Mild Hypertriglyceridemia Research Articles

Hypertriglyceridaemia as a risk factor for critical care admission in acute pancreatitis: A prospective study.

SummaryBackground and aimsHypertriglyceridaemia is both a primary cause of acute pancreatitis and an epiphenomenon. This study aimed to define the associations between hypertriglyceridaemia and clinical outcomes in patients admitted with acute pancreatitis.MethodsThis single-centre prospective observational study included patients with a confirmed clinical, biochemical or radiological diagnosis of acute pancreatitis from August 2017 to September 2018. Baseline demographics, aetiology of pancreatitis, and fasting triglyceride concentrations were recorded and assessed against the surrogate markers of severity: admission to critical care, length of stay (LOS), readmission to hospital, and mortality.ResultsIn total, 304 patients with a mean ± SD age of 56.1 ± 19.7 years met the inclusion criteria. There were 217 (71.4%) patients with normotriglyceridaemia (<150 mg/dL or <1.7 mmol/L), 47 (15.5%) with mild hypertriglyceridaemia (150–199 mg/dL or 1.7–2.25 mmol/L) and 40 (13.2%) with moderate-to-severe hypertriglyceridaemia (≥200 mg/dL or >2.25 mmol/L). The underlying aetiologies of acute pancreatitis were gallstones (55%), alcohol (18%), idiopathic (15%), hypertriglyceridaemia (9%), iatrogenic (2%) and bile duct abnormalities (1%). Patients with hypertriglyceridaemia were younger than those with normotriglyceridaemia (p < 0.05). On multivariate regression, moderate-to-severe hypertriglyceridaemia (OR 5.66, 95% CI: 1.87 to 17.19, p = 0.002) and an elevated C-reactive protein concentration ≥120 mg/L (OR 1.00, 95% CI: 1.00–1.01, p = 0.040) were associated with admission to critical care. Moderate-to-severe hypertriglyceridaemia was also associated with an increased LOS (p = 0.002) but not readmission (p = 0.752) or mortality (p = 0.069).ConclusionModerate-to-severe hypertriglyceridaemia in all aetiological causes of acute pancreatitis was predictive of admission to critical care and prolonged LOS but not readmission or mortality.

The triglyceride-lowering effects of PCSK9 inhibitor differ in patients with different baseline triglyceride levels

To investigate the triglyceride (TG)-lowering effects of PCSK9 inhibitor in patients with in different baseline triglyceride levels. Between February, 2019 and March, 2020, a total of 59 patients were treated with PCSK9 inhibitor (Evolocumab) in 5 hospitals, including Nanfang Hospital, Guangdong Provincial People's Hospital, First Affiliated Hospital of Sun Yat-sen University, Foshan Nanhai District People's Hospital and Yulin First People's Hospital. According to baseline triglyceride levels, the patients were divided into normal TG group (&lt; 1.70 mmol/L, n=24), mild hypertriglyceridemia group (1.70-2.29 mmol/L, n=11), moderate hypertriglyceridemia group (2.30-5.63 mmol/L, n=13), and severe hypertriglyceridemia group (≥5.64 mmol/L, n=11), and the changes in TG level after the treatment were compared among the 4 groups. In the groups with normal and mildly elevated baseline TG level, the patients did not show significant changes in TG levels after the treatment. In patients with moderately and severely elevated baseline TG levels, treatment with PCSK9 inhibitor significantly reduced their TG levels (P &lt; 0.005). PCSK9 inhibitor has a significant TG-lowering effect in patients with moderate to severe hypertriglyceridemia but not in patients with only mildly elevated baseline TG level.

