Severe Hypertriglyceridemia Research Articles

Abstract 10357: ARO-APOC3, an Investigational RNAi Therapeutic, Shows Similar Efficacy and Safety in Genetically Confirmed FCS and Non-FCS Participants with Severe Hypertriglyceridemia

Background: Familial chylomicronemia syndrome (FCS) is an ultrarare condition caused by biallelic pathogenic DNA variants in lipolysis-associated genes, resulting in severe hypertriglyceridemia (HTG) and associated with high risk of acute pancreatitis with few therapeutic options. In a 16-week Phase 1 study (NCT03783377), subcutaneously administered ARO-APOC3 reduced serum apolipoprotein C3 (APOC3) and TG in healthy volunteers and participants (pts) with HTG and was well tolerated. Purpose: To report on the safety/pharmacodynamic (PD) effects of ARO-APOC3 in both FCS pts with biallelic pathogenic variants and pts with severely elevated TG at screening (>880 mg/dL) but without biallelic pathogenic variants (chylomicronemia (MCM)). Methods: Four genetically confirmed FCS pts received 50 mg ARO-APOC3 and 26 MCM pts received 10, 25, 50, or 100 mg ARO-APOC3 on Days 1 and 29. Since similar PD responses were observed among MCM pts, results were pooled across dose levels. Safety and PD responses were examined. Maximal mean/median changes from baseline for APOC3, TG, non-HDL-C, and HDL-C were reported. Results: Baseline/demographics were comparable between groups, except for mean BMI (22.1 [FCS] and 30.5 [MCM] kg/m 2 ), and mean baseline HDL-C , which were lower in FCS pts (Table 1) (p<0.0001 for both). Mean APOC3 was reduced by 98% and 96% in FCS and MCM pts, respectively. Both groups also showed similar maximum median reductions in TG of 91% and 90%, respectively. Similar to the full study, non-HDL-C was reduced and HDL-C increased with treatment in both groups (Table 1). AEs were similar between groups, suggesting a comparable safety profile. Conclusions: In patients with severe HTG, ARO-APOC3 was safe, and consistently decreased APOC3, TG, and non-HDL-C, and increased HDL-C, regardless of underlying genetic cause of HTG, and may represent a promising RNAi therapeutic for the treatment of severe HTG.

Abstract 13168: Total Lipoprotein Lipase Deficiency Does Not Impact Atherosclerosis Development in Low Density Lipoprotein Receptor Deficient Mice

Introduction: Elevated LDL cholesterol (LDL-C) is a major causal factor for CVD. However, the importance of elevated triglyceride rich lipoproteins (TRLs) on CVD is still being investigated. Lipoprotein lipase (LpL) is the rate limiting enzyme hydrolyzing circulating very low density lipoprotein (VLDL) and chylomicrons. The effect of increased TRLs as an independent factor on atherosclerosis is not known, in part, because hypertriglyceridemia associates with low levels of LDL-C. Objective: We tested whether whole body LpL deficiency in mice combined with LDL receptor (LDLR) deficiency and an atherogenic diet affects lesion formation. Hypothesis: LpL deficient mice will not show increased atherosclerosis progression as compared to control mice, despite severe dyslipidemia, due to reduced infiltration of atherogenic lipids into the aortic endothelium. Methods: Induced global LpL deficiency (i Lpl -/- ) was created by tamoxifen injection to activate beta actin-driven cre. To knock down hepatic LDLR we utilized anti sense oligonucleotides (ASOs) as well as a PCSK9 expressing AAV. Results: i Lpl -/- mice on chow diet have elevated plasma triglycerides, increased VLDL cholesterol, lower LDL-C and lower high density lipoprotein cholesterol (HDL-C) compared to control Lpl fl/fl mice. However, when hepatic LDLR was knocked down with using LDLR ASO or AAV PCSK9, iLpl -/- mice displayed elevated LDL-C of about 150 mg/dl, similar to the levels seen in control mice with LDLR knockdown. When i Lpl -/- mice were fed an atherogenic Western diet for 16 weeks, i Lpl -/- mice developed severe hypertriglyceridemia (1500-8000 mg/dl) and increased total cholesterol to ~1500 mg/dl. LDL-C levels were similar to those of control mice with LDLR knockdown; ~200 mg/dl. HDL-C was lower in i Lpl -/- mice compared to the controls (~10 mg/dl vs ~30 mg/dl). i Lpl -/- mice had slightly smaller lesions in brachiocephalic arteries but macrophage content was similar to the controls. Aortic root lesion size was similar in both groups of mice. Conclusion: Despite severe hypertriglyceridemia, hypercholesterolemia and low HDL-C, iLpL -/- mice did not exhibit altered atherosclerosis progression, likely because of the absence of LpL-derived atherogenic lipids or remnant lipoproteins.

