scholarly journals SAT-570 Should Severe Hypertriglyceridemia Also Be Considered as a Contraindication for Use of Glucagon like Peptide 1 (GLP-1) Agonists?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Amelia Guzman

Abstract Background: Reported cases of acute pancreatitis have been associated with the use of GLP-1 agonists for treatment of diabetes mellitus. Hypertriglyceridemia is a well-established but underestimated cause of acute and recurrent pancreatitis. At the present time, there is insufficient data to know if there is a casual relationship. Clinical Case: A 46 y.o. male with past medical history of coronary artery disease, hyperlipidemia, type 2 diabetes mellitus, hypertension, and morbid obesity, was admitted to the hospital with severe abdominal pain radiating to the back associated with non-bilious vomiting, for 1 day. Patient endorsed that 4 years ago he was diagnosed with hypertriglyceridemia. Physical exam findings were notable for a distended abdomen with mild epigastric tenderness, heart rate at 120 bpm, and a body mass index of 37 kg/m2. Active medications include: atorvastatin 40 mg PO daily, fenofibrate 45 mg PO daily, metformin 1,000 mg PO twice a day, glipizide 5 mg PO daily, levemir 60 units SQ twice a day, and most recently he had been started on dulaglutide 0.75 mg SQ weekly. Initial tests were consistent with acute pancreatitis and diabetic ketoacidosis: lipase 944 U/L (n 8.0 - 78 U/L), anion gap 18 mEq/L (n 5 - 13 mEq/L), creatinine 1.6 mg/dL (n 0.72 - 1.25 mg/dL), glucose 479 (n 60–100 mg/dL), β-Hydroxybutyrate 5.3 mmol/L (n <0.3mmol/L), urine glucose >1,000 mg/dL (n Negative mg/dL), urine ketones 20 mg/dL (n Negative), Triglycerides (TG) 5,374 mg/dL (n <150 mg/dL) and Hgb A1C 11.9% (n <5.7%). CT abdomen and pelvis without contrast revealed moderate acute pancreatitis. Patient was admitted to the intensive care unit and was started on intravenous insulin, atorvastatin 80 mg PO daily and fenofibrate 145 mg PO daily. Despite optimization of lipid-lowering agents, TG remained above 2,000 mg/dL. Decision was made to start patient on plasmapheresis until TG was <500 mg/dL. Patient’s TG improved to 370 mg/dL after second treatment. Patient’s dulaglutide was discontinued and patient was advised to avoid GLP-1 agonist use, indefinitely. One-month post discharge patient’s TG level was 370 mg/dL. Conclusion: Pancreatitis should be considered in patients on GLP-1 agonists, that present with persistent severe abdominal pain (with or without nausea), and its use should be discontinued in such patients. Use of GLP-1 agonists should be avoided in subjects with severe hypertriglyceridemia. Further research should be made in order to determine if GLP-1 agonists should be contraindicated in patients with severe hypertriglyceridemia, as both increase risk for pancreatitis.

Author(s):  
Djordje S. Popovic ◽  
Nikolaos Papanas

AbstractThe growing proportion of type 1 diabetes mellitus (T1DM) patients with clinical features of insulin resistance (IR) has led to the description of a distinctive T1DM subgroup, still unrecognised by current guidelines, called double diabetes, assumingly associated with poorer metabolic phenotype and increased risk of micro- and macrovascular complications. The main goal of identifying double diabetes, estimated to be present in up to half of T1DM patients, is timely implementation of appropriate therapeutic interventions to reduce the increased risk of chronic complications and other adverse metabolic traits associated with this condition. Proposed diagnostic criteria are largely divided into three different groups: family history of type 2 diabetes mellitus (T2DM), obesity/metabolic syndrome, and IR. Estimated glucose disposal rate may prove the most reliable marker of double diabetes. In addition to general measures (diet, physical activity, antihypertensive, and lipid-lowering medications, etc.) and development of new insulin preparations with more hepatic action, double diabetes patients may derive more benefit from agents developed for T2DM. Indeed, such potentially promising agents include glucagon-like peptide-1 receptor agonists, sodium-glucose contrasporter-2 inhibitors, and their combination. We are now awaiting long-term trials assessing metabolic and vascular benefits of these medications in double diabetes.