Predictors of endothelial function improvement in patients with mild hypertriglyceridemia without evidence of coronary artery disease treated with purified eicosapentaenoic acid

Background and aimsEicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. MethodsForty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables. ResultsEPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p < 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p < 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = −0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048). ConclusionsEPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

SAT-577 Severe Asymptomatic Hypertriglyceridemia

BackgroundCase reports of patients with severely elevated serum triglyceride levels (>1000 mg/dL) have been documented where Insulin infusions, heparin and plasmapheresis have demonstrated rapid and successful decrease in serum Triglyceride levels. The benefits of one approach versus the other to prevent major complications such as cardiovascular events or acute pancreatitis has not been well investigated. We present the case of a patient with severely elevated serum triglyceride levels without any manifestations.Case DescriptionA 53-year-old male presented from his primary care provider’s office due to elevated Triglycerides levels over 6000 as per outpatient lab work. Inpatient labs were unattainable initially due to hemolysis secondary to the severely high lipid content. Patient was admitted to the medical ICU for closer monitoring and initiated on an insulin drip. Two days after insulin initiation patient’s triglyceride levels returned as 2,887 with a total cholesterol count of 848. His insulin drip was continued until his TAG levels were less than 1000. Upon discharge his levels were less than 600.DiscussionMost patients with hypertriglyceridemia are asymptomatic. However, in patients with levels above 1000 mg/dL, the risk of pancreatitis or cardiovascular event is of concern. Hypertriglyceridemia may account for 1 to 14 percent of cases of acute pancreatitis. Treatment is largely based upon symptoms and complications. In the event of pancreatitis or other cardiovascular complication, plasmapheresis is usually recommended. If asymptomatic, Insulin may be used. Insulin promotes synthesis of lipoprotein lipase which functions to hydrolyze triglycerides, and has been shown to be an effective lowering agent in the treatment of such individuals. Case reports of Heparin being used as a lipid lowering agent have also been documented, but was not used in our particular patient.Normal triglyceride plasma levels are defined as less than 150 mg/dL. Mild hypertriglyceridemia typically ranges between 150-499 mg/dL, moderate between 500-866 mg/dL, and severe is defined as levels greater than 886 mg/dL. Plasma triglyceride levels above 1000 mg/dL occur in fewer than 1 in 5000 individuals. It is said that patients with TAG levels above 2000 mg/dL almost always have both a secondary and a genetic form of Hypertriglyceridemia. For this reason it is very important to identify these patients as early as possible to treat appropriately. Our patient was a known alcohol abuser, yet without the presence of some polygenic familial disorder, the likelihood of our patient having TAG levels >6000 mg/dL, is very unlikely.

The Use of Sirolimus for Treatment of Orbital Lymphatic Malformations: A Systematic Review.

Orbital lymphatic malformations are rare congenital choristomas associated with pain, proptosis, exposure keratopathy, and vision loss. Current treatments of surgery, drainage, and sclerotherapy may have adverse effects including risk of damage to surrounding structures, swelling, and malformation persistence or recrudescence. Sirolimus, which inhibits mammalian target of rapamycin, a regulator of cell growth and vascular endothelial growth factor expression, has successfully treated systemic vascular malformations. However, its efficacy and safety have not yet been well established for orbital lymphatic malformations. Systematic review and analysis of relevant published literature were performed. PubMed, Embase, and World of Science searches were conducted for studies involving sirolimus treatment of orbital lymphatic malformations through July 2019. Nine case series and reports with 10 total patients who received sirolimus for treatment of orbital lymphatic malformations were included. The age at sirolimus initiation ranged from 1 week to 23 years. The malformation was lymphatic in 6 patients, lymphaticovenous in 3 patients, and lymphatic-arteriovenous in 1 patient. Six patients underwent ineffective prior therapy including sclerotherapy, surgery, or medical therapy. Initial sirolimus dosage ranged from 0.05 mg/kg twice a day to 1 mg twice a day, and duration ranged from 6 months to 53 months. Seven patients had partial response, and 3 patients, all of whom had a microcystic malformation component, experienced complete response. Adverse effects included mild reversible leukopenia, hypertriglyceridemia, hypercholesterolemia, and transaminitis with adverse effects denied or not specified for 6 patients. Sirolimus may be a safe and effective treatment for orbital lymphatic malformations, especially microcystic malformations.

Dyslipidemia at diagnosis of childhood acute lymphoblastic leukemia.