Abstract 12054: Evinacumab Reduces Atherogenic Lipids and Apolipoprotein B in Patients With Severe Hypertriglyceridemia

Background: Hypertriglyceridemia (HTG) is the consequence of elevated triglyceride-rich lipoproteins (TGRLs) containing apolipoprotein B (apoB), such as VLDL and chylomicrons. Epidemiological and genetic studies indicate that triglycerides (TGs) and the cholesterol within TGRLs causally contribute to coronary heart disease risk (CHD). Evinacumab (EVIN), an angiopoietin-like 3 inhibitor, lowers TGs by derepressing lipoprotein lipase (LPL) and endothelial lipase activity. In a Phase 2 trial in patients (pts) with severe HTG (sHTG, fasting TGs ≥500 mg/dL), EVIN was previously shown to reduce TGs in patients (pts) without familial chylomicronemia syndrome (FCS) and to be generally well tolerated (NCT03452228). This post-hoc analysis reports further details on the efficacy of EVIN in reducing atherogenic lipids/lipoproteins. Methods: Pts (N=51) were treated and assigned to cohorts based on genotype: Cohort 1 (n=17), FCS pts with bi-allelic loss-of-function (LOF) LPL pathway mutations; Cohort 2 (n=15), multifactorial chylomicronemia syndrome (MCS) pts with heterozygous LOF LPL pathway mutations; Cohort 3 (n=19), MCS pts without LPL pathway mutations. Pts were randomized (2:1) to IV EVIN 15 mg/kg or placebo every 4 weeks over a 12-week double-blind treatment (tx) period (DBTP), followed by a 12-week single-blind tx period where all pts received EVIN. Results: Of 51 pts with sHTG treated in the DBTP, 70.6% were categorized as high cardiovascular risk, and 21.6% had a history of CHD. In non-FCS pts (Cohorts 2 and 3), in addition to reducing TGs, EVIN reduced atherogenic lipids and apolipoproteins at Week (W) 12 compared with baseline (Table), including non-HDL-C, remnant cholesterol, and apoB (including apoB100 and apoB48). Overall, reductions observed at W12 were maintained through W24. Conclusions: In this post-hoc analysis, EVIN reduced atherogenic lipids and apoB, indicating it may have the potential to reduce CHD risk in pts with sHTG without genetic FCS.

CREBH normalizes dyslipidemia and halts atherosclerosis in diabetes by decreasing circulating remnant lipoproteins.

Loss-of-function mutations in the transcription factor CREB3L3 (CREBH) associate with severe hypertriglyceridemia in humans. CREBH is believed to lower plasma triglycerides by augmenting the activity of lipoprotein lipase (LPL). However, by using a mouse model of type 1 diabetes mellitus (T1DM), we found that greater liver expression of active CREBH normalized both elevated plasma triglycerides and cholesterol. Residual triglyceride-rich lipoprotein (TRL) remnants were enriched in apolipoprotein E (APOE) and impoverished in APOC3, an apolipoprotein composition indicative of increased hepatic clearance. The underlying mechanism was independent of LPL, as CREBH reduced both triglycerides and cholesterol in LPL-deficient mice. Instead, APOE was critical for CREBH's ability to lower circulating remnant lipoproteins because it failed to reduce TRL cholesterol in Apoe-/- mice. Importantly, individuals with CREB3L3 loss-of-function mutations exhibited increased levels of remnant lipoproteins that were deprived of APOE. Recent evidence suggests that impaired clearance of TRL remnants promotes cardiovascular disease in patients with T1DM. Consistently, we found that hepatic expression of CREBH prevented the progression of diabetes-accelerated atherosclerosis. Our results support the proposal that CREBH acts through an APOE-dependent pathway to increase hepatic clearance of remnant lipoproteins. They also implicate elevated levels of remnants in the pathogenesis of atherosclerosis in T1DM.

