goyal, Hemant; Smith, Betsy; Bayer, Chelsey; Rutherford, Carla; Shelnut, Danielle

2016-01-01

Background: Alcohol and hypertriglyceridemia (HTG) are among the most common causes of acute pancreatitis (AP) after gallstones. However, differences in severity at the time of presentation and outcomes have not been well-studied. Objective: The aim of this study is to assess the differences between severity at presentation and outcomes of AP of hypertriglyceridemic and alcoholic origins. Materials and Methods: A retrospective review of 177 patients who were discharged with diagnosis of AP was performed. Severity at presentation was identified by the presence of systemic inflammatory response syndrome, bedside index for severity in AP (BISAP) score, and Balthazar index. Outcomes were measured by the length of stay, intensive care unit care, surgical intervention, and mortality. Results: We found 147 patients with alcoholic pancreatitis and 30 patients with hypertriglyceridemic pancreatitis. A larger percentage of hypertriglyceridemic pancreatitis patients (23.33%) had a BISAP score of ≥2 compared to the alcoholic group (12.24%). Only 32.65% of the patients with alcoholic pancreatitis but 60% of the patients with hypertriglyceridemic pancreatitis had the presence of systemic inflammatory response syndrome (SIRS) at admission (P = 0.0067). There were 73.34% hypertriglyceridemic pancreatits patients and only 40.28% alcoholic pancreatitis patients with Balthazar index C or greater, suggesting a higher disease burden at admission for hypertriglyceridemic pancreatitis patients (P = 0.0047). There was a statistically significant difference in the relative number of hypertriglyceridemic and alcoholic pancreatitis patients receiving intensive care (P = 0.00030) and in receiving surgical interventions related to pancreatitis (P = 0.016). Conclusion: Our study found that patients with hypertriglyceridemic pancreatitis have a greater severity of disease and they experience less favorable outcomes than patients with alcoholic pancreatitis. PMID:27042605

Anthropometric measurements as predictive indicators of metabolic risk in a Mexican population

PubMed

Domínguez-Reyes, Teresa; Quiroz-Vargas, Irma; Salgado-Bernabé, Aralia Berenice; Salgado-Goytia, Lorenzo; Muñoz-Valle, José Francisco; Parra-Rojas, Isela

2017-02-01

Introduction: Currently, it is considered that the body fat accumulation at central level is associated with the presence of hypertriglyceridemia, hypertension and diabetes. The body mass index (BMI) has been used to identify obesity in the general population, but can not detect the distribution of body fat, so that can be used other anthropometric measures to assess adiposity and determine their relationship with the presence of metabolic disorders that present people with excess weight. Objective: To evaluate anthropometric measurements such as waist-hip ratio (WHR), BMI and waist circumference (WC) as predictive indicators of metabolic risk factors in Mexican adults. Methods:A descriptive cross-sectional study was conducted in a total of 490 subjects (27-46 years), grouped by gender. All participants were determined anthropometric measurements and biochemical parameters. ROC curves of anthropometric parameters were set to identify the best predictive indicator of metabolic risk. Results: The metabolic risk factor most prevalent after abdominal obesity in women was hypertriglyceridemia, followed by hyperglycemia, hypercholesterolemia and high blood pressure, which are found most often in men than in women, although the presence of abdominal obesity was found most frequently in women (73.9% vs.37.3%). WC was the best predictive indicator to have one or more metabolic risk factors [area under the curve AUC = 0.85 (95% CI, 0.78 to 0.92)], followed by the BMI [AUC = 0.79 (95% CI, 0.72 to 0.88)], and finally the WHC [AUC = 0.63 (95% CI, 0.52 to 0.74)]. Also shows that abdominal obesity duplicate the risk of metabolic syndrome. Conclusion: Waist circumference is a better indicator of metabolic risk in both genders compared with BMI and the WHC.

A Novel Selective PPARα Modulator (SPPARMα), K-877 (Pemafibrate), Attenuates Postprandial Hypertriglyceridemia in Mice.

PubMed

Sairyo, Masami; Kobayashi, Takuya; Masuda, Daisaku; Kanno, Koutaro; Zhu, Yinghong; Okada, Takeshi; Koseki, Masahiro; Ohama, Tohru; Nishida, Makoto; Sakata, Yasushi; Yamashita, Shizuya

2018-02-01

Fasting and postprandial hypertriglyceridemia (PHTG) are caused by the accumulation of triglyceride (TG)-rich lipoproteins and their remnants, which have atherogenic effects. Fibrates can improve fasting and PHTG; however, reduction of remnants is clinically needed to improve health outcomes. In the current study, we investigated the effects of a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), K-877 (Pemafibrate), on PHTG and remnant metabolism. Male C57BL/6J mice were fed a high-fat diet (HFD) only, or an HFD containing 0.0005% K-877 or 0.05% fenofibrate, from 8 to 12 weeks of age. After 4 weeks of feeding, we measured plasma levels of TG, free fatty acids (FFA), total cholesterol (TC), HDL-C, and apolipoprotein (apo) B-48/B-100 during fasting and after oral fat loading (OFL). Plasma lipoprotein profiles after OFL, which were assessed by high performance liquid chromatography (HPLC), and fasting lipoprotein lipase (LPL) activity were compared among the groups. Both K-877 and fenofibrate suppressed body weight gain and fasting and postprandial TG levels and enhanced LPL activity in mice fed an HFD. As determined by HPLC, K-877 and fenofibrate significantly decreased the abundance of TG-rich lipoproteins, including remnants, in postprandial plasma. Both K-877 and fenofibrate decreased intestinal mRNA expression of ApoB and Npc1l1; however, hepatic expression of Srebp1c and Mttp was increased by fenofibrate but not by K-877.Hepatic mRNA expression of apoC-3 was decreased by K-877 but not by fenofibrate. K-877 may attenuate PHTG by suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants more effectively than fenofibrate.

Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

PubMed

Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

2013-12-05

Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Clinical characteristics and beta cell function in Chinese patients with newly diagnosed type 2 diabetes mellitus with different levels of serum triglyceride.

PubMed

Zheng, Shuang; Zhou, Huan; Han, Tingting; Li, Yangxue; Zhang, Yao; Liu, Wei; Hu, Yaomin

2015-04-29

To explore clinical characteristics and beta cell function in Chinese patients with newly diagnosed drug naive type 2 diabetes mellitus (T2DM) with different levels of serum triglyceride (TG). Patients with newly diagnosed T2DM (n = 624) were enrolled and divided into different groups according to levels of serum TG. All patients underwent oral glucose tolerance tests and insulin releasing tests. Demographic data, lipid profiles, glucose levels, and insulin profiles were compared between different groups. Basic insulin secretion function index (homeostasis model assessment for beta cell function index, HOMA-β), modified beta cell function index (MBCI), glucose disposition indices (DI), and early insulin secretion function index (insulinogenic index, IGI) were used to evaluate the beta cell function. Patients of newly diagnosed T2DM with hypertriglyceridemia were younger, fatter and had worse lipid profiles, glucose profiles, and high insulin levels than those with normal TG. There is no difference in early phase insulin secretion among groups of newly diagnosed T2DM patients with different TG levels. The basal beta cell function (HOMA-β and MBCI) initially increased along rising TG levels and then decreased as the TG levels rose further. The insulin sensitivity was relatively high in patients with a low level of TG and low with a high level of TG. Hypertriglyceridemia influences clinical characteristics and β cell function of Chinese patients with newly diagnosed T2DM. A better management of dyslipidemia may, to some extent, reduce the effect of lipotoxicity, thereby improving glucose homeostasis in patients with newly diagnosed T2DM.

High Prevalence of Obesity, Hypertension, Hyperlipidemia, and Diabetes Mellitus in Japanese Outpatients with Schizophrenia: A Nationwide Survey.

PubMed

Sugai, Takuro; Suzuki, Yutaro; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Ozeki, Yuji; Matsuda, Hiroshi; Sugawara, Norio; Yasui-Furukori, Norio; Minami, Yoshitake; Okamoto, Kurefu; Sagae, Toyoaki; Someya, Toshiyuki

2016-01-01

Patients with schizophrenia have significantly shorter life expectancy than the general population, and a problem they commonly face is an unhealthy lifestyle, which can lead to obesity and metabolic syndrome. There is a very clear need to determine the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus which are components of metabolic syndrome in patients with schizophrenia, but there has been a paucity of large-scale studies examining this situation in Japan. The aim of our study was to address this need. We conducted a large-scale investigation of the prevalence of obesity, hypertension, hyperlipidemia, and diabetes mellitus using a questionnaire in 520 outpatient facilities and 247 inpatient facilities of the Japan Psychiatric Hospitals Association between January 2012 and July 2013. There were 7,655 outpatients and 15,461 inpatients with schizophrenia. The outpatients had significantly higher prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus than the inpatients. The prevalence of hypo-HDL cholesterolemia was higher in inpatients than outpatients. Age-specific analysis showed the prevalence of obesity, hypertension, hypertriglyceridemia, hyper-LDL cholesterolemia, and diabetes mellitus among outpatients to be 2- to 3-fold higher than among inpatients. In individuals aged ≥60 years, the prevalence of obesity and DM among outpatients was about 3-fold higher than among inpatients. Japanese outpatients with schizophrenia were more likely to have physical risk such as obesity, hypertension, hyperlipidemia, and diabetes mellitus than inpatients. The physical risk to patients with schizophrenia may be affected by environmental parameters, such as type of care. The physical risk to Japanese patients with schizophrenia demands greater attention.

Appearance of circulating and tissue /sup 14/C-lipids after oral /sup 14/C-tripalmitate administration in the late pregnant rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Argiles, J.; Herrera, E.

1989-02-01

Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this timemore » the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.« less

Impact of parenteral nutrition standardization on costs and quality in adult patients.

PubMed

Berlana, David; Barraquer, Anna; Sabin, Pilar; Chicharro, Luisa; Pérez, Agueda; Puiggrós, Carolina; Burgos, Rosa; Martínez-Cutillas, Julio

2014-08-01

Parenteral nutrition (PN) is a costly therapy that can also be associated with serious complications. Therefore, efforts are focusing on reducing rate of complications, and costs related to PN. The aim was to analyze the effect of the implementation of PN standardization on costs and quality criteria. Secondary aim was to assess the use of individualized PN based on patient's clinical condition. We compare the use of PN before and after the implementation of PN standardization. Demographic, clinical and PN characteristics were collected. Costs analysis was performed to study the costs associated to the two different periods. Quality criteria included were: 1) PN administration; 2) nutrition assessment (energy intake between 20-35 kcal/kg/day; protein contribution according to nitrogen balance); 3) safety and complications (hyperglycemia, hypertriglyceridemia, hepatic complications, catheter-related infection); 4) global efficacy (as serum albumin increase). Chi-square test was used to compare percentages; logistic regression analysis was performed to evaluate the use of customized PN. 296 patients were included with a total of 3,167 PN compounded. During the first period standardized PN use was 47.5% vs 85.7% within the second period (p < 0.05). No differences were found in the quality criteria tested. Use of individualized PN was related to critical care patients, hypertriglyceridemia, renal damage, and long-term PN. Mean costs of the PN decreased a 19.5%. Annual costs savings would be € 86,700. The use of customized or standard PN has shown to be efficient and flexible to specific demands; however customized PN was significantly more expensive. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Population prevalence of APOE, APOC3 and PPAR-alpha mutations associated to hypertriglyceridemia in French Canadians.

PubMed

Garenc, Christophe; Aubert, Samuel; Laroche, Jèrôme; Girouard, Joël; Vohl, Marie-Claude; Bergeron, Jean; Rousseau, François; Julien, Pierre

2004-01-01

Hypertriglyceridemia (HTG) is known as a common metabolic disorder associated with increased production, decrease catabolism and/or decreased hepatic uptake of triglyceride (TG)-rich particles. We assessed, in the Quebec City population, the allele frequency and haplotype distributions of mutations in genes related to HTG, such as the apolipoprotein E (APOE) (C112R and C158R), the apolipoprotein CIII (APOC3) (C-482T and C3238G) and the peroxisome proliferator-activated receptor alpha (PPARalpha) (L162V) genes. A total of 938 anonymous unlinked newborns from the metropolitan Quebec City area have been genotyped. Allele frequencies observed in the Quebec City population differed from known frequencies determined in other Caucasian populations. The co-transmitted allele distribution between the two-marker genotypes APOE/APOC3(C3238G) and APOC3(C-482T)/PPARalpha(L162V) presented a weak deviation from the assumption of genetic independence. Also, we observed a non-independent distribution of the T-482/G3238 allele combinations within the APOC3 gene, suggesting strong linkage disequilibrium between the C-482T and C3238G polymorphisms. Moreover, comparisons of allele frequencies observed in the population of Québec City to those obtained in other Caucasian populations suggested that the population of Québec City may be at a lower risk of developing HTG due to APOE, APOC3 and PPARalpha genetic variants. However, the strong linkage disequilibrium and the two-marker genotype distributions observed in the APOC3 gene suggest that these two variants may functionally interact in the Québec City population.

Hypertriglyceridemia Influences the Degree of Postprandial Lipemic Response in Patients with Metabolic Syndrome and Coronary Artery Disease: From the Cordioprev Study

PubMed Central

Alcala-Diaz, Juan F.; Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Marin, Carmen; Quintana-Navarro, Gracia M.; Gomez-Luna, Purificacion; Camargo, Antonio; Almaden, Yolanda; Caballero, Javier; Tinahones, Francisco J.; Ordovas, Jose M.

2014-01-01

Objective To determine whether metabolic syndrome traits influence the postprandial lipemia response of coronary patients, and whether this influence depends on the number of MetS criteria. Materials and Methods 1002 coronary artery disease patients from the CORDIOPREV study were submitted to an oral fat load test meal with 0.7 g fat/kg body weight (12% saturated fatty acids, 10% polyunsaturated fatty acids, 43% monounsaturated fatty acids), 10% protein and 25% carbohydrates. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Total and incremental area under the curves of the different postprandial parameters were calculated following the trapezoid rule to assess the magnitude of change during the postprandial state Results Postprandial lipemia response was directly related to the presence of metabolic syndrome. We found a positive association between the number of metabolic syndrome criteria and the response of postprandial plasma triglycerides (p<0.001), area under the curve of triglycerides (p<0.001) and incremental area under the curve of triglycerides (p<0.001). However, the influence of them on postprandial triglycerides remained statistically significant only in those patients without basal hypertriglyceridemia. Interestingly, in stepwise multiple linear regression analysis with the AUC of triglycerides as the dependent variable, only fasting triglycerides, fasting glucose and waist circumference appeared as significant independent (P<0.05) contributors. The multiple lineal regression (R) was 0.77, and fasting triglycerides showed the greatest effect on AUC of triglycerides with a standardized coefficient of 0.75. Conclusions Fasting triglycerides are the major contributors to the postprandial triglycerides levels. MetS influences the postprandial response of lipids in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients. PMID:24802225

Long-term and midterm outcomes of laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass: a systematic review and meta-analysis of comparative studies.

PubMed

Shoar, Saeed; Saber, Alan A

2017-02-01

This study aimed to compare midterm and long-term weight loss and resolution of co-morbidity with laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). LRYGB and LSG are the most common procedures performed in bariatric surgery. However, their weight loss efficacy in the midterm and long-term has not been well compared. A meta-analysis was performed by systematically identifying comparative studies conducted until the end of June 2016 that investigated weight loss outcome and resolution of co-morbidities (type 2 diabetes mellitus, hypertension, hyperlipidemia, hypertriglyceridemia, and obstructive sleep apnea) with LRYGB and LSG in the midterm (3-5 years) and long term (≥5 years). The primary endpoint was weight loss after LRYGB versus LSG. The secondary endpoint was resolution of co-morbidities after these procedures. Fourteen studies comprising 5264 patients were eligible. Follow-up ranged from 36 months to 75.8±8.4 months. The pooled result for weight loss outcomes did not show any significant difference in midterm weight loss (standardized mean difference = -0.03; 95% confidence interval (CI), -0.38-.33; P = .88) but a significant difference in the long-term weight loss outcome favoring LRYGB (standardized mean difference = .17; 95% CI, .05-.28; P= .005). The pooled results demonstrated no significant difference for resolution of type 2 diabetes mellitus, hypertension, hyperlipidemia, and hypertriglyceridemia. Despite the insignificant difference between LRYGB and LSG in midterm weight loss, LRYGB produced better weight loss in the long-term. There was no significant difference between the 2 procedures for co-morbidity resolution. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Detrimental effect of systemic vascular risk factors on brain hemodynamic function assessed with MRI.

PubMed

King, Kevin S; Sheng, Min; Liu, Peiying; Maroules, Christopher D; Rubin, Craig D; Peshock, Ron M; McColl, Roderick W; Lu, Hanzhang

2018-06-01

Background and purpose Vascular risk factors have been associated with decreased cerebral blood flow (CBF) but this is etiologically nonspecific and may result from vascular insufficiency or a response to decreased brain metabolic activity. We apply new MRI techniques to measure oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO 2 ), hypothesizing that decreased CBF related to these vascular risk factors will be associated with increased OEF, confirming a primary vascular insufficiency. Methods 3T MRI was obtained on 70 community-based participants in this IRB-approved study with informed consent, with previous assessment of systolic blood pressure, hypertension medication, elevated serum triglycerides, low serum HDL, and diabetes mellitus. CBF was measured using phase contrast adjusted for brain volume (ml/100 g/min), OEF (%) was obtained from T2-Relaxation-Under-Spin-Tagging (TRUST), and CMRO 2 (μmol/100 g/min) was derived using the Fick principle. Stepwise linear regression identified optimal predictors of CBF with age, sex, and hematocrit included for adjustment. This predictive model was then evaluated against OEF and CMRO 2 . Results Hypertriglyceridemia was associated with low CBF and high OEF. High systolic blood pressure was associated with high CBF and low OEF, which was primarily attributable to those with pressures above 160 mmHg. Neither risk factor was associated with significant differences in cerebral metabolic rate. Conclusion Low CBF related to hypertriglyceridemia was accompanied by high OEF with no significant difference in CMRO 2 , confirming subclinical vascular insufficiency. High CBF related to high systolic blood pressure likely reflected limitations of autoregulation at higher blood pressures.

Prevalence of dyslipidemia in Iranian children and adolescents: A systematic review.

PubMed

Hovsepian, Silva; Kelishadi, Roya; Djalalinia, Shirin; Farzadfar, Farshad; Naderimagham, Shohreh; Qorbani, Mostafa

2015-05-01

Dyslipidemia is considered as an important modifiable risk factor for cardiovascular disease (CVD). The link between childhood dyslipidemia and occurrence of atherosclerosis and its sequels in adulthood are well-documented. This study aimed to systematically review the prevalence of dyslipidemia among Iranian children and adolescents. An electronic search was conducted on studies published from January 1990 to January 2014. The main international electronic data sources were PubMed and the NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS. For Persian databases, we used domestic databases with systematic search capability including IranMedex, Irandoc, and Scientific Information Database (SID). We included all available population-based studies and national surveys conducted in the pediatric age group (aged <21 years). In this review, 1772 articles were identified (PubMed: 1464; Scopus: 11; ISI: 58; SID: 90; IranMedex: 149; Irandoc: 57). During three refine steps and after removing of duplicates, 182 articles related to the study domain were selected. After quality assessment, 46 studies were selected for text appraisal, of which 26 qualified articles were evaluated at the final step. The prevalence range of hypercholesterolemia, hypertriglyceridemia, elevated low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol (HDL-C) were 3-48%, 3-50%, 5-20% and 5-88%, respectively. Low HDL-C and hypertriglyceridemia were the most prevalent lipid disorders in this group of population. Dyslipidemia is a common health problem among Iranian children and adolescents. Few data were available in preschool children. This finding provides useful information for health policy makers to implement action-oriented interventions for prevention and early control of this important CVD risk factor.

A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

PubMed Central

Liu, Chi-Ming; Tung, Tao-Hsin; Liu, Jorn-Hon; Chen, Victor Tze-Kai; Lin, Ching-Heng; Hsu, Chung-Te; Chou, Pesus

2005-01-01

AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study. PMID:15786537

Long-term outcomes in children with chronic kidney disease stage 5 over the last 40 years.

PubMed

Adamczuk, Dominika; Roszkowska-Blaim, Maria

2017-04-01

We evaluated outcomes in children with chronic kidney disease stage 5 (CKD 5) treated in the first pediatric dialysis unit in Poland during 1973-2012. The retrospective analysis included 208 children with CKD 5 undergoing renal replacement therapy (RRT), stratified into four decades of treatment: 1973-1982, 1983-1992, 1993-2002, and 2003-2012. The most common causes of CKD 5 included glomerulonephritis in 27.4% and pyelonephritis secondary to urinary tract anomalies in 25.5% of children. Among 208 children, 172 (82.7%) survived and 17.3% died. Kidney transplantation (KTx) was performed in 47.6% of children, including pre-emptive KTx in 1.92% of children. Chronic dialysis was continued in 34.1% of children, and RRT was withdrawn in 1%. The overall mortality rate was 6.2 per 100 patient-years, and 3-year survival was 83.9%. The highest mortality rate of 23.4 per 100 patient-years was observed among children in whom RRT was initiated in 1973-1982, with subsequent reduction of the mortality rate to 4.5 and 2.1 per 100 patient-years in 1993-2002 and 1983-1992 respectively. No deaths were noted after 2002. Cardiovascular problems were the most common cause of death, found in 36.1% of patients ( p < 0.01). Identified risk factors for mortality included young age, low residual diuresis, anemia at the time of RRT initiation, and hypertriglyceridemia and hypoalbuminemia during RRT. In years 1973-2012 significant improvement in prognosis among children with CKD 5 was achieved. Identified predictors of mortality included young age at initiation of RRT, low residual diuresis, anemia and hypertriglyceridemia.

Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women.

PubMed

Sun, Liang; Hu, Caiyou; Zheng, Chenguang; Huang, Zezhi; Lv, Zeping; Huang, Jin; Liang, Siying; Shi, Xiaohong; Zhu, Xiaoquan; Yuan, Huiping; Yang, Ze

2014-07-01

The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects is limited; in addition, the majority of oldest-old subjects are females. Evidence has accumulated that multiple genetic factors play important roles in determining susceptibility to dyslipidemia and extended life span. Cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible candidate genes for human longevity owing to their functionally related modulation of circulating lipid homeostasis; however, few studies have considered their interplay. In this study, we analyzed the distribution of CETP*V (rs5882) and APOE*4 (rs429358 and rs7412) in 372 oldest-old Chinese women (aged 80-109) and 340 controls (aged 20-58). In addition to replicating the association of longevity, our main goal was to evaluate the contribution of CETP*V, APOE*4 and CETP*APOE interaction to the risk of dyslipidemia. Only APOE*4 conferred a risk against longevity and was associated with high-cholesterol (hTC) and mixed dyslipidemia for oldest-old females. Moreover, CETP*V was found to be associated with hypertriglyceridemia (hTG) independently from APOE*4, age, BMI, alcohol drinking, TC, TG, HDL-c, and LDL-c. The stratification test, multivariable-adjusted logistic regression, and nonparametric MDR analysis all suggested a significant CETP*APOE interaction associated with hTG. The unadjusted odds for hTG were more than 4-fold in subjects with CETP*V and APOE*4 than those without either (OR=4.36, P<0.001). These results provide evidence of strong independent associations between hTG and CETP*V in oldest-old Chinese females, and APOE*4, as an independently non-significant variant, might interact with CETP*V resulting in an increased risk for hTG. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of acute and chronic moderate red or white wine consumption on fasted and postprandial lipemia in the rat.

PubMed

Daher, Costantine F; Slaiby, Rita; Haddad, Najib; Boustany, Karim; Baroody, George M

2006-06-01

The effects of acute and chronic (10 wk) red or white wine consumption on fasted and postprandial lipemia in the rat model are reported. Fasted rats, in the acute study, were loaded intragastrically with 5 ml of an olive oil emulsion (30% w/v) in the presence or absence of wine (8% v/v ethanol), and either mesenteric lymph or blood was collected 3 h postprandially. Animals in the chronic study received either red or white wine in drinking water for a period of 10 wk (3% v/v ethanol). Blood samples were collected from animals in either the fasted state or after fat-wine loading. Postprandially, wine delayed gastric emptying, reduced lymph triacylglycerol (TAG) secretion concomitantly with increased number and decreased chylomicron (CM) size, and increased plasma TAG and CM concentrations. Phospholipid and cholesterol contents of CM, but not very-low-density lipoprotein (VLDL), were increased, indicating enhanced liver bile secretion; however, a significant increase in plasma VLDL concentration was observed. In the chronic study, a wine-fat load resulted in increased high-density lipoprotein (HDL) cholesterol concentration and less pronounced postprandial hypertriglyceridemia and hyperchylomicronemia. In the fasted state, plasma TAG and total apolipoprotein B concentrations were not modified in these animals, and an increase in HDL and a decrease in low-density lipoprotein (LDL)/HDL cholesterol ratios were observed. No liver function or intestinal lipid absorption impairment was observed. In conclusion, unlike binge drinking, chronic moderate wine consumption appears to have a cardioprotective effect in the fasted state, an effect attenuated by the observed temporary postprandial hyperchylomicronemia and hypertriglyceridemia resulting from a direct effect of alcohol on CM size and number.

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia.

PubMed

Ahn, Hyeon Yeong; Kim, Minjoo; Chae, Jey Sook; Ahn, Young-Tae; Sim, Jae-Hun; Choi, Il-Dong; Lee, Sang-Hyun; Lee, Jong Ho

2015-08-01

Previous studies have indicated that supplementation with probiotics might improve lipid metabolism. The objective of the study was to evaluate the effect of supplementation with probiotic strains Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on triglyceride (TG) and apolipoprotein A-V (apo A-V) levels. A randomized, double-blinded, placebo-controlled study was conducted with 128 non-diabetic subjects with hypertriglyceridemia. Over a 12-week test period, the probiotic group consumed 2 g/day of a powdered supplement containing L. curvatus HY7601 and L. plantarum KY1032, whereas the placebo group consumed a powder lacking probiotics. After the treatment, the probiotic group showed an 18.3% (P < 0.001) reduction in TGs and increases of 21.1% (P = 0.001) and 15.6% (P < 0.001) in the apo A-V and LDL particle size, respectively. The probiotic group had a significant reduction in TGs (P = 0.040) and increases in the plasma apo A-V (P = 0.003) and LDL particle size (P < 0.001) compared with the placebo group. In the probiotic group, the reduction in the TG levels was negatively correlated with changes in the apo A-V and baseline TGs, regardless of the APOA5 -1131T > C genotype. The consumption of two probiotic strains for 12 weeks reduced TGs and increased the apo A-V and LDL particle size in hypertriglyceridemic subjects. This effect was more pronounced in subjects with higher levels of fasting TGs regardless of their APOA5 -1131T > C genotype. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Update on the management of severe hypertriglyceridemia--focus on free fatty acid forms of omega-3.

PubMed

Pirillo, Angela; Catapano, Alberico Luigi

2015-01-01

High levels of plasma triglycerides (TG) are a risk factor for cardiovascular diseases, often associated with anomalies in other lipids or lipoproteins. Hypertriglyceridemia (HTG), particularly at very high levels, significantly increases also the risk of acute pancreatitis. Thus, interventions to lower TG levels are required to reduce the risk of pancreatitis and cardiovascular disease. Several strategies may be adopted for TG reduction, including lifestyle changes and pharmacological interventions. Among the available drugs, the most commonly used for HTG are fibrates, nicotinic acid, and omega-3 polyunsaturated fatty acids (usually a mixture of eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA). These last are available under different concentrated formulations containing high amounts of omega-3 fatty acids, including a mixture of EPA and DHA or pure EPA. The most recent formulation contains a free fatty acid (FFA) form of EPA and DHA, and exhibits a significantly higher bioavailability compared with the ethyl ester forms contained in the other formulations. This is due to the fact that the ethyl ester forms, to be absorbed, need to be hydrolyzed by the pancreatic enzymes that are secreted in response to fat intake, while the FFA do not. This higher bioavailability translates into a higher TG-lowering efficacy compared with the ethyl ester forms at equivalent doses. Omega-3 FFA are effective in reducing TG levels and other lipids in hypertriglyceridemic patients as well as in high cardiovascular risk patients treated with statins and residual HTG. Currently, omega-3 FFA formulation is under evaluation to establish whether, in high cardiovascular risk subjects, the addition of omega-3 to statin therapy may prevent or reduce major cardiovascular events.

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing.

PubMed

Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Ingrassia, Valeria; Valenti, Vincenza; Giammanco, Antonina; Fayer, Francesca; Misiano, Gabriella; Cocorullo, Gianfranco; Scrimali, Chiara; Palesano, Ornella; Altieri, Grazia I; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG. We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL-10 mmol/L): 4 positive controls in whom pathogenic mutations had previously been identified by Sanger sequencing and 7 patients in whom the molecular defect was still unknown. The customized panel was accurate, and it allowed to confirm genetic variants previously identified in all positive controls with primary severe HTG. Only 1 patient of 7 with HTG was found to be carrier of a homozygous pathogenic mutation of the third novel mutation of LMF1 gene (c.1380C>G-p.Y460X). The clinical and molecular familial cascade screening allowed the identification of 2 additional affected siblings and 7 heterozygous carriers of the mutation. We showed that our targeted resequencing approach for genetic diagnosis of severe HTG appears to be accurate, less time consuming, and more economical compared with traditional Sanger resequencing. The identification of pathogenic mutations in candidate genes remains challenging and clinical resequencing should mainly intended for patients with strong clinical criteria for monogenic severe HTG. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Treatment of primary hypertriglyceridemia states--General approach and the role of extracorporeal methods.

PubMed

Stefanutti, Claudia; Julius, Ulrich

2015-05-01

Hypertriglyceridemia (HTG) is a common metabolic disorder in which the concentration of very low density lipoproteins (VLDL) and of chylomicrons (CMs) is elevated in the plasma. HTG may be caused by primary and/or secondary causes and affected subjects may express HTG when children or in adulthood. In children and adults a genetic cause may underlie HTG which can be expressed as CMs a severe clinical picture known as Familial Hyperchylomicronemia due to lipoprotein lipase (LPL) or apolipoprotein (apo) CII deficiencies. Genetically determined HTG includes Familial Dysbetalipoproteinemia due to deficiency of apolipoprotein EIII of VLDL and Familial HTG. However, recent data suggest that classical Fredrickson phenotypes describing clinically HTG, which were once considered to be distinct based on biochemical features, have a shared genetic set up. The HTG has been classified according to a recent international paper: mild HTG: 2-10 mmol/L (176-882 mg/dL); severe HTG: > 10 mmol/L (>882 mg/dL) associated to CMs remnants, or Intermediate Density lipoprotein (IDL) like particles, and/or CMs. The treatment includes limitation of dietary content of saturated fat and alcohol, fibrates and omega3 fatty acids. When TG are severely elevated and associated to CMs the risk of acute pancreatitis suggests the use of more drastic therapeutic option such as therapeutic plasma exchange. This paper summarizes the experience with conventional plasmapheresis (Plasma-Exchange, PEX) and different Lipoprotein Apheresis methods with respect to acutely lowering TG levels in patients with normal TG, with mild and severe HTG. Upcoming promising therapies are gene therapy, novel apolipoprotein CIII inhibitors and lomitapide. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Severe insomnia is associated with hypertriglyceridemia in women with major depression treated in psychiatry settings.