As survival of acute lymphoblastic leukemia (ALL) exceeds 90%, limiting therapy-related toxicity has become a key challenge. Cardio-metabolic dysfunction is a challenge during and after childhood ALL therapy. In a single center study, we measured triglycerides (TG), total cholesterol (TC), high (HDL) and low density lipoproteins (LDL) levels at diagnosis and assessed the association with BMI, early therapy response, on-therapy hyperlipidemia and the toxicities; thromboembolism, osteonecrosis and pancreatitis. We included 127 children (1.0–17.9 years) all treated according to the NOPHO ALL2008 protocol. Dyslipidemia was identified at ALL-diagnosis in 99% of the patients, dominated by reduced HDL levels (98%) and mild hypertriglyceridemia (61%). Hypertriglyceridemia was not associated with body mass index (P = 0.71). Five percent of patients had mild hypercholesterolemia, 14% had mild hypocholesterolemia, 13% had decreased and 1% elevated LDL-levels. Increased TG and TC levels at ALL-diagnosis were not associated with any on-therapy lipid levels. Lipid levels and BMI were not associated to MRD after induction therapy; However, BMI and hypercholesterolemia were associated with worse risk group stratification (P<0.045 for all). The cumulative incidence of thromboembolism was increased both for patients with hypo- (20.0%) and hypercholesterolemia (16.7%) compared to patients with normal TC levels (2.2%) at diagnosis (P = 0.0074). In conclusion, dyslipidemic changes were present prior to ALL-therapy in children with ALL but did not seem to affect dysmetabolic traits during therapy and were not predictive of on-therapy toxicities apart from an association between dyscholesterolemia at time of ALL-diagnosis and risk of thromboembolism. However, the latter should be interpreted with caution due to low number in the groups.

Marine n-3 fatty acids and CVD: new insights from recent follow-up studies and clinical supplementation trials.

Marine n-3 PUFA exert beneficial effects that might inhibit atherosclerosis and reduce vascular disease. Previous studies have, however, reported conflicting results and here we have summarised the early history and the most recent findings from follow-up studies and randomised clinical trials investigating marine n-3 PUFA in relation to the risk of atherosclerotic CVD. Most follow-up studies have suggested that the intake of marine n-3 PUFA may be associated with a lower risk of CVD. Recent studies have also shown that it is important to focus on substitution issues and dietary patterns. Further, the use of gold standard biomarkers of fatty acid exposure such as adipose tissue should be encouraged. Findings from clinical supplemental trials have shown conflicting results and findings from previous meta-analyses and guidelines have generally not supported the use of fish oil supplements for the prevention of CVD. However, a recent meta-analysis including three recent large clinical trials with fish oil supplements reported a moderate beneficial effect on cardiovascular endpoints. Interestingly, results from a large clinical trial (REDUCE-IT) have suggested that supplementation with a high dose of purified EPA ethyl ester for 4⋅9 years significantly and markedly reduced the risk of cardiovascular events in patients with CVD and mild hypertriglyceridaemia; findings that need to be confirmed. While it seems appropriate to recommend consumption of fish, particular fatty fish for prevention of CVD, an effect of fish oil supplements is probably at best marginal perhaps apart from patients with hypertriglyceridaemia.

173-OR: Effects of Mild Acute Hypertriglyceridemia on Fasting and Post-Load Glucose Homeostasis