Thrombosis Prophylaxis with Apixaban in Patients Treated with Asparaginase

Thrombosis Prophylaxis with Apixaban in Patients Treated with Asparaginase

Complications of lipodystrophy syndromes

Lipodystrophy syndromes are rare complex multisystem disorders caused by generalized or partial lack of adipose tissue. Adipose tissue dysfunction in lipodystrophy is associated with leptin deficiency. Lipodystrophy leads to severe metabolic problems. These abnormalities include, but are not limited to, insulin-resistant diabetes, severe hypertriglyceridemia, and lipid accumulation in ectopic organs such as the liver, and are associated with end-organ complications. Metabolic abnormalities can be present at the time of diagnosis or may develop over time as the disease progresses. In addition to metabolic abnormalities, subtype-specific presentations due to underlying molecular etiology in genetic forms and autoimmunity in acquired forms contribute to severe morbidity in lipodystrophy.

Fructose-induced severe hypertriglyceridemia and diabetes mellitus: a cautionary tale.

SummaryDrinking fruit juice is an increasingly popular health trend, as it is widely perceived as a source of vitamins and nutrients. However, high fructose load in fruit beverages can have harmful metabolic effects. When consumed in high amounts, fructose is linked with hypertriglyceridemia, fatty liver and insulin resistance. We present an unusual case of a patient with severe asymptomatic hypertriglyceridemia (triglycerides of 9182 mg/dL) and newly diagnosed type 2 diabetes mellitus, who reported a daily intake of 15 L of fruit juice over several weeks before presentation. The patient was referred to our emergency department with blood glucose of 527 mg/dL and glycated hemoglobin (HbA1c) of 17.3%. Interestingly, features of diabetic ketoacidosis or hyperosmolar hyperglycemic state were absent. The patient was overweight with an otherwise unremarkable physical exam. Lipase levels, liver function tests and inflammatory markers were closely monitored and remained unremarkable. The initial therapeutic approach included i.v. volume resuscitation, insulin and heparin. Additionally, plasmapheresis was performed to prevent potentially fatal complications of hypertriglyceridemia. The patient was counseled on balanced nutrition and detrimental effects of fruit beverages. He was discharged home 6 days after admission. At a 2-week follow-up visit, his triglyceride level was 419 mg/dL, total cholesterol was 221 mg/dL and HbA1c was 12.7%. The present case highlights the role of fructose overconsumption as a contributory factor for severe hypertriglyceridemia in a patient with newly diagnosed diabetes. We discuss metabolic effects of uncontrolled fructose ingestion, as well as the interplay of primary and secondary factors, in the pathogenesis of hypertriglyceridemia accompanied by diabetes.Learning pointsExcessive dietary fructose intake can exacerbate hypertriglyceridemia in patients with underlying type 2 diabetes mellitus (T2DM) and absence of diabetic ketoacidosis or hyperosmolar hyperglycemic state.When consumed in large amounts, fructose is considered a highly lipogenic nutrient linked with postprandial hypertriglyceridemia and de novo hepatic lipogenesis (DNL).Severe lipemia (triglyceride plasma level > 9000 mg/dL) could be asymptomatic and not necessarily complicated by acute pancreatitis, although lipase levels should be closely monitored.Plasmapheresis is an effective adjunct treatment option for rapid lowering of high serum lipids, which is paramount to prevent acute complications of severe hypertriglyceridemia.

Eruptive xanthomas secondary to severe hypertriglyceridemia

Xanthomas are benign cutaneous manifestations of extracellular lipid accumulation. Eruptive xanthoma is characterized by the acute, widespread presentation of a papular rash and usually involves the back, buttocks, and extremities. Eruptive xanthoma is associated with hyperlipidemia, hypertriglyceridemia, and an increased long-term risk of atherosclerotic cardiovascular disease. We present a case of eruptive xanthoma accompanied by severe hypertriglyceridemia (10,164 mg/dL) in which the course of the disease was reversed following implementation of lipid-lowering pharmacotherapy.