PubMed

Costemale-Lacoste, Jean-François; Trabado, Séverine; Verstuyft, Céline; El Asmar, Khalil; Butlen-Ducuing, Florence; Colle, Romain; Ferreri, Florian; Polosan, Mircea; Haffen, Emmanuel; Balkau, Beverley; Falissard, Bruno; Feve, Bruno; Becquemont, Laurent; Corruble, Emmanuelle

2017-08-01

Hypertriglyceridemia (HTG) is a cardiovascular risk factor. In the general population, elevated fasting triglyceridemia (TG) is associated with insomnia. Since insomnia is a core symptom of Major Depressive Episodes (MDE), we studied the association of severe insomnia with HTG in major depression. We used the baseline data of the METADAP cohort, comprising 624 patients with a current MDE in a context of Major Depressive Disorder treated in psychiatry settings, without current alcohol use disorders. Patients were screened for severe insomnia, defined by a score of four or more on the three Hamilton Depression Rating Scale (HDRS) sleep items, and for HTG characterised by TG≥200mg/dL. Severe insomnia was observed in 335(54%) patients with a current MDE, of whom 234(70%) were women; 49(8%) patients had HTG, of whom 25(51%) were women. 69(11%) patients were treated with lipid-lowering drugs. Severe insomnia was associated with a higher frequency of HTG in the whole sample (9.9% vs 5.6%, p=0.046) and in the subgroup of women (9.0% vs 2.0%, p=0.002). Multivariate logistic regression analyses adjusted for age, education levels, BMI and total HDRS scores confirmed the association between severe insomnia and HTG in the whole sample (OR=2.02, 95%CI [1.00-4.08], p=0.05) as well as in the subgroup of women (OR=4.82, 95%CI [1.5-15.5], p=0.008). No association was shown in men. HTG should be systematically investigated in depressed patients with severe insomnia and particularly in women. Further studies are needed to explain the association we observed between severe insomnia and HTG. Copyright © 2017 Elsevier B.V. All rights reserved.

Different risk factors between reflux symptoms and mucosal injury in gastroesophageal reflux disease.

PubMed

Li, Chung-Hsien; Hsieh, Tsung-Cheng; Hsiao, Tsung-Hsien; Wang, Pin-Chao; Tseng, Tai-Chung; Lin, Hans Hsienhong; Wang, Chia-Chi

2015-06-01

Gastroesophageal reflux disease (GERD) is diagnosed based on typical symptoms in clinical practice. It can be divided into two groups using endoscopy: erosive and nonerosive reflux disease (NERD). This study aims to determine the risk factors of reflux symptoms and mucosal injury. This was a two-step case-control study derived from a cohort of 998 individuals having the data of reflux disease questionnaire (RDQ) and endoscopic findings. Those with minor reflux symptoms were excluded. The first step compared symptomatic GERD patients with healthy controls. The 2(nd) step compared patients with erosive esophagitis with healthy controls. In this study, the prevalence of symptomatic GERD and erosive esophagitis were 163 (16.3%) and 166 (16.6%), respectively. A total of 507 asymptomatic individuals without mucosal injury of the esophagus on endoscopy were selected as healthy controls. Compared with healthy controls, multivariate analyses showed that symptomatic GERD patients had a higher prevalence of hypertriglyceridemia [odds ratio (OR), 1.83; 95% confidence interval (CI) 1.13-2.96] and obesity (OR, 1.85; 95% CI 1.08-3.02). By contrast, male sex (OR, 2.24; 95% CI 1.42-3.52), positive Campylo-like organism (CLO) test (OR, 0.56; 95% CI 0.37-0.84), and hiatus hernia (OR, 14.36; 95% CI 3.05-67.6) were associated with erosive esophagitis. In conclusion, obesity and hypertriglyceridemia were associated with reflux symptoms. By contrast, male sex, negative infection of Helicobacter pylori, and hiatus hernia were associated with mucosal injury. Our results suggested that risk factors of reflux symptoms or mucosal injury might be different in GERD patients. The underlying mechanism awaits further studies to clarify. Copyright © 2015. Published by Elsevier Taiwan.

Steroid-induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi-ethnic lupus cohort.

PubMed

Shaharir, Syahrul Sazliyana; Gafor, Abdul Halim Abdul; Said, Mohd Shahrir Mohamed; Kong, Norella C T

2015-06-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid-induced diabetes mellitus (SDM) ranged between 1-53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE. A total of 100 SLE patients attending the Nephrology/SLE and Rheumatology Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) who received corticosteroid treatment were recruited. The diagnosis of diabetes mellitus was based on the 2010 American Diabetes Association's criteria. Prevalent cases of SDM were also included. Statistical analysis was performed to determine the factors associated with SDM. Thirteen of them (13%) developed SDM, with the median onset of diagnosis from commencement of glucocorticoid treatment being 8 years (range 0.5-21 years). Although only seven Indians were recruited into the study, three of them (42.9%) had SDM compared to Malays (9.3%) and Chinese (12.8%) (P ≤ 0.05). Univariate and multivariate analysis showed that higher numbers of system or organ involvement in SLE, abdominal obesity, hypertriglyceridemia and daily prednisolone of ≥ 1 mg/kg/day were the important associated factors of SDM (P ≤ 0.05). Meanwhile, hydroxychloroquine (HCQ) use was associated with reduced SDM prevalence (P < 0.05). The prevalence of SDM among SLE patients was 13% and Indians were more prone to develop SDM compared to other races. Higher numbers of system involvement, abdominal obesity, hypertriglyceridemia and the use of oral prednisolone of ≥ 1 mg/kg/day were associated with SDM, while HCQ use potentially protects against SDM. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Hypertriglyceridemia: Is there a role for prophylactic apheresis? A case report.

PubMed

Francisco, Ana Rita; Gonçalves, Inês; Veiga, Fátima; Pedro, Mónica Mendes; Pinto, Fausto J; Brito, Dulce

2016-01-01

Severe hypertriglyceridemia has been consistently associated with an increased risk of cardiovascular disease and other complications, namely acute pancreatitis. We report a case of a 64 year-old woman with hypertrophic cardiomyopathy and metabolic syndrome with triglyceride level of 3260 mg/dL. Plasma exchange was performed with simultaneous medical treatment to achieve a rapid and effective lowering of triglycerides in order to prevent clinical complications. After three plasmapheresis sessions a marked reduction in triglyceride and total cholesterol levels was observed. Several cases have shown the importance of plasmapheresis in the treatment of acute pancreatitis. We intend to demonstrate the applicability of this technique as primary prophylaxis in the presence of extremely high serum triglyceridemia levels. Resumo A hipertrigliceridemia grave tem sido associada de forma consistente ao aumento do risco cardiovascular e a outras complicações, nomeadamente, pancreatite aguda. Descrevemos um caso de uma mulher de 64 anos, com miocardiopatia hipertrófica e síndrome metabólica com valor sérico de triglicerídeos de 3260 mg/dL. Foi efectuada plasmaferese e optimizado o tratamento médico para alcançar uma redução rápida e efectiva dos níveis dos triglicerídeos, prevenindo complicações clínicas. Após três sessões de plasmaferese, verificou-se uma redução marcada dos triglicerídeos e do colesterol total. Existem alguns casos descritos na literatura demonstrado a importância da plasmaferese no tratamento da pancreatite aguda em contexto de hipertrigliceridemia grave. Os autores pretendem com este caso demonstrar a aplicabilidade desta técnica em contexto de prevenção primária em doentes com níveis de triglicerídeos extremamente aumentados.

A common variant association study in ethnic Saudi Arabs reveals novel susceptibility loci for hypertriglyceridemia.

PubMed

Ram, R; Wakil, S M; Muiya, N P; Andres, E; Mazhar, N; Hagos, S; Alshahid, M; Meyer, B F; Morahan, G; Dzimiri, N

2017-03-01

Hypertriglyceridemia (hTG) is a lipid disorder, resulting from an elevation in triglyceride levels, with a strong genetic component. It constitutes a significant risk factor for coronary artery disease (CAD), a leading cause of death worldwide. In this study, we performed a common variant association study for hTG in ethnic Saudi Arabs. We genotyped 5501 individuals in a two-phase experiment using Affymetrix Axiom ® Genome-Wide CEU 1 Array (Affymetrix, Santa Cruz, CA) that contains a total of 587,352 single nucleotide polymorphisms (SNPs). The lead variant was the rs1558861 [1.99 (1.73-2.30); p = 7.37 × 10 -22 ], residing on chromosome (chr) 11 at the apolipoprotein A-I/A-5 (APOA1/APOA5) locus. The rs780094 [1.34 (1.21-1.49); p = 8.57 × 10 -8 ] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 × 10 -6 ] on chr1 at the laminin subunit gamma-1 (LAMC1) locus showed suggestive association with disease. Furthermore, the rs17145738 [0.68 (0.60-0.77); p = 6.69 × 10 -9 ] on chr7 at the carbohydrate-responsive element-binding protein-encoding (MLXIPL) gene locus displayed significant protective characteristics, while another variant rs6982502 [0.76 (0.68-0.84); p = 5.31 × 10 -7 ] on chr8 showed similar but weaker properties. These findings were replicated in 317 cases vs 1415 controls from the same ethnic Arab population. Our study identified several variants across the human genome that are associated with hTG in ethnic Arabs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Laparoscopic Roux-en-Y gastric bypass vs. laparoscopic sleeve gastrectomy for morbid obesity: a systematic review and meta-analysis of lipid effects at one year postsurgery.

PubMed

Climent, Elisenda; Benaiges, David; Pedro-Botet, Juan; Goday, Albert; Solà, Ivan; Ramón, José M; Flores-LE Roux, Juana A; Checa, Miguel Á

2018-03-01

Results of the effects of Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) on triglyceride and high-density lipoprotein (HDL) cholesterol levels are controversial. Moreover, previous meta-analyses focused on global dyslipidemia remission, but did not include the separate remission rates of the different lipid fractions. Hence, the aim of the present meta-analysis was to compare the outcomes (concentration change and remission rates) of GB and SG on diverse lipid disorders one year postbariatric surgery (BS). An exhaustive electronic search carried out on MedLine, Embase and The Cochrane Central Register of Controlled Trials (Central) until July 2016 yielded 2621 records, of which 17, totaling 4699 obese patients with one-year follow-up after BS were included in the meta-analysis. GB was superior to SG in terms of total cholesterol (mean difference= 19.77 mg/dL, 95% CI: 11.84-27.69) and low-density lipoprotein (LDL) cholesterol (mean difference: 19.29 mg/dL, 95% CI: 11.93-26.64) decreases as well as in hypercholesterolemia remission (RR: 1.43, 95% CI: 1.27-1.61). No differences were found between GB and SG in terms of HDL cholesterol increase or triglyceride concentration change after surgery, as well as in hypertriglyceridemia and low HDL remission rates. The effect of GB on total and LDL cholesterol concentration decreases and remission was greater than that of SG, whereas no differences were observed with respect to HDL cholesterol and triglyceride concentration evolution. Conclusions cannot be drawn from hypertriglyceridemia and low HDL remission rates based on this meta-analysis.

Hipertriglyceridemia induced acute pancreatitis in pregnancy.

PubMed

Mañas García, María Dolores; Marchán Carranza, Enrique; Galiana Gómez Del Pulgar, Jesús; Fernández de Bobadilla Pascual, Belén

Hypertrigliceridemia is the third most common cause of acute pancreatitis. The risk of developing acute pancreatitis is 5% in healthy patients and 4% during pregnancy with triglyceride levels >1,000mg/dl. During pregnancy there are changes in the lipid profile that increase between two and four times triglyceride levels. Its increase in excessive form produces an oxidative environment with injury of the endothelium and appearance of complications such as preeclampsia or pancreatitis. We present the case of a pregnant woman with pancreatitis secondary to hypertriglyceridemia. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Berardinelli-Seip congenital lipodystrophy in two siblings

PubMed Central

Rao, T. S. Mohana; Chennamsetty, Kavya

2014-01-01

Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare autosomal recessive disorder characterized by various dermatological and systemic manifestations such as lipoatrophy, hypertriglyceridemia, hepatomegaly, acanthosis nigricans, and acromegaloid features. BSCL type 2 is more common and severe, with onset in the neonatal period or in early infancy. The locus for BSCL2 has been identified on chromosome 11q13. Early recognition and differentiation from other congenital generalized lipodystrophies help in the initiation of appropriate preventive and therapeutic measures such as lifestyle modification and pharmacotherapy that helps postpone the onset of metabolic syndrome. We report BSCL type 2 in two siblings with several cutaneous manifestations like acanthosis nigricans, hypertrichosis, prominent subcutaneous veins, and increased lanugo hair. PMID:25506557

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases

PubMed Central

Geldenhuys, Werner J.; Lin, Li; Darvesh, Altaf S.; Sadana, Prabodh

2017-01-01

Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL. PMID:27771332

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C.

PubMed

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-02-14

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 μg/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C

PubMed Central

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-01-01

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit. PMID:27713142

Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.

PubMed

Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

2017-01-01

Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10 -5 ) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients with hypertriglyceridemia-induced acute pancreatitis.

PubMed

Wang, Yuchen; Fuentes, Harry E; Attar, Bashar M; Jaiswal, Palash; Demetria, Melchor

Recent studies attribute promising prognostic values to various inflammatory biomarkers in acute pancreatitis, including the following: the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell distribution width (RDW). We aimed to determine the performance of these biomarkers for detecting disease severity in patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). We retrospectively reviewed 110 patients with HTG-AP and compared the NLR, PLR, and RDW in different severity groups. We performed receiver-operating characteristic (ROC) analysis to identify the optimal cut-off value for NLR to predict severe AP. NLR was significantly higher in patients with severe AP than mild and moderately severe AP (14.6 vs. 6.9, p < 0.001), and higher with organ failure upon presentation (9.1 vs. 7.1, p = 0.026). After dichotomization by the optimal cut-off value of 10 as determined by the ROC curve, the high-NLR group had a significantly longer length of stay (9.1 vs. 6.6 days, p = 0.001), duration of nil per os (4.9 vs. 3.7 days, p = 0.007), and higher rates of complications, including systemic inflammatory response syndrome (81.5% vs. 44.6%, p = 0.001) and persistent acute kidney injury (25.9% vs. 3.6%, p < 0.001). High NLR independently predicted severe acute pancreatitis in multivariate analysis (Odds ratio 6.71, p = 0.019). NLR represents an inexpensive, readily available test with a promising value to predict disease severity in HTG-AP. Among the three inflammatory biomarkers, NLR has the highest discriminatory capacity for severe HTG-AP, with an optimal cut-off value of 10. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Therapeutic actions of an insulin receptor activator and a novel peroxisome proliferator-activated receptor gamma agonist in the spontaneously hypertensive obese rat model of metabolic syndrome X.

PubMed

Velliquette, Rodney A; Friedman, Jacob E; Shao, J; Zhang, Bei B; Ernsberger, Paul

2005-07-01

Insulin resistance clusters with hyperlipidemia, impaired glucose tolerance, and hypertension as metabolic syndrome X. We tested a low molecular weight insulin receptor activator, demethylasterriquinone B-1 (DMAQ-B1), and a novel indole peroxisome proliferator-activated receptor gamma agonist, 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (PPEIA), in spontaneously hypertensive obese rats (SHROB), a genetic model of syndrome X. Agents were given orally for 19 days. SHROB showed fasting normoglycemia but impaired glucose tolerance after an oral load, as shown by increased glucose area under the curve (AUC) [20,700 mg x min/ml versus 8100 in lean spontaneously hypertensive rats (SHR)]. Insulin resistance was indicated by 20-fold excess fasting insulin and increased insulin AUC (6300 ng x min/ml versus 990 in SHR). DMAQ-B1 did not affect glucose tolerance (glucose AUC = 21,300) but reduced fasting insulin 2-fold and insulin AUC (insulin AUC = 4300). PPEIA normalized glucose tolerance (glucose AUC = 9100) and reduced insulin AUC (to 3180) without affecting fasting insulin. PPEIA also increased food intake, fat mass, and body weight gain (81 +/- 12 versus 45 +/- 8 g in untreated controls), whereas DMAQ-B1 had no effect on body weight but reduced subscapular fat mass. PPEIA but not DMAQ-B1 reduced blood pressure. In skeletal muscle, insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate protein 1-associated phosphatidylinositol 3-kinase activity were decreased by 40 to 55% in SHROB relative to lean SHR. PPEIA, but not DMAQ-B1, enhanced both insulin actions. SHROB also showed severe hypertriglyceridemia (355 +/- 42 mg/dl versus 65 +/- 3 in SHR) attenuated by both agents (DMAQ-B1, 228 +/- 18; PPEIA, 79 +/- 3). Both these novel antidiabetic agents attenuate insulin resistance and hypertriglyceridemia associated with metabolic syndrome but via distinct mechanisms.

[The epidemic status of metabolic syndrome among Chinese adolescents aged 10-17 years in 2010-2012].

PubMed

He, Y N; Zhao, W H; Zhao, L Y; Yu, D M; Zhang, J; Yu, W T; Yang, X G; Ding, G G

2017-06-06

Objective: To invesigate the epidemic status of the metabolic syndrome (MS) among mainland Chinese adolescents aged 10-17 in 2010-2012. Methods: Data were collected from Chinese Nutrition and Health Surveillance in 2010-2012. Multi-stage stratified proportion to the population cluster random sampling method was conducted to determine 16 872 adolescents in 150 counties from 31 provinces in mainland China. The epidemic status of metabolic syndrome was analyzed by China criterion (defined by Chinese Pediatric Society, Chinese Medical Association) and Cook criterion, respectively. The prevalence of MS and 95 %CI were calculated through weighted complex sampling processing by population data released by the National Bureau of Statistics in 2009. Results: Based on China criterion, the weighted prevalence of MS was 2.4% (95 % CI: 2.1%-2.6%) among Chinese adolescents aged 10-17. Prevalence in urban was higher than in rural (2.8%, 95 %CI: 2.4%-3.2% and 1.9%, 95 %CI: 1.6%-2.3%, respectively). Prevalence in boys and girls were 2.7% (95 % CI: 2.3%-3.0%), and 2.0% (95 % CI: 1.7%-2.4%), respectively. Based on Cook criterion, the weighted prevalence was 4.3% (95 % CI: 4.0%-4.7%) . The highest weighted prevalence of the components of the metabolic syndrome was low high-density lipoprotein cholesterol (26.8%, 95 % CI: 26.0%-27.5%), followed by high fasting glucose (11.5%, 95 % CI: 11.0%-12.0%), abdominal obesity (11.1%, 95 %CI: 10.6%-11.7%) , hypertriglyceridemia (8.8%, 95 %CI: 8.4%-9.3%) , and high blood pressure (6.4%, 95 % CI: 6.0%-6.8%). Conclusion: Among the five indicators of metabolic syndrome, the prevalence of central obesity and hypertriglyceridemia were relative high in Chinese adolescents aged 10-17 years, though the prevalence of metabolic syndrome was not high.

Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-Blind, randomized, placebo-controlled study

PubMed Central

2014-01-01

Background Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. Methods In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). Results A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. Conclusions In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. Trial registration Current Controlled Trials ClinicalTrials.gov ID NCT01928342. PMID:24382338

Clinical features and treatment of hypertriglyceridemia-induced acute pancreatitis during pregnancy: A retrospective study.

PubMed

Huang, Chunlan; Liu, Jie; Lu, Yingying; Fan, Junjie; Wang, Xingpeng; Liu, Jun; Zhang, Wei; Zeng, Yue

2016-12-01

To analyze the features and treatment of hypertriglyceridemia-induced acute pancreatitis (HTGP) during pregnancy. A retrospective study of 21 pregnant women diagnosed with acute pancreatitis (AP) was performed. Patients were divided into acute biliary pancreatitis (ABP), HTGP, and idiopathic groups according to etiology. 95% of the patients were in the third trimester of gestation. The percentage of patients with HTGP was higher than that of ABP (48% vs.14%). The percentage of severe acute pancreatitis (SAP) in the HTGP group was higher than that in the ABP group (40.0% vs.0%). The Ranson scores for moderately severe acute pancreatitis (MSAP) and SAP in the HTGP group were significantly different (2.50 ± 0.58 vs.3.60 ± 0.89, P < 0.05, respectively). The mean serum triglyceride (TG) levels in the MSAP and SAP HTGP groups were not significantly different (18.81 ± 11.13 vs. 30.53 ± 24.20 mmol/L, P > 0.05, respectively). In the HTGP group, there were five patients given plasma exchange therapy and five not. Plasmapheresis decreased the incidence of systemic inflammatory response syndrome (SIRS) from 100% to 28.6% and the TG level from 20.36 ± 7.41 mmol/L to 5.23 ± 3.62 mmol/L (P < 0.05). The length of hospitalization of the plasmapheresis group was shorter than that of the nonplasmapheresis group (17.3 ± 6.7 days vs. 37.0 ± 20.8 days). Plasma exchange may be safe and effectively administered for HTGP patients during pregnancy with SIRS or multiple organ dysfunction syndrome (MODS). J. Clin. Apheresis 31:571-578, 2016. © 2015 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Prevalence of hyperlipidemia and possible risk factors in rural Chinese adults: cohort study of health population in Yuhuan rural].

PubMed

Su, Meifang; Fu, Chaowei; Li, Songtao; Ying, Xuhua; He, Na; Jiang, Qingwu

2013-09-01

To examine the prevalence of hyperlipidemia and its related factors in adults in rural Yuhuan, China. A cross-sectional study was carried out as a baseline study of Rural Yuhuan Health Population Cohort in all communities in Yuhuan County, Zhejiang Province, China. A total of 118,571 subjects aged 35 years old or above participated in this study. The trained health/medical workers collected the general information, health conditions and so on by the face-to-face interview. Totally, 5 ml blood samples were taken. Hyperlipidemia was defined as blood triglyceride > or = 1.70 mmol/L and/or total cholesterols > or = 5.18 mmol/L. SPSS 16.0 was used for statistical analysis. Data of the fifth China population census 2000 was used as the standard population. Among 118,571 eligible subjects, the averages of blood triglyceride and total cholesterols were (1.71 +/- 14.42) mmol/L and (5.48 +/- 40.25 ) mmol/L, respectively, and there was a statistical difference in gender on blood triglyceride (t = 4.163, P < 0.001) but not on blood total cholesterols. The crude prevalences of hyperchol-esterolemia, hypertriglyceridemia, both hypercholesterolemia and hypertriglyceridemia, and hyperlipidemia were 38.4%, 24.2%, 13.2% and 49.3% and the age-standardized prevalence were 36.6%, 23.8%, 12.7% and 47.7% based on 2000 China national population, respectively. These prevalences were higher in male than in female significantly and varied statistically over different age groups from the lowest group of 35-39 years old to highest group of 55-59 years old or 60-64 years old. A non-conditional binary logistic model showed that age, male, farmer, education levels, smoking, alcohol consumption and body mass index were significantly related to hyperlipidemia. Hyperlipidemia, especial hypercholesterolemia, was common in adults aged 35 years old or above living in rural China.

Identifying an optimal cutpoint value for the diagnosis of hypertriglyceridemia in the nonfasting state

PubMed Central

White, Khendi T.; Moorthy, M.V.; Akinkuolie, Akintunde O.; Demler, Olga; Ridker, Paul M; Cook, Nancy R.; Mora, Samia

2015-01-01

Background Nonfasting triglycerides are similar to or superior to fasting triglycerides at predicting cardiovascular events. However, diagnostic cutpoints are based on fasting triglycerides. We examined the optimal cutpoint for increased nonfasting triglycerides. Methods Baseline nonfasting (<8 hours since last meal) samples were obtained from 6,391 participants in the Women’s Health Study, followed prospectively for up to 17 years. The optimal diagnostic threshold for nonfasting triglycerides, determined by logistic regression models using c-statistics and Youden index (sum of sensitivity and specificity minus one), was used to calculate hazard ratios for incident cardiovascular events. Performance was compared to thresholds recommended by the American Heart Association (AHA) and European guidelines. Results The optimal threshold was 175 mg/dL (1.98 mmol/L), corresponding to a c-statistic of 0.656 that was statistically better than the AHA cutpoint of 200 mg/dL (c-statistic of 0.628). For nonfasting triglycerides above and below 175 mg/dL, adjusting for age, hypertension, smoking, hormone use, and menopausal status, the hazard ratio for cardiovascular events was 1.88 (95% CI, 1.52–2.33, P<0.001), and for triglycerides measured at 0–4 and 4–8 hours since last meal, hazard ratios (95%CIs) were 2.05 (1.54– 2.74) and 1.68 (1.21–2.32), respectively. Performance of this optimal cutpoint was validated using ten-fold cross-validation and bootstrapping of multivariable models that included standard risk factors plus total and HDL cholesterol, diabetes, body-mass index, and C-reactive protein. Conclusions In this study of middle aged and older apparently healthy women, we identified a diagnostic threshold for nonfasting hypertriglyceridemia of 175 mg/dL (1.98 mmol/L), with the potential to more accurately identify cases than the currently recommended AHA cutpoint. PMID:26071491

Short Sleep Duration Increases Metabolic Impact in Healthy Adults: A Population-Based Cohort Study.

PubMed

Deng, Han-Bing; Tam, Tony; Zee, Benny Chung-Ying; Chung, Roger Yat-Nork; Su, Xuefen; Jin, Lei; Chan, Ta-Chien; Chang, Ly-Yun; Yeoh, Eng-Kiong; Lao, Xiang Qian

2017-10-01

The metabolic impact of inadequate sleep has not been determined in healthy individuals outside laboratories. This study aims to investigate the impact of sleep duration on five metabolic syndrome components in a healthy adult cohort. A total of 162121 adults aged 20-80 years (men 47.4%) of the MJ Health Database, who were not obese and free from major diseases, were recruited and followed up from 1996 to 2014. Sleep duration and insomnia symptoms were assessed by a self-administered questionnaire. Incident cases of five metabolic syndrome components were identified by follow-up medical examinations. Cox proportional hazard ratios (HRs) were calculated for three sleep duration categories "< 6 hours/day (short)," "6-8 hours/day (regular)," and "> 8 hours/day (long)" with adjustment for potential confounding factors. Analyses were stratified by insomnia symptoms to assess whether insomnia symptoms modified the association between sleep duration and metabolic syndrome. Compared to regular sleep duration, short sleep significantly (p < .001) increased the risk for central obesity by 12% (adjusted HR 1.12 [1.07-1.17]), for elevated fasting glucose by 6% (adjusted HR 1.06 [1.03-1.09]), for high blood pressure by 8% (adjusted HR 1.08 [1.04-1.13]), for low high-density lipoprotein-cholesterol by 7% (adjusted HR 1.07 [1.03-1.11]), for hypertriglyceridemia by 9% (adjusted HR 1.09 [1.05-1.13]), and for metabolic syndrome by 9% (adjusted HR 1.09 [1.05-1.13]). Long sleep decreased the risk of hypertriglyceridemia (adjusted HR 0.89 [0.84-0.94]) and metabolic syndrome (adjusted HR 0.93 [0.88-0.99]). Insomnia symptoms did not modify the effects of sleep duration. Sleep duration may be a significant determinant of metabolic health. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Rare genetic variants with large effect on triglycerides in subjects with a clinical diagnosis of familial vs nonfamilial hypertriglyceridemia.

PubMed

De Castro-Orós, Isabel; Civeira, Fernando; Pueyo, María Jesús; Mateo-Gallego, Rocío; Bolado-Carrancio, Alfonso; Lamíquiz-Moneo, Itziar; Álvarez-Sala, Luis; Fabiani, Fernando; Cofán, Montserrat; Cenarro, Ana; Rodríguez-Rey, José Carlos; Ros, Emilio; Pocoví, Miguel

2016-01-01

Most primary severe hypertriglyceridemias (HTGs) are diagnosed in adults, but their molecular foundations have not been completely elucidated. We aimed to identify rare dysfunctional mutations in genes encoding regulators of lipoprotein lipase (LPL) function in patients with familial and non-familial primary HTG. We sequenced promoters, exons, and exon-intron boundaries of LPL, APOA5, LMF1, and GPIHBP1 in 118 patients with severe primary HTG (triglycerides >500 mg/dL) and 53 normolipidemic controls. Variant functionality was analyzed using predictive software and functional assays for mutations in regulatory regions. We identified 29 rare variants, 10 of which had not been previously described: c.(-16A>G), c.(1018+2G>A), and p.(His80Arg) in LPL; p.(Arg143Alafs*57) in APOA5; p.(Val140Ile), p.(Leu235Ile), p.(Lys520*), and p.(Leu552Arg) in LMF1; and c.(-83G>A) and c.(-192A>G) in GPIHBP1. The c.(1018+2G>A) variant led to deletion of exon 6 in LPL cDNA, whereas the c.(-16A>G) analysis showed differences in the affinity for nuclear proteins. Overall, 20 (17.0%) of the patients carried at least one allele with a rare pathogenic variant in LPL, APOA5, LMF1, or GPIHBP1. The presence of a rare pathogenic variant was not associated with lipid values, family history of HTG, clinical diagnosis, or previous pancreatitis. Less than one in five subjects with triglycerides >500 mg/dL and no major secondary cause for HTG may carry a rare pathogenic mutation in LPL, APOA5, LMF1, or GPIHBP1. The presence of a rare pathogenic variant is not associated with a differential phenotype. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[CHRONIC FLUORIDE INTOXICATION AS A RISK FACTOR FOR THE DEVELOPMENT OF ATHEROSCLEROSIS].

PubMed

Korotenko, O Yu; Panev, N I; Zakharenkov, V V; Filimonov, S N; Semenova, E A; Panev, R N

2015-01-01

In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology. Hypertension and elevated levels of LDL cholesterol were established to increase the relative risk of developing atherosclerosis in metallurgists with chronic fluoride intoxication. At that there are no significant differences in the prevalence of common risk factors for atherosclerosis (smoking, diabetes, hypercholesterolemia, hypertriglyceridemia).

Global metabolomic profiling targeting childhood obesity in the Hispanic population.

PubMed

Butte, Nancy F; Liu, Yan; Zakeri, Issa F; Mohney, Robert P; Mehta, Nitesh; Voruganti, V Saroja; Göring, Harald; Cole, Shelley A; Comuzzie, Anthony G

2015-08-01

Metabolomics may unravel important biological pathways involved in the pathophysiology of childhood obesity. We aimed to 1) identify metabolites that differ significantly between nonobese and obese Hispanic children; 2) collapse metabolites into principal components (PCs) associated with obesity and metabolic risk, specifically hyperinsulinemia, hypertriglyceridemia, hyperleptinemia, and hyperuricemia; and 3) identify metabolites associated with energy expenditure and fat oxidation. This trial was a cross-sectional observational study of metabolomics by using gas chromatography-mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry analyses performed on fasting plasma samples from 353 nonobese and 450 obese Hispanic children. Branched-chained amino acids (BCAAs) (Leu, Ile, and Val) and their catabolites, propionylcarnitine and butyrylcarnitine, were significantly elevated in obese children. Strikingly lower lysolipids and dicarboxylated fatty acids were seen in obese children. Steroid derivatives were markedly higher in obese children as were markers of inflammation and oxidative stress. PC6 (BCAAs and aromatic AAs) and PC10 (asparagine, glycine, and serine) made the largest contributions to body mass index, and PC10 and PC12 (acylcarnitines) made the largest contributions to adiposity. Metabolic risk factors and total energy expenditure were associated with PC6, PC9 (AA and tricarboxylic acid cycle metabolites), and PC10. Fat oxidation was inversely related to PC8 (lysolipids) and positively related to PC16 (acylcarnitines). Global metabolomic profiling in nonobese and obese children replicates the increased BCAA and acylcarnitine catabolism and changes in nucleotides, lysolipids, and inflammation markers seen in obese adults; however, a strong signature of reduced fatty acid catabolism and increased steroid derivatives may be unique to obese children. Metabolic flexibility in fuel use observed in obese children may occur through the activation of alternative intermediary pathways. Insulin resistance, hyperleptinemia, hypertriglyceridemia, hyperuricemia, and oxidative stress and inflammation evident in obese children are associated with distinct metabolomic profiles. © 2015 American Society for Nutrition.

Double filtration plasmapheresis in the treatment of pancreatitis due to severe hypertriglyceridemia.