Background: Mild hypertriglyceridemia is associated with reduced glucose tolerance and increased risk of type 2 diabetes, independent of obesity and insulin sensitivity, in cross-sectional and prospective studies. To what extent these effects are directly produced by triglycerides and which are the major glucose homeostatic mechanisms involved is unclear. Methods: We examined the effects of acute triglyceride elevation on tracer-derived glucose metabolic fluxes, model-derived β-cell function, insulin sensitivity, and insulin clearance during two 3-h oral glucose tolerance tests with infusion of either normal saline or 20% Intralipid (25 ml/min/m2, without heparin) in 8 healthy lean volunteers. Results: A 2-h Intralipid infusion increased plasma TG by 2.7-fold (from 52±7 to 192±29 mg/dl; p=0.0003) without affecting plasma FFA, glucose, or insulin levels. After glucose ingestion, the lipid infusion elicited a marked increase in plasma glucose (iAUC +60%, p=0.01) and insulin (iAUC +52%, p=0.02) levels, while FFA were similarly suppressed. The deterioration in glucose tolerance was associated with reduced insulin sensitivity (Matsuda index -22%, p=0.04) and glucose clearance (-16%, p&amp;lt;0.05), and occurred despite a mild inhibition of the endogenous glucose production (-17%, p&amp;lt;0.05). Hyperinsulinemia was produced by reduced insulin clearance (-15%, p=0.04) and enhanced insulin secretion (assessed by C-peptide deconvolution; +29%, p=0.02) due to higher glucose levels and increased β-cell potentiation (+53%; p=0.04). Conclusions: Mild acute hypertriglyceridemia, independent of FFA, impairs glucose tolerance in healthy subjects by reducing insulin sensitivity and glucose clearance. The magnitude of these effects on glucose tolerance exceeds that of hyperinsulinemia resulting from enhanced β-cell potentiation and reduced insulin clearance. Disclosure D. Trico: None. A. Mengozzi: None. M. Seghieri: None. A. Mari: Consultant; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim International GmbH. A. Natali: None. Funding Italian Society of Diabetology; European Foundation for the Study of Diabetes

Safety of aggressive nutrition bundle-aggressive parenteral nutrition, standardized feeding policy, human milk fortification and probiotics in babies born less than 34 weeks of gestation: a prospective analytical cohort study

Background: Despite changes in nutritional interventions in neonatal intensive care units worldwide, significant proportion of preterm babies are growth restricted at discharge. Authors intended to look at the feasibility of aggressive nutrition bundle (aggressive parenteral nutrition, standardized feeding policy, fortification and probiotics) in preterm neonates.Methods: This single centre prospective analytical cohort study, involving babies born before 34 weeks of gestation, was conducted in a tertiary hospital. Aggressive parenteral nutrition and enteral nutrition bundle intervention was started within 24 hours of birth. Clinical, laboratory and anthropometrical parameters were monitored longitudinally to ensure safety of this intervention.Results: Mean gestational age and birth weight of the cohort (n=107) was 30.6 weeks (SD±2.6) and 1147 grams (SD±287) respectively. Out of 107 babies, 67.3% (n=72) have extra uterine growth retardation (EUGR) at discharge and was more in small for gestational age neonates (p=0.001). With this aggressive parenteral and enteral nutrition bundle intervention, medical necrotizing enterocolitis (NEC) developed in 7.4 % (n=8) babies while surgical NEC was seen in 1.9%. (n=2). Early onset and late-onset sepsis occurred in 1.8% and 5.4% of babies respectively while mild hyperammonemia, mild hypertriglyceridemia, raised creatinine and urea developed in 12.4%, 4.6%, 7.4% and 11.7% respectively. Hyperglycemia and hypoglycemia were present in 8.8% and 5.6% babies respectively.Conclusions: Aggressive nutrition bundle (aggressive parenteral nutrition, standardized feeding policy, fortification and probiotics) can be safely employed in preterm babies. There is an urgent need to design a study to see the impact of this approach on incidence of EUGR in preterm babies.

Phenotypic characterization of a novel type 2 diabetes animal model in a SHANXI MU colony of Chinese hamsters.

