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Hussein EA. Factors affecting clinical outcomes of continuous and intermittent plasmapheresis in patients with severe hypertriglyceridemia. Ther Apher Dial 2024; 28:775-783. [PMID: 38676441 DOI: 10.1111/1744-9987.14134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/08/2024] [Accepted: 04/17/2024] [Indexed: 04/28/2024]
Abstract
INTRODUCTION Acute hypertriglyceridemia is considered a category III indication for plasmapheresis. The use of plasma as replacement fluid (RF) has been suggested to replace the consumed lipoprotein lipase. Heparin when used as an anticoagulant could possibly release lipoprotein lipase, thereby increasing triglyceride clearance. METHODS The impact of RF (albumin vs fresh frozen plasma (FFP) and anticoagulant (ACD-A vs. heparin) on triglycerides following plasmapheresis in 27 patients with severe hypertriglyceridemia (SHTG) was investigated. A paired study of four patients with recurrent SHTG was conducted, evaluating continuous (Optia) versus intermittent flow plasmapheresis (Haemonetics). RESULTS Shorter procedures positively impacted triglycerides (TG) drop post-sessions p < 0.05. In albumin sessions, patients who used heparin demonstrated significantly greater drop in TG and required less sessions than did those with citrate p < 0.05. In heparin sessions, patients who used albumin demonstrated significantly greater drop in triglycerides and required less sessions than did those with FFP p < 0.05. Three of six patients who used FFP and heparin showed a triglyceride drop of 11.7% following three sessions and a 50% drop with one albumin session. Compared with Haemonetics, Optia removed comparable volumes of plasma in less time, processing smaller blood volumes and using less citrate p < 0.05. Patients demonstrated significantly lower drop in TG and required more sessions with Haemonetics than they did with Optia p < 0.05. CONCLUSION Shorter procedure was the main predictor for effective TG clearance. This can be achieved by continuous apheresis technology, particularly when using albumin as RF. TG removal via Optia seems to be optimized by using heparin.
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Affiliation(s)
- Eiman A Hussein
- Department of Clinical and Chemical Pathology, Division of Transfusion Medicine, Apheresis unit of Kasr Alainy Blood Bank, Faculty of Medicine, Cairo University, Cairo, Egypt
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2
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Thanh NH, Nhi PY, Huyen NT, Hai PD. Comparative efficacy of therapeutic plasma exchange and insulin in hypertriglyceridemia-induced acute pancreatitis. Indian J Gastroenterol 2024:10.1007/s12664-024-01669-0. [PMID: 39196279 DOI: 10.1007/s12664-024-01669-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 07/31/2024] [Indexed: 08/29/2024]
Abstract
INTRODUCTION Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) presents a therapeutic challenge with no currently definitive treatment, including therapeutic plasma exchange (TPE) and insulin. TPE aims to quickly reduce serum triglyceride (TG); however, its efficacy lacks convincing evidence. Intravenous insulin is a promising and convenient alternative, while comparative data is limited. METHODS This retrospective, single-center study compared TPE and insulin treatment in HTG-AP patients. The primary outcome measured was the percentage of TG reduction within 48 hours of admission. RESULTS The study included 33 TPE-treated and 56 insulin-treated patients. The TPE groups were more severe than those with medical therapy at baseline characteristics. A trend towards higher TG reduction within 24 hours was observed in the TPE group (62.5% [IQR 51.7-83.3] vs. 55.7% [IQR 34.2-74.7], p = 0.038). However, no significant difference in TG reduction at 48 hours was found between insulin and TPE groups (83.6% and 81.9%, respectively, p = 0.715). The TPE group exhibited extended hospital stays (10.0 [IQR 7.0-13.5] days vs. 6.0 [4.0-8.7] days, p = 0.001) without any difference in in-hospital mortality or time needed to lower TG below < 11.3 mmol/L. CONCLUSION In patients with HTG-AP, TPE decreased plasma triglyceride levels faster in the first 24 hours than insulin therapy. However, there was no significant advantage after 48 hours. Therefore, insulin may be a promising alternative and convenient treatment in carefully selected patients with HTG-AP.