PubMed

Galán Carrillo, Isabel; Demelo-Rodriguez, Pablo; Rodríguez Ferrero, María Luisa; Anaya, Fernando

2015-01-01

Severe hypertriglyceridemia (HTG) leads to major complications such as acute pancreatitis. Lipoprotein apheresis has been proposed as a therapeutic tool for decreasing triglyceride levels, although experience is limited. To describe our experience with double filtration plasmapheresis (DFPP) in patients with severe HTG and pancreatitis in the plasmapheresis unit of a tertiary hospital in Spain. We recruited 4 patients with severe HTG (triglycerides [TGs] >1000 mg/dL) and acute pancreatitis. All the patients underwent DFPP as part of their treatment. Epidemiologic and laboratory data were collected before and after each plasmapheresis session. The average TG level before plasmapheresis was 3136 mg/dL (35.44 mmol/L; range, 1306-6693 mg/dL, 14.76-75.63 mmol/L), and the average Acute Physiology And Chronic Health Evaluation (APACHE) II level before the first session was 6 (range, 3-8). All patients made a full recovery, with a significant improvement in TG levels after plasmapheresis. The mean number of sessions was 2.1 (range, 1-3), and mean TG level after plasmapheresis was 428 mg/dL (4.84 mmol/L; range, 169-515 mg/dL; 1.91-5.82 mmol/L). After the first session, the mean decrease in TG levels was 69.16% (2169 mg/dL, range, 945-5925 mg/dL; 24.51 mmol/L, range, 10.78-66.95 mmol/L), and after the last session, TG levels fell by 89.09% (2794 mg/dL, range, 945-6198 mg/dL; 31.57 mmol/L, range, 10.68-70.04 mmol/L). None of the patients developed complications related to plasmapheresis. According to available evidence and our own experience, DFPP can be an effective and rapid treatment option in patients with severe HTG and complications. However, further research, including randomized controlled studies, is necessary. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Urbanization, mainly rurality, but not altitude is associated with dyslipidemia profiles.

PubMed

Lazo-Porras, Maria; Bernabe-Ortiz, Antonio; Quispe, Renato; Málaga, German; Smeeth, Liam; Gilman, Robert H; Checkley, William; Miranda, J Jaime

Geographical and environmental features such as urbanization and altitude may influence individual's lipid profiles because of the diversity of human-environment interactions including lifestyles. To characterize the association between altitude and urbanization and lipid profile among Peruvian adults aged ≥35 years. Cross-sectional analysis of the CRONICAS Cohort Study. The outcomes of interest were 6 dyslipidemia traits: hypertriglyceridemia, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol (HDL-c), nonisolated low HDL-c, isolated low HDL-c, and high non-HDL-c. The exposures of interest were urbanization level (highly urban, urban, semi-urban, and rural) and altitude (high altitude vs sea level). Prevalence ratios (PRs) and 95% confidence intervals (95% CIs) were calculated using Poisson regression models with robust variance adjusting for potential confounders. Data from 3037 individuals, 48.5% males, mean age of 55.6 (standard deviation ±12.7) years, were analyzed. The most common dyslipidemia pattern was high non-HDL-c with a prevalence of 88.0% (95% CI: 84.9%-90.7%) in the rural area and 96.0% (95% CI: 94.5%-97.1%) in the semi-urban area. Relative to the highly urban area, living in rural areas was associated with a lower prevalence of hypertriglyceridemia (PR = 0.75; 95% CI: 0.56-0.99) and high non-HDL-c (PR = 0.96; 95% CI: 0.93-0.99), whereas living in semi-urban areas was associated with higher prevalence high low-density lipoprotein cholesterol (PR = 1.37; 95% CI: 1.11-1.67). Compared with sea level areas, high-altitude areas had lower prevalence of high non-HDL-c (PR = 0.97; 95% CI: 0.95-0.99). Urbanization but not altitude was associated to several dyslipidemia traits, with the exception of high non-HDL-c in high altitude settings. Copyright © 2017 National Lipid Association. All rights reserved.

Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease.

PubMed

Bril, Fernando; Barb, Diana; Portillo-Sanchez, Paola; Biernacki, Diane; Lomonaco, Romina; Suman, Amitabh; Weber, Michelle H; Budd, Jeffrey T; Lupi, Maria E; Cusi, Kenneth

2017-04-01

The cut-off point of intrahepatic triglyceride (IHTG) content to define nonalcoholic fatty liver disease (NAFLD) by proton magnetic resonance spectroscopy ( 1 H-MRS) was established based on the 95th percentile in a group of healthy individuals (i.e., ≥5.56%). Whether this threshold correlates with metabolic and histological changes and whether a further accumulation of IHTG is associated with worsening of these parameters has not been properly assessed in a large cohort of patients. In this cross-sectional study, 352 subjects were carefully characterized with the following studies: liver 1 H-MRS; euglycemic insulin clamp with measurement of glucose turnover; oral glucose tolerance test; and a liver biopsy. Hepatic insulin sensitivity (suppression of endogenous glucose production by insulin) was affected early on after IHTG content was ∼1.5% and remained uniformly impaired (∼40%-45%), regardless of further IHTG accumulation. Skeletal muscle insulin sensitivity showed a gradual impairment at low degrees of IHTG accumulation, but remained unchanged after IHTG content reached the ∼6 ± 2% threshold. A similar pattern was observed for metabolic changes typically associated with NAFLD, such as hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). In contrast, adipose tissue insulin sensitivity (suppression of free fatty acids by insulin) showed a continuous worsening across the spectrum of IHTG accumulation in NAFLD (r = -0.38; P < 0.001). Histological severity of liver disease (inflammation, ballooning, and fibrosis) was not associated with the amount of IHTG content. IHTG accumulation is strongly associated with adipose tissue insulin resistance (IR), supporting the current theory of lipotoxicity as a driver of IHTG accumulation. Once IHTG accumulation reaches ∼6 ± 2%, skeletal muscle IR, hypertriglyceridemia, and low HDL-C become fully established. Histological activity appears to have an early threshold and is not significantly influenced by increasing amounts of IHTG accumulation. (Hepatology 2017;65:1132-1144). © 2016 by the American Association for the Study of Liver Diseases.

Triglyceride-based screening tests fail to recognize cardiometabolic disease in African immigrant and African-American men.

PubMed

Yu, Sophia S K; Ramsey, Natalie L M; Castillo, Darleen C; Ricks, Madia; Sumner, Anne E

2013-02-01

The prevalence of cardiometabolic disease in Africa now rivals that of Western nations. Therefore, screening programs that lead to effective prevention of cardiometabolic disease in Africans is imperative. Most screening tests for cardiometabolic disease use triglyceride (TG) levels as a criterion. However, the failure rate of TG-based screening tests in African Americans is high. In Africans, the efficacy of TG-based screening tests is unknown. Our goal was to determine the association between hypertriglyceridemia (TG ≥150 mg/dL) and cardiometabolic disease in African and African-American men. This was a cross-sectional study of 155 men (80 African immigrants, 75 African Americans) [age, 35±9 years, mean±standard deviation (SD), body mass index (BMI) 28.5±5.2 kg/m(2)] who self-identified as healthy. Lipid profiles were performed. Glucose tolerance and insulin resistance was determined by oral glucose tolerance tests (OGTT) and the insulin sensitivity index (S(I)), respectively. Cardiometabolic disease was defined by four possible subtypes--prediabetes, diabetes, insulin resistance, or metabolic triad [hyperinsulinemia, hyperapolipoprotein B, small low-density lipoprotein (LDL) particles]. TG levels were higher in men with cardiometabolic disease than without (88±43 versus 61±26 mg/dL, P<0.01). However, <10% of men with cardiometabolic disease had TG ≥150 mg/dL. Even within each cardiometabolic disease subtype, the prevalence of TG ≥150 mg/dL was <10%. Furthermore, TG levels in the 5% of men identified by OGTT as diabetic were ≤100 mg/dL (mean 71±24, range 45-100 mg/dL). Hypertriglyceridemia is a poor marker of cardiometabolic disease in men of African descent. Therefore TG-based screening tests fail to identify both African immigrants and African-American men with cardiometabolic disease. As a consequence, the opportunity for early intervention and prevention is lost.

Prevalence and Management of Dyslipidemia in Korea: Korea National Health and Nutrition Examination Survey during 1998 to 2010.

PubMed

Roh, Eun; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Kim, Nan Hee; Kim, Jae Hyeon; Kim, Chul Sik; Song, Kee-Ho; Won, Jong Chul; Kim, Dae Jung; Choi, Sung Hee; Lim, Soo; Cha, Bong-Yun

2013-12-01

Dyslipidemia is a major risk factor of cardiovascular disease. The aim of this study was to investigate the changing trends in the prevalence and management status of dyslipidemia among Korean adults. The prevalence of dyslipidemia and the rates of awareness, treatment, and control of dyslipidemia were investigated in adults aged ≥20 years from the Korea National Health and Nutrition Surveys (KNHANES) 1998 to 2010. The updated National Cholesterol Education Program criteria was used, which define dyslipidemia as having one or more of the following lipid abnormalities: hypercholesterolemia (total cholesterol ≥240 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), hypertriglyceridemia (≥150 mg/dL), hyper-low density lipoprotein (LDL) cholesterolemia (≥160 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), and hypo-high density lipoprotein (HDL)-cholesterolemia (<40 mg/dL in men and <50 mg/dL in women). The number of participants was 6,921, 4,894, 5,312, 2,733, 6,295, 6,900, and 5,738 in KNHANES 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Age-standardized prevalence rates of dyslipidemia were 54.0%, 65.8%, 66.5%, 60.6%, 58.7%, 58.9%, and 59.0% in 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Hypertriglyceridemia and hypo-HDL-cholesterolemia were the two most frequent lipid abnormalities. The overall prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased by 1.36- and 1.35-fold in 2010 compared with 2007, respectively. Awareness, treatment, and control rates of dyslipidemia improved over the period of surveys in both sexes. In 2010, about 30% of dyslipidemic patients who received lipid-lowering treatment reached target levels. Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.

Prevalence and features of fatty liver detected by physical examination in Guangzhou

PubMed Central

Liao, Xian-Hua; Cao, Xu; Liu, Jie; Xie, Xiao-Hua; Sun, Yan-Hong; Zhong, Bi-Hui

2013-01-01

AIM: To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics. METHODS: A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou, China from June 2010 to December 2010 were retrospectively enrolled in the study. Results of biochemical tests, abdominal ultrasound, electrocardiography, and chest X-ray were collected. The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria: (1) liver and kidney echo discrepancy and presence of an increased liver echogenicity (bright); (2) unclear intrahepatic duct structure; and (3) liver far field echo decay. RESULTS: The study population consisted of 2201 males and 1232 females, with a mean age of 37.4 ± 12.8 years. When all 3433 patients were considered, the overall prevalence of hyperlipidemia was 38.1%, of fatty liver was 26.0%, of increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels was 11.9%, of gallstone was 11.4%, of hyperglycemia was 7.3%, of hypertension was 7.1%, and of hyperuricemia was 6.2%. Of the 2605 patients who completed the abdominal ultrasonography exam, 677 (26.0%) were diagnosed with fatty liver and the prevalence was higher in males (32.5% vs females: 15.3%, P < 0.001). The overall prevalence of fatty liver increased with age, with the peak prevalence (39.5%) found in the 60 to 70-year-old age group. Among patients between the ages of 18 to 50-year-old, the prevalence of fatty liver was significantly higher in males (20.2% vs females: 8.7%, P < 0.001); the difference in prevalence between the two sexes in patients > 50-year-old did not reach statistical significance. Only 430 of the patients diagnosed with fatty liver had complete information; among those, increased ALT and/or AST levels were detected in only 30%, with all disturbances being mild or moderate. In these 430 patients, the overall prevalence of hypertriglyceridemia was 31.4%, of mixed type hyperlipidemia was 20.9%, of hypercholesterolemia was 12.3%, of hyperglycemia was 17.6%, of hypertension was 16.0%, of hyperuricemia was 15.3%, and of gallstone was 14.4%. Again, the prevalences of hypertriglyceridemia and hyperuricemia were higher in males (hypertriglyceridemia, 36.0% vs females: 12.0%, P < 0.05; hyperuricemia, 17.3% vs females: 7.2%, P < 0.05); in contrast, however, the prevalences of mixed type hyperlipidemia and hypercholesterolemia was higher in females (mixed type hyperlipidemia, 18.7% vs females: 30.1%, P < 0.05, hypercholesterolemia, 9.5% vs females: 24.1%, P < 0.05). Finally, comparison of the fatty liver group to the non-fatty liver group showed that prevalences of hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia were higher in the former (all P < 0.01). CONCLUSION: A high prevalence of fatty liver is detected upon physical examination in Guangzhou, and the primary associated clinical findings are hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia. PMID:23983438

Prevalence and features of fatty liver detected by physical examination in Guangzhou.

PubMed

Liao, Xian-Hua; Cao, Xu; Liu, Jie; Xie, Xiao-Hua; Sun, Yan-Hong; Zhong, Bi-Hui

2013-08-28

To investigate the prevalence of fatty liver discovered upon physical examination of Chinese patients and determine the associated clinical characteristics. A total of 3433 consecutive patients who received physical examinations at the Huangpu Division of the First Affiliated Hospital at Sun Yat-sen University in Guangzhou, China from June 2010 to December 2010 were retrospectively enrolled in the study. Results of biochemical tests, abdominal ultrasound, electrocardiography, and chest X-ray were collected. The diagnosis of fatty liver was made if a patient met any two of the three following ultrasonic criteria: (1) liver and kidney echo discrepancy and presence of an increased liver echogenicity (bright); (2) unclear intrahepatic duct structure; and (3) liver far field echo decay. The study population consisted of 2201 males and 1232 females, with a mean age of 37.4 ± 12.8 years. When all 3433 patients were considered, the overall prevalence of hyperlipidemia was 38.1%, of fatty liver was 26.0%, of increased alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels was 11.9%, of gallstone was 11.4%, of hyperglycemia was 7.3%, of hypertension was 7.1%, and of hyperuricemia was 6.2%. Of the 2605 patients who completed the abdominal ultrasonography exam, 677 (26.0%) were diagnosed with fatty liver and the prevalence was higher in males (32.5% vs females: 15.3%, P < 0.001). The overall prevalence of fatty liver increased with age, with the peak prevalence (39.5%) found in the 60 to 70-year-old age group. Among patients between the ages of 18 to 50-year-old, the prevalence of fatty liver was significantly higher in males (20.2% vs females: 8.7%, P < 0.001); the difference in prevalence between the two sexes in patients > 50-year-old did not reach statistical significance. Only 430 of the patients diagnosed with fatty liver had complete information; among those, increased ALT and/or AST levels were detected in only 30%, with all disturbances being mild or moderate. In these 430 patients, the overall prevalence of hypertriglyceridemia was 31.4%, of mixed type hyperlipidemia was 20.9%, of hypercholesterolemia was 12.3%, of hyperglycemia was 17.6%, of hypertension was 16.0%, of hyperuricemia was 15.3%, and of gallstone was 14.4%. Again, the prevalences of hypertriglyceridemia and hyperuricemia were higher in males (hypertriglyceridemia, 36.0% vs females: 12.0%, P < 0.05; hyperuricemia, 17.3% vs females: 7.2%, P < 0.05); in contrast, however, the prevalences of mixed type hyperlipidemia and hypercholesterolemia was higher in females (mixed type hyperlipidemia, 18.7% vs females: 30.1%, P < 0.05, hypercholesterolemia, 9.5% vs females: 24.1%, P < 0.05). Finally, comparison of the fatty liver group to the non-fatty liver group showed that prevalences of hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia were higher in the former (all P < 0.01). A high prevalence of fatty liver is detected upon physical examination in Guangzhou, and the primary associated clinical findings are hyperlipidemia, hyperglycemia, hypertension, and hyperuricemia.

Spontaneous diabetes mellitus in captive Mandrillus sphinx monkeys: a case report.

PubMed

Pirarat, N; Kesdangsakolwut, S; Chotiapisitkul, S; Assarasakorn, S

2008-06-01

Case history The two obese mandrills (Mandrillus sphinx) showed clinical signs of depression, anorexia, hyperglycemia, hypertriglyceridemia, glucosuria, proteinuria and ketonuria. Septic bed sore wounds were noted on both fore and hind limbs. Results Histopathological study revealed severe islet amyloidosis in both mandrills. Immunohistochemical study using polyclonal anti-cat amylin antibody confirmed derivation of the islet amyloid from islet amyloid polypeptide (IAPP). Cardiomyopathy and myocardial fibrosis were also evident. Conclusions The present study documents diabetes mellitus in two obese mandrills. Diabetes in these animals had features very similar type 2 diabetes mellitus of humans, including the development of severe, IAPP-derived islet amyloidosis. The mandrill may, therefore, serve as an animal model of human type 2 diabetes mellitus.

Clinical and laboratory parameters in adult diabetics with and without calcific shoulder periarthritis.

PubMed

Mavrikakis, M E; Sfikakis, P P; Kontoyannis, S A; Antoniades, L G; Kontoyannis, D A; Moulopoulou, D S

1991-10-01

The clinical and laboratory parameters of calcific shoulder periarthritis (CSP) were examined in 900 patients with type II diabetes mellitus as well as in 350 age- and sex-matched control subjects. A threefold increased prevalence of CSP in diabetics compared with the control group was associated with the presence of longstanding and poorly controlled diabetes, hypercholesterolemia, and hypertriglyceridemia suggesting pronounced diabetic angiopathy, as well as with minor trauma and hypomagnesemia. Aging and serum calcium concentrations were not related to the presence of CSP. Thirty-two percent of diabetics with CSP were symptomatic; 15% of them presented with severe pain and restriction of shoulder movement. These findings confirm a close pathogenetic interrelation between CSP and diabetes mellitus.

The sweet path to metabolic demise: fructose and lipid synthesis

PubMed Central

Herman, Mark A.; Samuel, Varman T.

2016-01-01

Epidemiological studies link fructose consumption with metabolic disease, an association attributable in part to fructose mediated lipogenesis. The mechanisms governing fructose-induced lipogenesis and disease remain debated. Acutely, fructose increases de novo lipogenesis through the efficient and uninhibited action of Ketohexokinase and Aldolase B, which yields substrates for fatty-acid synthesis. Chronic fructose consumption further enhances the capacity for hepatic fructose metabolism via activation of several key transcription factors (i.e. SREBP1c and ChREBP), which augment expression of lipogenic enzymes, increasing lipogenesis, further compounding hypertriglyceridemia, and hepatic steatosis. Hepatic insulin resistance develops from diacylglycerol-PKCε mediated impairment of insulin signaling and possibly additional mechanisms. Initiatives that decrease fructose consumption and therapies that block fructose mediated lipogenesis are needed to avert future metabolic pandemics. PMID:27387598

[Dyslipidemias : Diagnostics and management].

PubMed

Sinning, D; Landmesser, U

2017-09-01

For disorders of lipid metabolism the risk-adapted adjustment of low-density lipoprotein (LDL) cholesterol remains the primary treatment target, as a causal role in minimizing the progression of ACVD has been shown. Because of their efficacy in reducing cardiovascular morbidity and mortality, statins are recommended as first-line pharmacological treatment in dyslipidemias. Additionally, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have been shown to significantly reduce cardiovascular events in high-risk patients. Life style changes can improve the plasma lipid profile, particularly in the setting of hypertriglyceridemia. Evaluation of high-density lipoprotein (HDL) cholesterol and lipoprotein(a) provides further information when assessing the individual cardiovascular risk, but direct evidence that pharmacologically targeting HDL cholesterol or Lp(a) results in a reduction of cardiovascular events has not yet been shown.

DEAE-Dextran in the treatment of primary hypercholesterolemia and/or hypercholesterolemia combined with hypertriglyceridemia. A multicentric randomized study on the efficacy of DEAE-Dextran compared with Cholestyramine.

PubMed

Fedele, F

2003-01-01

This study was carried out to verify the therapeutic homogeneity between DEAE-Dextran and Cholestyramine. Blood levels of total cholesterol, HDL, LDL and triglycerides were evaluated in 202 patients affected by dyslipidemia and treated with DEAD-D at 2.5 g/day or with Cholestyramine at 12 g/day for 30 days. At the end of treatment both drugs caused significant reduction of total cholesterol, LDL and triglycerides blood levels; DEAD-D was generally more effective than Cholestyramine, in particular on triglycerides values (30.6% and 13.7% of reduction respectively), and produced also a significant increase in HDL cholesterol, differently from Cholestyramine that was ineffective on this parameter.

Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia.

PubMed

Benes, Lane B; Bassi, Nikhil S; Davidson, Michael H

2016-01-01

The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin.

ERICA: prevalence of dyslipidemia in Brazilian adolescents

PubMed Central

Faria, José Rocha; Bento, Vivian Freitas Rezende; Baena, Cristina Pellegrino; Olandoski, Marcia; Gonçalves, Luis Gonzaga de Oliveira; Abreu, Gabriela de Azevedo; Kuschnir, Maria Cristina Caetano; Bloch, Katia Vergetti

2016-01-01

ABSTRACT OBJECTIVE To determine the distribution of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in Brazilian adolescents, as well as the prevalence of altered levels of such parameters. METHODS Data from the Study of Cardiovascular Risks in Adolescents (ERICA) were used. This is a country-wide, school-based cross-sectional study that evaluated 12 to 17-year old adolescents living in cities with over 100,000 inhabitants. The average and distribution of plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were evaluated. Dyslipidemia was determined by levels of total cholesterol ≥ 170 mg/dl, LDL cholesterol ≥ 130 mg/dl, HDL cholesterol < 45 mg/dL, or triglycerides ≥ 130 mg/dl. The data were analyzed by gender, age, and regions in Brazil. RESULTS We evaluated 38,069 adolescents – 59.9% of females, and 54.2% between 15 and 17 years. The average values found were: total cholesterol = 148.1 mg/dl (95%CI 147.1-149.1), HDL cholesterol = 47.3 mg/dl (95%CI 46.7-47.9), LDL cholesterol = 85.3 mg/dl (95%CI 84.5-86.1), and triglycerides = 77.8 mg/dl (95%CI 76.5-79.2). The female adolescents had higher average levels of total cholesterol, LDL cholesterol, and HDL cholesterol, without differences in the levels of triglycerides. We did not observe any significant differences between the average values among 12 to 14 and 15- to 17-year old adolescents. The most prevalent lipid alterations were low HDL cholesterol (46.8% [95%CI 44.8-48.9]), hypercholesterolemia (20.1% [95%CI 19.0-21.3]), and hypertriglyceridemia (7.8% [95%CI 7.1-8.6]). High LDL cholesterol was found in 3.5% (95%CI 3.2-4.0) of the adolescents. Prevalence of low HDL cholesterol was higher in Brazil’s North and Northeast regions. CONCLUSIONS A significant proportion of Brazilian adolescents has alterations in their plasma lipids. The high prevalence of low HDL cholesterol and hypertriglyceridemia, especially in Brazil’s North and Northeast regions, must be analyzed in future studies, to support the creation of strategies for efficient interventions. PMID:26910544

Adherence to Mediterranean Diet and Non-Alcoholic Fatty Liver Disease: Effect on Insulin Resistance.

PubMed

Baratta, Francesco; Pastori, Daniele; Polimeni, Licia; Bucci, Tommaso; Ceci, Fabrizio; Calabrese, Cinzia; Ernesti, Ilaria; Pannitteri, Gaetano; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

2017-12-01

The prevalence of cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), is increasing in western countries, because of changes in lifestyle and dietary habits. Mediterranean Diet (Med-Diet) is effective for cardiovascular prevention, but its relationship with NAFLD has been scarcely investigated. We included 584 consecutive outpatients presenting with one or more cardiovascular risk factor such as type 2 diabetes mellitus (T2DM), arterial hypertension, overweight/obesity, and dyslipidemia. Liver steatosis was assessed using ultrasonography. Med-Diet adherence was investigated by a validated semiquantitative nine-item dietary questionnaire; patients were divided into low, intermediate, and high adherence. Insulin resistance was defined by the 75th percentile of homeostasis model of insulin resistance (HOMA-IR; ≥3.8). The mean age was 56.2±12.4 years and 38.2% were women. Liver steatosis was present in 82.7%, and its prevalence decreased from low to high adherence group (96.5% vs. 71.4%, P<0.001). In a multiple logistic regression analysis, hypertriglyceridemia (odds ratio (OR): 2.913; P=0.002), log (ALT) (OR: 6.186; P<0.001), Med-Diet adherence (intermediate vs. low OR: 0.115; P=0.041, high vs. low OR: 0.093; P=0.030), T2DM (OR: 3.940; P=0.003), and high waist circumference (OR: 3.012; P<0.001) were associated with NAFLD. Among single foods, low meat intake (OR: 0.178; P<0.001) was inversely significantly associated with NAFLD. In 334 non-diabetic NAFLD patients, age (OR: 1.035, P=0.025), high waist circumference (OR: 7.855, P<0.001), hypertriglyceridemia (OR: 2.152, P=0.011), and Log (ALT) (OR: 2.549, P=0.002) were directly associated with HOMA-IR, whereas Med-Diet score was inversely associated (OR: 0.801, P=0.018). We found an inverse relationship between Med-Diet and NAFLD prevalence. Among NAFLD patients, good adherence to Med-Diet was associated with lower insulin resistance. Our findings suggest that Med-Diet may be a beneficial nutritional approach in NAFLD patients.

Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι.

PubMed

Sajan, Mini P; Nimal, Sonali; Mastorides, Stephen; Acevedo-Duncan, Mildred; Kahn, C Ronald; Fields, Alan P; Braun, Ursula; Leitges, Michael; Farese, Robert V

2012-04-01

Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly reversed or markedly improved most if not all metabolic abnormalities. Here, we examined effects of 2 newly developed small-molecule PKC-ι/λ inhibitors. We used the mouse model of heterozygous muscle-specific knockout of PKC-λ, in which partial deficiency of muscle PKC-λ impairs glucose transport in muscle and thereby causes glucose intolerance and hyperinsulinemia, which, via hepatic aPKC activation, leads to abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. One inhibitor, 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)], binds to the substrate-binding site of PKC-λ/ι, but not other PKCs. The other inhibitor, aurothiomalate, binds to cysteine residues in the PB1-binding domains of aPKC-λ/ι/ζ and inhibits scaffolding. Treatment with either inhibitor for 7 days inhibited aPKC, but not Akt, in liver and concomitantly improved insulin signaling to Akt and aPKC in muscle and adipocytes. Moreover, both inhibitors diminished excessive expression of hepatic, aPKC-dependent lipogenic, proinflammatory, and gluconeogenic factors; and this was accompanied by reversal or marked improvements in hyperglycemia, hyperinsulinemia, abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. Our findings highlight the pathogenetic importance of insulin signaling to hepatic PKC-ι in obesity, the metabolic syndrome, and type 2 diabetes mellitus and suggest that 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)] and aurothiomalate or similar agents that selectively inhibit hepatic aPKC may be useful treatments. Published by Elsevier Inc.

Prevalence of dyslipidemia and metabolic syndrome risk factor in overweight and obese children.

PubMed

Casavalle, Patricia L; Lifshitz, Fima; Romano, Laura S; Pandolfo, Marcela; Caamaño, Anabella; Boyer, Patricia M; Rodríguez, Patricia N; Friedman, Silvia M

2014-12-01

To study the prevalence of dyslipidemia and metabolic syndrome risk factors in overweight/ obese children and adolescents. The study included 139 healthy white Argentinean children/adolescents (aged 8-14 years) who were overweight (n = 30) or obese (n = 109), based on BMI z score according to WHO, 2007. Children were referred to the Nutrition Clinic, San Martin University Hospital, Buenos Aires, Argentina for evaluation and treatment. Dyslipidemia was considered when one or more serum lipids (mg/dL) were out of range: total cholesterol ≥ 200, high-density lipoprotein (HDL-C) ≤ 40, triglycerides (TG) > 110, low-density lipoprotein (LDL-C) > 130 or non-HDL-C > 145 and fasting blood glucose (FBG) > 110. Additional metabolic syndrome risk factors included: increased waist circumference (WC, ≥ 90th percentile) and high blood pressure (> 90th percentile). A history of low birth weight (< 2.5 kg) and a family history of: dyslipidemia (FHDL), premature acute myocardial infarction (FHPAMI) and/or type 2 diabetes mellitus (FHT2DM) were also assessed. The prevalence of dyslipidemia among overweight and obese children was 50.4% and its pattern was: hypertriglyceridemia 31.9%, low HDL-C 29.7%, high non-HDL-C 15.8%, hypercholesterolemia 11.9%, and elevated LDL-C 10.7%. The dyslipidemia was more often detected among those with increased WC (55.4%), FHDL (51.1%), and FHT2DM (48%); prevalence was lower in those with FHPAMI (18.7%) and low birth weight (4.3%). Most children presented a variety of metabolic syndrome risk factors; only 25.8% did not have any such alterations identified. BMI z score showed a positive association with TG and negative with HDL-C. Overweight and obesity increased the odds ratios of metabolic syndrome risk factors, hypertriglyceridemia and low HDL-C. Overweight/obese children were prone to have dyslipidemia and metabolic syndrome. Excess body weight is an important harbinger of health that requires the assessment of multiple parameters to discern further health concerns that may be amenable to specific treatment.

Metabolic implications of menstrual cycle length in non-hyperandrogenic women with polycystic ovarian morphology.

PubMed

Alebić, Miro Šimun; Stojanović, Nataša; Baldani, Dinka Pavičić; Duvnjak, Lea Smirčić

2016-12-01

This cross-sectional study aimed to investigate the association between menstrual cycle lenght and metabolic parameters in non-hyperandrogenic women with polycystic ovarian morphology, n = 250. Metabolic profiles of all participants were evaluated using anthropometric parameters (body mass index, waist circumference), parameters of dyslipidemia (total cholesterol, HDL-cholesterol, triglycerides) and markers of insulin resistance (fasting insulin, homeostasis model assessment for insulin resistance index). The associations between menstrual cycle lenght and cardiometabolic risk factors such as insulin resistance, dyslipidemia, and obesity were investigated. In non-hyperandrogenic women with polycystic ovarian morphology, menstrual cycle lenght was associated with hypertriglyceridemia and insulin resistance independently of body mass index. Moreover, menstrual cycle lenght added value to body mass index in predicting hypertriglyceridemia. The optimal menstrual cycle lenght cut-off value for identifying of non-hyperandrogenic women with polycystic ovarian morphology at metabolic risk was found to be 45 days. Metabolic profile of non-hyperandrogenic women with polycystic ovarian morphology (n = 75) with menstrual cycle lenght >45 days was similar to that of hyperandrogenic women with polycystic ovarian morphology (n = 138) while metabolic profile of non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght ≤45 days (n = 112) was similar to that of controls (n = 167). Non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght >45 days had higher prevalence of cardiometabolic risk factors compared to those with menstrual cycle lenght ≤45 days. Non-hyperandrogenic women with polycystic ovarian morphology are not metabolically homogeneous. Menstrual cycle lenght is an easy-to-obtain clinical parameter positively associated with the probability of unfavorable metabolic status in non-hyperandrogenic women with polycystic ovarian morphology. Menstrual cycle lenght cut-off value of 45 days was found to have the best capacity in discriminating non-hyperandrogenic women with polycystic ovarian morphology with and without metabolic derangement(s) corroborating in favor of the cardiometabolic risk factors screening and management in non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght >45 days through strategies for prevention of cardiovascular disease.

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S.

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days.more » Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights: >Fructose administration as a liquid solution to Sprague-Dawley male rats induced hypertriglyceridemia, hyperleptinemia, hepatic steatosis and necroinflammation. >Atorvastatin administration: >Abolished histological sings of necroinflammation and reduced plasma and liver triglyceride concentrations. >Reduced the expression of phospho-I{kappa}B >Reduced the expression of fructokinase, a key enzyme controlling fructose metabolism« less

Dyslipidemia, Diet and Physical Exercise in Children on Treatment With Antiretroviral Medication in El Salvador: A Cross-sectional Study.