Developing animal models for human diseases is critical for studying complex diseases such as type 2 diabetes mellitus (T2DM). Since inbred colonies of Chinese hamsters tend toward spontaneous development of diabetes, we investigated them as a possible model. We regarded individuals with fasting blood glucose (FBG) higher than 6.0 mmol/L and post-prandial blood glucose (PBG) higher than 7.0 mmol/L as diabetic based on the mean and 95% frequency distribution values of FBG and PBG. Diabetic hamsters were characterized based on metabolic profiles, histopathological features, and changes in the expression of genes involved in glucose and lipid metabolism. Metabolic analyses showed that diabetic hamsters exhibited mild hyperglycemia, hypertriglyceridemia, glucose intolerance, and insulin resistance. Histopathological analysis revealed that cell nuclei migrated inward in skeletal muscle and obvious partial liver lipid deposition and focal necrosis was found. We additionally observed mild injury, atrophy, and occasional vacuolization in islet cells. Changes in the expression of several genes related to glucose and lipid metabolism were observed. Decreased expression of adiponectin and GLUT4 and increased expression of PPARγ, Akt, and leptin was observed in skeletal muscle. Decreased expression of adiponectin with increased expression of PPARγ and leptin was observed in the liver. These results indicate that we have established a spontaneous diabetic hamster line that closely mimics human T2DM, which may hold potential for further research on the pathogenesis and treatment of this disease.

The effect of high fat dietary modification and nutritional status on the outcome of critically ill ventilated children: single-center study.

Background Ventilator dependency constitutes a major problem in the intensive care setting. Malnutrition is considered a major determinant of extubation failure, however, attention has been attracted to modulating carbon dioxide production through decreasing carbohydrate loading and increasing the percent of fat in enteral feeds. The detected interrelation between substrate oxidation and ventilation outcome became the base of several research to determine the appropriate composition of the nonprotein calories of diet in ventilated patients.Purpose We aimed to assess the effect of high-fat dietary modification and nutritional status on ventilatory and final outcomes of pediatric intensive care.Methods Fifty-one ventilated children (1 month to 12 years of age) with pulmonary disease who could be enterally fed, in the Cairo University Pediatric intensive care unit, were divided into 2 groups: group A included 25 patients who received isocaloric high-fat, low-carbohydrate diet; group B included 26 patients who received standard isocaloric diet. Comprehensive nutritional assessment was done for all patients.Results Group A had a significant reduction in carbon dioxide tension, but no similar reduction in the duration or level of ventilatory support. Assisted minute ventilation was predicted by weight-for-age and caloric intake rather than the type of diet. Poor nutritional status was associated with higher mortality and lower extubation rates. Mild hypertriglyceridemia and some gastrointestinal intolerance were significant in group A, with no impact on the adequacy of energy or protein delivery.Conclusion The high-fat enteral feeding protocol may contribute to reducing carbon dioxide tension, with mild hypertriglyceridemia and negligible gastrointestinal intolerance as potential adverse effects. Optimization of nutritional status rather than dietary modification may improve ventilatory and survival outcomes in critically ill-ventilated children.

Intractable Coronary Artery Disease in a Patient With Type 2 Diabetes Presenting With Triglyceride Deposit Cardiomyovasculopathy.

The patient was a 51-year-old man who had been overweight since adolescence and was diagnosed with type 2 diabetes at age 26. He had been treated with a sulfonylurea, but his glycemic control was poor. When his medication was replaced with insulin injection at age 35, KITT, a marker of insulin sensitivity (1), was severely deteriorated to 0.87%, and resulting endogenous hyperinsulinemia was suspected from total daily urinary C-peptide excretion (242.8 μg). At that time, he was overweight by BMI (27.1 kg/m2). Lipid profiles showed mild hypertriglyceridemia with apolipoprotein E3/3 phenotype. His …

Efficacy of DHA and EPA on Serum Triglyceride Levels of Healthy Participants: Systematic Review