Healthcare ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 150
Author(s):  
Georgios Mavraganis ◽  
Sofia Ioannou ◽  
Anastasios Kallianos ◽  
Gianna Rentziou ◽  
Georgia Trakada

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a high incidence of arterial and venous thrombotic complications. However, thromboembolic events in unusual sites such as limb and visceral arterial ischemia are reported rarely in the literature. Herein, we describe a rare case of a patient with severe coronavirus disease 2019 (COVID-19) infection who experienced severe abdominal pain during the hospitalization and presented simultaneously renal artery, splenic artery and vein as well as aortic thrombi despite prophylactic antithrombotic treatment. Information about his follow-up post discharge is also provided. This case report raises significant clinical implications regarding the correct dose of antithrombotic treatment during the acute phase of the severe COVID-19 infection and highlights the need for incessant vigilance in order to detect thrombosis at unusual sites as a possible diagnosis when severe abdominal pain is present in severe COVID-19 patients.


Author(s):  
Sarah W Y Poon ◽  
Karen K Y Leung ◽  
Joanna Y L Tung

Summary Severe hypertriglyceridemia is an endocrine emergency and is associated with acute pancreatitis and hyperviscosity syndrome. We describe an infant with lipoprotein lipase deficiency with severe hypertriglyceridemia who presented with acute pancreatitis. She was managed acutely with fasting and intravenous insulin infusion, followed by low-fat diet with no pharmacological agent. Subsequent follow-up until the age of 5 years showed satisfactory lipid profile and she has normal growth and development. Learning points: Hypertriglyceridemia-induced acute pancreatitis has significant morbidity and mortality, and prompt treatment is imperative. When no secondary causes are readily identified, genetic evaluation should be pursued in hypertriglyceridemia in children. Intravenous insulin is a safe and effective acute treatment for hypertriglyceridemia in children, even in infants. Long-term management with dietary modifications alone could be effective for primary hypertriglyceridemia due to lipoprotein lipase deficiency, at least in early childhood phase.


2007 ◽  
Vol 41 (9) ◽  
pp. 1345-1351 ◽  
Author(s):  
John S Sampalis ◽  
Stéphane Bissonnette ◽  
Rafik Habib ◽  
Stella Boukas

Background: The aim of lipid-lowering treatment is to reduce the risk for cardiovascular events. Patients not at target lipid levels while on hydroxymethylglutaryl coenzyme A reductase inhibitors (statin) monotherapy are at increased cardiovascular risk. Objective: To describe the impact of coadministration of ezetimibe with a statin on the estimated 10 year risk for coronary artery disease (E-RCAD) in patients with hypercholesterolemia and above-target low-density lipoprotein cholesterol (LDL-C) levels after statin monotherapy. Methods: Post hoc analysis was conducted of a prospective, open-label, single-cohort, multicenter Canadian study of 953 patients who were treated for 6 weeks with ezetimibe 10 mg/day coadministered with their current statin at an unaltered dose. For each patient, E-RCAD at baseline and at 6 weeks was calculated using the Framingham model. The primary outcome measure of the analysis was the change in E-RCAD. Results: A total of 825 patients with data at baseline and 6 weeks were included in the analysis. There were 423 (51.3%) patients with hypertension, 107 (13.0%) with diabetes mellitus but not metabolic syndrome, 160 (19.4%) with metabolic syndrome but not diabetes mellitus, and 235 (28.5%) with both diabetes mellitus and metabolic syndrome. After 6 weeks of ezetimibe coadministration with statin therapy, mean E-RCAD was reduced by 4.1% from 15.6% to 11.5%, which is equivalent to a 25.3% risk reduction (p < 0.001). Of the 225 (27.3%) patients with high E-RCAD (≥20.1%) at baseline, 144 (64.0%) converted to a lower E-RCAD category (p < 0.001). Patients with both diabetes mellitus and metabolic syndrome experienced the highest mean percent reduction in E-RCAD of –29.4% (p < 0.001). Conclusions: For patients with above-target LDL-C levels while on statin monotherapy, coadministration of ezetimibe with the statin is effective in significantly reducing the E-RCAD.