PubMed

Sonego, Michela; Sagrado, Maria José; Escobar, Gustavo; Lazzerini, Marzia; Rivas, Estefanie; Martín-Cañavate, Rocio; Pérez de López, Elsy; Ayala, Sandra; Castaneda, Luis; Aparicio, Pilar; Custodio, Estefanía

2016-10-01

Dyslipidemias are common in HIV-infected children, especially if treated with protease inhibitors, but there are few data on how to treat dyslipidemias in this population. We estimated the dyslipidemia prevalence and its association with treatment, diet and physical exercise in children on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). Information was gathered regarding socio-demographic characteristics, treatment, diet and physical activity of 173 children aged 5-18 years and receiving antiretroviral therapy. Triglycerides, total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), viral load and CD4 T-lymphocytes were measured. Abnormal concentrations were defined as triglycerides ≥130 mg/dL in 10- to 18-year olds and ≥100 mg/dL in <10-year olds; total cholesterol ≥200 mg/dL; LDL-C ≥130 mg/dL and HDL-C ≤35 mg/dL. We adjusted 4 different multivariate models to assess the independent association of each type of dyslipidemia with protease inhibitors, diet and physical exercise. Of the 173 children, 83 (48%) had hypertriglyceridemia and 25 (14.5%) hypercholesterolemia. High LDL-C concentrations were observed in 17 children (9.8%) and low HDL-C in 38 (22%). Treatment with protease inhibitors was significantly associated with hypertriglyceridemia [prevalence ratio (PR) 2.8; 95% confidence interval (CI): 2.0-3.8] and hypercholesterolemia (PR 9.0; 95% CI: 3.6-22.2). Higher adherence to a "high fat/sugar diet" was associated with hypercholesterolemia (PR 1.6; 95% CI: 1.1-2.3) and high LDL-C (PR 1.7; 95% CI: 1.0-2.9). Compared with those exercising <3 times/week, children exercising ≥7 times were less likely to have low HDL-C (PR = 0.4; 95% CI: 0.2-0.7). These results suggest that a healthy diet and exercise habits can contribute to controlling some aspects of the lipid profile in this population.

n-3 PUFA esterified to glycerol or as ethyl esters reduce non-fasting plasma triacylglycerol in subjects with hypertriglyceridemia: a randomized trial.

PubMed

Hedengran, Anne; Szecsi, Pal B; Dyerberg, Jørn; Harris, William S; Stender, Steen

2015-02-01

To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28% in the AG-PUFA group and 22% in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2% in the AG-PUFA group and 58.5% in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.

Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

PubMed

Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Effects of dietary oat, barley, and guar gums on serum and liver lipid concentrations in diet-induced hypertriglyceridemic rats.

PubMed

Oda, T; Aoe, S; Imanishi, S; Kanazawa, Y; Sanada, H; Ayano, Y

1994-04-01

Effects of dietary oat, barley, and guar gums on serum and liver triglyceride or cholesterol concentrations were examined in diet-induced hypertriglyceridemic rats. Male Sprague-Dawley rats were fed a hypertriglyceridemic diet that contained 20% coconut oil, 17.5% fructose, 17.5% sucrose, and 5% cellulose at 4 weeks of age for 14 days. In the gum-supplemented diets, 2% cellulose was replaced by oat gum, barley gum, or guar gum. Hypertriglyceridemia was observed in the control group, whereas serum cholesterol concentration was not increased. All of the gums lowered serum and liver cholesterol concentrations except barley gum which had no significant effect on liver cholesterol. Both oat and barley gums suppressed the elevation of serum and liver triglyceride concentrations but guar gum had no effect.

Synthesis, characterization, and preclinical evaluation of new thiazolidin-4-ones substituted with p-chlorophenoxy acetic acid and clofibric acid against insulin resistance and metabolic disorder.

PubMed

Gowdra, Vasantharaju S; Mudgal, Jayesh; Bansal, Punit; Nayak, Pawan G; Manohara Reddy, Seethappa A; Shenoy, Gautham G; Valiathan, Manna; Chamallamudi, Mallikarjuna R; Nampurath, Gopalan K

2014-01-01

We synthesized twenty thiazolidin-4-one derivatives, which were then characterized by standard chromatographic and spectroscopic methods. From the in vitro glucose uptake assay, two compounds behaved as insulin sensitizers, where they enhanced glucose uptake in isolated rat diaphragm. In high-carbohydrate diet-induced insulin resistant mice, these two thiazolidin-4-ones attenuated hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and glucose intolerance. They raised the plasma leptin but did not reverse the diabetes-induced hypoadiponectinemia. Additionally, compound 3a reduced adiposity. The test compounds were also able to reverse the disturbed liver antioxidant milieu. To conclude, these two novel thiazolidin-4-ones modulated multiple mechanisms involved in metabolic disorders, reversing insulin resistance and thus preventing the development of type-2 diabetes.

Metabolic Syndrome, Androgens, and Hypertension

PubMed Central

Moulana, Mohadetheh; Lima, Roberta; Reckelhoff, Jane F.

2013-01-01

Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and metabolic syndrome is associated with increases in androgen levels. In men reductions in androgen levels is associated with inflammation. Androgen supplements reduce inflammation in men. In women, increases in androgens are associated with increases in inflammatory cytokines, and reducing androgens reduces inflammation. In this review the possibility that androgens may have different effects on metabolic syndrome and its sequelae in males and females will be discussed. PMID:21274756

[The impaired glucose tolerance in the pathogenesis of dyslipidemia].

PubMed

Ikoue, I; Takahashi, K; Katayama, S

1996-10-01

It is well known that hyperlipidemia is often present in patient with impaired glucose tolerance, obesity and/or hypertension. All of these are risk factors for coronary artery disease (CAD). The coexistence of these risk factors markedly increase the likelihood of CAD. Recently, it has been reported that the impaired glucose tolerance and insulin resistence are associated with the increased proinsulin, which is linked to the risk of CAD. We review that the impaired glucose tolerance is an important factor causing dyslipidemia. The characteristic of dyslipidemia associated with the impaired glucose tolerance include hypertriglyceridemia, high level of VLDL and low level of HDL cholesterol. They also associate with accumulation of remnant lipoproteins and appearance of small dense LDL. In addition, we pointed out that the increased number of risk factors is associated with elevated insulin and proinsulin level.

[Dietary intake and macrovascular disease in a Japanese-Brazilian population: a cross-sectional study].

PubMed

Salvo, Vera Lúcia Morais Antonio de; Cardoso, Marly Augusto; Barros Junior, Newton de; Ferreira, Sandra R G; Gimeno, Suely Godoy Agostinho

2009-10-01

To describe the food intake of Japanese-Brazilians with and without macrovascular disease (MVD). MVD was defined, for 1,165 Japanese-Brazilians, by scores attributed to the health historical, electrocardiogram and ankle-brachial index values. The usual dietary intake was determined using a food frequency questionnaire. The MVD prevalence was of 3.2%, being similar among genders. Statistically higher frequencies of individuals with MVD were observed among those of first generation, with age > 60 years, tobacco user, with hypertension, hypertriglyceridemia and diabetes. Subjects with MVD were older, with smaller hip circumference, and higher systolic blood pressure levels, triglycerides and glycemia concentration; they informed higher consumption of iron source food and smaller of grains fibers. Statistically significant difference was found to saturated fat (crude analysis: second tercile versus first tercile). Programs of nutritional education should be stimulated in this group with high prevalence of non-communicable chronic diseases.

Comprehensive genotyping in dyslipidemia: mendelian dyslipidemias caused by rare variants and Mendelian randomization studies using common variants.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Yamagishi, Masakazu

2017-04-01

Dyslipidemias, especially hyper-low-density lipoprotein cholesterolemia and hypertriglyceridemia, are important causal risk factors for coronary artery disease. Comprehensive genotyping using the 'next-generation sequencing' technique has facilitated the investigation of Mendelian dyslipidemias, in addition to Mendelian randomization studies using common genetic variants associated with plasma lipids and coronary artery disease. The beneficial effects of low-density lipoprotein cholesterol-lowering therapies on coronary artery disease have been verified by many randomized controlled trials over the years, and subsequent genetic studies have supported these findings. More recently, Mendelian randomization studies have preceded randomized controlled trials. When the on-target/off-target effects of rare variants and common variants exhibit the same direction, novel drugs targeting molecules identified by investigations of rare Mendelian lipid disorders could be promising. Such a strategy could aid in the search for drug discovery seeds other than those for dyslipidemias.

Berardinelli–Seip syndrome: highlight of treatment challenge

PubMed Central

Ferraria, Nélia; Pedrosa, Cristina; Amaral, Daniela; Lopes, Lurdes

2013-01-01

Berardinelli–Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal-recessive disease characterised by lipoatrophy and associated with deregulations of glycidic and lipid metabolism. We report three BSCL cases with its typical clinical picture and complications. Clinically, they all show marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. Two cases present attention deficit hyperactivity and developmental learning disorders; another patient has hypertrophic myocardiopathy and polycystic ovary syndrome. In all the cases AGPAT2 was the identified mutation. All the cases present hypertriglyceridemia. One case has developed hyperinsulinism controlled with metformin and another case already has type 2 diabetes with a difficult clinical control. There is no curative treatment and the current treatment options are based only on symptomatic control of the complications. Recently, published studies showed that leptin-replacement therapy appears a promising tool in the metabolic correction of BSCL complications, highlighting the importance of further investigations in BSCL treatment. PMID:23362058

Metabolic Abnormalities and Clinical Lipodystrophy in Children With Human Immunodeficiency Virus Infection: A Report From a Tertiary Care Center in India.

PubMed

Kumar, Prasanna; Suri, Deepti; Vignesh, Pandiarajan; Verma Attri, Savita; Kumar Bhalla, Anil; Singh, Surjit

2017-12-01

A cross-sectional study from a tertiary care center in India was undertaken to assess and compare the prevalence of blood glucose and lipid profile aberrations in children who received first-line antiretroviral therapy (ART; n = 63) and in children who were naïve to ART (n = 46). Impaired fasting blood glucose values were found in 7 children in ART-experienced group but none in ART-naïve group (P = 0.02). Low concentrations of high-density lipoprotein cholesterol were more prevalent in the ART-naïve group compared with ART-experienced group (54.3% vs. 22.2%; P = 0.001). Hypertriglyceridemia was noted in a significant proportion of both ART-naïve (43.5%) and ART-experienced children (39.7%). Incidence of clinical lipodystrophy was 47.7%, and there was no significant association noted between lipid profile abnormalities and lipodystrophy.

Rank in Self-Defense Forces and risk factors for atherosclerotic disease.

PubMed

Sakuta, Hidenari; Suzuki, Takashi

2005-10-01

Socioeconomic status is associated with prevalence of and risk for atherosclerotic disease. We investigated the relationship between rank in the Self-Defense Forces (SDFs) and risk factors for atherosclerotic disease among middle-aged, male, SDFs personnel. Subjects were classified into five groups according to their ranks in the SDFs, i.e., class 1 (lowest, n = 289), class 2 (low, n = 170), class 3 (middle, n = 229), class 4 (high, n = 197), and class 5 (highest, n = 89). Low rank was associated with current cigarette smoking, alcohol abstaining, and poorer vegetable consumption. It was also associated with prevalence of type 2 diabetes, elevated gamma-glutamyltransferase activity, and high white blood cell counts. Prevalence of obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, or hyperuricemia was not associated with rank in this population. Rank may be regarded as one of the markers that reflect individual health states among middle-aged male personnel.

Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome.

PubMed

Xiong, Yong-lao; Liang, Xiao-yan; Yang, Xing; Li, Yi; Wei, Li-na

2011-11-01

The purpose of this study was to investigate chronic inflammation in the peripheral blood and ovaries of patients with polycystic ovary syndrome (PCOS). 86 PCOS patients and 50 controls were randomly enrolled in the study. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), blood routine test, lipid metabolism index, inflammation cytokines were detected. Ovary samples from PCOS group and control group were collected for macrophage and lymphocyte immunohistochemistry staining. Patients with PCOS showed significantly higher serum CRP, lymphocytes, monocytes, eosinophilic granulocytes, as well as higher triglycerides (TG), TNF-α and IL-6. PCOS ovary had greater number of macrophages and lymphocytes immersed throughout. In conclusion, PCOS patients exhibited hypertriglyceridemia and chronic inflammation, with elevated peripheral lymphocytes, monocytes, and eosinophilic granulocytes. In addition, their ovaries showed persistent chronic inflammation with a larger number of inflammatory cells immersed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Congenital generalized lipodystrophy in a patient with Dandy Walker anomaly].

PubMed

Luna, Cecilia Inés; Fernández Cordero, Marisa; Escruela, Romina; Sierra, Valeria; Córdoba, Antonela; Goñi, Ignacio María; Berridi, Ricardo

2014-10-01

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance should be given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.

Triglyceride-Lowering Effects of Two Probiotics, Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601, in a Rat Model of High-Fat Diet-Induced Hypertriglyceridemia.

PubMed

Choi, Il-Dong; Kim, Sung-Hwan; Jeong, Ji-Woong; Lee, Dong Eun; Huh, Chul-Sung; Hong, Seong Soo; Sim, Jae-Hun; Ahn, Young-Tae

2016-03-01

The triglyceride-lowering effect of probiotics Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 were investigated. Male SD Wistar rats were randomly divided into three groups and fed high-fat diet (HFD), HFD and probiotics (5 X 10(9) CFU/day of L. plantarum KY1032 and 5 X 10(9) CFU/day of L. curvatus HY7601), or normal diet for 6 weeks. Probiotic treatment significantly lowered the elevated plasma triglyceride and increased plasma free fatty acid, glycerol, and plasma apolipoprotein A-V (ApoA-V) levels. The probiotic-treated group showed elevated hepatic mRNA expression of PPARα, bile acid receptor (FXR), and ApoA-V. These results demonstrate that L. plantarum KY1032 and L. curvatus HY7601 lower triglycerides in hypertriglyceridemic rats by upregulating ApoA-V, PPARα, and FXR.

CE: Triglycerides: Do They Matter?

PubMed

Scordo, Kristine; Pickett, Kim Anne

2017-01-01

: Since the introduction of HMG-CoA reductase inhibitors, also known as statins, as an adjunct to diet in the treatment of hyperlipidemia and the greater emphasis placed on reducing low-density lipoprotein (LDL) cholesterol levels in the prevention of atherosclerosis and cardiovascular disease (CVD), there has been less focus on the value of lowering serum triglyceride levels. Many patients are aware of their "good" and "bad" cholesterol levels, but they may not be aware of their triglyceride level or of the association between high triglycerides and the development of CVD. In recent years, however, in light of the increasing incidences of obesity, insulin resistance, and type 2 diabetes, lowering triglyceride levels has gained renewed interest. In addition to the focus on lowering LDL cholesterol levels in CVD prevention, clinicians need to be aware of the role of triglycerides-their contribution to CVD, and the causes and treatment of hypertriglyceridemia.

A new pure ω-3 eicosapentaenoic acid ethyl ester (AMR101) for the management of hypertriglyceridemia: the MARINE trial.

PubMed

Jacobson, Terry A

2012-06-01

ω-3 fatty acids reduce triglyceride (TG) levels, but corresponding increases in low-density lipoprotein cholesterol (LDL-C) levels may compromise achievement of lipid goals in patients with elevated cardiovascular risk. AMR101 is an investigational agent containing ≥96% of pure icosapent ethyl (the ethyl ester of eicosapentaenoic acid). The Phase III Multi-Center, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study with an Open-Label Extension (MARINE) investigated the efficacy and safety of AMR101 in 229 patients with very high TG levels (≥500 mg/dl). AMR101 4 g/day significantly reduced median placebo-adjusted TG levels from baseline by 33.1% (p < 0.0001), and AMR101 2 g/day reduced TG levels by 19.7% (p = 0.0051). Changes in LDL-C were minimal and nonsignificant. AMR101 may offer substantial TG lowering without increases in LDL-C levels.

New Frontiers in the Treatment of Diabetic Dyslipidemia

PubMed Central

Wang, Shu-Yi; Hsieh, Ming-Chia; Tu, Shih-Te; Chuang, Chieh-Sen

2013-01-01

Dyslipidemia is a major risk factor for cardiovascular complications in people with diabetes. Lowering low-density lipoprotein cholesterol (LDL-C) levels is effective in the primary and secondary prevention of diabetic vascular complications. However, LDL-C levels do not reflect all aspects of diabetic dyslipidemia, which is characterized by hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). Statins, nicotinic acid, and fibrates play a role in treating diabetic dyslipidemia. Atherosclerosis is a major disorder of the blood vessel wall in patients with diabetes. A number of antihyperlipidemic agents may be beneficial and exhibit effects at the actual site of vascular disease and not only on plasma lipoprotein concentrations. Several novel therapeutic compounds are currently being developed. These include additional therapeutics for LDL-C, triglycerides, HDL-C, and modulators of inflammation that can be used as possible synergic agents for the treatment of atherosclerosis and irregularities in plasma lipoprotein concentrations. PMID:24380093

Cardiometabolic risk factors in the Agarwal business community in India: Jaipur Heart Watch-6

PubMed Central

Dhabriya, Ritu; Agrawal, Mukta; Gupta, Rajeev; Mohan, Indu; Sharma, Krishna Kumar

2015-01-01

Background Agarwal is one of the largest business communities in India. To determine prevalence of cardiovascular risk factors and their distribution according to educational status (ES) in this community we performed a study. Methods 1781 (men 1039, women 742) of 2500 selected subjects (71.2%) were evaluated and fasting blood sample obtained in 1130. Results Age-adjusted prevalence of risk factors was tobacco use 12.2%, sedentary habits 54.2%, overweight/obesity 54.4%, obesity 19.5%, abdominal obesity 61.2%, hypertension 36.0%, diabetes 19.2%, hypercholesterolemia ≥200 mg/dl 25.8%, low HDL cholesterol 29.2%, hypertriglyceridemia 32.8% and metabolic syndrome 22.3%. Low ES subjects had significantly greater prevalence of sedentary habits, low fruit/vegetable intake, hypertension, low HDL cholesterol and diabetes. Conclusions Cardiometabolic risk factors are highly prevalent in the Agarwal business community. Prevalence is greater in subjects with low educational status. PMID:26304567

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess

PubMed Central

Samino, Sara; Vinaixa, Maria; Díaz, Marta; Beltran, Antoni; Rodríguez, Miguel A.; Mallol, Roger; Heras, Mercedes; Cabre, Anna; Garcia, Lorena; Canela, Nuria; de Zegher, Francis; Correig, Xavier; Ibáñez, Lourdes; Yanes, Oscar

2015-01-01

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide. PMID:26099471

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

PubMed

Samino, Sara; Vinaixa, Maria; Díaz, Marta; Beltran, Antoni; Rodríguez, Miguel A; Mallol, Roger; Heras, Mercedes; Cabre, Anna; Garcia, Lorena; Canela, Nuria; de Zegher, Francis; Correig, Xavier; Ibáñez, Lourdes; Yanes, Oscar

2015-06-23

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide.

Venous thromboembolism and arterial complications.

PubMed

Prandoni, Paolo; Piovella, Chiara; Pesavento, Raffaele

2012-04-01

An increasing body of evidence suggests the likelihood of a link between venous and arterial thrombosis. The two vascular complications share several risk factors, such as age, obesity, smoking, diabetes mellitus, blood hypertension, hypertriglyceridemia, and metabolic syndrome. Moreover, there are many examples of conditions accounting for both venous and arterial thrombosis, such as the antiphospholipid antibody syndrome, hyperhomocysteinemia, malignancies, infections, and the use of hormonal treatment. Finally, several recent studies have consistently shown that patients with venous thromboembolism are at a higher risk of arterial thrombotic complications than matched control individuals. We, therefore, speculate the two vascular complications are simultaneously triggered by biological stimuli responsible for activating coagulation and inflammatory pathways in both the arterial and the venous system. Future studies are needed to clarify the nature of this association, to assess its extent, and to evaluate its implications for clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management of Parenteral Nutrition in Hospitalized Adult Patients [Formula: see text].

PubMed

Mundi, Manpreet S; Nystrom, Erin M; Hurley, Daniel L; McMahon, M Molly

2017-05-01

Despite the high prevalence of malnutrition in adult hospitalized patients, surveys continue to report that many clinicians are undertrained in clinical nutrition, making targeted nutrition education for clinicians essential for best patient care. Clinical practice models also continue to evolve, with more disciplines prescribing parenteral nutrition (PN) or managing the cases of patients who are receiving it, further adding to the need for proficiency in general PN skills. This tutorial focuses on the daily management of adult hospitalized patients already receiving PN and reviews the following topics: (1) PN basics, including the determination of energy and volume requirements; (2) PN macronutrient content (protein, dextrose, and intravenous fat emulsion); (3) PN micronutrient content (electrolytes, minerals, vitamins, and trace elements); (4) alteration of PN for special situations, such as obesity, hyperglycemia, hypertriglyceridemia, refeeding, and hepatic/renal disease; (5) daily monitoring and adjustment of PN formula; and (6) PN-related complications (PN-associated liver disease and catheter-related complications).

Association of educational, occupational and socioeconomic status with cardiovascular risk factors in Asian Indians: a cross-sectional study.

PubMed

Gupta, Rajeev; Deedwania, Prakash C; Sharma, Krishnakumar; Gupta, Arvind; Guptha, Soneil; Achari, Vijay; Asirvatham, Arthur J; Bhansali, Anil; Gupta, Balkishan; Gupta, Sunil; Jali, Mallikarjuna V; Mahanta, Tulika G; Maheshwari, Anuj; Saboo, Banshi; Singh, Jitendra; Gupta, Rajiv

2012-01-01

To determine correlation of multiple parameters of socioeconomic status with cardiovascular risk factors in India. The study was performed at eleven cities using cluster sampling. Subjects (n = 6198, men 3426, women 2772) were evaluated for socioeconomic, demographic, biophysical and biochemical factors. They were classified into low, medium and high socioeconomic groups based on educational level (<10, 10-15 and >15 yr formal education), occupational class and socioeconomic scale. Risk factor differences were evaluated using multivariate logistic regression. Age-adjusted prevalence (%) of risk factors in men and women was overweight or obesity in 41.1 and 45.2, obesity 8.3 and 15.8, high waist circumference 35.7 and 57.5, high waist-hip ratio 69.0 and 83.8, hypertension 32.5 and 30.4, hypercholesterolemia 24.8 and 25.3, low HDL cholesterol 34.1 and 35.1, high triglycerides 41.2 and 31.5, diabetes 16.7 and 14.4 and metabolic syndrome in 32.2 and 40.4 percent. Lifestyle factors were smoking 12.0 and 0.5, other tobacco use 12.7 and 6.3, high fat intake 51.2 and 48.2, low fruits/vegetables intake 25.3 and 28.9, and physical inactivity in 38.8 and 46.1%. Prevalence of > = 3 risk factors was significantly greater in low (28.0%) vs. middle (23.9%) or high (22.1%) educational groups (p<0.01). In low vs. high educational groups there was greater prevalence of high waist-hip ratio (odds ratio 2.18, confidence interval 1.65-2.71), low HDL cholesterol (1.51, 1.27-1.80), hypertriglyceridemia (1.16, 0.99-1.37), smoking/tobacco use (3.27, 2.66-4.01), and low physical activity (1.15, 0.97-1.37); and lower prevalence of high fat diet (0.47, 0.38-0.57),overweight/obesity (0.68, 0.58-0.80) and hypercholesterolemia (0.79, 0.66-0.94). Similar associations were observed with occupational and socioeconomic status. Low educational, occupational and socioeconomic status Asian Indians have greater prevalence of truncal obesity, low HDL cholesterol, hypertriglyceridemia, smoking or tobacco use and low physical activity and clustering of > = 3 major cardiovascular risk factors.

Association of Educational, Occupational and Socioeconomic Status with Cardiovascular Risk Factors in Asian Indians: A Cross-Sectional Study

PubMed Central

Gupta, Rajeev; Deedwania, Prakash C.; Sharma, Krishnakumar; Gupta, Arvind; Guptha, Soneil; Achari, Vijay; Asirvatham, Arthur J.; Bhansali, Anil; Gupta, Balkishan; Gupta, Sunil; Jali, Mallikarjuna V.; Mahanta, Tulika G.; Maheshwari, Anuj; Saboo, Banshi; Singh, Jitendra; Gupta, Rajiv

2012-01-01

Background To determine correlation of multiple parameters of socioeconomic status with cardiovascular risk factors in India. Methods The study was performed at eleven cities using cluster sampling. Subjects (n = 6198, men 3426, women 2772) were evaluated for socioeconomic, demographic, biophysical and biochemical factors. They were classified into low, medium and high socioeconomic groups based on educational level (<10, 10–15 and >15 yr formal education), occupational class and socioeconomic scale. Risk factor differences were evaluated using multivariate logistic regression. Results Age-adjusted prevalence (%) of risk factors in men and women was overweight or obesity in 41.1 and 45.2, obesity 8.3 and 15.8, high waist circumference 35.7 and 57.5, high waist-hip ratio 69.0 and 83.8, hypertension 32.5 and 30.4, hypercholesterolemia 24.8 and 25.3, low HDL cholesterol 34.1 and 35.1, high triglycerides 41.2 and 31.5, diabetes 16.7 and 14.4 and metabolic syndrome in 32.2 and 40.4 percent. Lifestyle factors were smoking 12.0 and 0.5, other tobacco use 12.7 and 6.3, high fat intake 51.2 and 48.2, low fruits/vegetables intake 25.3 and 28.9, and physical inactivity in 38.8 and 46.1%. Prevalence of > = 3 risk factors was significantly greater in low (28.0%) vs. middle (23.9%) or high (22.1%) educational groups (p<0.01). In low vs. high educational groups there was greater prevalence of high waist-hip ratio (odds ratio 2.18, confidence interval 1.65–2.71), low HDL cholesterol (1.51, 1.27–1.80), hypertriglyceridemia (1.16, 0.99–1.37), smoking/tobacco use (3.27, 2.66–4.01), and low physical activity (1.15, 0.97–1.37); and lower prevalence of high fat diet (0.47, 0.38–0.57),overweight/obesity (0.68, 0.58–0.80) and hypercholesterolemia (0.79, 0.66–0.94). Similar associations were observed with occupational and socioeconomic status. Conclusions Low educational, occupational and socioeconomic status Asian Indians have greater prevalence of truncal obesity, low HDL cholesterol, hypertriglyceridemia, smoking or tobacco use and low physical activity and clustering of > = 3 major cardiovascular risk factors. PMID:22952886

A case-control study of HIV-associated pancreatic abnormalities during HAART era. Focus on emerging risk factors and specific management.

PubMed

Manfredi, Roberto; Calza, L; Chiodo, F

2004-12-22

The epidemiological and clinical features of HIV-associated pancreatic abnormalities are expected to change after HAART introduction. The frequency, risk factors, and clinical and therapeutic features of pancreatic alterations were assessed in an observational case-control study. Nine hundred and 20 were evaluated for pancreatic abnormalities in a case-control study including the whole follow-up period of each considered patient; 128 subjects with high and prolonged laboratory anomalies were assessed, to outline the profile of pancreatic disease before and during the HAART era. Compared with controls, the 334 patients (36.3%) who experienced at least one episode of confirmed pancreatic laboratory abnormality had a longer duration of seropositivity, exposure to protease inhibitors, a more frequent immunodeficiency, AIDS diagnosis, liver or biliary disease, and hypertriglyceridemia, while no relation was found with antiretroviral administration, and the duration of nucleoside analogue use. Among these 334 patients, high and prolonged laboratory alterations eventually associated with signs of organ involvement occurred in 128 cases, and were related to the administration of didanosine, stavudine, lamivudine, pentamidine, cotrimoxazole, or anti-tubercular therapy, substance or alcohol abuse, opportunistic infections, liver or biliary disease, a protease inhibitor-based HAART, and hypertriglyceridemia. However, no difference was noticed between the 32 patients with clinical and/or imaging evidence of pancreatic involvement and the remaining 96 asymptomatic cases, as to the same risk factors. Although recurrences of enzyme alterations involved >70% of patients, in only 33.8% of cases a change of antiretroviral or antimicrobial therapy was necessary. An acute but uncomplicated pancreatitis occurred in 7 patients of 26 overall symptomatic subjects. A 2-4-week gabexate and/or octreotide administration (performed in 59 cases of 128), attained a significant laboratory, clinical, and imaging cure or improvement in 71.2% of cases, with a better success rate of combined versus single therapy; a reduced tendency to disease recurrences, and a better tolerability of antiretrovirals were also noticed. Epidemiological and pathogenetic studies are needed to assess pancreatic abnormalities especially in the HAART era, and their consequences on continued antiretroviral and antimicrobial therapy. The antiretroviral management and the indication to gabexate and/or octreotide administration in the different clinical and laboratory situations, warrant controlled investigation.

A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study.

PubMed

Davidson, Michael H; Johnson, Judith; Rooney, Michael W; Kyle, Michael L; Kling, Douglas F

2012-01-01

Omega-3 (OM-3) fatty acid products are indicated for the treatment of severe hypertriglyceridemia; however, the omega-3-acid ethyl ester (OM-3 EE) formulations require significant pancreatic lipase stimulation with high-fat meals for adequate intestinal absorption of the metabolites eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A novel omega-3 free fatty acid (OM-3 FFA) formulation (Epanova(®), Omthera Pharmaceuticals Inc., Princeton, NJ) was developed to maximize EPA and DHA bioavailability during a low-fat diet. To compare the relative bioavailability of EPA and DHA from single 4-gram doses of OM-3 FFA and a prescription OM-3 EE (Lovaza(®), GlaxoSmithKline, Research Triangle Park, NC). This was a randomized, open-label, single dose, 4-way crossover, bioavailability study of OM-3 FFA and OM-3 EE administered during periods of low-fat and high-fat consumption to 54 overweight adults. Bioavailability was determined by the ln-transformed area under the plasma concentration versus time curve (AUC(0-t)) during a 24-hour interval for EPA and DHA (baseline-adjusted). The baseline-adjusted AUC(0-t) for total EPA + DHA during the low-fat period was 4.0-fold greater with OM-3 FFA compared with OM-3 EE (2650.2 vs 662.0 nmol·h/mL, respectively; P < .0001). During the high-fat period, AUC(0-t) for OM-3 FFA was approximately 1.3-fold greater than OM-3 EE (P < .0001). During the low-fat period, 30 of 51 (58.8%) subjects dosed with OM-3 FFA maintained an AUC(0-t) that was ≥50% of the respective high-fat AUC(0-t) in contrast to only 3 of 50 (6.0%) subjects dosed with OM-3 EE. During a low-fat consumption period, the OM-3 FFA formulation provided dramatically improved bioavailability over the OM-3 EE formulation in overweight subjects. These findings offer a potential therapeutic advantage of the OM-3 FFA formulation for the treatment of severe hypertriglyceridemia as these patients are expected to adhere to a low-fat diet. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Correlation of CRP, fasting serum triglycerides and obesity as cardiovascular risk factors.