Background Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are categorized as omega-3 poly unsaturated fatty acids (PUFAs) that are present in fish oil, etc. DHA and EPA omega-3 PUFAs have a well-established fasting serum triglycerides (TG) lowering effect that may result in normal lipidemia in hyperlipidemic patients. In general, omega-3 PUFAs, such as DHA and EPA, can be ingested easily, and because they are highly safe, they are assumed to be suitable for controlling fasting serum TG in the serum of those who do not require drug treatment. To the best of our knowledge, however, almost all systematic reviews on the effects of omega-3 PUFAs on lowering fasting serum TG are directed at patients fulfilling the diagnostic criteria of dyslipidemia. Objectives To review and confirm the preventive effect of omega-3 PUFAs against hypertriglyceridemia or the effect on nondrug treatment in patients with a mild disease, a systematic review was conducted to determine whether there was a fasting serum TG-lowering effect in subjects without disease and those with a slightly higher triglyceride level who consumed DHA and/or EPA orally compared to those with placebo or no intake of DHA and/or EPA. Search Methods We evaluated articles from searches of PubMed (1946-February 2016), Ichushi-Web (1977-February 2016), and J Dream III (JST Plus, 1981-February 2016; JMED Plus, 1981-February 2016). The keywords were set as follows: “DHA” or “docosahexaenoic acid” or “EPA” or “eicosapentaenoic acid” and “TG” or “triglyceride” or “triglycerol” or “triacylglycerol” or “neutral lipid.”. In addition to the literature group obtained by the database search, we included participants not suffering from any disease (i.e., excluding mild hypertriglyceridemia). Eligibility Criteria Before the test selection process, the following inclusion criteria were defined. Participants were healthy men and women including those with mild hypertriglyceridemia (fasting serum TG level, 150-199 mg/dL [1.69-2.25 mmol/L)). Intervention was defined as orally ingested DHA and/or EPA. Comparison was made to placebo intake or no intake of DHA and/or EPA. Results were measured for the fasting serum TG level. The test design was RCT, and quasi-RCT. Data Abstraction Various characteristics were extracted from original reports using a standardized data extraction form, including the author of the study, research year, research design, subject characteristics (sex, age, sample size), period, dose of DHA and/or EPA (mg/day), and comparison group. Main Results We identified 37 documents for review. Among the 37 reports used to integrate literature results, 25 revealed a decrease in fasting serum TG level ​​due to the oral ingestion of DHA and/or EPA. Sixteen studies on subjects without disease and 21 on subjects with slightly higher fasting serum TG levels were separated and stratified analysis was conducted. Ten of the 16 (normal TG participant) and 15 of the 21 studies (slightly higher TG participant) respectively, indicated that at least 133 mg/day of DHA and/or EPA intervention provided a statistically significant decrease in the fasting serum TG level between an intervention group versus a placebo group.

Very Severe Hypertriglyceridemia-Casre Report with General Considerations

Abstract Hypertriglyceridemia is defined as a value of fasting serum triglyceride over 150 mg/dl. The classification of hypertriglyceridemia according to the Endocrinology Society include mild and moderate hypertriglyceridemia, severe hypertriglyceridemia and very severe hypertriglyceridemia. Mild and moderate hypertriglyceridemia increase the risk for cardiovascular events while severe and very severe hypertriglyceridemia is a risk factor for acute pancreatitis. Conventional pharmacological therapy of hypertriglyceridemia includes: fibrates, niacin, statins, ezetimibe, omega-3-fatty acid. Other triglyceridelowering therapies are represented by plasmapheresis and lipoprotein lipase gene therapy. The present work refers to a 59-year old man without history of family diabetes, dyslipidemia, premature coronary artery disease, diagnosed with T2DM in 2012, from 2014 on insulin treatment; he was hospitalized for endocrine evaluation. History: high blood pressure for approximately 25 years, chronic kidney disease, very severe hypertriglyceridemia, thyroid papillary carcinoma. The patient followed treatment with hypoglycemic, hypolipemic, low salt content diet, fibrates, statins, omega-3-fatty acid. Due to the fact that the patient did not respond to conventional therapy plasmapheresis was considered.