Hypertriglyceridaemia: contemporary management of a neglected cardiovascular risk factor.

Hypertriglyceridaemia represents one of the most prevalent lipid abnormalities, however it is often eclipsed by focus on LDL cholesterol and is frequently overlooked by clinicians, despite it being an important cardiovascular risk factor. For most patients, hypertriglyceridaemia arises from a combination of environmental factors and multiple genetic variations with small effects. Even in cases with apparent familial clustering of hypertriglyceridaemia, a monogenetic cause is rarely identified. Common secondary causes include obesity, uncontrolled diabetes, alcohol, and various commonly used drugs. Correction of these factors, along with lifestyle optimisation, should be prioritised prior to commencing medication. The goal of drug treatment is to reduce the risk of cardiovascular disease in those with moderate hypertriglyceridaemia and the risk of pancreatitis in those with severe hypertriglyceridaemia. Recent and ongoing trials demonstrate the important role of triglycerides (TG) in determining residual risk in patients with cardiovascular disease (CVD) already established on statin therapy. Novel and emerging data on omega-3 fatty acids (high-dose icosapent ethyl) and the selective PPAR modulator pemafibrate are eagerly awaited and may provide further clarity for clinicians in determining which patients will benefit from TG lowering and help inform clinical guidelines. There are numerous novel therapies on the horizon that reduce TG by decreasing the activity of proteins that inhibit lipoprotein lipase such as apolipoprotein C-III (including Volanesorsen which was recently approved in Germany) and ANGPTL 3/4 which may offer promise for the future.

Transcriptomic therapy for dyslipidemias utilizing nucleic acids targeted at ANGPTL3.

Angiopoietin-like protein 3 (ANGPTL3) is a key physiological regulator of plasma lipid and lipoproteinmetabolism that involves the control of enzymes, lipoprotein and endothelial lipases. Inhibition of ANGPTL3 offers a new approach for correcting the health risks of dyslipidemia, including familial hypercholesterolemia, mixed hyperlipidemia, metabolic syndromeand/or severe hypertriglyceridemia. ANGPTL3 inhibition with nucleic acid-based antisense oligonucleotide and siRNA can correct dyslipidemia chiefly by reducing production and increasing catabolism of triglyceride-rich lipoprotein and LDL particles. Early clinical trials have demonstrated that these agents can safely and effectively lower plasma triglyceride and LDL-cholesterol levels by up to 70and 50%, respectively. However, the long-term safety and cost-effectiveness of these agents await to be confirmed in anongoing and future clinical trials.

Acute pancreatitis due to severe hypertriglyceridemia in the COVID-19 era: The role of therapeutic plasma exchange

The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too.Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality.Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.

Successful therapeutic plasma exchange in a case with extremely severe hypertriglyceridemia secondary to diabetic ketoacidosis concomitant with type IX glycogen storage disease

Herein, we aimed to present a child with extremely severe hypertriglyceridemia (ESHTG) secondary to diabetic ketoacidosis concomitant with type IX glycogen storage disease (GSD). Extremely severe hypertriglyceridemia (10 700 mg/dL) was detected through the apparent lipemic appearance of the sampled blood in a 17-year-old male patient with severe diabetic ketoacidosis. In spite of insulin infusion, the patient’s clinical condition deteriorated to acute pancreatitis. Single sessions of therapeutic plasma exchange (TPE) along with insulin treatment have successfully intercepted the progression of the state of acute pancreatitis. The patient was also diagnosed with type IX GSD on the basis of the genetic analyses performed for the potential underlying metabolic diseases. In conclusion, underlying metabolic diseases, such as glycogen storage disease, should be investigated in patients with diabetic ketoacidosis accompanied by severe hypertriglyceridemia. If ESHTG does not relieve despite insulin infusion, and/or acute pancreatitis occurs as a complication, TPE should be kept in mind.

A Tale of Two Approaches.