PubMed

Firdous, Samar

2014-05-01

To determine the correlation of C-reactive protein (CRP) with fasting triglycerides (TG) among pre-obese and obese patients without established diagnosis of coronary artery disease (CAD). A comparative cross-sectional study. Mayo Hospital, Lahore, from January to June 2010. Patients with BMI > 23 kg/m2 aged between 18 - 65 years were inducted and above variables were studied. Patients with signs of fluid retention, collagen vascular disease, CAD, patients on corticosteroids, immunomodulators or lipid lowering medications and febrile patients were not recruited. Body mass index was also determined. Independent sample t-test was applied to see the mean difference of age, CRP level and triglycerides level in relation to gender. Chi-square test was used to see the association between qualitative variables. ANOVA was applied to see CRP and fasting serum TG level in relation to BMI categories. Pearson correlation and simple linear regression was applied to see the dependency of CRP and triglycerides with BMI. P-value ² 0.05 was taken as significant. Raised CRP was major finding among all groups of BMI. Most of obese and pre-obese patients were young and middle aged and belonged to pre-obese group followed by class-1 and class-2 obesity. CRP level increased with body mass index. No such trend was observed for triglycerides. There was an intermediate positive correlation between CRP and BMI and triglycerides and BMI showed a weak negative correlation. If BMI increases by 1 unit on the average, CRP rises by 0.239 times and this unit rise was significant. Whereas 1 unit rise increase in triglycerides on the average cause CRP to decrease -0.006 times but this value was insignificant. Raised CRP and high fasting TG were major findings in all age groups especially among young and middle aged people. Obesity, hypertriglyceridemia and raised CRP are interrelated suggesting that obesity is not only linked to hypertriglyceridemia but vascular inflammation among pre-obese and obese without overt diabetes mellitus causes high CRP as well and this can be used as a marker to predict the future risk of CAD. However, in the absence of dyslipidaemia, raised CRP can still be considered as a strong predictor of CAD and stroke.

Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

PubMed

Santos, Ana Paula Caires Dos; Couto, Ricardo David

2018-05-16

Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Metabolic syndrome does not detect metabolic risk in African men living in the U.S.

PubMed

Ukegbu, Ugochi J; Castillo, Darleen C; Knight, Michael G; Ricks, Madia; Miller, Bernard V; Onumah, Barbara M; Sumner, Anne E

2011-10-01

Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn. Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia. MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans. African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans.

Use of the triglyceride to HDL cholesterol ratio for assessing insulin sensitivity in overweight and obese children in rural Appalachia

PubMed Central

Bridges, Kristie Grove; Jarrett, Traci; Thorpe, Anthony; Baus, Adam; Cochran, Jill

2015-01-01

Background Studies have suggested that triglyceride to HDL-cholesterol ratio (TRG/HDL) is a surrogate marker of insulin resistance (IR), but information regarding its use in pediatric patients is limited. Objective This study investigated the ability of TRG/HDL ratio to assess IR in obese and overweight children. Subjects The sample consisted of de-identified electronic medical records of patients aged 10–17 years (n = 223). Materials and methods Logistic regression was performed using TRG/HDL ratio as a predictor of hyperinsulinemia or IR defined using homeostasis model assessment score. Results TRG/HDL ratio had limited ability to predict hyperinsulinemia (AUROC 0.71) or IR (AUROC 0.72). Although females had higher insulin levels, male patients were significantly more likely to have hypertriglyceridemia and impaired fasting glucose. Conclusions TRG/HDL ratio was not adequate for predicting IR in this population. Gender differences in the development of obesity-related metabolic abnormalities may impact the choice of screening studies in pediatric patients. PMID:26352085

Harmful effects of shisha: literature review

PubMed Central

2014-01-01

Tobacco is a preventable cause of morbidity and mortality across the world. A recently infamous way of smoking tobacco is shisha. Shisha smoking is also known as water pipe, hookah and Narghile smoking. The percentage of shisha smokers is on the rise rapidly spanning the globe. A literature review was conducted to identify all evidence on the epidemiological variations and health effects of shisha smoking. “Pub med” is used as a searching tool to identify all relevant empirical studies conducted worldwide. A qualitative overview of evidence is presented. Exposure to Shisha smoking is significantly associated with low infant weight, heart rate variations, hyperglycemia and hypertriglyceridemia. Increased risk of carcinoma is also leagued with it including carcinomas of the pancreas and lung being at the forefront. In conclusion, this review identifies grounds of several adverse conditions being associated with the habit of shisha smoking. It also evaluates the relevant epidemiological variations around the globe. The review culminates in the importance of enlightening shisha smokers regarding its deleterious effects. PMID:24708750

Hemophagocytic syndrome as the initial manifestation of systemic lupus erythematosus.

PubMed

Egües Dubuc, César Antonio; Uriarte Ecenarro, Miren; Meneses Villalba, Carlos; Aldasoro Cáceres, Vicente; Hernando Rubio, Iñaki; Belzunegui Otano, Joaquín

2014-01-01

Hemophagocytic syndrome (HS) occurs in autoimmune diseases and belongs to the hemophagocytic lymphohistiocytosis group of diseases. This paper describes the features of 2 patients with systemic lupus erythematosus (SLE) who presented HS as the initial clinical manifestation. Both patients had prolonged fever not associated to an infectious process and did not respond to broad-spectrum antibiotics. The diagnosis of HS secondary to SLE is complicated, because it has some features in common, but HS is characterized by hyperferritinemia, hipofibrinogemia, hypertriglyceridemia and a decrease in the erythrocyte sedimentation rate, unlike SLE. HS treatment when associated to SLE is not well established, but steroids and/or immunoglobulins are effective as the initial treatment, and in refractory cases, cyclosporine or cyclophosphamide may be associated. HS can be the initial manifestation of SLE and should be suspected in patients with organ enlargement, cytopenias, clotting disorders, liver disorders and prolonged fever unresponsive to antibiotics. Anakinra may be a treatment option in adult HS associated to SLE. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Indigenous plant medicines for health care: treatment of Diabetes mellitus and hyperlipidemia.

PubMed

Parikh, Nisha H; Parikh, Palak K; Kothari, Charmy

2014-05-01

Medicinal plants have played an important role in treating and preventing a variety of diseases throughout the world. Metabolic syndrome had become a global epidemic, defined as a cluster of three of five criteria: insulin resistance and glucose intolerance, abdominal obesity, hypertension, low high-density cholesterol, and hypertriglyceridemia. The current review focuses on Indian medicinal plant drugs and plants used in the treatment of diabetes and hyperlipidemia. Though there are various approaches to reduce the ill-effects of diabetes and hyperlipidemia and its secondary complications, plant-based drugs are preferred due to lesser side effects and low cost. The current review focuses on twenty-three medicinal plants used in the treatment of Diabetes mellitus and nine medicinal plants used in the treatment of hyperlipidemia. The wealth of knowledge on medicinal plants points to a great potential for research and the discovery of new drugs to fight diseases, including diabetes and hyperlipidemia. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Clinical outcomes in metabolic syndrome.

PubMed

Bhatheja, Rohit; Bhatt, Deepak L

2006-01-01

Metabolic syndrome is a clustering of cardiovascular risk factors. Its definition is the presence of any 3 of the following: obesity, hypertriglyceridemia, low high-density lipoprotein, hypertension, and impaired fasting glucose. The development of coronary artery disease is the most dreaded complication of this disease. In the United States, Mexican Americans and African American women are the most affected. Management of this syndrome includes physical exercise, weight loss, and effective drug treatment of dyslipidemia, high blood pressure, and impaired fasting blood glucose. Because of the increasing prevalence of obesity and diabetes, there is a rise in fatal and nonfatal cardiovascular events. With the development of effective antiplatelet medication and newer drug-eluting stents, percutaneous coronary intervention has become an effective revascularization strategy for those with coronary artery disease. Rates of stent restenosis and target-lesion revascularization have been reduced. Oral hypoglycemic drugs like thiazolidinediones improve insulin resistance and may have a favorable effect in those with metabolic syndrome. Diagnosis and appropriate management of metabolic syndrome are challenges as the presence of risk factors predates the coronary event.

Cardiometabolic risk factors in the Agarwal business community in India: Jaipur Heart Watch-6.

PubMed

Dhabriya, Ritu; Agrawal, Mukta; Gupta, Rajeev; Mohan, Indu; Sharma, Krishna Kumar

2015-01-01

Agarwal is one of the largest business communities in India. To determine prevalence of cardiovascular risk factors and their distribution according to educational status (ES) in this community we performed a study. 1781 (men 1039, women 742) of 2500 selected subjects (71.2%) were evaluated and fasting blood sample obtained in 1130. Age-adjusted prevalence of risk factors was tobacco use 12.2%, sedentary habits 54.2%, overweight/obesity 54.4%, obesity 19.5%, abdominal obesity 61.2%, hypertension 36.0%, diabetes 19.2%, hypercholesterolemia ≥200 mg/dl 25.8%, low HDL cholesterol 29.2%, hypertriglyceridemia 32.8% and metabolic syndrome 22.3%. Low ES subjects had significantly greater prevalence of sedentary habits, low fruit/vegetable intake, hypertension, low HDL cholesterol and diabetes. Cardiometabolic risk factors are highly prevalent in the Agarwal business community. Prevalence is greater in subjects with low educational status. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Prevalence and prevention of cardiovascular disease and diabetes mellitus.

PubMed

Balakumar, Pitchai; Maung-U, Khin; Jagadeesh, Gowraganahalli

2016-11-01

Noncommunicable diseases (NCDs) have become important causes of mortality on a global scale. According to the report of World Health Organization (WHO), NCDs killed 38 million people (out of 56 million deaths that occurred worldwide) during 2012. Cardiovascular diseases accounted for most NCD deaths (17.5 million NCD deaths), followed by cancers (8.2 million NCD deaths), respiratory diseases (4.0 million NCD deaths) and diabetes mellitus (1.5 million NCD deaths). Globally, the leading cause of death is cardiovascular diseases; their prevalence is incessantly progressing in both developed and developing nations. Diabetic patients with insulin resistance are even at a greater risk of cardiovascular disease. Obesity, high cholesterol, hypertriglyceridemia and elevated blood pressure are mainly considered as major risk factors for diabetic patients afflicted with cardiovascular disease. The present review sheds light on the global incidence of cardiovascular disease and diabetes mellitus. Additionally, measures to be taken to reduce the global encumbrance of cardiovascular disease and diabetes mellitus are highlighted. Published by Elsevier Ltd.

Diagnosis and treatment of high density lipoprotein deficiency.

PubMed

Schaefer, Ernst J; Anthanont, Pimjai; Diffenderfer, Margaret R; Polisecki, Eliana; Asztalos, Bela F

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Dietary patterns and metabolic syndrome components in women with excess weight 18 to 45 years old].

PubMed

Hernández-Ruiz, Zugey; Rodríguez-Ramírez, Sonia; Hernández-Cordero, Sonia; Monterrubio-Flores, Eric

2018-01-01

To analyze the association between dietary patterns and metabolic syndrome (MS) components in adult women with excess weight. Cross-sectional study with anthropometric, dietary, biochemical and blood pressure data. Dietary patterns were identified by factor analysis and multiple logistic regression models were used to analyze associations. The prevalence of altered glucose was 14.6%, of hypertriglyceridemia 40.4%, of altered concentration of high density lipoprotein cholesterol(HDLc) 45.0%, hypertension 4.6% and MS 30%. The pattern with high consumption of corn tortillas, meats and legumes, was associated with less possibility of hyperglycemia (OR= 0.62; 95%CI 0.39-0.98). The pattern with high consumption of sweet and salty snacks, milk, rice, soaps and pasta, was inversely associated with the possibility of low HDLc concentration (OR= 0.76; 95%CI 0.60-0.97). A dietary pattern with greater consumption of legumes, meats and corn tortillas was associated with less possibility of having hyperglycemia.

Time trends in the etiology of chronic pancreatitis in South India.

PubMed

Rajesh, Gopalakrishna; Girish, Banavara Narasimhamurthy; Panicker, Suprabha; Balakrishnan, Vallath

2014-01-01

Recent reports indicate a decline in prevalence of classical tropical chronic pancreatitis (TCP). We studied the etiologies and risk factors over a 14-year period at a tertiary care university hospital. We compared the etiology in chronic pancreatitis (CP) patients presenting and followed-up in our Pancreas Clinic over two time periods (2000-06 and 2007-13). Idiopathic chronic pancreatitis (ICP) was the predominant etiology seen over the two time periods. However an increase in prevalence of alcoholic chronic pancreatitis (ACP) during the latter time period suggests that it may be emerging as a dominant etiology over recent years. Hypertriglyceridemia and hyperparathyroidism were uncommon causes of non-alcoholic CP. Autoimmune pancreatitis was noted only during 2007-13, but remains a rare cause of CP. There are multiple risk factors for CP in our population. The high prevalence of ICP indicates need closer examination of risk factors and ICP pathogenesis. ACP appears to be emerging as a dominant cause of CP which suggests a need to reorient preventive strategies.

Triglycerides Revisited to the Serial.

PubMed

Viecili, Paulo Ricardo Nazário; da Silva, Brenda; Hirsch, Gabriela E; Porto, Fernando G; Parisi, Mariana M; Castanho, Alison R; Wender, Michele; Klafke, Jonatas Z

This review discusses the role of triglycerides (TGs) in the normal cardiovascular system as well as in the development and clinical manifestation of cardiovascular diseases. Regulation of TGs at the enzymatic and genetic level, in addition to their possible relevance as preclinical and clinical biomarkers, is discussed, culminating with a description of available and emerging treatments. Due to the high complexity of the subject and the vast amount of material in the literature, the objective of this review was not to exhaust the subject, but rather to compile the information to facilitate and improve the understanding of those interested in this topic. The main publications on the topic were sought out, especially those from the last 5 years. The data in the literature still give reason to believe that there is room for doubt regarding the use of TG as disease biomarkers; however, there is increasing evidence for the role of hypertriglyceridemia on the atherosclerotic inflammatory process, cardiovascular outcomes, and mortality. © 2017 Elsevier Inc. All rights reserved.

The status of diabetes care in Mexican population: are we making a difference? Results of the National Health and Nutrition Survey 2006.

PubMed

González-Villalpando, Clicerio; López-Ridaura, Ruy; Campuzano, Julio César; González-Villalpando, María Elena

2010-01-01

Examine clinical indicators to evaluate diabetes care in Mexico. Diabetics (self reported, with therapy) were examined with standardized questionnaires, anthropometry, glucose, lipids and glycohemoglobin. Data were analyzed statistically. There were 2 644 patients, 677 cases without access to medical care (73% women), most lived in rural communities and spoke aboriginal dialect. Prevalence of obesity for private access group was 21.2%, for other or non access group was between 31 and 65%. The group without or basic education was most common, 76% of the cases had HDL <40 mg/dl and 36% had hypertriglyceridemia. Only 6.6% of patients had HbA1c <7%. There was no significant difference between HbA1c values observed in the group with or without access. Most patients were treated with oral agents. A significant group was without therapy. Assessments for complications was infrequent. Current model for diabetes care in Mexico is inefficacious and a paradigm change is necessary.

Tax on sugar sweetened beverages in Spain.

PubMed

Ortún, Vicente; G López-Valcárcel, Beatriz; Pinilla, Jaime

2016-10-13

This article provides a critical review about the challenges that taxes on sugary drinks as an instrument of health policy must face to reverse the trend of the current epidemics of obesity. We analyzed the experiences of the leading countries, particularly Mexico, and reflect on the counterweight exerted by the industry against obesity policies, and on the power of lobbyists. Those tax policies for public health have to overcome the enormous strength of the industry, which is exerted in several-science and research, brand reputation, influence on regulators-levels. We suggest that a specific tax on sugary drinks has enough potential to reduce noncommunicable diseases and risk -diabetes, Hypertriglyceridemia, hyperholesterolemia LDL, hypertension- via reduced consumption thanks to the high price elasticity of those drinks. Furthermore, the effects are amplified even in the medium term, once established new habits to healthier eating. These taxes could encourage business innovation without inflicting costs of lost jobs and contribute to reducing the social gradient in obesity.

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation.

PubMed

Mory, Patricia B; Crispim, Felipe; Kasamatsu, Teresa; Gabbay, Monica A L; Dib, Sergio A; Moisés, Regina S

2008-11-01

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

Vitamin D Deficiency in HIV-Infected Women on Antiretroviral Therapy Living in the Tropics.

PubMed

Conrado, Tereza; Miranda-Filho, Demócrito de Barros; Ximenes, Ricardo Arraes de Alencar; Albuquerque, Maria de Fátima; Lacerda, Heloísa Ramos; Ramos, Regina Coeli F; Araújo, Paulo Sérgio Ramos de; Montarroyos, Ulisses; Bandeira, Francisco

2011-01-01

The effects of HIV/AIDS and antiretroviral drugs on vitamin D metabolism are still mostly unknown. This was a cross-sectional study to estimate the prevalence of vitamin D deficiency and identify its association with the clinical and metabolic parameters among 214 HIV-positive female patients on antiretroviral therapy (ART) in Brazil. The prevalence of vitamin D deficiency (< 30 ng/ml) was 40.65% (87/214). Hypercholesterolemia, high LDL-c, duration of use of current antiretroviral regimen, hypertriglyceridemia, body mass index, age, hypertension, time with AIDS ≥ 10 years and hyperglycemia were selected for multivariate analysis (p < 0.20). After this analysis, hypercholesterolemia and use of current antiretroviral regimen ≥ 3 years remained independently associated with vitamin D deficiency. There was an inverse statistically significant correlation between total cholesterol and serum 25(OH)D levels. High prevalence of vitamin D deficiency was found among HIV-positive women on ART and was independently associated with its prolonged use and with hypercholesterolemia.

The role of xanthine oxidoreductase and uric acid in metabolic syndrome.

PubMed

Battelli, Maria Giulia; Bortolotti, Massimo; Polito, Letizia; Bolognesi, Andrea

2018-08-01

Xanthine oxidoreductase (XOR) could contribute to the pathogenesis of metabolic syndrome through the oxidative stress and the inflammatory response induced by XOR-derived reactive oxygen species and uric acid. Hyperuricemia is strongly linked to hypertension, insulin resistance, obesity and hypertriglyceridemia. The serum level of XOR is correlated to triglyceride/high density lipoprotein cholesterol ratio, fasting glycemia, fasting insulinemia and insulin resistance index. Increased activity of endothelium-linked XOR may promote hypertension. In addition, XOR is implicated in pre-adipocyte differentiation and adipogenesis. XOR and uric acid play a role in cell transformation and proliferation as well as in the progression and metastatic process. Collected evidences confirm the contribution of XOR and uric acid in metabolic syndrome. However, in some circumstances XOR and uric acid may have anti-oxidant protective outcomes. The dual-face role of both XOR and uric acid explains the contradictory results obtained with XOR inhibitors and suggests caution in their therapeutic use. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

[Prevalence of Hypertriglyceridemia: New Data Across the Russian Population. The PROMETHEUS Study].

PubMed

Karpov On Behalf Of Participants Of The Prometheus Study, Yu A

2016-07-01

The main purpose of the study was to estimate prevalence of subjects with hypertriglyceridemia (HTG) in Russia. Secondary objectives were to explore HTG prevalence by levels, age and sex, and to assess correlation between glycated hemoglobin (HbA1C) and triglyceride (TG) level. Additionally, we analyzed geographical differences in HTG prevalence in regions of Russia. This was a cross-sectional, retrospective, observational study using database of results of lipid profile determination in 357,072 subjects from 254 Russian cities during the 3-year period from 2011 to 2013. Altogether, 29.2% (95% confidence interval [CI] 29.1-29.4%) of Russian individuals had HTG (serum TG more or equal 1.7 mmol/L). The percentage of patients with very high (TG more or equal 5.6 mmol/L) and severe HTG (TG more or equal 10.0mmol/L) was low (0.01% and 0.011%, respectively). At the same time, the portion of subjects with mixed hyperlipidemia (total cholesterol [TC] more or equal 5.2mmol/L, low-density lipoprotein cholesterol [LDL-C] more or equal 3.4 mmol/L, TG more or equal 1.7 mmol/L) was 19% of the study population. Men had 1.25 (95% CI, 1.24-1.26) times higher risk of HTG than women. Prevalence of HTG increased with age: in women TG level was maximal in the age group 60-69 years (34%), whereas in men TG level was maximal in the age group 40-49 years (43%). Prevalence of HTG increased from 2011 to 2013 from 28 to 30% (p<0.0001). Risk of HTG was 1.69 times greater when high HbA1C more or equal 6.5% was present, and vice versa, risk of HbA1C more or equal 6.5% was 2.04 times higher in individuals with HTG. Distribution of HTG and dyslipidemia by regions of Russia had large variability being higher in the south and lower in the northern regions of European part of Russia. Almost a third of Russian population has HTG. Men have higher risk of HTG than women. Prevalence of HTG increases with age and reaches its peak in age groups 60-69 years in (women) and 40-49 years (men). There is a linear association between high HbA- and high level of TG. Prevalence of HTG and dyslipidemia is heterogeneous in Russian regions.

Risk of metabolic syndrome for stroke is not greater than the sum of its components: Thai Epidemiologic Stroke (TES) study.

PubMed

Hanchaiphiboolkul, Suchat; Suwanwela, Nijasri Charnnarong; Poungvarin, Niphon; Nidhinandana, Samart; Puthkhao, Pimchanok; Towanabut, Somchai; Tantirittisak, Tasanee; Suwantamee, Jithanorm; Samsen, Maiyadhaj

2013-11-01

Limited information is available on the association between the metabolic syndrome (MetS) and stroke. Whether or not MetS confers a risk greater than the sum of its components is controversial. This study aimed to assess the association of MetS with stroke, and to evaluate whether the risk of MetS is greater than the sum of its components. The Thai Epidemiologic Stroke (TES) study is a community-based cohort study with 19,997 participants, aged 45-80 years, recruited from the general population from 5 regions of Thailand. Baseline survey data were analyzed in cross-sectional analyses. MetS was defined according to criteria from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III, the American Heart Association/National Heart, Lung, and Blood Institute (revised NCEP), and International Diabetes Federation (IDF). Logistic regression analysis was used to estimate association of MetS and its components with stroke. Using c statistics and the likelihood ratio test we compared the capability of discriminating participants with and without stroke of a logistic model containing all components of MetS and potential confounders and a model also including the MetS variable. We found that among the MetS components, high blood pressure and hypertriglyceridemia were independently and significantly related to stroke. MetS defined by the NCEP (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.32-2.04), revised NCEP (OR, 2.27; 95% CI, 1.80-2.87), and IDF definitions (OR, 1.70; 95% CI, 1.37-2.13) was significantly associated with stroke after adjustment for age, sex, geographical area, education level, occupation, smoking status, alcohol consumption, and low-density lipoprotein cholesterol. After additional adjustment for all MetS components, these associations were not significant. There were no statistically significant difference (P=.723-.901) in c statistics between the model containing all MetS components and potential confounders and the model also including the MetS variable. The likelihood ratio test also showed no statistically significant (P=.166-.718) difference between these 2 models. Our findings suggest that MetS is associated with stroke, but not to a greater degree than the sum of its components. Thus, the focus should be on identification and appropriate control of its individual components, particularly high blood pressure and hypertriglyceridemia, rather than of MetS itself. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

[A retrospective study on nutritional status and growth and development of 37 children with chronic kidney disease stage 3 to 5].

PubMed

Bao, R; Chen, C Y

2016-09-01

To retrospectively analyze the nutritional status and growth and development situation of the children with chronic kidney disease stage 3 to 5 when they were diagnosed at the first visit. After searching for the data of all the hospitalized cases during January 2007 to September 2015 in the Department of Nephrology of Children's Hospital Affiliated to the Capital Institute of Pediatrics from the medical record system, data of 37 cases with complete clinical data were collected; all these cases were diagnosed as chronic kidney disease stage 3 to 5 according to the diagnostic criteria.We recorded these children's age, height, weight, body mass index, albumin, blood lipids and acidosis situation when they were first diagnosed, and then, analyzed and summarized their nutritional status and growth and development situation. In these 37 cases, 24 cases were boys and 13 cases were girls; 23 cases (62%) were shorter than the third percentile of age-sex-specific height; 18 cases (49%) exhibited lower weight than the third percentile of age-sex-specific weight; 5 cases (13.5%) showed lower BMI than the third percentile of height-age BMI, and 5 cases (13.5%) had obesity. The level of albumin was (37.0±8.7) g/L, and no statistically significant difference was observed within each stage. In all of these cases, 10 cases were hypoalbuminemia (27%), and the difference of its frequency between stage 3-4 and stage 5 was not statistically significant. Triglyceride was (2.2±1.1) mmol/L. The mean level was higher than the normal range, but with no statistically significant difference within each stage; 21 cases (62%) were diagnosed as hypertriglyceridemia, which were more frequent compared with the occurrence of the hypercholesterolemia (32%), the high low density lipoprotein (26%) and the low high density lipoprotein(12%). And the occurrence of decompensated metabolic acidosis in stage 5 (69%) was significantly higher than that in stage 3-4 (38%) (P=0.036 6, <0.05). Growth retardation is highly prevalent among the children with chronic kidney disease stage 3 to 5. It would become more frequent and more serious as the stage worsening. Both underweight and obesity could be observed in this kind of children. Low serum albumin level is not a sensitive indicator of malnutrition in these children. The mean value of triglyceride in the children with chronic kidney disease was higher than the normal range. And hypertriglyceridemia is the most common abnormal lipid metabolism in our study.

[The optimal cutoff point of waist-to-hip ratio for screening Uyghur population aged 35 years and over at high-risk of cardiovascular diseases in Xinjiang].

PubMed

Abudukeremu, Nuremanguli; Pan, Shuo; Ma, Yitong; Yang, Yining; Ma, Xiang; Li, Xiaomei; Fu, Zhenyan; Huang, Ying; Xie, Xiang; Liu, Fen; Chen, Bangdang; Yu, Zixiang; Chen, You; He, Chunhui; Zheng, Yingying; Li, Shuangshuang; Jia, Lin; Wang, Yongtao

2015-02-01

To explore the appropriate waist-to-hip ratio (WHR) cutoffs to identify people at high risk of cardiovascular disease of Uygur population aged 35 years and over in Xinjiang. The cardiovascular risk survey (CRS) in Xinjiang was conducted from October 2007 to March 2010, using 4-stagestratified random sampling method and 14 618 representative participated this survey, and the questionnaire survey, anthropometric data, blood pressure, serum total cholesterol, triglyceride, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) and fasting glucose were measured. A total of 4 657 participants aged 35 years and over with complete anthropometric data were analyzed. The sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of different WHR levels predicting risk factors of cardiovascular disease were calculated. The analysis method of ROC curve was used to determine the optimum cut-off point of WHR predicting risk factors of cardiovascular disease. (1) There were significantly differences in prevalence of hypertension, diabetes mellitus, hypercholesterolemia, low HDL-C level, and hypertriglyceridemia between WHR < 0.75,0.75 ≤ WHR < 0.80,0.80 ≤ WHR < 0.85,0.85 ≤ WHR < 0.90,0.90 ≤ WHR < 0.95,0.95 ≤ WHR < 1.00, WHR ≥ 1.00 in male participants (P < 0.01 or 0.05), LDL-C level was similar among groups in males (P = 0.139). There were significantly differences in prevalence of hypertension, diabetes mellitus, hypercholesterolemia and hypertriglyceridemia between WHR < 0.75,0.75 ≤ WHR < 0.80,0.80 ≤ WHR < 0.85,0.85 ≤ WHR < 0.90,0.90 ≤ WHR < 0.95,0.95 ≤ WHR < 1.00, WHR ≥ 1.00 in female participants (all P < 0.01), and there were no significantly differences in prevalence of high LDL-C level and low HDL-C level among groups in females (both P > 0.05). (2) ROC analysis for hypertension, dyslipidemia, diabetes and ≥ 2 of these risk factors suggested a WHR cutoff of 0.92 for men and 0.90 for women as the optimal cutoff value for predicting high risk of cardiovascular disease of Uygur population aged 35 years and over in Xinjiang. Higher WHR cutoffs are needed for screening people at high risk of cardiovascular disease among Uygur population aged 35 years and over in Xinjiang.

The feasibility of transradial laser atherectomy for chronic total occlusion using the 5 Fr sheath system.

PubMed

Sherif, Khaled; Yaqub, Yasir; Suarez, Jose A

2016-05-01

We present a case of chronic total occlusion (CTO) approached with LASER endovascular intervention by radial artery approach using a 5 French sheath. A 57-year-old man presented to our hospital having had retrosternal chest pain for two days. Physical examination was normal at the time of presentation. The laboratory tests were within normal limits, including cardiac enzymes except the lipid panel which showed hypertriglyceridemia. The patient underwent a myocardial perfusion scintigraphy stress test that revealed inferior wall ischemia, with normal left ventricular ejection fraction. A 5-French vascular sheath was placed in the right radial artery. Selective coronary artery angiography was performed, which showed right coronary artery (RCA) CTO. A 5-French JR4 guide catheter successfully engaged the RCA and Laser angioplasty was performed across the CTO into the RCA. A marked improvement of flow was evident thereafter. To best of our knowledge this is the first case report showing the feasibility of laser atherectomy using the 5 French sheath system in a coronary arterial CTO. Copyright © 2016 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Metabolic Syndrome Does Not Detect Metabolic Risk in African Men Living in the U.S.

PubMed Central

Ukegbu, Ugochi J.; Castillo, Darleen C.; Knight, Michael G.; Ricks, Madia; Miller, Bernard V.; Onumah, Barbara M.; Sumner, Anne E.

2011-01-01

OBJECTIVE Metabolic risk and metabolic syndrome (MetSyn) prevalence were compared in Africans who immigrated to the U.S. and African Americans. If MetSyn were an effective predictor of cardiometabolic risk, then the group with a worse metabolic risk profile would have a higher rate of MetSyn. RESEARCH DESIGN AND METHODS Cross-sectional analyses were performed on 95 men (39 Africans, 56 African Americans, age 38 ± 6 years [mean ± SD]). Glucose tolerance was determined by oral glucose tolerance test, visceral adipose tissue (VAT) was determined by computerized tomography, and MetSyn was determined by the presence of three of five factors: central obesity, hypertriglyceridemia, low levels of HDL cholesterol, hypertension, and fasting hyperglycemia. RESULTS MetSyn prevalence was similar in Africans and African Americans (10 vs. 13%, P = 0.74), but hypertension, glycemia (fasting and 2-h glucose), and VAT were higher in Africans. CONCLUSIONS African immigrants have a worse metabolic profile than African Americans but a similar prevalence of MetSyn. Therefore, MetSyn may underpredict metabolic risk in Africans. PMID:21873563

Metabolic syndrome: pathogenesis, medical care and dental implications.

PubMed

Friedlander, Arthur H; Weinreb, Jane; Friedlander, Ida; Yagiela, John A

2007-02-01

The dental literature contains little information about metabolic syndrome (MetS) and its dental implications. The authors conducted a MEDLINE search for the period 2000 through 2005, using the term "metabolic syndrome" to define its pathophysiology, medical treatment and dental implications. MetS is the co-occurrence of abdominal obesity, hyper-triglyceridemia, reduced high-density lipoprotein cholesterol levels, hypertension and impaired fasting glucose, which results from consumption of a high-calorie diet and decreased levels of physical activity superimposed on the appropriate genetic setting. Components of MetS synergistically promote the development of atherosclerosis, resulting in myocardial infarction and stroke. Deteriorating oral health status is associated with worsening of the atherogenic profile. Tooth loss often results in chewing difficulties because of inadequate occlusive surfaces and may lead to alterations in food selection and dietary quality. This, in turn, adversely affects body composition and nutritional status, both of which are related to vascular health. Dentists should develop treatment plans that preserve and restore the dentition, thus ensuring maximum masticatory efficiency and affording patients the optimum opportunity to consume food that will not foster atherogenesis.

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

PubMed

Hadigan, C; Meigs, J B; Corcoran, C; Rietschel, P; Piecuch, S; Basgoz, N; Davis, B; Sax, P; Stanley, T; Wilson, P W; D'Agostino, R B; Grinspoon, S

2001-01-01

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

The role of keto acids in the supportive treatment of children with chronic renal failure.