2017 ◽  
Vol 9 (04) ◽  
pp. 329-331 ◽  
Author(s):  
Prabhat Kumar ◽  
Abhishek Sakwariya ◽  
Amit Ranjan Sultania ◽  
Renu Dabas

AbstractDiabetic ketoacidosis (DKA) is a frequently encountered complication of diabetes mellitus. DKA is an insulin deficit state and results in moderate to severe hypertriglyceridemia (HTG). HTG is the third leading cause of acute pancreatitis (AP) and often goes unnoticed. The triad of DKA, HTG, and AP is rarely seen, and literature on the same is sparse. We report a case of AP which was due to DKA-induced secondary HTG in an adult with previously undiagnosed type 1 diabetes. His HbA1c was significantly raised, and C-peptide level was low, confirming chronic hyperglycemia. He was treated successfully with insulin infusion, intravenous crystalloid, and analgesics.


2019 ◽  
Vol 39 (12) ◽  
pp. 2531-2541 ◽  
Author(s):  
Laura D’Erasmo ◽  
Alessia Di Costanzo ◽  
Francesca Cassandra ◽  
Ilenia Minicocci ◽  
Luca Polito ◽  
...  

Objective: Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the prototypes of monogenic and polygenic conditions underlying genetically based severe hypertriglyceridemia. These conditions have been only partially investigated so that a systematic comparison of their characteristics remains incomplete. We aim to compare genetic profiles and clinical outcomes in FCS and MCS. Approach and Results: Thirty-two patients with severe hypertriglyceridemia (triglyceride >1000 mg/dL despite lipid-lowering treatments with or without history of acute pancreatitis) were enrolled. Rare and common variants were screened using a panel of 18 triglyceride-raising genes, including the canonical LPL , APOC2 , APOA5 , GP1HBP1 , and LMF1 . Clinical information was collected retrospectively for a median period of 44 months. Across the study population, 37.5% were classified as FCS due to the presence of biallelic, rare mutations and 59.4% as MCS due to homozygosity for nonpathogenic or heterozygosity for pathogenic variants in canonical genes, as well as for rare and low frequency variants in noncanonical genes. As compared with MCS, FCS patients showed a lower age of hypertriglyceridemia onset, higher levels of on-treatment triglycerides, and 3-fold higher incidence rate of acute pancreatitis. Conclusions: Our data indicate that the genetic architecture and natural history of FCS and MCS are different. FCS expressed the most severe clinical phenotype as determined by resistance to triglyceride-lowering medications and higher incidence of acute pancreatitis episodes. The most common genetic abnormality underlying FCS was represented by biallelic mutations in LPL while APOA5 variants, in combination with high rare polygenic burden, were the most frequent genotype of MCS.


2019 ◽  
Vol 3 (8) ◽  
pp. 1595-1607 ◽  
Author(s):  
Maria Isabel Esparza ◽  
Xilong Li ◽  
Beverley Adams-Huet ◽  
Chandna Vasandani ◽  
Amy Vora ◽  
...  