To summarize and assess the literature on the performances of methods beyond the Friedewald formula (FF) used in routine practice to determine low-density lipoprotein cholesterol (LDL-C). A literature review was performed by searching the PubMed database. Many peer-reviewed articles were assessed. The examined methods included direct homogeneous LDL-C assays, the FF, mathematical equations derived from the FF, the Martin-Hopkins equation (MHE), and the Sampson equation. Direct homogeneous assays perform inconsistently across manufacturers and disease status, whereas most FF-derived methods exhibit variable levels of performance across populations. The MHE consistently outperforms the FF but cannot be applied in the setting of severe hypertriglyceridemia. The Sampson equation shows promise against both the FF and MHE, especially in severe hypertriglyceridemia, but data are still limited on its validation in various settings, including disease and therapeutic states. There is still no consensus on a universal best method to estimate LDL-C in routine practice. Further studies are needed to assess the performance of the Sampson equation.

S51 Severe Hypertriglyceridemia Is Associated With Increased Risk of Necrosis in Patients With Hypertriglyceridemia-Induced Pancreatitis

S51 Severe Hypertriglyceridemia Is Associated With Increased Risk of Necrosis in Patients With Hypertriglyceridemia-Induced Pancreatitis

A UNIQUE CASE OF XANTHOMATOSIS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypertriglyceridemia (TGL) is the abnormal concentration of triglycerides in the blood associated with atherosclerosis. It is known to cause skin lesions when the blood levels are more than 3000 mg/dl. It is also associated with 1 to 10 percent cases of acute pancreatitis and 10 to 20 percent when levels are higher than 2000 mg/dl. CASE PRESENTATION: A 36-year old morbidly obese man with medication non-compliance was evaluated by a dermatologist via a video tele visit due to COVID19 Pandemic. He has a history of uncontrolled IDDM, hypertriglyceridemia status post plasmapheresis a year ago associated with pancreatitis. He has no family history of hypertriglyceridemia. He reported rashes on his forearms and thighs for 3 weeks and was advised to go to the Emergency Department to rule out cutaneous manifestation of his underlying conditions. He initially reported epigastric pain radiating to his back, but his lipase and CT abdomen were negative for pancreatitis. He was vitally stable, and his exam was significant for yellowish papules on his forearms, legs bilaterally with erythematous borders. Labs: TGL 1618, total cholesterol 647, Glucose 223, A1c 12.6%, no Anion Gap.Imaging: Splenomegaly with Hepatic Steatosis likely due to TGL deposition.Patient was placed on Insulin drip to prevent pancreatitis and was started on fenofibrate, fish oil and rosuvastatin. Kept NPO initially with dextrose infusion to increase insulin drip & metabolize the triglycerides. Triglycerides gradually improved, and insulin drip was d/c. Shave Biopsy confirmed Eruptive Xanthoma. DISCUSSION: Eruptive xanthomas are characterized by an eruption of yellowish skin papules, encircled by an erythematous halo, most commonly arising over the extensor surfaces of the extremities, buttocks and shoulders in the setting of high triglyceride levels secondary to diabetes, diet or familial causes. The lipid deposits in these xanthomas are derived from circulating plasma lipoproteins. CONCLUSIONS: This case was unique as our patient developed eruptive xanthomas even at TGL level under 2000 mg/dl which is rarely seen. Clinically diagnosing Xanthomas are extremely important in order to treat hypertriglyceridemia in order to prevent pancreatitis, which has a grim prognosis. It is also important for reducing CAD risk. Xanthomas should be evaluated to prevent pancreatitis and long-term cardiac events rather than the lipid deposit itself. They can also be the only signs of underlying metabolic diseases like diabetes. Management should include pharmacological agents, counseling for compliance, nutrition & lifestyle modifications. All these patients with high TGLs will benefit from E3/E4 genotype testing as it is associated with higher cardiac disease and low response to statins. REFERENCE #1: Severe hypertriglyceridemia presenting as eruptive xanthomatosisSameera S Vangara, Kyle D Klingbeil, Raymond M Fertig, Jason L RadickDepartment of Internal Medicine, University of Miami Miller School of Medicine, Florida, USA REFERENCE #2: Eruptive Xanthomas as a cutaneous Manifestation of HypertriglyceridemiaA Case ReportMichael Digby, Md, Robert Belli, MS, Timothy McGraw, and Abigail Lee, MD DISCLOSURES: no disclosure on file for Moses Bachan; no disclosure on file for Zinobia Khan; No relevant relationships by Robert Siegel, source=Web Response No relevant relationships by Goutham Talluri, source=Web Response

CREBH Systemically Regulates Lipid Metabolism by Modulating and Integrating Cellular Functions.

Cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor expressed in the liver and small intestine. The activity of CREBH is regulated not only at the transcriptional level but also at the posttranslational level. CREBH governs triglyceride metabolism in the liver by controlling gene expression, with effects including the oxidation of fatty acids, lipophagy, and the expression of apolipoproteins related to the lipoprotein lipase activation and suppression of lipogenesis. The activation and functions of CREBH are controlled in response to the circadian rhythm. On the other hand, intestinal CREBH downregulates the absorption of lipids from the diet. CREBH deficiency in mice leads to severe hypertriglyceridemia and fatty liver in the fasted state and while feeding a high-fat diet. Therefore, when crossing CREBH knockout (KO) mice with an atherosclerosis model, low-density lipoprotein receptor KO mice, these mice exhibit severe atherosclerosis. This phenotype is seen in both liver- and small intestine-specific CREBH KO mice, suggesting that CREBH controls lipid homeostasis in an enterohepatic interaction. This review highlights that CREBH has a crucial role in systemic lipid homeostasis to integrate cellular functions related to lipid metabolism.

Clinical Management of Hypertriglyceridemia in the Prevention of Cardiovascular Disease and Pancreatitis.

Purpose of ReviewHypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in reducing atherosclerosis risk. Novel therapies for severe HTG treatment and pancreatitis risk reduction are likely to be available soon. These novel therapies are expected to have broader applications for more moderate HTG and atherosclerosis risk reduction as well.Recent FindingsNHANES 2012 data has confirmed a reduction in average triglyceride (TG) levels in the US population. Dietary modification and weight reduction when needed remain the core treatment elements for all individuals with HTG, while statin therapy is a foundational pharmacologic care for atherosclerotic cardiovascular disease (ASCVD) event risk reduction. In addition, the REDUCE-IT study provides evidence for additional benefit from the use of high-dose icosapent ethyl (IPE) on top of background medical therapy in adults with moderate HTG and ASCVD or type 2 diabetes mellitus (T2D) and additional ASCVD risk factors. However, treatment with eicosapentaenoic acid (EPA) combined with docosahexanoic acid (DHA) did not reduce ASCVD in a similar population studied in the STRENGTH trial. Furthermore, novel therapeutics targeting PPAR-ɑ, as well as ApoC-III and AngPTL3, effectively lower TG levels in individuals with moderate and severe HTG, respectively. These treatments may have applicability for reducing risk from ASCVD among individuals with chylomicronemia; in addition, ApoC-III and AngPTL3 treatments may have a role in treating individuals with the rare monogenic familial chylomicronemia syndrome (FCS) at risk for acute pancreatitis (AP).SummaryResidual ASCVD risk in individuals treated with contemporary care may be due in part to non-LDL lipid abnormalities including HTG. The findings from REDUCE-IT, but not STRENGTH, confirm that consumption of high-dose EPA may reduce ASCVD risk, while combination therapy of EPA plus DHA does not reduce ASCVD in a similar population. TG lowering likely reduces ASCVD risk in individuals with HTG, but ASCVD risk is multifactorial; the added benefit of IPE to contemporary preventive therapy is the consequence of differential non-TG biologic properties between the two fatty acids. Acute pancreatitis is more difficult to study prospectively since it is less common; however, TG lowering is likely critical for the care of at-risk individuals. Additional benefit from novel therapy that has an impact on this otherwise refractory condition is anticipated.