PubMed

Mir, Sevgi; Ozkayin, Nese; Akgun, Aysegul

2005-07-01

According to the hyperfiltration theory of renal diseases characterized by a decrease in the number of functional nephrons, increased arterial blood pressure, excessive protein intake in the diet, high levels of calcium (Ca) and phosphorus (P), secondary hyperparathyroidism, hypertriglyceridemia and/or hypercholesterolemia, proteinuria and metabolic acidosis are some factors that impair the prognosis of the disease. The amount of protein in the diet is the most important of these factors. A protein-restricted diet administered to patients with chronic renal failure results in the risk of inadequate amino acid intake. To overcome this problem, the use of dysaminated alpha-keto analogues has been considered to reduce the risk of nitrogenemia resulting from the continuous intake of essential amino acids. Currently, the necessity of essential amino acids even in adult patients with chronic renal failure is controversial; besides, trials on the use of these amino acids in pediatric patients are scarce. The aim of this study is to investigate the efficacy and applicability of conservative therapy with a protein-restricted diet supplemented with keto acids in the management of chronic renal insufficiency or failure.

Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koo, Hyun-Young; Miyashita, Michio; Department of Pediatrics, Nihon University School of Medicine, Itabashi, Tokyo

2009-12-11

Diets high in fructose cause hypertriglyceridemia and insulin resistance in part due to simultaneous induction of gluconeogenic and lipogenic genes in liver. We investigated the mechanism underlying the unique pattern of gene induction by dietary fructose. Male Sprague-Dawley rats (n = 6 per group) were meal-fed (4 h/d) either 63% (w/w) glucose or 63% fructose diet. After two weeks, animals were killed at the end of the last meal. Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats. Nuclear FoxO1 was elevated 1.7 times in fructose group, but did not reach significance (P = 0.08). Unexpectedly, nomore » difference was observed in nuclear ChREBP between two groups. However, ChREBP DNA binding was 3.9x higher in fructose-fed animals without an increase in xylulose-5-phospate, a proposed ChREBP activator. In conclusion, the gene induction by dietary fructose is likely to be mediated in part by simultaneously increased ChREBP activity, SREBP-1 and possibly FoxO1 protein in nucleus.« less

Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids.

PubMed

Deckelbaum, Richard J; Leaf, Alexander; Mozaffarian, Dariush; Jacobson, Terry A; Harris, William S; Akabas, Sharon R

2008-06-01

After the symposium "Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids," faculty who presented at the conference submitted manuscripts relating to their conference topics, and these are presented in this supplement. The content of these manuscripts was reviewed, and 2 conference calls were convened. The objective was to summarize existing evidence, gaps in evidence, and future research needed to strengthen recommendations for specific intakes of n-3 fatty acids for different conditions relating to cardiovascular disease. The following 2 questions were the main items discussed. What are the roles of n-3 fatty acids in primary versus secondary prevention of coronary heart disease? What are the roles of n-3 fatty acids in hypertriglyceridemia, in the metabolic syndrome and type 2 diabetes, and in sudden cardiac death, cardiac arrhythmias, and vulnerable plaque? Each area was summarized by using 2 general categories: 1) current knowledge for which general consensus exists, and 2) recommendations for research and policy. Additional references for these conclusions can be found in the articles included in the supplement.

Cardiovascular Consequences of Metabolic Syndrome

PubMed Central

Tune, Johnathan D.; Goodwill, Adam G.; Sassoon, Daniel J.; Mather, Kieren J.

2017-01-01

The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiologic mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review we highlight current knowledge regarding the pathophysiologic consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiologic and molecular mechanisms that may contribute to these adverse outcomes. PMID:28130064

Cholesterol treatment guidelines update.

PubMed

Safeer, Richard S; Ugalat, Prabha S

2002-03-01

Hypercholesterolemia is one of the major contributors to atherosclerosis and coronary heart disease in our society. The National Cholesterol Education Program of the National Institutes of Health has created a set of guidelines that standardize the clinical assessment and management of hypercholesterolemia for practicing physicians and other professionals in the medical community. In May 2001, the National Cholesterol Education Program released its third set of guidelines, reflecting changes in cholesterol management since their previous report in 1993. In addition to modifying current strategies of risk assessment, the new guidelines stress the importance of an aggressive therapeutic approach in the management of hypercholesterolemia. The major risk factors that modify low-density lipoprotein goals include age, smoking status, hypertension, high-density lipoprotein levels, and family history. The concept of "CHD equivalent" is introduced-conditions requiring the same vigilance used in patients with coronary heart disease. Patients with diabetes and those with a 10-year cardiac event risk of 20 percent or greater are considered CHD equivalents. Once low-density lipoprotein cholesterol is at an accepted level, physicians are advised to address the metabolic syndrome and hypertriglyceridemia.

The effect of high-fructose corn syrup consumption on triglycerides and uric acid.

PubMed

Angelopoulos, Theodore J; Lowndes, Joshua; Zukley, Linda; Melanson, Kathleen J; Nguyen, Von; Huffman, Anik; Rippe, James M

2009-06-01

Rates of overweight and obesity have been on a steady rise for decades, and the problems society faces from this and associated metabolic diseases are many. As a result, the need to understand the contributing factors is great. A very compelling case can be made that excess sugar consumption has played a significant role. In addition, fructose, as a component of the vast majority of caloric sweeteners, is seen to be particularly insidious. Evidence shows that fructose bypasses many of the body's satiating signals, thus potentially promoting overconsumption of energy, weight gain, and the development on insulin resistance. It has also been shown to increase uric acid levels, which in turn promotes many of the abnormalities seen in the metabolic syndrome including hypertriglyceridemia. However, the main source of fructose in the diet is high-fructose corn syrup (HFCS), an artificially manufactured disaccharide that is only 55% fructose. This review highlights the fact that limited data are available about the metabolic effects of HFCS compared with other caloric sweeteners. The data suggest that HFCS yields similar metabolic responses to other caloric sweeteners such as sucrose.

The Production of Nitric Oxide, IL-6, and TNF-Alpha in Palmitate-Stimulated PBMNCs Is Enhanced through Hyperglycemia in Diabetes

PubMed Central

Volpe, Caroline Maria Oliveira; Abreu, Luana Farnese Machado; Gomes, Pollyanna Stephanie; Gonzaga, Raquel Miranda; Veloso, Clara Araújo; Nogueira-Machado, José Augusto

2014-01-01

We examined nitric oxide (NO), IL-6, and TNF-α secretion from cultured palmitate-stimulated PBMNCs or in the plasma from type 2 diabetes mellitus (T2MD) patients or nondiabetic (ND) controls. Free fatty acids (FFA) have been suggested to induce chronic low-grade inflammation, activate the innate immune system, and cause deleterious effects on vascular cells and other tissues through inflammatory processes. The levels of NO, IL-6, TNF-α, and MDA were higher in supernatant of palmitate stimulated blood cells (PBMNC) or from plasma from patients. The results obtained in the present study demonstrated that hyperglycemia in diabetes exacerbates in vitro inflammatory responses in PBMNCs stimulated with high levels of SFA (palmitate). These results suggest that hyperglycemia primes PBMNCs for NO, IL-6, and TNF-alpha secretion under in vitro FFA stimulation are associated with the secretion of inflammatory biomarkers in diabetes. A combined therapy targeting signaling pathways activated by hyperglycemia in conjunction with simultaneous control of hyperglycemia and hypertriglyceridemia would be suggested for controlling the progress of diabetic complications. PMID:24803982

Metabolic syndrome: a common problem among office workers.

PubMed

Alavi, S S; Makarem, J; Mehrdad, R; Abbasi, M

2015-01-01

Metabolic syndrome (MSx) is associated with several health problems. Workers are an important part of any organization. To determine the prevalence of MSx and related variables among office workers. This cross-sectional study evaluated 1488 office workers in Qom province, Central Iran, by using a multi-stage cluster sampling. Diagnosis of MSx was based on blood HDL-cholesterol, triglyceride, and fasting blood sugar (FBS) levels and waist circumference, and blood pressure. The overall prevalence of MSx was 35.9% (95% CI 33.5% to 38.3%), higher in men (37.2%) than in women (20.6%), and increased with age. The most common laboratory findings of MSx were hypertriglyceridemia (45.9%) and low HDL-cholesterol level (45.5%). Office workers with MSx had a significantly (p<0.001) higher body mass index than those without MSx. Lack of regular leisure time physical activity (p=0.003), and low intake of fruits (p=0.02) were associated with MSx. The prevalence of MSx was very high among office workers. Workplace health improvement programs through identifying and preventing MSx are necessary for improvement of staff's health.

Targeting APOC3 in the familial chylomicronemia syndrome.

PubMed

Gaudet, Daniel; Brisson, Diane; Tremblay, Karine; Alexander, Veronica J; Singleton, Walter; Hughes, Steven G; Geary, Richard S; Baker, Brenda F; Graham, Mark J; Crooke, Rosanne M; Witztum, Joseph L

2014-12-04

The familial chylomicronemia syndrome is a genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis due to a deficiency in lipoprotein lipase (LPL). Currently, there are no effective therapies except for extreme restriction in the consumption of dietary fat. Apolipoprotein C-III (APOC3) is known to inhibit LPL, although there is also evidence that APOC3 increases the level of plasma triglycerides through an LPL-independent mechanism. We administered an inhibitor of APOC3 messenger RNA (mRNA), called ISIS 304801, to treat three patients with the familial chylomicronemia syndrome and triglyceride levels ranging from 1406 to 2083 mg per deciliter (15.9 to 23.5 mmol per liter). After 13 weeks of study-drug administration, plasma APOC3 levels were reduced by 71 to 90% and triglyceride levels by 56 to 86%. During the study, all patients had a triglyceride level of less than 500 mg per deciliter (5.7 mmol per liter) with treatment. These data support the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.

Role of the blood–brain barrier in the evolution of feeding and cognition

PubMed Central

Banks, William A

2012-01-01

The blood–brain barrier (BBB) regulates the blood-to-brain passage of gastrointestinal hormones, thus informing the brain about feeding and nutritional status. Disruption of this communication results in dysregulation of feeding and body weight control. Leptin, which crosses the BBB to inform the CNS about adiposity, provides an example. Impaired leptin transport, especially coupled with central resistance, results in obesity. Various substances/conditions regulate leptin BBB transport. For example, triglycerides inhibit leptin transport. This may represent an evolutionary adaptation in that hypertriglyceridemia occurs during starvation. Inhibition of leptin, an anorectic, during starvation could have survival advantages. The large number of other substances that influence feeding is explained by the complexity of feeding. This complexity includes cognitive aspects; animals in the wild are faced with cost/benefit analyses to feed in the safest, most economical way. This cognitive aspect partially explains why so many feeding substances affect neurogenesis, neuroprotection, and cognition. The relation between triglycerides and cognition may be partially mediated through triglyceride's ability to regulate the BBB transport of cognitively active gastrointestinal hormones such as leptin, insulin, and ghrelin. PMID:22612379

[The polymetabolic syndrome. The experiences of the DRECE study. Dieta y Riesgo de Enfermedades Cardiovasculares en España].

PubMed

Gutiérrez Fuentes, J A

1995-01-01

Different risk factors frequent in NIDDM predispose to suffer an early atherosclerosis. Among these and beside lipidic disorders (hypercholesterolemia, hypertriglyceridemia and low HDL-cholesterol levels), hyperinsulinemia and/or insulin resistance, obesity and arterial hypertension are placed. In Spain, 135,000/year deaths from cardiovascular diseases (42% of total deaths) are produced. To plan a preventive strategy requires the knowledge and previous analysis among the population of the situation with regard to risk factors. In order to know in Spain the actual prevalence of cholesterol and other lipidic fractions and their relationship with different dietetic habits and other cardiovascular risk factors, a study on "Diet and Cardiovascular Risk Diseases in Spain": DRECE, was performed. Remains to be explained in the mediterranean countries the low incidence of coronary morbid/mortality, in spite of a high fat consume and cholesterol levels. In this direction, the role of a few micronutrients and other common elements in our diet, some of them with antioxidant properties, may have as protector agents in the atherosclerotic ischemic heart disease process, acquires interest.

[Severe hypertriglyceridemia--an important cause of pancreatitis].

PubMed

Graesdal, Asgeir

2008-05-01

Moderate hypertriglyceridaemia is a risk factor for cardiovascular disease and serious hypertriglyceridaemia, with triglyceride values above 10 mmol/L, increases the risk of pancreatitis. Gallstones and alcohol abuse are regarded as the two most important causes of acute pancreatitis, but the considerable risk posed by hypertriglyceridaemia has probably been underrated. It is therefore crucial to acquire updated knowledge and awareness of the fact that high levels of triglycerides can cause pancreatitis. This article is based on current literature retrieved though a search on the topic and clinical experience. Serious hypertriglyceridaemia is a relatively rare condition and its usual cause is genetic predisposition combined with obesity, diabetes or alcohol abuse. Certain types of medication, as well as pregnancy, are also well known causes. Current literature suggests that hypertriglyceridaemia is the cause of pancreatitis in 1-38% of the cases--a substantial variation. The condition is often accompanied by low amylase values and may therefore be underrated as a cause. Our case reports illustrate that the etiology is complex. Plasmapheresis or LDL-apheresis may be indicated when conservative treatment proves insufficient.

Severe hypertriglyceridemia secondary to venlafaxine use in an older adult on dialysis -case report.

PubMed

Lin, Hsiang-Wen; Simonavice, Cory A; Lu, Chiung-Ray; Lin, Wen-Ling; Wu, Po-Lun; Chou, Che-Yi; Liao, Chun-Hui; Lane, Hsieh-Yuan

2017-04-13

Although the prescribing information for Venlafaxine extended release includes a discussion about possible increases in total cholesterol and triglycerides (TG) seen in healthier adult patients during premarketing clinical trials, no post-marketing studies or case reports, that discuss the effects of venlafaxine on TG in elderly patients with chronic kidney disease. We report a 71 year-old male patient with end-stage renal disease on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia, and hypertension. This patient twice demonstrated the severe rises in triglycerides while taking the antidepressant, i.e., venlafaxine, and discontinuing the long-term use of fenofirate. The adverse drug reaction sub-committee at the hospital rated the second event as a "probable reaction" using the Naranjo nomogram, accordingly. This case demonstrates the risk of changes in lipid profiles while taking venlafaxine and receiving on and off fenofibrate therapy in the older adult patient with chronic kidney disease and under hemodialysis. Regular monitoring for lipid changes after starting venlafaxine is strongly advised for patients with existing risk factors.

Lipemia retinalis preceding acute pancreatitis.

PubMed

Horton, Matt; Thompson, Kelly

2011-08-01

Lipemia retinalis is a visible ophthalmic manifestation of severe hypertriglyceridemia. It may also be the only systemic sign present if triglycerides are acutely elevated in an asymptomatic patient. It may be the harbinger of more serious complications, such as acute pancreatitis and coronary artery disease. A 39-year-old woman presented for a diabetic eye examination. Dilated fundus examination found diffuse whitening of the retinal arteries and veins. The patient was asymptomatic without other remarkable ocular or systemic signs. The patient subsequently experienced an episode of acute pancreatitis. After a relative normalization of the triglyceride levels, the retina returned to baseline appearance. The patient's ocular health is monitored annually, and her endocrinologist modified the treatment regimen for improved lipid control. Although lipemia retinalis does not typically result in vision loss, it is a sign of a systemic condition that can have potentially fatal consequences. While the retinal appearance normalizes soon after resolution of the acute lipid imbalance, a multidisciplinary approach is necessary to obtain the desirable systemic outcome. Optometrists play a critical role in prompt referral of these patients for appropriate management of their lipids. Published by Elsevier Inc.

Metabolic syndrome, insulin resistance and other cardiovascular risk factors in university students.

PubMed

Barbosa, José Bonifácio; dos Santos, Alcione Miranda; Barbosa, Marcelo Mesquita; Barbosa, Márcio Mesquita; de Carvalho, Carolina Abreu; Fonseca, Poliana Cristina de Almeida; Fonseca, Jessica Magalhães; Barbosa, Maria do Carmo Lacerda; Bogea, Eduarda Gomes; da Silva, Antônio Augusto Moura

2016-04-01

A cross-sectional population-based study using questionnaire and anthropometric data was conducted on 968 university students of São Luís, Brazil, from which 590 showed up for blood collection. In the statistical analysis the Student t-test, Mann-Whitney and chi-square tests were used. The prevalence of metabolic syndrome by the Joint Interim Statement (JIS) criteria was 20.5%, almost three times more prevalent in men (32.2%) than in women (13.5%) (P < 0.001). The prevalence of insulin resistance was 7.3% and the prevalence of low HDL-cholesterol was high (61.2%), both with no statistically significant differences by sex. Men showed a higher percentage of smoking, overweight, high blood pressure, high blood glucose and increased fasting hypertriglyceridemia. Women were more sedentary. University students of private institutions had higher prevalences of sedentary lifestyle, obesity, abdominal obesity, elevated triglycerides and metabolic syndrome than students from public institutions. High prevalences of metabolic syndrome, insulin resistance and other cardiovascular risk factors were found in this young population. This suggests that the burden of these diseases in the future will be increased.

Fructose impairs glucose-induced hepatic triglyceride synthesis

PubMed Central

2011-01-01

Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases. PMID:21261970

A visceral adiposity index-related dietary pattern and the cardiometabolic profiles in women with polycystic ovary syndrome.

PubMed

Ehsani, Behnaz; Moslehi, Nazanin; Mirmiran, Parvin; Ramezani Tehrani, Fahimeh; Tahmasebinejad, Zhale; Azizi, Fereidoun

2016-10-01

Visceral adiposity index (VAI), an indicator of visceral adiposity, has been found to be associated with cardiometabolic disturbances in women with polycystic ovary syndrome (PCOS). The association of dietary intakes with VAI, and subsequently cardiometabolic variables is still unclear. The aims of this study were to identify a dietary pattern associated with VAI and to investigate whether this pattern is associated with cardiometabolic variables in PCOS women. The study was conducted on 53 PCOS women, aged 18-45 years, diagnosed according to National Institutes of Health (NIH) criteria, and 167 age-matched normo-ovulatory women who were recruited from the Tehran Lipid and Glucose Study. Reduced rank regression was applied to determine a dietary pattern that explains the maximum variation of the VAI. Associations between the dietary pattern and cardiometabolic profiles were investigated using linear and logistic regression, adjusted for age and BMI. A VAI dietary pattern was identified characterized by high consumption of fried vegetables, vegetable oils (except olive oil), salty snacks, legumes, eggs, fast foods and low consumption of traditional sweets, high and low fat dairy, cruciferous vegetables, sugars and honey. A one standard deviation (SD) increase in dietary pattern score was significantly associated with higher triglycerides (TGs) (βcontrol = 0.22, p = 0.003; βcase = 0.48, p = 0.001) and TGs/HDL-C ratio (βcontrol = 0.23, p = 0.002; βcase = 0.52, p = 0.001) in both groups. After adjusting for age and BMI, a 1-SD increase in dietary pattern score was associated with increased risk of VAD in PCOS (OR 2.77; 95% CI 1.15, 6.66) and control groups (OR 2.41; 95% CI 1.41-4.12). In the control group, the risk of hypercholesterolemia, hypertriglyceridemia, high LDL-C, low HDL-C, hyperglycemia and IGT + IFG increased significantly per 1-SD increase in dietary pattern score, which all remained significant after adjusting for age and BMI, except for the risk of high LDL-C. Among the cardiometabolic abnormalities, only the risk of hypertriglyceridemia was significantly associated with dietary pattern score in women with PCOS, which lost its significance after adjusting for age and BMI. The VAI dietary pattern affects most cardiometabolic variables in controls, but to a lesser extent in PCOS women. Our study suggests that relationships between diet and cardiometabolic risk profiles may be modified by PCOS status. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Arterial function parameters in patients with metabolic syndrome and severe hypertriglyceridemia.

PubMed

Rinkūnienė, Egidija; Butkutė, Eglė; Puronaitė, Roma; Petrulionienė, Žaneta; Dženkevičiūtė, Vilma; Kasiulevičius, Vytautas; Laucevičius, Aleksandras

Hypertriglyceridemia (hTG) is 1 of the dyslipidemia manifestations in patients with metabolic syndrome (MetS). However, for several decades, the role of hTG in cardiovascular risk was not well established. The aim of this study was to assess the parameters of the vascular structure and function in patients with MetS and different degree of hTG. Patients (aged 40-65 years) with MetS were divided into 3 groups by triglyceride (TG) levels according to National Cholesterol Education Program Adult Treatment Panel III Guidelines: severe hTG (TG ≥ 500 mg/dL), moderate hTG (TG 200-499 mg/dL), and a control (TG < 150 mg/dL) groups. Noninvasive assessment of vascular parameters (aortic augmentation index adjusted for heart rate 75 bpm [AixHR75], pulse wave velocity [PWV], flow-mediated dilatation, and common carotid artery intima-media thickness (IMT)) were performed. Among the 1938 patients analyzed, 1041 had hTG. Moderate hTG was observed in 90.40% (n = 941), whereas severe TG was observed in 9.6% (n = 100) of patients. Overall TG concentration was 231.17 ± 184.23 mg/dL; in severe hTG group, TG concentration was 795.36 ± 368.45 mg/dL, in moderate hTG group 285.20 ± 70.86 mg/dL, and 112.48 ± 24.80 mg/dL in control group. AIxHR75 and IMT were the lowest in the severe hTG group (P < .001 for both). Mean arterial pressure, carotid-radial PWV (9.25 ± 1.13 vs 9.24 ± 1.28 vs 8.91 ± 1.28; P < .001) as well as carotid-femoral PWV (8.63 ± 1.65 vs 8.75 ± 1.58 vs 8.51 ± 1.6; P = .006) were the higher in hTG groups compared with control. There were no significant differences between groups in flow-mediated dilatation (3.39 ± 2.01 vs 3.26 ± 2.43 vs 3.45 ± 2.61, P = .283). Patients with MetS and severe hTG have lower IMT and AIxHR75 and higher PWV and mean arterial pressure. Many factors could affect arterial parameters, and more research are needed to investigate arterial parameters and hTG connection. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects: comparison with dextrose and sucrose.

PubMed

Al-Waili, Noori S

2004-01-01

This study included the following experiments: (1) effects of dextrose solution (250 mL of water containing 75 g of dextrose) or honey solution (250 mL of water containing 75 g of natural honey) on plasma glucose level (PGL), plasma insulin, and plasma C-peptide (eight subjects); (2) effects of dextrose, honey, or artificial honey (250 mL of water containing 35 g of dextrose and 40 g of fructose) on cholesterol and triglycerides (TG) (nine subjects); (3) effects of honey solution, administered for 15 days, on PGL, blood lipids, C-reactive protein (CRP), and homocysteine (eight subjects); (4) effects of honey or artificial honey on cholesterol and TG in six patients with hypercholesterolemia and five patients with hypertriglyceridemia; (5) effects of honey for 15 days on blood lipid and CRP in five patients with elevated cholesterol and CRP; (6) effects of 70 g of dextrose or 90 g of honey on PGL in seven patients with type 2 diabetes mellitus; and (7) effects of 30 g of sucrose or 30 g of honey on PGL, plasma insulin, and plasma C-peptide in five diabetic patients. In healthy subjects, dextrose elevated PGL at 1 (53%) and 2 (3%) hours, and decreased PGL after 3 hours (20%). Honey elevated PGL after 1 hour (14%) and decreased it after 3 hours (10%). Elevation of insulin and C-peptide was significantly higher after dextrose than after honey. Dextrose slightly reduced cholesterol and low-density lipoprotein-cholesterol (LDL-C) after 1 hour and significantly after 2 hours, and increased TG after 1, 2, and 3 hours. Artificial honey slightly decreased cholesterol and LDL-C and elevated TG. Honey reduced cholesterol, LDL-C, and TG and slightly elevated high-density lipoprotein-cholesterol (HDL-C). Honey consumed for 15 days decreased cholesterol (7%), LDL-C (1%), TG (2%), CRP (7%), homocysteine (6%), and PGL (6%), and increased HDL-C (2%). In patients with hypertriglyceridemia, artificial honey increased TG, while honey decreased TG. In patients with hyperlipidemia, artificial honey increased LDL-C, while honey decreased LDL-C. Honey decreased cholesterol (8%), LDL-C (11%), and CRP (75%) after 15 days. In diabetic patients, honey compared with dextrose caused a significantly lower rise of PGL. Elevation of PGL was greater after honey than after sucrose at 30 minutes, and was lower after honey than it was after sucrose at 60, 120, and 180 minutes. Honey caused greater elevation of insulin than sucrose did after 30, 120, and 180 minutes. Honey reduces blood lipids, homocysteine, and CRP in normal and hyperlipidemic subjects. Honey compared with dextrose and sucrose caused lower elevation of PGL in diabetics.

Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice

PubMed Central

De Souza, Angus T.; Dai, Xudong; Spencer, Andrew G.; Reppen, Tom; Menzie, Ann; Roesch, Paula L.; He, Yudong; Caguyong, Michelle J.; Bloomer, Sherri; Herweijer, Hans; Wolff, Jon A.; Hagstrom, James E.; Lewis, David L.; Linsley, Peter S.; Ulrich, Roger G.

2006-01-01

RNA interference (RNAi) has great potential as a tool for studying gene function in mammals. However, the specificity and magnitude of the in vivo response to RNAi remains to be fully characterized. A molecular and phenotypic comparison of a genetic knockout mouse and the corresponding knockdown version would help clarify the utility of the RNAi approach. Here, we used hydrodynamic delivery of small interfering RNA (siRNA) to knockdown peroxisome proliferator activated receptor alpha (Ppara), a gene that is central to the regulation of fatty acid metabolism. We found that Ppara knockdown in the liver results in a transcript profile and metabolic phenotype that is comparable to those of Ppara−/− mice. Combining the profiles from mice treated with the PPARα agonist fenofibrate, we confirmed the specificity of the RNAi response and identified candidate genes proximal to PPARα regulation. Ppara knockdown animals developed hypoglycemia and hypertriglyceridemia, phenotypes observed in Ppara−/− mice. In contrast to Ppara−/− mice, fasting was not required to uncover these phenotypes. Together, these data validate the utility of the RNAi approach and suggest that siRNA can be used as a complement to classical knockout technology in gene function studies. PMID:16945951

Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

PubMed Central

Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

2016-01-01

Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment. PMID:27570415

Uric Acid Stimulates Fructokinase and Accelerates Fructose Metabolism in the Development of Fatty Liver

PubMed Central

Lanaspa, Miguel A.; Sanchez-Lozada, Laura G.; Cicerchi, Christina; Li, Nanxing; Roncal-Jimenez, Carlos A.; Ishimoto, Takuji; Le, Myphuong; Garcia, Gabriela E.; Thomas, Jeffrey B.; Rivard, Christopher J.; Andres-Hernando, Ana; Hunter, Brandi; Schreiner, George; Rodriguez-Iturbe, Bernardo; Sautin, Yuri Y.; Johnson, Richard J.

2012-01-01

Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-phosphate; intracellular uric acid is also generated as a consequence of the transient ATP depletion that occurs during this reaction. Here we show in human hepatocytes that uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. Inhibition of uric acid production markedly blocked fructose-induced triglyceride accumulation in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates KHK expression involves the activation of the transcription factor ChREBP, which, in turn, results in the transcriptional activation of KHK by binding to a specific sequence within its promoter. Since subjects sensitive to fructose often develop phenotypes associated with hyperuricemia, uric acid may be an underlying factor in sensitizing hepatocytes to fructose metabolism during the development of fatty liver. PMID:23112875

[Allelic variants of apolipoproteins B and CII genes in patients with ischemic heart disease and in healthy persons from the Moscow population].

PubMed

Pogoda, T V; Nikonova, A L; Kolosova, T V; Liudvikova, E K; Perova, N V; Limborskaia, S A

1995-07-01

Allelic frequencies of a microsatellite of the apolipoprotein CII gene (APOCII) and a minisatellite of the apolipoprotein B gene (APOB) were studied using polymerase chain reaction (PCR). The study was conducted on a random sample of male Moscow inhabitants and a sample of patients with coronary heart disease (CHD) from the same population. Fourteen variants of the APOB minisatellite (the 82% heterozygosity level) and 13 alleles of the APOCII microsatellite (the 85% heterozygosity level) were found. CHD patients significantly differed from the control group in the distributions of alleles in these loci: APOB 32, APOB 46, APOB 48, and APOB 50 as well as APOCII 17 and APOCII 29 were found more frequently. A relationship was found between the distributions of APOB and APOCII in the CHD patients. The CHD patients with alleles APOCII 21 and APOCII 30 very often had the allele APOB 32; and patients with the genotype APOB 34, 36 had the allele APOCII 29 even more often than affected individuals in general. Individuals of the control group with the allele APOCII 30 exhibited hypertriglyceridemia without increased levels of total cholesterol and apolipoprotein B in plasma.

Postprandial endothelial dysfunction: role of glucose, lipids and insulin.

PubMed

Nitenberg, A; Cosson, E; Pham, I

2006-09-01

Endothelium plays a key role in the regulation of vascular tone and development of atherosclerosis. Endothelial function is impaired early in patients with risk factors and endothelial dysfunction is a strong and independent predictor of cardiovascular events. Because in normal subjects blood concentrations of glucose, lipids and insulin are increased after each meals, and postprandial changes last a long time after the meals, these changes might be of importance in the process of atherosclerosis initiation and development. Experimental and human studies have shown that a transient increase of blood concentrations of glucose, triglycerides and fatty acids, and insulin are able to depress endothelium-dependent vasodilation in healthy subjects and that hyperglycemia, hypertriglyceridemia and hyperinsulinemia are generator of reactive oxygen species at the origin of a cascade of pathophysiological events resulting in the activation of nuclear factor-kappaB. Nuclear factor-kappaB is an ubiquitous transcription factor controlling the expression of numerous genes and is involved in immunity, inflammation, regulation of cell proliferation and growth and apoptosis. These mechanisms may be involved in the development of atherosclerosis in normal subjects when food intake is chronically modified towards glucids and lipids with cumulative effects both on depression of endothelium dependent dilation and oxidative stress.

Could post-weaning dietary chia seed mitigate the development of dyslipidemia, liver steatosis and altered glucose homeostasis in offspring exposed to a sucrose-rich diet from utero to adulthood?

PubMed

Fortino, M A; Oliva, M E; Rodriguez, S; Lombardo, Y B; Chicco, A

2017-01-01

The present work analyzes the effects of dietary chia seeds during postnatal life in offspring exposed to a sucrose-rich diet (SRD) from utero to adulthood. At weaning, chia seed (rich in α-linolenic acid) replaced corn oil (rich in linoleic acid) in the SRD. At 150 days of offspring life, anthropometrical parameters, blood pressure, plasma metabolites, hepatic lipid metabolism and glucose homeostasis were analyzed. Results showed that chia was able to prevent the development of hypertension, liver steatosis, hypertriglyceridemia and hypercholesterolemia. Normal triacylglycerol secretion and triacylglycerol clearance were accompanied by an improvement of de novo hepatic lipogenic and carnitine-palmitoyl transferase-1 enzymatic activities, associated with an accretion of n-3 polyunsaturated fatty acids in the total composition of liver homogenate. Glucose homeostasis and plasma free fatty acid levels were improved while visceral adiposity was slightly decreased. These results confirm that the incorporation of chia seed in the diet in postnatal life may provide a viable therapeutic option for preventing/mitigating adverse outcomes induced by an SRD from utero to adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

PubMed Central

Mbata, Osinakachukwu; Abo El-Magd, Nada Fawzy; El-Remessy, Azza Bahram

2017-01-01

Diabetic retinopathy (DR) is the most feared ocular manifestation of diabetes. DR is characterized by progressive retinal damage that may eventually result in blindness. Clinically, this blindness is caused by progressive damage to the retinal microvasculature, which leads to ischemia, retinal swelling, and neovascularization. Retinopathy is associated with both type 1 and type 2 diabetes, with DR being the leading cause of new onset blindness in United States adults. Despite this strong association with diabetes, it must be noted that the development of retinopathy lesions is multifactorial and may occur in individuals without an established history of diabetes. Metabolic syndrome is a multifactorial condition of central obesity, hypertriglyceridemia, dyslipidemia, hypertension, fasting hyperglycemia, and insulin resistance. Although several studies examined the individual components observed in the metabolic syndrome in relation to the development of DR, there is conflicting data as to the association of the metabolic syndrome with the development of retinopathy lesions in non-diabetic subjects. This review will summarize the current literature on the evidence of the metabolic syndrome on retinopathy in subjects with and without an established history of diabetes. This review will also discuss some of the mechanisms through which metabolic syndrome can contribute to the development of retinopathy. PMID:28751954

Association of leptin with cardiometabolic factors in schoolchildren and adolescents with congenital adrenal hyperplasia.