Abstract Context Patients with very severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL; 22.6 mmol/L) require aggressive treatment. However, little research exists on the underlying etiologies and management of very severe hypertriglyceridemia. Objective We hypothesized (i) very severe hypertriglyceridemia in adults is mostly associated with secondary causes and (ii) most patients with very severe hypertriglyceridemia lack appropriate follow-up and treatment. Design We queried electronic medical records at Parkland Health and Hospital Systems for lipid measurements in the year 2016 and identified patients with serum triglyceride levels ≥2000 mg/dL (22.6 mmol/L). We extracted data on demographics, underlying causes, lipid-lowering therapy, and follow-up. Results One hundred sixty-four serum triglyceride measurements were ≥2000 mg/dL (22.6 mmol/L) in 103 unique patients. Of these, 60 patients were admitted to the hospital (39 for acute pancreatitis). Most were Hispanic (79%). The major conditions associated with very severe hypertriglyceridemia included uncontrolled diabetes mellitus (74%), heavy alcohol use (10%), medication use (7%), and hypothyroidism (2%). Two patients were known to have monogenic causes of hypertriglyceridemia. After the index measurement of triglycerides ≥2000 mg/dL (22.6 mmol/L), the use of triglyceride-lowering drugs increased, most prominently the use of fish oil supplements, which increased by 80%. However, in follow-up visits, hypertriglyceridemia was addressed in only 50% of encounters, and serum triglycerides were remeasured in only 18%. Conclusion In summary, very severe hypertriglyceridemia was quite prevalent (∼0.1% of all lipid measurements) in our large county health care system, especially in Hispanic men. Most cases were related to uncontrolled diabetes mellitus, and follow-up monitoring was inadequate.


BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030344
Author(s):  
Miguel Angel Salinero-Fort ◽  
Jose M Mostaza-Prieto ◽  
Carlos Lahoz-Rallo ◽  
José Ignacio Vicente Díez ◽  
Juan Cárdenas-Valladolid

ObjectivesTo evaluate the risk profile, achievement of cardiometabolic goals, and frequency and optimal use of cardiovascular preventive therapies among nonagenarians with type 2 diabetes mellitus (T2DM). To investigate possible sex differences.Design and settingA cross-sectional population study of 11 645 persons aged ≥90 years with T2DM living in Madrid (Spain). Sociodemographic, clinical and therapy profiles were collected through electronic records in primary care. We considered antihypertensive therapy and lipid-lowering therapy to be optimal when known patients with hypertension with albuminuria received renin–angiotensin system blockers and statins had been prescribed for overt cardiovascular disease.ResultsThe prevalence of coronary artery disease was higher in males than in females (21.5% vs 12.6%, p<0.01), as was that of peripheral artery disease (8.5% vs 2.3%, p<0.01). However, the prevalence of cerebrovascular disease was similar in both sexes (16.5% vs 16%; p=0.44). Haemoglobin A1c was lower than 7% in 64.4% of cases, with female predominance in patients with known dementia (67.1% female vs 59.9% male; p<0.01). Antiplatelet therapy was significantly more frequent in males than in females (48.1% vs 44.3%; p<0.01), as were statins (43.2% vs 40.2%; p<0.01). Both in primary and in secondary prevention, rates for simultaneous achievement of the HbA1c, blood pressure, LDL-C goals were significantly lower among females (p<0.01). For each criterion of optimal use of cardiovascular preventive therapies, adherence was significantly better in males than in females.ConclusionOur study showed that the risk of cerebrovascular disease was similar in both male and female Spanish nonagenarians. Adherence was poorer in females for all criteria of optimal use of cardiovascular preventive therapies. Our findings indicate that the known sex differences in younger patients with T2DM persist in patients aged ≥90 years. There is considerable room for improvement in standards of preventive care in nonagenarians with T2DM, especially in females.


2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Aura Diana Reghina ◽  
Silvia Craciun ◽  
Simona Fica

A 30-year-old obese male patient had been diagnosed with diabetes mellitus due to acute hyperglycemia and ketonuria. He also presented with severe hypertriglyceridemia and high levels of serum lipase. He was initially misdiagnosed with type 1 diabetes and treated with insulin for one month. At two months from first presentation, pancreatic antibodies were negative, and the C-peptide level was normal. A1c level was 5.9% without insulin treatment. The association between diabetes mellitus and acute pancreatitis is well established. We reported a case of severe transient hyperglycemia during mild acute pancreatitis in a metabolically ill patient.


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