Skimmed breast milk for treatment of hypertriglyceridemia in an infant with congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) is a complex condition that requires multidisciplinary care. Hyperlipidemia is a characteristic feature with elevation of serum cholesterol and triglycerides. Little evidence is available to guide treatment of dyslipidemia in infants with CNS. We describe successful treatment of severe hypertriglyceridemia through dietary changes in a boy with CNS. A 9-day-old boy presented to the emergency department with lower extremity edema caused by deep venous thrombosis. Laboratory evaluation identified hypoalbuminemia, nephrotic-range proteinuria, and a pathogenic variant of the NPHS1 gene. The initial triglyceride concentration of 369 mg/dl increased to 3096 mg/dl by 5 weeks of age, when his diet consisted of breast milk. Refrigerated breast milk was skimmed by removing the top layer after allowing it to separate for 24 h. This process was repeated prior to use. Skimmed breast milk was supplemented with medium-chain triglyceride oil and an infant protein powder. After 2 days, the triglyceride concentration declined to 481 mg/dl and, by day 10, to 148 mg/dl. When breast milk supply decreased, a 1:1 ratio of skimmed maternal breast milk to an elemental, very low-fat formula was utilized. The triglyceride concentration remained below 400 mg/dl for the first year of life, except when skimmed breast milk was not available during hospitalization. Severe hypertriglyceridemia caused by CNS can present in the neonatal period and be difficult to manage. In our patient, skimmed maternal breast milk was successful in reducing the triglyceride concentration and should be considered a therapeutic option for children with hyperlipidemia caused by CNS.

Incidence, predictors and patterns of care of patients with very severe hypertriglyceridemia in Ontario, Canada: a population-based cohort study

BackgroundThe incidence of severe (S-HTG) and very severe hypertriglyceridemia (VS-HTG) among Canadians is unknown. This study aimed to determine the incidence, characteristics, predictors and care patterns for individuals with VS-HTG.MethodsUsing linked administrative healthcare databases, a population-based cohort study of Ontario adults was conducted to determine incidence of new onset S-HTG (serum triglycerides (TG) > 10–20 mmol/L) and VS-HTG (TG > 20 mmol/L) between 2010 and 2015. Socio-demographic and clinical characteristics of those with VS-HTG were compared to those who had no measured TG value > 3 mmol/L. Univariable and multivariable logistic regression were used to determine predictors for VS-HTG. Healthcare patterns were evaluated for 2 years following first incidence of TG > 20 mmol/L.ResultsIncidence of S-HTG and VS-HTG in Ontario was 0.16 and 0.027% among 10,766,770 adults ≥18 years and 0.25 and 0.041% among 7,040,865 adults with at least one measured TG, respectively. Predictors of VS-HTG included younger age [odds ratios (OR) 0.64/decade, 95% confidence intervals (CI) 0.62–0.66], male sex (OR 3.83; 95% CI 3.5–4.1), diabetes (OR 5.38; 95% CI 4.93–5.88), hypertension (OR 1.69; 95% CI 1.54–1.86), chronic liver disease (OR 1.71; 95% CI 1.48–1.97), alcohol abuse (OR 2.47; 95% CI 1.90–3.19), obesity (OR 1.49; 95% CI 1.13–1.98), and chronic kidney disease (OR 1.39; 95% CI 1.19–1.63).ConclusionThe 5-year incidence of S-HTG and VS-HTG in Canadian adults was 1 in 400 and 1 in 2500, respectively. Males, those with diabetes, obese individuals and those with alcohol abuse are at highest risk for VS-HTG and may benefit from increased surveillance.

Very severe hypertriglyceridemia in a subject with poor glycemic control: a case report with general consideration

Hypertriglyceridemia is defined as a value of fasting serum triglyceride over 150 mg/dl. The classification of hypertriglyceridemia according to the Endocrine Society includes mild and moderate hypertriglyceridemia, severe hypertriglyceridemia and very severe hypertriglyceridemia. Mild and moderate hypertriglyceridemia increases 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, and omega-3 fatty acid. Other triglyceride-lowering therapies are represented by plasmapheresis and lipoprotein lipase gene therapy. The present work refers to a 55-year-old man without a history of family diabetes mellitus (DM), dyslipidemia, premature coronary artery disease, diagnosed with type 2 DM in 2016, from 2018 on insulin treatment; he was hospitalized for endocrine evaluation. The patient had a history of high blood pressure for approximately 15 years, chronic kidney disease, very severe hypertriglyceridemia, and chronic obstructive pulmonary disease. The patient followed treatment with hypoglycemic, hypolipemic, low-salt diet, fibrates, statins, omega-3 fatty acid.