Pancreatitis due to Clomiphene Citrate-Induced Hypertriglyceridemia: A Case Report and Literature Review

Objective: Clomiphene citrate-induced hypertriglyceridemia causing acute pancreatitis is rare. The aim of this case report is to alert physicians to the possibility of clomiphene citrate-induced hypertriglyceridemia that can lead to acute, and even chronic, pancreatitis. Methods: We describe a patient with known mild hypertriglyceridemia who presented with acute pancreatitis and severe hypertriglyceridemia after initiation of clomiphene citrate. Results: The patient had mid-epigastric tenderness with radiation around her bilateral flanks in a band-like distribution. Lab studies showed a triglyceride level greater than 4,425 mg/dL, a lipase level greater than 3,000 U/L, and computed tomography of the abdomen showed acute interstitial edematous pancreatitis. The patient's Naranjo Adverse Drug Reaction score was calculated to be a 7, and was therefore probable as clomiphene being the causative agent. The patient's triglyceride levels improved after initiation of fibrate therapy and discontinuation of clomiph...

Effects of docosahexanoic acid on metabolic and fat parameters in HIV-infected patients on cART: A randomized, double-blind, placebo-controlled study

Hypertriglyceridemia is common in HIV-infected patients. Polyunsaturated fatty acids reduce fasting serum triglyceride (TG) levels in HIV-infected patients. It is not known whether docosahexanoic acid (DHA) supplementation can reduce hypertriglyceridemia and modify fat distribution in HIV-infected patients. We conducted a randomized, double-blind, placebo-controlled trial with 84 antiretroviral-treated patients who had fasting TG levels from 2.26 to 5.65mmol/l and were randomized to receive DHA or placebo for 48 weeks. TG levels were assessed at baseline, week 4 and every 12 weeks. Body composition was assessed at baseline and at week 48. Registered under ClinicalTrials.gov Identifier no. NCT02005900. Patients receiving DHA had a 43.9% median decline in fasting TG levels at week 4 (IQR:-31% to-56%), compared with-2.9% (-18.6% to 16.5%) in the placebo group (P<0.0001). DHA levels and decrease in TG at week 4 in the DHA arm correlated significantly (r=0.7110, P<0.0001). The median reduction in TG levels in the DHA arm was-43.7% (-32.4% to-57.5%), and in the placebo arm+2.9% (-21.3% to+30.1%) at week 12. The difference remained statistically significant at week 48 (P=0.0253). LDL cholesterol levels significantly increased at week 4 by 7.1% (IQR:-4.8% to+35.3%) in the DHA arm but not in the placebo group. No significant changes were observed in HDL cholesterol, insulin, and HOMA-IR during the study. Limb fat significantly increased in both arms, without statistically significant differences between groups (P=0.3889). DHA was well tolerated; only 3 patients experienced treatment-limiting toxicity. Supplementation with DHA reduced fasting TG levels in antiretroviral-treated HIV-infected patients with mild hypertriglyceridemia. DHA was well tolerated with minor GI symptoms. Peripheral fat significantly increased in the DHA group but did not increase significantly compared with placebo.

A 1-month-old infant with chylomicronemia due toGPIHBP1gene mutation treated by plasmapheresis

Chylomicronemia is a severe type of hypertriglyceridemia characterized by chylomicron accumulation that arises from a genetic defect in intravascular lipolysis. It requires urgent and proper management, because serious cases can be accompanied by pancreatic necrosis or persistent multiple organ failure. We present the case of a 1-month-old infant with chylomicronemia treated by plasmapheresis. His chylomicronemia was discovered incidentally when lactescent plasma was noticed during routine blood sampling during a hospital admission for fever and irritability. Laboratory investigation revealed marked triglyceridemia (>5,000 mg/dL) with high chylomicron levels. We therefore decided to perform a therapeutic plasmapheresis to prevent acute pancreatitis. Sequence analysis revealed a homozygous novel mutation in exon 4 of GPIHBP1: c.476delG (p.Gly159Alafs). Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) stabilizes the binding of chylomicrons near lipoprotein lipase and supports lipolysis. Mutations of GPIHBP1, the most recently discovered gene, can lead to severe hyperlipidemia and are known to make up only 2% of the monogenic mutations associated with chylomicronemia. The patient maintains mild hypertriglyceridemia without rebound after single plasmapheresis and maintenance fibrate medication so far. Here, we report an infant with chylomicronemia due to GPIHBP1 mutation, successfully treated by plasmapheresis.