PubMed

Zurita-Cruz, Jessie Nallely; Villasís-Keever, Miguel Ángel; Damasio-Santana, Leticia; Manuel-Apolinar, Leticia; Ferrusca-Ceja, Rosalba; Nishimura-Meguro, Elisa; Rivera-Hernández, Aleida de J; Garrido-Magaña, Eulalia

2018-01-01

In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson's correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight. Copyright: © 2018 SecretarÍa de Salud.

Overweight and metabolic and hormonal parameter disruption are induced in adult male mice by manipulations during lactation period.

PubMed

Loizzo, Alberto; Loizzo, Stefano; Galietta, Gabriella; Caiola, Stefania; Spampinato, Santi; Campana, Gabriele; Seghieri, Giuseppe; Ghirlanda, Giovanni; Franconi, Flavia

2006-01-01

Neonatal manipulations (10 min of maternal separation plus s.c. sham injection, daily for the first 21 d of life) determine overweight in male adult mice. In this work, we investigated the mechanisms underlying mild obesity and the alteration of caloric balance. Neonatally manipulated mice become overweight after onset of maturity, showing increased fat tissue and hypertrophic epididymal adipocytes. Increase in body weight occurs in the presence of a small increase in daily food intake (significant only in the adult period) and the absence of a decrease in spontaneous locomotor activity, while the calculated caloric efficiency is higher in manipulated mice, especially in adulthood. Fasting adult animals show hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and hyperleptinemia. Soon after weaning and in the adulthood, plasma corticosterone and adrenocorticotropin (ACTH) are also significantly increased. Thus, neonatal manipulations in nongenetically susceptible male mice program mild obesity, with metabolic and hormonal alterations that are similar to those found in experimental models of diabetes mellitus, suggesting that this metabolic derangement may have at least part of its roots early on in life and, more interestingly, that psychological and nociceptive stimuli induce these features.

Prevalence of Canine Obesity, Obesity-Related Metabolic Dysfunction, and Relationship with Owner Obesity in an Obesogenic Region of Spain.

PubMed

Montoya-Alonso, J Alberto; Bautista-Castaño, Inmaculada; Peña, Cristina; Suárez, Lourdes; Juste, M Candelaria; Tvarijonaviciute, Asta

2017-01-01

The main objective of this study was to evaluate the prevalence of canine obesity and obesity-related metabolic dysfunction (ORMD) in the obesogenic area in Spain. The prevalence of overweight/obesity among owners of obese pets was also evaluated. In the sample population studied (93 client-owned dogs), 40.9% of dogs presented obesity (body condition score 7-9/9), 40.9% of dogs presented hypertension, 20.4% of dogs presented fasting hypertriglyceridemia, 20.4% fasting hypercholesterolemia, and 5.4% of dogs presented fasting hyperglycemia. The overall prevalence of ORMD was of 22.6%. Seventy-eight percent of overweight/obese owners had overweight/obese dogs ( P  < 0.001) including all dogs diagnosed with ORMD. In conclusion, in the studied obesogenic region of Spain, the prevalence of canine obesity and ORMD was shown to be elevated and related to the presence of overweight/obesity in owners. All dogs with ORMD were owned by overweight/obese persons. These results provide new inputs for future studies highlighting the relationship between owner and pet obesity and indicating the need of further efforts to control and reduce obesity prevalence in both.

The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

PubMed Central

Thent, Zar Chi; Sapri, Shaiful Ridzwan; Sahruddin, Natasya Nadia; Mohd Yusof, Mohd Rafizul; Haji Suhaimi, Farihah

2014-01-01

Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW) in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome. PMID:25045660

Association between triglyceride levels and cardiovascular disease in patients with acute pancreatitis.

PubMed

Copeland, Laurel A; Swendsen, C Scott; Sears, Dawn M; MacCarthy, Andrea A; McNeal, Catherine J

2018-01-01

Conventional wisdom supports prescribing "fibrates before statins", that is, prioritizing treatment of hypertriglyceridemia (hTG) to prevent pancreatitis ahead of low-density lipoprotein cholesterol to prevent coronary heart disease. The relationship between hTG and acute pancreatitis, however, may not support this approach to clinical management. This study analyzed administrative data from the Veterans Health Administration for evidence of (1) temporal association between assessed triglycerides level and days to acute pancreatitis admission; (2) association between hTG and outcomes in the year after hospitalization for acute pancreatitis; (3) relative rates of prescription of fibrates vs statins in patients with acute pancreatitis; (4) association of prescription of fibrates alone versus fibrates with statins or statins alone with rates of adverse outcomes after hospitalization for acute pancreatitis. Only modest association was found between above-normal or extremely high triglycerides and time until acute pancreatitis. CHD/MI/stroke occurred in 23% in the year following AP, supporting cardiovascular risk management. Fibrates were prescribed less often than statins, defying conventional wisdom, but the high rates of cardiovascular events in the year following AP support a clinical focus on reducing cardiovascular risk factors.

Prevalence of metabolic syndrome and obesity in renal transplanted Mexican children.

PubMed

Ramirez-Cortes, Guadalupe; Fuentes-Velasco, Yolanda; García-Roca, Pilar; Guadarrama, Omar; López, Mónica; Valverde-Rosas, Saúl; Velásquez-Jones, Luis; Romero, Benjamin; Toussaint, Georgina; Medeiros, Mara

2009-08-01

The purpose of the study was to evaluate the prevalence of MS and obesity in Mexican children with more than one yr post-renal transplantation. Thirty-two children transplanted between January 2004 and February 2006 were included in the study. The weight and height at the time of renal transplant were obtained. A fasting blood sample was drawn for serum creatinine, adiponectin, and complete lipid profile, and a three-h glucose tolerance test was also taken. A complete nutritional evaluation was performed including anthropometry. There was a statistically significant increase in BMI at one yr post-transplant that was maintained at two yr post-transplant. Three patients exhibited obesity and were overweight. Seventeen patients had hypertension, 14 patients had low HDL, 12 patients had hypertriglyceridemia, all had normal fasting glucose, six of them had glucose intolerance, and two had waist circumference higher than 90%. Eight patients (25%) had MS. Patients with MS had higher proportion of deceased donor grafts, acute rejection episodes, and received more methylprednisolone pulses; also they had a statistically significant higher pretransplant BMI than patients without MS. There was a significant relationship between BMI at one yr post-renal transplant and creatinine clearance estimated by Schwartz formula.

The effect of shift work on red blood cell distribution width.

PubMed

Loprinzi, Paul D

2015-04-01

Limited research demonstrates that shift work (e.g., evening shift, night shift, rotating shift) increases the risk of certain health outcomes, such as hypertriglyceridemia and metabolic syndrome. Red blood cell distribution width (RDW), which is commonly assessed and reported by physicians, is a novel biomarker of cardiovascular disease. However, no study has examined the association of shift work on RDW, which was the purpose of this study. Data from the 2005-2010 NHANES were used. RDW was assessed from a blood sample; shift work was assessed from a questionnaire, and various demographic, behavioral/psychological, occupational, and biological parameters were included as covariates. The fully adjusted model showed that the odds of having an elevated RDW for women on rotating shift vs. day shift increased by 46% (OR=1.46; 95% CI: 1.03-2.08). Women on a rotating shift had increased odds of having an elevated RDW, which is concerning as elevated RDW increases the risk of cardiovascular disease and mortality. Health care professionals are encouraged to include questions about organization of work schedules and their tolerance of such schedules during the patient's consultation. Copyright © 2015 Elsevier Inc. All rights reserved.

Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.

PubMed

Kim, Chai-Wan; Addy, Carol; Kusunoki, Jun; Anderson, Norma N; Deja, Stanislaw; Fu, Xiaorong; Burgess, Shawn C; Li, Cai; Ruddy, Marcie; Chakravarthy, Manu; Previs, Steve; Milstein, Stuart; Fitzgerald, Kevin; Kelley, David E; Horton, Jay D

2017-08-01

Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074 increased plasma triglycerides by 200%. To further investigate, mice that lack ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation of SREBP-1c and increased VLDL secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

Health Implications of High-Fructose Intake and Current Research12

PubMed Central

Dornas, Waleska C; de Lima, Wanderson G; Pedrosa, Maria L; Silva, Marcelo E

2015-01-01

Although fructose consumption has dramatically increased and is suspected to be causally linked to metabolic abnormalities, the mechanisms involved are still only partially understood. We discuss the available data and investigate the effects of dietary fructose on risk factors associated with metabolic disorders. The evidence suggests that fructose may be a predisposing cause in the development of insulin resistance in association with the induction of hypertriglyceridemia. Experiments in animals have shown this relation when they are fed diets very high in fructose or sucrose, and human studies also show this relation, although with conflicting results due to the heterogeneity of the studies. The link between increased fructose consumption and increases in uric acid also has been confirmed as a potential risk factor for metabolic syndrome, and insulin resistance/hyperinsulinemia may be causally related to the development of hypertension. Collectively, these results suggest a link between high fructose intake and insulin resistance, although future studies must be of reasonable duration, use defined populations, and improve comparisons regarding the effects of relevant doses of nutrients on specific endpoints to fully understand the effect of fructose intake in the absence of potential confounding factors. PMID:26567197

Choline supplementation restores substrate balance and alleviates complications of Pcyt2 deficiency.

PubMed

Schenkel, Laila C; Sivanesan, Sugashan; Zhang, Junzeng; Wuyts, Birgitte; Taylor, Adrian; Verbrugghe, Adronie; Bakovic, Marica

2015-11-01

Choline plays a critical role in systemic lipid metabolism and hepatic function. Here we conducted a series of experiments to investigate the effect of choline supplementation on metabolically altered Pcyt2(+/-) mice. In Pcyt2(+/-) mice, the membrane phosphatidylethanolamine (PE) turnover is reduced and the formation of fatty acids (FA) and triglycerides (TAG) increased, resulting in hypertriglyceridemia, liver steatosis and obesity. One month of choline supplementation reduced the incorporation of FA into TAG and facilitated TAG degradation in Pcyt2(+/-) adipocytes, plasma and liver. Choline particularly stimulated adipocyte and liver TAG lipolysis by specific lipases (ATGL, LPL and HSL) and inhibited TAG formation by DGAT1 and DGAT2. Choline also activated the liver AMPK and mitochondrial FA oxidation gene PPARα and reduced the FA synthesis genes SREBP1, SCD1 and FAS. Liver (HPLC) and plasma (tandem mass spectroscopy and (1)H-NMR) metabolite profiling established that Pcyt2(+/-) mice have reduced membrane cholesterol/sphingomyelin ratio and the homocysteine/methionine cycle that were improved by choline supplementation. These data suggest that supplementary choline is beneficial for restoring FA and TAG homeostasis under conditions of obesity caused by impaired PE synthesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulation of Phosphatidylethanolamine Homeostasis—The Critical Role of CTP:Phosphoethanolamine Cytidylyltransferase (Pcyt2)

PubMed Central

Pavlovic, Zvezdan; Bakovic, Marica

2013-01-01

Phosphatidylethanolamine (PE) is the most abundant lipid on the protoplasmatic leaflet of cellular membranes. It has a pivotal role in cellular processes such as membrane fusion, cell cycle regulation, autophagy, and apoptosis. CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) is the main regulatory enzyme in de novo biosynthesis of PE from ethanolamine and diacylglycerol by the CDP-ethanolamine Kennedy pathway. The following is a summary of the current state of knowledge on Pcyt2 and how splicing and isoform specific differences could lead to variations in functional properties in this family of enzymes. Results from the most recent studies on Pcyt2 transcriptional regulation, promoter function, autophagy, and cell growth regulation are highlighted. Recent data obtained from Pcyt2 knockout mouse models is also presented, demonstrating the essentiality of this gene in embryonic development as well as the major physiological consequences of deletion of one Pcyt2 allele. Those include development of symptoms of the metabolic syndrome such as elevated lipogenesis and lipoprotein secretion, hypertriglyceridemia, liver steatosis, obesity, and insulin resistance. The objective of this review is to elucidate the nature of Pcyt2 regulation by linking its catalytic function with the regulation of lipid and energy homeostasis. PMID:23354482

[Diabetes in Mexico. CARMELA study].

PubMed

Escobedo-de la Peña, Jorge; Buitrón-Granados, Luisa Virginia; Ramírez-Martínez, Jesús Cenobio; Chavira-Mejía, Raymundo; Schargrodsky, Herman; Champagne, Beatriz Marcet

2011-01-01

Diabetes has demonstrated an epidemic behavior in Mexico, which is among the top countries with the highest number of patients with diabetes. The objective of this study was to estimate the prevalence of type 2 diabetes in Mexico City and its relation with some cardiovascular risk factors. A cross-sectional study was conducted. A total of 1,772 adults of both genders, aged 25 to 64 years, were randomly selected. Type 2 diabetes and impaired fasting glucose prevalence were estimated as well as its relation with some cardiovascular risk factors such as hypertension, dyslipidemia, obesity, abdominal obesity and the common carotid artery intima-media thickness. The prevalence of type 2 diabetes was 9.7% in women and 8.0% in men. An age effect was evident. The proportion of patients who were unaware of having diabetes was 26%. The main risk factors related to diabetes were age, abdominal obesity, hypertension, low high-density cholesterol lipoproteins (HDL-c) and hypertriglyceridemia. Metabolic control was low. Prevalence of type 2 diabetes in Mexico is high and is a major health problem. Its close relation with cardiovascular risk factors demand health policies aimed to diminish risk factors related to its occurrence.

[Mutations of APOC3 gene, metabolism of triglycerides and reduction of ischemic cardiovascular events].

PubMed

Pirillo, Angela; Catapano, Alberico Luigi

2015-05-01

A direct relationship between high plasma triglyceride (TG) levels and increased risk of cardiovascular disease has been shown in several studies. TG are present in the blood associated with different lipoprotein classes, including hepatically-derived very low density lipoproteins (VLDL) and intestinally-derived chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG, releasing free fatty acids that accumulate in peripheral tissues and remnant lipoproteins, that are then cleared by the liver. LPL activity is finely modulated by several cofactors, including apolipoprotein C-III (apoC-III) which acts as a LPL inhibitor. The key role of apoCIII has been established in several studies: animal models lacking APOC3 gene exhibit reduced plasma TG levels, whereas the overexpression of APOC3 gene led to increased TG levels. In humans, several mutations in APOC3 gene have been identified, leading to lower apoC-III levels and associated with reduced plasma TG levels. Recently, these mutations were found to be associated with a reduced risk for cardiovascular ischemia and coronary heart disease, thus confirming the negative role of apoC-III in TG metabolism and suggesting apoC-III as possible therapeutic target for the management of hypertriglyceridemia.

Role of the blood-brain barrier in the evolution of feeding and cognition.

PubMed

Banks, William A

2012-08-01

The blood-brain barrier (BBB) regulates the blood-to-brain passage of gastrointestinal hormones, thus informing the brain about feeding and nutritional status. Disruption of this communication results in dysregulation of feeding and body weight control. Leptin, which crosses the BBB to inform the CNS about adiposity, provides an example. Impaired leptin transport, especially coupled with central resistance, results in obesity. Various substances/conditions regulate leptin BBB transport. For example, triglycerides inhibit leptin transport. This may represent an evolutionary adaptation in that hypertriglyceridemia occurs during starvation. Inhibition of leptin, an anorectic, during starvation could have survival advantages. The large number of other substances that influence feeding is explained by the complexity of feeding. This complexity includes cognitive aspects; animals in the wild are faced with cost/benefit analyses to feed in the safest, most economical way. This cognitive aspect partially explains why so many feeding substances affect neurogenesis, neuroprotection, and cognition. The relation between triglycerides and cognition may be partially mediated through triglyceride's ability to regulate the BBB transport of cognitively active gastrointestinal hormones such as leptin, insulin, and ghrelin. © 2012 New York Academy of Sciences.

Cytophagic histiocytic panniculitis and hemophagocytic lymphohistiocytosis: an overview.

PubMed

Aronson, Iris K; Worobec, Sophie M

2010-01-01

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis that is associated with systemic features including fevers, hepatosplenomegaly, lymphadenopathy, pancytopenia, hepatic abnormalities, hypertriglyceridemia, and coagulopathy without an elevated erythrocyte sedimentation rate. The panniculitis lesions show adipose tissue lymphocytic and histiocytic infiltration along with hemophagocytosis, which may also appear in bone marrow, spleen, lymph nodes, and liver. Patients may have a rapidly fatal disease course, a longer disease course with intermittent remissions and exacerbations for many years prior to death, or a nonfatal acute or intermittent course responsive to treatment. The cytophagocytic disorder in these patients is a hemophagocytic lymphohistiocytosis (HLH), similar to the infection-activated reaction associated with perforin mutations found in familial hemophagocytic lymphohistiocytosis. HLH is a group of autoinflammatory disorders, which include macrophage activation syndrome and infection-associated hemophagocytic syndrome, which if not treated rapidly, can be fatal. The relationship of CHP and HLH is discussed. CHP associated diseases include: subcutaneous panniculitis-like T cell lymphomas; infections, connective tissue diseases, other malignancies, and the molecular disorders that cause HLH. Treatment of CHP includes: glucocorticoids in combination with cyclosporine, combined chemotherapeutic medications and most recently, anakinra, an Interleukin-1 receptor antagonist; along with supportive care, search for underlying malignancies and treatment thereof, and control of associated infections.

Drinking orange juice increases total antioxidant status and decreases lipid peroxidation in adults.

PubMed

Foroudi, Shahrzad; Potter, Andrew S; Stamatikos, Alexis; Patil, Bhimanagouda S; Deyhim, Farzad

2014-05-01

Cardiovascular disease (CVD) is the leading cause of death in the world and is the primary cause of mortality among Americans. One of the many reasons for the pathogenesis of CVD is attributed to eating diets high in saturated fat and refined carbohydrates and low in fruits and vegetables. Epidemiological evidence has supported a strong association between eating diets rich in fruits and vegetables and cardiovascular health. An experiment was conducted utilizing 24 adults with hypercholesterolemia and hypertriglyceridemia to evaluate the impact of drinking 20 fl oz of freshly squeezed orange juice daily for 90 days on blood pressure, lipid panels, plasma antioxidant capacity, metabolic hormones, lipid peroxidation, and inflammatory markers. Except for addition of drinking orange juice, subjects did not modify their eating habits. The findings suggested that drinking orange juice does not affect (P>.1) blood pressure, lipid panels, metabolic hormones, body fat percentage, or inflammatory markers. However, total plasma antioxidant capacity was significantly increased (P<.05) and lipid peroxidation was significantly decreased (P<.05) after orange juice consumption. Drinking orange juice may protect the cardiovascular system by increasing total plasma antioxidant status and by lowering lipid peroxidation independent of other cardiovascular risk markers evaluated in this study.

Identification of a botanical inhibitor of intestinal diacylglyceride acyltransferase 1 activity via in vitro screening and a parallel, randomized, blinded, placebo-controlled clinical trial.

PubMed

Velliquette, Rodney A; Grann, Kerry; Missler, Stephen R; Patterson, Jennifer; Hu, Chun; Gellenbeck, Kevin W; Scholten, Jeffrey D; Randolph, R Keith

2015-01-01

Diacylglyceride acyltransferase 1 (DGAT1) is the enzyme that adds the final fatty acid on to a diacylglyceride during triglyceride (TG) synthesis. DGAT1 plays a key role in the repackaging of dietary TG into circulating TG rich chylomicrons. A growing amount of research has indicated that an exaggerated postprandial circulating TG level is a risk indicator for cardiovascular and metabolic disorders. The aim of this research was to identify a botanical extract that inhibits intestinal DGAT1 activity and attenuates postprandial hypertriglyceridemia in overweight and obese humans. Twenty individual phytochemicals and an internal proprietary botanical extract library were screened with a primary cell-free DGAT1 enzyme assay that contained dioleoyl glycerol and palmitoleoyl Coenzyme A as substrates plus human intestinal microsomes as the DGAT1 enzyme source. Botanical extracts with IC50 values < 100 μg/mL were evaluated in a cellular DGAT1 assay. The cellular DGAT1 assay comprised the analysis of (14)C labeled TG synthesis in cells incubated with (14)C-glycerol and 0.3 mM oleic acid. Lead botanical extracts were then evaluated in a parallel, double-blind, placebo-controlled clinical trial. Ninety healthy, overweight and obese participants were randomized to receive 2 g daily of placebo or individual botanical extracts (the investigational product) for seven days. Serum TG levels were measured before and after consuming a high fat meal (HFM) challenge (0.354 L drink/shake; 77 g fat, 25 g carbohydrate and 9 g protein) as a marker of intestinal DGAT1 enzyme activity. Phenolic acids (i.e., gallic acid) and polyphenols (i.e., cyanidin) abundantly found in nature appeared to inhibit DGAT1 enzyme activity in vitro. Four polyphenolic rich botanical extracts were identified from in vitro evaluation in both cell-free and cellular model systems: apple peel extract (APE), grape extract (GE), red raspberry leaf extract (RLE) and apricot/nectarine extract (ANE) (IC50 = 1.4, 5.6, and 10.4 and 3.4 μg/mL, respectively). In the seven day clinical trial, compared to placebo, only GE significantly reduced the baseline subtracted change in serum TG AUC following consumption of the HFM (AUC = 281 ± 37 vs. 181 ± 30 mg/dL*h, respectively; P = 0.021). Chromatographic characterization of the GE revealed a large number of closely eluting components containing proanthocyanidins, catechins, anthocyanins and their secondary metabolites that corresponded with the observed DGAT1 enzyme inhibition in the cell-free model. These data suggest that a dietary GE has the potential to attenuate postprandial hypertriglyceridemia in part by the inhibition of intestinal DGAT1 enzyme activity without intolerable side effects. This trial was registered with ClinicalTrials.gov NCT02333461.

Severe hypertriglyceridemia and factors associated with acute pancreatitis in an integrated health care system.

PubMed

Rashid, Nazia; Sharma, Puza P; Scott, Ronald D; Lin, Kathy J; Toth, Peter P

2016-01-01

To evaluate patient characteristics, treatment patterns, comorbidities, and risk factors associated with the development of acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG) in an integrated health care delivery system. We identified a retrospective cohort of severe HTG patients with a fasting triglyceride level ≥ 1000 mg/dL during January 1, 2007 to June 30, 2013 (index date) in an integrated health care delivery system. Patients were aged ≥18 years on index date and had 12 months of continuous membership and drug eligibility before the index date and during postindex including index date. Baseline patient characteristics, comorbidities, and risk factors were evaluated during 12-month preindex. Outcomes such as development of AP, treatment patterns, adherence to index therapy, and change in triglyceride (TG) laboratory levels were evaluated during postindex. Descriptive statistics were used to identify differences between patients developing AP vs no development of AP. A stepwise multivariate logistic regression and backward elimination method were used to assess statistically significant predictive factors associated with development of AP vs no AP. We identified 5550 patients with severe HTG, and 5.4% of these patients developed AP during postindex. Patients were mostly male (≥70%) in both groups; however, younger in the AP group (45 years ± 10.6) vs no AP group (50 years ± 11.4) with P value < .0001. The AP group had higher baseline Charslon Comorbidity Index score, alcohol abuse history (42.2%), any pancreatitis history (51.5%), diabetes (47%), and hypertension (55%), vs the no AP group (P values < .05). Patients in the AP group had higher baseline mean TG levels (2148, SD ± 1578) vs the no AP group (1559, SD ± 861), P value < .0001. Over 50% of the patients were prescribed their index therapy by a primary care provider. Predictive factors associated with the development of AP included younger age, alcohol use, and prior history of any pancreatitis, hypertension, renal disease stage 4, and other prescriber specialty. From parameters estimates, for each 100 mg/dL unit of increase in the TG level above 1000 mg/dL, there was a 3 percent increase in risk of developing AP. Patients with severe HTG are at a higher risk of developing AP. A number of comorbidities, risk factors, and baseline TG levels are associated with an increased incidence of AP. Patients with severe HTG are underdiagnosed, undertreated and are nonadherent to their index lipid therapy. There is a need to better define optimal approaches to treating severe HTG so as to reduce the incidence of AP. Economic studies are also needed to evaluate the burden of AP on various health care systems. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Metabolic Risk Factors, Leisure Time Physical Activity, and Nutrition in German Children and Adolescents

PubMed Central

Haas, Gerda-Maria; Liepold, Evelyn; Schwandt, Peter

2012-01-01

Purpose. We assessed the five components of the metabolic syndrome (MetS) as defined by the International Diabetes Federation (IDF) in 6040 (3158 males) youths aged 6–16 years who participated in the Präventions-Erziehungs-Programm (PEP Family Heart Study) in Nuernberg between 2000 and 2007. The purpose of this cross-sectional study was to examine associations with lifestyle habits. Results and Discussion. The prevalence of MetS was low in children (1.6%) and adolescents (2.3%). High waist circumference (WC) and low HDL-C were slightly higher in females (9.5% and 7.5%, resp.) than in males (8.8% and 5.7%, resp.). Low leisure time physical activity (LTPA) was significantly associated with low HDL-C (odds ratio [OR] 2.4; 95% CI 1.2–5.0) and inversely associated with hypertension (r = −0.146), hypertriglyceridemia (r = −0.141), and central adiposity (r = −0.258). The risk for low HDL-C (≤1.3 mmol/L) was 1.7-fold (CI 1.0–2.6) higher in youth with high (≥33%) saturated fat consumption. A low polyunsaturated/saturated fat ratio (P/S ratio) was significantly associated with fasting hyperglycemia (OR 1.4; 95% CI 1.0–1.2). PMID:22778928

Effect of Euterpe oleracea Mart. (Açaí) Oil on Dyslipidemia Caused by Cocos nucifera L. Saturated Fat in Wistar Rats.

PubMed

Faria E Souza, Belmira S; Carvalho, Helison O; Taglialegna, Talisson; Barros, Albenise Santana A; da Cunha, Edilson Leal; Ferreira, Irlon Maciel; Keita, Hady; Navarrete, Andres; Carvalho, José Carlos Tavares

2017-09-01

Dyslipidemia is caused by disturbances in lipid metabolism that lead to chronic elevations of serum lipids, especially low-density lipoprotein (LDL)-cholesterol and triglycerides, increasing the risk of metabolic syndrome, obesity, diabetes, atherogenic processes, and cardiovascular diseases. The oil from the fruits of Euterpe oleracea (OFEO) is rich in unsaturated fatty acids with potential for treating alterations in lipid metabolism. In this study, we aimed to investigate the effect of OFEO on hyperlipidemia induced by Cocos nucifera L. saturated fat (GSC) in Wistar rats. Chromatographic profile showed that unsaturated fatty acids account for 66.08% in OFEO, predominately oleic acid (54.30%), and saturated fatty acids (palmitic acid 31.6%) account for 33.92%. GSC-induced dyslipidemia resulted in an increase in total cholesterol, LDL-cholesterol, triglycerides, glucose, and liver and abdominal fat, as well as atherogenic processes in the thoracic aorta. OFEO treatment did not reduce hypertriglyceridemia, but did reduce total cholesterol and LDL-cholesterol, thus contributing to the antiatherogenic action of OFEO. OFEO treatment inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats, as well as those who were treated with simvastatin. The results obtained suggest that OFEO has an antiatherogenic effect in a rat model of dyslipidemia.

Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective

PubMed Central

Feng, Hui-Yi; Chen, Yang-Chao

2016-01-01

The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis. PMID:27672269

A two-stage design for multiple testing in large-scale association studies.

PubMed

Wen, Shu-Hui; Tzeng, Jung-Ying; Kao, Jau-Tsuen; Hsiao, Chuhsing Kate

2006-01-01

Modern association studies often involve a large number of markers and hence may encounter the problem of testing multiple hypotheses. Traditional procedures are usually over-conservative and with low power to detect mild genetic effects. From the design perspective, we propose a two-stage selection procedure to address this concern. Our main principle is to reduce the total number of tests by removing clearly unassociated markers in the first-stage test. Next, conditional on the findings of the first stage, which uses a less stringent nominal level, a more conservative test is conducted in the second stage using the augmented data and the data from the first stage. Previous studies have suggested using independent samples to avoid inflated errors. However, we found that, after accounting for the dependence between these two samples, the true discovery rate increases substantially. In addition, the cost of genotyping can be greatly reduced via this approach. Results from a study of hypertriglyceridemia and simulations suggest the two-stage method has a higher overall true positive rate (TPR) with a controlled overall false positive rate (FPR) when compared with single-stage approaches. We also report the analytical form of its overall FPR, which may be useful in guiding study design to achieve a high TPR while retaining the desired FPR.

High Risk of Metabolic and Adipose Tissue Dysfunctions in Adult Male Progeny, Due to Prenatal and Adulthood Malnutrition Induced by Fructose Rich Diet

PubMed Central

Alzamendi, Ana; Zubiría, Guillermina; Moreno, Griselda; Portales, Andrea; Spinedi, Eduardo; Giovambattista, Andrés

2016-01-01

The aim of this work was to determine the effect of a fructose rich diet (FRD) consumed by the pregnant mother on the endocrine-metabolic and in vivo and in vitro adipose tissue (AT) functions of the male offspring in adulthood. At 60 days of age, rats born to FRD-fed mothers (F) showed impaired glucose tolerance after glucose overload and high circulating levels of leptin (LEP). Despite the diminished mass of retroperitoneal AT, this tissue was characterized by enhanced LEP gene expression, and hypertrophic adipocytes secreting in vitro larger amounts of LEP. Analyses of stromal vascular fraction composition by flow cytometry revealed a reduced number of adipocyte precursor cells. Additionally, 60 day-old control (C) and F male rats were subjected to control diet (CC and FC animals) or FRD (CF and FF rats) for three weeks. FF animals were heavier and consumed more calories. Their metabolic-endocrine parameters were aggravated; they developed severe hyperglycemia, hypertriglyceridemia, hyperleptinemia and augmented AT mass with hypertrophic adipocytes. Our study highlights that manipulation of maternal diet induced an offspring phenotype mainly imprinted with a severely unhealthy adipogenic process with undesirable endocrine-metabolic consequences, putting them at high risk for developing a diabetic state. PMID:27011203

Dietary trans fatty acids intake and its relation to dyslipidemia in a sample of adults in Depok city, West Java, Indonesia.

PubMed

Sartika, Ratu Ayu Dewi

2011-12-01

The Basic Health Research of the Ministry of Health Indonesia in 2008 reported that the single most important cause of death was stroke, in both urban and rural populations. The risk factors underlying the cause of death are associated with hypertension, obesity and dyslipidemia. The purpose of this study was to determine the mean intake of trans fatty acids and its relation to dyslipidemia in a sample of Indonesian adults. A cross-sectional study was conducted on a total of 180 adult male and female respondents aged 35-60 years living in rural and urban areas of Depok city, West Java. Dietary intake was assessed by means of 24-hour recall and semi-quantitative FFQ. The mean intake of trans fatty acids was 0.48% of total calories (urban 0.40% and rural 0.55%). The prevalence of dyslipidemia in the rural and urban subjects were 61.1% and 66.7%, respectively. There was a statistically significant relationship between trans fatty acids intake and hypercholesterolemia and hypertriglyceridemia. The intake of trans fatty acid among the Indonesian adults studied was half the recommended level. The high prevalence of dyslipidemia found indicates the need for intervention to reduce the rising incidence of cardiovascular diseases in Indonesia.