Hypertriglyceridemia–induced acute pancreatitis: a systematic review of the literature

Objective: To summarize the current evidence about the hypertriglyceridemia–induced acute pancreatitis (HAP). Methods: Systematic review of the English language literature was conducted using PubMed/ Medline database from its inception until August 2016. As a searching methodology, we have used a combination of ‘acute pancreatitis’ and ‘hypertriglyceridemia’ as keywords into the title. Results: The diagnosis of HAP should be based on two out of the three criteria recommended by the international guidelines: characteristic clinical picture, serum pancreatic enzymes, and appropriate imagistics. The diagnosis of HAP should be distinguished between mild hypertriglyceridemia (> 150 mg/dL), which accompanies around one-third of all-causes acute pancreatitis, and severe hypertriglyceridemia (> 1 000 mg/dL) which generates acute pancreatitis. There is mixed evidence regarding a worse prognosis for patients with HAP, and a clear conclusion cannot be drawn. Similar to all the other etiologies, in HAP the initial treatment efforts should be nonspecific and addressed to acute pancreatitis, while pharmacologic and mechanical techniques should be added to lower the serum triglycerides as soon as possible. Conclusions: We may conclude that HAP should be managed to respect all the general principles, also adding all the available resources to lower the serum triglycerides value, as early as possible in the acute setting and on long-term to prevent recurrences.

ApoA-IMilano phospholipid complex (ETC-216) infusion in human volunteers. Insights into the phenotypic characteristics of ApoA-IMilano carriers

Epidemiological studies support an inverse correlation between HDL-C and cardiovascular disease. However, low HDL-C levels do not always segregate with premature disease. These include, LCAT deficiency and the apolipoproteinA-IMilano (AIM) variant. AIM has a cysteine for arginine at position 173 in the otherwise cysteine free protein permitting AIM homodimerization and apoA-II heterodimerization. We relate the biochemical characteristics of low HDL-C phenotype AIM carriers to lipoprotein changes in humans administered recombinant dimeric AIM/palmitoyl-oleoyl phosphatidyl choline (ETC-216). Pharmacokinetic analysis of infused ETC-216 suggest a slow distribution of AIM into peripheral tissue and an extremely long terminal half-life in plasma. Following ETC-216 administration to normal human volunteers, an initial dose-dependent HDL-C elevation was observed. Thereafter, subjects transiently acquired a lipoprotein profile similar to that of AIM carriers, including reduced HDL-C and mild hypertriglyceridemia. The time-dependent changes in plasma lipids/lipoproteins may support an increased tissue cholesterol removing capacity of ETC-216. These findings provide mechanistic insight into the rapid removal of atheromatous plaques observed in humans, possibly linked to enhanced cholesterol removal capacity of ETC-216.

Highly Active Antiretroviral Therapy (HAART)-Related Hypertriglyceridemia Is Associated With Failure of Recovery of CD14lowCD16+ Monocyte Subsets in AIDS Patients.

As cellular reservoirs, CD16+ monocyte subsets play important roles in the progression of HIV infection. Previous studies have shown that highly active antiretroviral therapy (HAART) reduced the percentages of CD14highCD16+ monocyte subsets, but did not recover the percentages of CD14lowCD16+ subsets. Eighty-four chronic HIV-infected, HAART-naïve individuals and 55 HIV-negative subjects (31 without hyperlipidemia and 24 with hypertriglyceridemia) were enrolled. Plasma HIV-1 RNA levels, CD4+ T-cell counts, triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein were followed up for 48 weeks during HAART treatment in the longitudinal study. We found that mild hypertriglyceridemia in HIV-negative subjects and HIV-infected patients, naïve to HAART, did not affect the percentage of monocyte subsets. However, a failure of CD14lowCD16+ subset recovery was observed in patients with HAART-related hypertriglyceridemia at 48 weeks. Thus, HAART-related hypertriglyceridemia altered homeostasis of monocyte subsets to antiviral therapy, which might further affect immune reconstitution.