Cardiovascular risk factor investigation: a pediatric issue

PubMed Central

Rodrigues, Anabel N; Abreu, Glaucia R; Resende, Rogério S; Goncalves, Washington LS; Gouvea, Sonia Alves

2013-01-01

Objectives To correlate cardiovascular risk factors (e.g., hypertension, obesity, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, sedentariness) in childhood and adolescence with the occurrence of cardiovascular disease. Sources A systematic review of books and selected articles from PubMed, SciELO and Cochrane from 1992 to 2012. Summary of findings Risk factors for atherosclerosis are present in childhood, although cardiovascular disease arises during adulthood. This article presents the main studies that describe the importance of investigating the risk factors for cardiovascular diseases in childhood and their associations. Significant rates of hypertension, obesity, dyslipidemia, and sedentariness occur in children and adolescents. Blood pressure needs to be measured in childhood. An increase in arterial blood pressure in young people predicts hypertension in adulthood. The death rate from cardiovascular disease is lowest in children with lower cholesterol levels and in individuals who exercise regularly. In addition, there is a high prevalence of sedentariness in children and adolescents. Conclusions Studies involving the analysis of cardiovascular risk factors should always report the prevalence of these factors and their correlations during childhood because these factors are indispensable for identifying an at-risk population. The identification of risk factors in asymptomatic children could contribute to a decrease in cardiovascular disease, preventing such diseases as hypertension, obesity, and dyslipidemia from becoming the epidemics of this century. PMID:23515212

Physical Activity and Reported Barriers to Activity Among Type 2 Diabetic Patients in the United Arab Emirates

PubMed Central

Al-Kaabi, Juma; Al-Maskari, Fatma; Afandi, Bachar; Parkar, Hasratali; Nagelkerke, Nicolaas

2009-01-01

OBJECTIVES: This study was designed to assess the physical activity practice among type 2 diabetic patients in the United Arab Emirates (UAE). METHODS: This is a cross-sectional study of type 2 diabetic patients who participated in the outpatient clinics in Al-Ain District, during 2006. The patients completed an interviewer-administered questionnaire, and measurements of blood pressure, body mass index, body fat, abdominal circumference, glycemic control (HbA1c), and fasting lipid profile. RESULTS: Of the 390 patients recruited, only 25% reported an increase in their physical activity levels following the diagnosis of diabetes, and only 3% reported physical activity levels that meet the recommended guidelines. More than half of the study subjects had uncontrolled hypertension (53%) and unacceptable lipid profiles; 71% had a high low-density lipoprotein (LDL), 73% had low high-density lipoprotein (HDL), and 59% had hypertriglyceridemia. Forty-four percent were obese and a further 34% were overweight. Abdominal obesity was also common (59%). Only 32% had an acceptable glycemic control. CONCLUSIONS: The physical activity practice of type 2 diabetic patients in the UAE is largely inadequate to meet the recommended level necessary to prevent or ameliorate diabetic complications. Interventions aiming at overcoming the barriers to physical activity are urgently needed. PMID:20043039

Functional-drink rich in antioxidant cardamom-rhizome (Amomum cardamomum willd) suppresses inflammation and improves lipid profile

NASA Astrophysics Data System (ADS)

Winarsi, H.; Susilowati, S. S.

2018-01-01

The aim of this research was to know the effect of functional drink rich in antioxidant cardamom rhizome (Fd-Carrhi) on level of IL-6, C-RP, and lipid profile of atherosclerotic. A total of 30 women with atherosclerosis, age 40-65 years old, hypertension, hypercholesterolemia, hypertriglyceridemia, lived in Purwokerto, Banyumas, Central Java, Indonesia, and were willing to sign informed consent, recruited as research subjects. They consumed simvastatin from doctors, divided by 3 groups of 10 people each. Group I, given Fd-Carrhi; II, placebo; and III, only simvastatin, for 2 months. As many as 100 ml of Fd-Carrhi or placebo were given every morning. Blood samples were taken 3 times, 1 ml, at baseline, 1 and 2 months after intervention. Blood plasma was determined levels of IL-6, C-RP, as well as total cholesterol (total-c), triglycerides (TG), LDL-c, and HDL-c. Result showed Fd-Carrhi versus placebo significantly decreased plasma level of IL-6, C-RP, total-c, and LDL-c, and otherwise increased HDL-c, but no differences were seen in TG. The findings clearly support Fd-Carrhi inhibit the development of atherosclerosis towards cardiovascular heart diseases (CHD) by suppressing IL-6 and CRP levels, and improving lipid profile.

[Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas].

PubMed

Vašura, Adam; Blaho, Martin; Dítě, Petr; Kupka, Tomáš; Svoboda, Pavel; Martínek, Arnošt

Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described. Less is known so far about the relation to the pancreas disease, particularly with respect to the status referred to as non-alcoholic fatty pancreas disease. The hormone selectively produced by adipose tissue is adiponectin. This protein is studied as a possible biomarker in people with metabolic syndrome, including obesity. Besides that, there is a question studied whether adiponectin can also play a significant role in the pathogenesis of diseases associated with fat building up in parenchymatous organs. Finding a reliable biomarker for patients with metabolic syndrome or diseases of the liver, biliary system and pancreas in relation to metabolic syndrome, presents a big challenge. And adiponectin is one of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic syndrome - pancreatic steatosis - steatohepatitis.

Prevalence of metabolic syndrome and its risk factors in adult Malaysians: results of a nationwide survey.

PubMed

Mohamud, Wan Nazaimoon Wan; Ismail, Aziz al-Safi; Khir, Amir Sharifuddin Md; Ismail, Ikram Shah; Musa, Kamarul Imran; Kadir, Khalid Abdul; Kamaruddin, Nor Azmi; Yaacob, Nor Azwany; Mustafa, Norlaila; Ali, Osman; Isa, Siti Harnida Md; Bebakar, Wan Mohamad Wan

2012-04-01

Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk factors among adult Malaysians (>18 years old) based on World Health Organization (WHO), the National Cholesterol Education Program Expert Panel III (ATP III), International Diabetes Federation (IDF) and the 'Harmonized' criteria.Methods: A multi-stage stratified sampling method was used to select 4341 subjects from Peninsular and East Malaysia. Subjects underwent physical and clinical examinations.Results: Based on the WHO, ATP III, IDF and Harmonized definitions, the overall crude prevalences of MetS were 32.1, 34.3, 37.1 and 42.5%, respectively. Regardless of the criteria used, MetS was higher in urban areas, in females, in the Indian population and increased significantly with age. Risk factors also increased with age; abdominal obesity was most prevalent (57.4%), was higher in females (64.2%) and was highest in Indians (68.8%).Hypertension was higher in males (56.5%) and highest among Malays (52.2%). In contrast,the Chinese had the highest prevalence of hypertriglyceridemia (47.4%).Conclusions: Malaysia has a much higher prevalence of MetS compared with other Asian countries and, unless there is immediate intervention to reduce risk factors, this may pose serious implications on the country's healthcare costs and services.

Effects of dietary fish oil on serum lipids and blood coagulation in peritoneal dialysis patients.

PubMed

Lempert, K D; Rogers, J S; Albrink, M J

1988-02-01

The effects of a daily fish oil supplement rich in eicosapentaenoic acid were studied in 11 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Serum lipids, platelet aggregation studies, and template bleeding times were determined before and after 4 weeks of fish oil treatment. The lipid studies were repeated approximately 20 weeks after stopping fish oil supplement. At the end of the treatment period, serum triglycerides (mean +/- SEM) decreased from 297 +/- 42 to 211 +/- 29 mg/dL (P less than .01), high density lipoprotein (HDL) cholesterol fell from 45 +/- 3 to 41 +/- 3 mg/dL (P less than .05), and low density lipoprotein (LDL) cholesterol increased from 172 +/- 16 to 208 +/- 19 mg/dL (P less than .05). After discontinuing the fish oil supplement, the triglycerides increased to 278 +/- 39 mg/dL, which was no different than the value before fish oil treatment. No significant changes occurred in template bleeding time (TBT), platelet count, hematocrit, or platelet aggregation response. Clinically important uremic bleeding was not apparent. We conclude that in CAPD patients a fish oil supplement favorably effects hypertriglyceridemia and can be ingested without promoting uremic bleeding. The likely beneficial impact on atherogenesis resulting from the lowering of the triglycerides may, however, be counteracted by concomitant changes in HDL- and LDL-cholesterol.

Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats

PubMed Central

Gun, Aburrahman; Bilgic, Sedat; Kocaman, Nevin; Ozan, Gonca

2016-01-01

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment. PMID:27042260

A quantitative assay measuring the function of lipase maturation factor 1

PubMed Central

Yin, Fen; Doolittle, Mark H.; Péterfy, Miklós

2009-01-01

Newly synthesized lipoprotein lipase (LPL) and related members of the lipase gene family require an endoplasmic reticulum maturation factor for attainment of enzyme activity. This factor has been identified as lipase maturation factor 1 (Lmf1), and mutations affecting its function and/or expression result in combined lipase deficiency (cld) and hypertriglyceridemia. To assess the functional impact of Lmf1 sequence variations, both naturally occurring and induced, we report the development of a cell-based assay using LPL activity as a quantitative reporter of Lmf1 function. The assay uses a cell line homozygous for the cld mutation, which renders endogenous Lmf1 nonfunctional. LPL transfected into the mutant cld cell line fails to attain activity; however, cotransfection of LPL with wild-type Lmf1 restores its ability to support normal lipase maturation. In this report, we describe optimized conditions that ensure the detection of a complete range of Lmf1 function (full, partial, or complete loss of function) using LPL activity as the quantitative reporter. To illustrate the dynamic range of the assay, we tested several novel mutations in mouse Lmf1. Our results demonstrate the ability of the assay to detect and analyze Lmf1 mutations having a wide range of effects on Lmf1 function and protein expression. PMID:19471043

Concentration, composition and apolipoprotein B species of very low density lipoprotein subfractions from normolipidemic and hypertriglyceridemic humans.

PubMed

Bittolo Bon, G; Cazzolato, G; Zago, S; Avogaro, P

1985-01-01

Lipoproteins in the d less than 1.006 g/ml density range obtained form 13 healthy normolipidemic subjects and from 15 patients affected by primary endogenous hypertriglyceridemia after 14-h fasting were subfractionated by filtration in Biogel A-15 M columns. The mass values and chemical composition of very low density lipoprotein (VLDL) subfractions 1 and 2 thus obtained were studied. In each subfraction the behavior of apolipoprotein B (Apo B) was tested by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. VLDL2 was higher and richer in cholesterol and proteins than VLDL1, while the percentage content of triglycerides was lower. In hypertriglyceridemic patients both VLDL1 and VLDL2 were higher than in normolipidemic subjects, the difference being particularly evident for VLDL1. In both VLDL1 and VLDL2 of nearly all the subjects studied the presence in electrophoretic gels of a large Apo B-100 band and of a minor Apo B-48 band with the appropriate mobility of lymph chylomicrons was detected. The Apo B-100/Apo B-48 ratio was about 6 in VLDL1 and 24 in VLDL2. A trend of a reduced Apo B-100/Apo B-48 ratio was observed in VLDL1 of hypertriglyceridemic patients.

Alcohol extract of North American ginseng (Panax quinquefolius) reduces fatty liver, dyslipidemia, and other complications of metabolic syndrome in a mouse model.

PubMed

Singh, Ratnesh K; Lui, Edmund; Wright, David; Taylor, Adrian; Bakovic, Marica

2017-09-01

We investigated whether North American ginseng (Panax quinquefolius) could reduce development of the metabolic syndrome phenotype in a mouse model (ETKO) of the disease. Young ETKO mice have no disease but similar to humans start to develop the fatty liver, hypertriglyceridemia, obesity, and insulin resistance at 25-30 weeks of age, and the disease continues to progress with ageing. ETKO mice were orally given an ethanol extract of ginseng roots at 4 and 32 weeks of age. Treatments with ginseng eliminated the ETKO fatty liver, reduced hepatic and intestinal lipoprotein secretion, and reduced the level of circulating lipids. Improvements by ginseng treatments were manifested as a reduction in the expression of genes involved in the regulation of fatty acid and triglyceride (fat) synthesis and secretion by the lipoproteins on one hand, and the stimulation of fatty acid oxidation and triglyceride degradation by lipolysis on the other hand. These processes altogether improved glucose, fatty acid, and triglyceride metabolism, reduced liver fat load, and reversed the progression of metabolic syndrome. These data confirm that treatments with North American ginseng could alleviate metabolic syndrome through the maintenance of a better balance between glucose and fatty acid metabolism, lipoprotein secretion, and energy homeostasis in disease-prone states.

Issues in Hypertriglyceridemic Pancreatitis - An Update

PubMed Central

Scherer, John; Singh, Vijay; Pitchumoni, C. S; Yadav, Dhiraj

2014-01-01

Hypertriglyceridemia (HTG) is a well established but underestimated cause of acute (AP) and recurrent AP (RAP). The clinical presentation of HTG-induced pancreatitis (HTG pancreatitis) is similar to other causes. Pancreatitis secondary to HTG is typically seen in the presence of one or more secondary factors (uncontrolled diabetes, alcoholism, medications, pregnancy) in a patient with an underlying common genetic abnormality of lipoprotein metabolism (Familial combined hyperlipidemia or Familial HTG). Less commonly, a patient with rare genetic abnormality (Familial chylomicronemic syndrome) with or without an additional secondary factor is encountered. The risk of AP in patients with serum triglycerides >1000 mg/dl and >2000 mg/dl is ∼5% and 10-20% respectively. It is not clear whether HTG pancreatitis is more severe than when it is due to other causes. Clinical management of HTG pancreatitis is similar to that of other causes. Insulin infusion in diabetic patients with HTG can rapidly reduce triglyceride levels. Use of apheresis is still experimental and better designed studies are needed to clarify its role in management of HTG pancreatitis. Diet, lifestyle changes, control of secondary factors are key to the treatment and medications are useful adjuncts to long term management of triglyceride levels. Control of triglyceride levels to well below 500 mg/dl can effectively prevent recurrences of pancreatitis. PMID:24172179

[Metabolic syndrome prevalence and clinical features in blood donors].

PubMed

Cruz del Castillo, Aaron H; García Fierro, Rafael; Hess Moreno, María I; Vigil Pérez, Claudia A; Córdova Fernández, José A; Chuck Santiago, Marco P; Domínguez Moreno, Rogelio

2012-01-01

Metabolic syndrome (MS) including obesity, diabetes mellitus, hypertension, dyslipidemia, etc.. is a major cause of morbidity and mortality worldwide. It was reported that 15.9% of blood donors showed changes in fasting plasma glucose. To determine the prevalence of MS in a population of healthy donors in a secondary hospital. A cross-sectional study, included 726 healthy donors who attended the blood bank HGZ36. The SM was identified with at least 3 of 5 criteria of the NCEP ATPIII, we applied a structured questionnaire. We determined HDL cholesterol, triglycerides, glucose Abnormal Fasting (GAA), hypertension (SAH), body mass index (BMI), waist circumference (WC), hip circumference (NCC). Plan Analysis: prevalence, t student, Chi2. Of the 726 donors, 85.1% were male, according to the ATPIII criteria, 54.8% (398) had a GAA, 63.2% (458) had hypertriglyceridemia, almost 17% (121) presented HDL hypocholesterolemia, 44.1% (320) were overweight by BMI, the prevalence of metabolic syndrome was 54.4%, in comparison by gender, men had a statistically significant difference compared to women, showing an OR = 2.27 (p = 0.0001, 95% CI 1.44-3.60). MS is highly prevalent in this population, which involves implementing preventive measures, changes in lifestyles and identify risk factors to be free from diseases like diabetes, hypertension, obesity and MS itself.

Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes.

PubMed

Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario; Ramírez-Rentería, Claudia; Vargas, Guadalupe; Gonzalez, Baldomero; Isibasi, Armando; Archundia-Riveros, Irma; Mendoza, Victoria

2015-01-01

To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n = 61), 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. . We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.

Experimental study on effect of hydroalcoholic extract of Emblica officinalis fruits on glucose homeostasis and metabolic parameters

PubMed Central

Patel, Snehal S.; Goyal, Ramesh K.; Shah, Rajendra S.; Tirgar, Pravin R.; Jadav, Pinakin D.

2013-01-01

Polyphenols from natural source are potential therapeutics that act alone or supplement anti-diabetic drugs in the prevention and treatment of diabetes. The present investigation was undertaken to study the effect of hydroalcoholic extract (HE) of fruits of Emblica officinalis on type 1 diabetic rats. Diabetes was induced by streptozotocin (STZ) (45 mg/kg i.v.). HE (100 mg/kg, p.o.) was administered for 4 weeks and at the end of treatment, blood samples were collected and analyzed for various biochemical parameters. STZ produced a diabetic state exhibiting all the cardinal symptoms such as loss of body weight, polydipsia, polyuria, glucosuria, polyphagia, hypoinsulinemia, and hyperglycemia associated with hypercholesterolemia and hypertriglyceridemia. Treatment with HE prevented cardinal symptoms and caused significant decrease in fasting serum glucose, AUCglucose, cholesterol, triglyceride, low-density lipoprotein (LDL) and very LDL in diabetic rats. However, insulin, AUCinsulin, and serum high-density lipoprotein level were not significantly altered by treatment. Treatment also reduced lipid peroxidation and increased anti-oxidant parameters in the liver homogenates of diabetic rats. Polyphenol enriched fraction of HE significantly improved disarranged carbohydrate and lipid metabolism of chemically induced diabetes in rats. The mechanism of its anti-diabetic activity appears to be either improvement in peripheral glucose utilization, increased insulin sensitivity, or anti-oxidant property. PMID:24696584

Zeolite Nanoparticles for Selective Sorption of Plasma Proteins

NASA Astrophysics Data System (ADS)

Rahimi, M.; Ng, E.-P.; Bakhtiari, K.; Vinciguerra, M.; Ahmad, H. Ali; Awala, H.; Mintova, S.; Daghighi, M.; Bakhshandeh Rostami, F.; de Vries, M.; Motazacker, M. M.; Peppelenbosch, M. P.; Mahmoudi, M.; Rezaee, F.

2015-11-01

The affinity of zeolite nanoparticles (diameter of 8-12 nm) possessing high surface area and high pore volume towards human plasma proteins has been investigated. The protein composition (corona) of zeolite nanoparticles has been shown to be more dependent on the plasma protein concentrations and the type of zeolites than zeolite nanoparticles concentration. The number of proteins present in the corona of zeolite nanoparticles at 100% plasma (in vivo state) is less than with 10% plasma exposure. This could be due to a competition between the proteins to occupy the corona of the zeolite nanoparticles. Moreover, a high selective adsorption for apolipoprotein C-III (APOC-III) and fibrinogen on the zeolite nanoparticles at high plasma concentration (100%) was observed. While the zeolite nanoparticles exposed to low plasma concentration (10%) exhibited a high selective adsorption for immunoglobulin gamma (i.e. IGHG1, IGHG2 and IGHG4) proteins. The zeolite nanoparticles can potentially be used for selectively capture of APOC-III in order to reduce the activation of lipoprotein lipase inhibition during hypertriglyceridemia treatment. The zeolite nanoparticles can be adapted to hemophilic patients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX deficient)) with a risk of bleeding, and thus might be potentially used in combination with the existing therapy.

Zeolite Nanoparticles for Selective Sorption of Plasma Proteins.

PubMed

Rahimi, M; Ng, E-P; Bakhtiari, K; Vinciguerra, M; Ali Ahmad, H; Awala, H; Mintova, S; Daghighi, M; Bakhshandeh Rostami, F; de Vries, M; Motazacker, M M; Peppelenbosch, M P; Mahmoudi, M; Rezaee, F

2015-11-30

The affinity of zeolite nanoparticles (diameter of 8-12 nm) possessing high surface area and high pore volume towards human plasma proteins has been investigated. The protein composition (corona) of zeolite nanoparticles has been shown to be more dependent on the plasma protein concentrations and the type of zeolites than zeolite nanoparticles concentration. The number of proteins present in the corona of zeolite nanoparticles at 100% plasma (in vivo state) is less than with 10% plasma exposure. This could be due to a competition between the proteins to occupy the corona of the zeolite nanoparticles. Moreover, a high selective adsorption for apolipoprotein C-III (APOC-III) and fibrinogen on the zeolite nanoparticles at high plasma concentration (100%) was observed. While the zeolite nanoparticles exposed to low plasma concentration (10%) exhibited a high selective adsorption for immunoglobulin gamma (i.e. IGHG1, IGHG2 and IGHG4) proteins. The zeolite nanoparticles can potentially be used for selectively capture of APOC-III in order to reduce the activation of lipoprotein lipase inhibition during hypertriglyceridemia treatment. The zeolite nanoparticles can be adapted to hemophilic patients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX deficient)) with a risk of bleeding, and thus might be potentially used in combination with the existing therapy.

Zeolite Nanoparticles for Selective Sorption of Plasma Proteins

PubMed Central

Rahimi, M.; Ng, E.-P.; Bakhtiari, K.; Vinciguerra, M.; Ahmad, H. Ali; Awala, H.; Mintova, S.; Daghighi, M.; Bakhshandeh Rostami, F.; de Vries, M.; Motazacker, M. M.; Peppelenbosch, M. P.; Mahmoudi, M.; Rezaee, F.

2015-01-01

The affinity of zeolite nanoparticles (diameter of 8–12 nm) possessing high surface area and high pore volume towards human plasma proteins has been investigated. The protein composition (corona) of zeolite nanoparticles has been shown to be more dependent on the plasma protein concentrations and the type of zeolites than zeolite nanoparticles concentration. The number of proteins present in the corona of zeolite nanoparticles at 100% plasma (in vivo state) is less than with 10% plasma exposure. This could be due to a competition between the proteins to occupy the corona of the zeolite nanoparticles. Moreover, a high selective adsorption for apolipoprotein C-III (APOC-III) and fibrinogen on the zeolite nanoparticles at high plasma concentration (100%) was observed. While the zeolite nanoparticles exposed to low plasma concentration (10%) exhibited a high selective adsorption for immunoglobulin gamma (i.e. IGHG1, IGHG2 and IGHG4) proteins. The zeolite nanoparticles can potentially be used for selectively capture of APOC-III in order to reduce the activation of lipoprotein lipase inhibition during hypertriglyceridemia treatment. The zeolite nanoparticles can be adapted to hemophilic patients (hemophilia A (F-VIII deficient) and hemophilia B (F-IX deficient)) with a risk of bleeding, and thus might be potentially used in combination with the existing therapy. PMID:26616161

Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats.

PubMed

Gun, Aburrahman; Ozer, Mehmet Kaya; Bilgic, Sedat; Kocaman, Nevin; Ozan, Gonca

2016-01-01

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats.

PubMed

Rezg, Raja; Mornagui, Bessem; Benahmed, Malika; Chouchane, Sonia Gharsalla; Belhajhmida, Nadia; Abdeladhim, Maha; Kamoun, Abdelaziz; El-fazaa, Saloua; Gharbi, Najoua

2010-06-01

Exposure to organophosphate (OP) pesticides is virtually ubiquitous. These inevitable agents are neurotoxicants, but recent evidence also points to lasting effects on carbohydrate metabolism. The aim of this study was to investigate the effects of 32 repeated treatment days with malathion, an OP insecticide, on some molecular and metabolic parameters. Malathion at 100 mg/kg was administered by gavage in Wistar rats. Results of this study indicate a significant decrease in hypothalamic corticotropin-releasing hormone mRNA, of malathion-treated rats. This result, in accordance with that of diabetic type 2 rat model, may be due to very potent negative feedback effects of glucocorticoids on hypothalamo-pituitary-adrenal (HPA) axis activity. In addition, we have recorded a significant increase in hypothalamic inducible NO synthase mRNA which probably enhances the negative feedback. These alterations are accompanied with hypertriglyceridemia that may be a favourable condition to insulin resistance. Thus, results of the present study suggest that malathion can be considered as an important risk factor in the development of diabetes type 2, which prevalence increased substantially in our country and around the world. Clearly, we need to focus further research on the specific incidences of hazardous food chemical contaminant that might be contributing to epidemic health perspectives. Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.

Antioxidant, antihyperglycemic, and antidyslipidemic effects of Brazilian-native fruit extracts in an animal model of insulin resistance.

PubMed

de Souza Cardoso, Juliane; Oliveira, Pathise Souto; Bona, Natália Pontes; Vasconcellos, Flávia Aleixo; Baldissarelli, Jucimara; Vizzotto, Marcia; Soares, Mayara Sandrielly Pereira; Ramos, Vanessa Plasse; Spanevello, Roselia Maria; Lencina, Claiton Leoneti; Tavares, Rejane Giacomelli; Stefanello, Francieli Moro

2018-12-01

Insulin resistance (IR) plays an important role in the development of many diseases, such as diabetes mellitus. Therefore, the aim of the present study was to evaluate the effects of the extracts from fruits native to Brazil on metabolic parameters and hepatic oxidative markers in an animal model of insulin resistance induced by dexamethasone (DEX). Wistar rats received water or extracts of Eugenia uniflora or Psidium cattleianum, once a day for 21 days. For the last 5 days, the rats received an intraperitoneal injection of saline or DEX. DEX caused a reduction in body weight gain and relative pancreatic weight, as well as glucose intolerance, and an increase in serum glucose and triacylglycerol levels. The extracts were found to prevent hyperglycemia and hypertriglyceridemia. DEX caused an increase in the levels of thiobarbituric acid-reactive substances and reactive oxygen species production in the liver of rats, and both extracts prevented these changes. In addition, hepatic glutathione peroxidase activity was reduced by DEX. However, total thiol content and activities of catalase, superoxide dismutase, and delta-aminolevulinate dehydratase were not altered in any of the tested groups. Fruit extracts of E. uniflora and P. cattleianum exhibited considerable antihyperglycemic, antidyslipidemic, and antioxidant effects, and may be useful in the therapeutic management of alterations due to IR.

[Chronic complications of diabetes mellitus. What is the prevalence of diabetes in a family medical unit?].

PubMed

Sabag-Ruiz, Enrique; Alvarez-Félix, Andrés; Celiz-Zepeda, Sergio; Gómez-Alcalá, Alejandro V

2006-01-01

The role of the family doctor in fundamental in the prevention of diabetic complications, because these complications will be minor if there is good glycemic control during life. Determine the frequency of late complications of diabetes mellitus (DM) among IMSS-insured population in Ciudad Obregón, Sonora, México. A retrospective analysis included 252 diabetic patients selected by a systematized and stratified randomized sampling including all patient files available in the Family Medicine Unit 1 in Ciudad Obregón, Sonora. The information was taken from the clinical charts got by family physicians and specialists. We used descriptive statistics and correlation of Pearson looking for the association between glicemia's level and enough time to produce complications. Arterial hypertension was found in 168 cases (67%), hypertriglyceridemia in 148 (59.4%), neuropathy in 106 (42.6%), hypercholesterolemia in 89 (35.7%), retinopathy in 69 (27.5%), nephropathy in 51 (20.5%), diabetic foot in 27 (10.8%), ischemic cardiopathy in 25 (10%), cerebral thrombosis in 11 (4.4%). The period between DM diagnosis and the appearance of complications was 3.2 to 13.1 years. The correlations were high and significant in every complication. The frequency of DM complications in this study was very high, with an increasing tendency of developing complications throughout the time.

Glucose Regulates the Expression of the Apolipoprotein A5 Gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey

2008-04-07

The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter.more » We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.« less

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

PubMed

Bocco, B M; Fernandes, G W; Lorena, F B; Cysneiros, R M; Christoffolete, M A; Grecco, S S; Lancellotti, C L; Romoff, P; Lago, J H G; Bianco, A C; Ribeiro, M O

2016-03-01

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin

PubMed Central

Erkan, Nazif; Yakan, Savas; Yildirim, Mehmet; Carti, Erdem; Ucar, Deniz; Oymaci, Erkan

2015-01-01

Introduction Hypertriglyceridaemia (HT)-induced pancreatitis rarely occurs unless triglyceride levels exceed 1000 mg/dl. Hypertriglyceridaemia over 1,000 mg/dl can provoke acute pancreatitis (AP) and its persistence can worsen the clinical outcome. In contrast, a rapid decrease in triglyceride level is beneficial. Insulin-stimulated lipoprotein lipase is known to decrease serum triglyceride levels. However, their efficacy in HT-induced AP is not well documented. Aim To present 12 cases of AP successfully treated by insulin administration. Material and methods Three hundred and forty-three cases of AP were diagnosed at our clinic between 2005 and 2012. Twelve (3.5%) of these cases were HT-induced AP. Twelve patients who suffered HT-induced AP are reported. Initial blood triglyceride levels were above 1000 mg/dl. Besides the usual treatment of AP, insulin was administered intravenously in continuous infusion. The patients’ medical records were retrospectively evaluated in this study. Results Serum triglyceride levels decreased to < 500 mg/dl within 2–3 days. No complications of treatment were seen and good clinical outcome was observed. Conclusions Our results are compatible with the literature. Insulin may be used safely and effectively in HT-induced AP therapy. Administration of insulin is efficient when used to reduce triglyceride levels in patients with HT-induced AP. PMID:25960810

Gemfibrozil in Combination with Statins-Is It Really Contraindicated?

PubMed

Wiggins, Barbara S; Saseen, Joseph J; Morris, Pamela B

2016-04-01

Gemfibrozil is a lipid-modifying agent that belongs to the fibric acid derivative class. Fibric acid derivatives activate peroxisome proliferator activated receptor α (PPAR-α). The primary role of these agents in clinical practice is for the management of hypertriglyceridemia. Triglycerides may be reduced by as much as 74 % in some patients. In addition to lowering triglycerides, these agents can also decrease very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as raise high-density lipoprotein cholesterol (HDL-C). Based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and the National Lipid Association, pharmacologic therapy to reduce triglycerides should be considered when triglyceride levels are ≥500 mg/dL. While the use of gemfibrozil has decreased over the years for a variety of reasons, muscle-associated adverse effects is the predominant reason and the one that is most clinically relevant. However, despite these concerns, there are situations in which the use of gemfibrozil in combination with a statin may be necessary. Understanding the metabolism of gemfibrozil and the degree of interaction with the various statins will assist health-care providers to optimize safety when this combination is clinically indicated.

Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities.

PubMed

McIntyre, R S; McCann, S M; Kennedy, S H

2001-04-01

To review published and nonpublished literature describing changes in weight, glucose homeostasis, and lipid milieu with antipsychotics. A Medline search was completed using the words weight gain, diabetes mellitus, cholesterol, triglycerides, risperidone, clozapine, olanzapine, quetiapine, ziprasidone, predictors, prolactin, obesity, and conventional antipsychotics. Publications, including original articles, review articles, letters to the editor, abstracts or posters presented at professional meetings in the last 4 years, and references from published articles, were collected. Manufacturers, including Eli Lilly Canada Inc, JanssenOrtho Inc, Pfizer Canada Inc, AstraZeneca Inc, and Novartis Pharmaceuticals, were contacted to retrieve additional medical information. The topic of antipsychotic-induced weight gain is understudied, and there are relatively few well-controlled studies. Weight gain as a side effect has been described with both conventional and atypical antipsychotics. Moreover, some atypical antipsychotics are associated with de novo diabetes mellitus and increased serum triglyceride levels. Predictors of weight gain may be age, baseline body mass index, appetite stimulation, previous antipsychotic exposure, and antipsychotic treatment duration. Significant weight gain is reported with the existing atypical antipsychotics. The weight gain described is highly distressing to patients, may reduce treatment adherence, and may increase the relative risk for diabetes mellitus and hypertriglyceridemia. Physicians employing these agents should routinely monitor weight, fasting blood glucose, and lipid profiles.