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Affiliation(s)
| | - Pham Yen Nhi
- Medical Intensive Care Unit, 108 Military Central Hospital, Ha Noi, Vietnam
| | - Nguyen Thu Huyen
- Medical Intensive Care Unit, 108 Military Central Hospital, Ha Noi, Vietnam
| | - Pham Dang Hai
- Medical Intensive Care Unit, 108 Military Central Hospital, Ha Noi, Vietnam.
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Zheng C, Zheng Y, Zheng Z. Therapeutic plasma exchange decreases serum triglyceride level rapidly and reduces early recurrence rate but no advantages in improving outcomes for patients with hyperlipidemic acute pancreatitis: a retrospective propensity score matching analysis based on twenty year's experience. BMC Endocr Disord 2024; 24:32. [PMID: 38443883 PMCID: PMC10916013 DOI: 10.1186/s12902-024-01562-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 02/23/2024] [Indexed: 03/07/2024] Open
Abstract
BACKGROUND Hyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study. METHODS A retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups. RESULTS A total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P = .589), local complications (P = .451) or motality between two groups. CONCLUSIONS TPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty.
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Affiliation(s)
- Canbin Zheng
- Department of Endocrine and Metabolic Disease, Shantou Central Hospital, Shantou, Guangdong, China
| | - Yongping Zheng
- Department of Gastroenterology, Shantou Central Hospital, 114 Waima Road, Shantou,, 515031, Guangdong, China.
| | - Zihui Zheng
- Department of Anesthesiology, Shantou Central Hospital, Shantou, Guangdong, China
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Ibarra F. Acute Management of Hypertriglyceridemia With a Disease-Specific Intravenous Insulin Infusion Order Set. Ann Pharmacother 2023; 57:1248-1254. [PMID: 36840326 DOI: 10.1177/10600280231155921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND Hypertriglyceridemia-associated acute pancreatitis is a disease lacking a standardized management approach. OBJECTIVE The main objective of this study was to evaluate the safety and efficacy of a continuous intravenous insulin infusion order set specifically designed for managing hypertriglyceridemia. METHODS This study compared the safety and efficacy of a standardized (postintervention) approach to managing hypertriglyceridemia to a nonstandardized (preintervention) approach. The primary efficacy outcome was the percentage of patients who achieved a triglyceride level less than 500 mg/dL. Additional outcomes included the time to achieving a triglyceride level less than 500 mg/dL and the percent reduction in triglyceride levels. The primary safety outcome was the number of patients who experienced hypoglycemia (glucose less than 70 mg/dL). RESULTS Twenty patients were included in both the preintervention and postintervention groups. There was a significantly greater reduction in triglyceride levels observed in the postintervention group. The number of patients who achieved a triglyceride level less than 500 mg/dL in the preintervention and postintervention groups were 10 (50%) and 17 (85%), respectively, P = 0.018. Within the postintervention group, the time to achieving a triglyceride level less than 500 mg/dL in those with and without diabetes was 56.8 hours (38.2-64.0) versus 27.6 hours (19.7-45.0), respectively, P = 0.028. CONCLUSION AND RELEVANCE Our findings demonstrate that insulin infusions are safe and effective when therapy is standardized and accounts for nursing to patient ratios. Our results provide the medical community with a standardized approach to acutely managing hypertriglyceridemia.
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Affiliation(s)
- Francisco Ibarra
- Department of Pharmacy Services, Community Regional Medical Center, Fresno, CA, USA
- College of Osteopathic Medicine, California Health Sciences University, Clovis, CA, USA
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5
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Gubensek J. The role of apheresis and insulin therapy in hypertriglyceridemic acute pancreatitis-a concise review. BMC Gastroenterol 2023; 23:341. [PMID: 37789261 PMCID: PMC10546782 DOI: 10.1186/s12876-023-02957-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 09/12/2023] [Indexed: 10/05/2023] Open
Abstract
Severe hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP) and is involved in its pathogenesis. Chylomicrons increase blood viscosity and induce ischemia, while free fatty acids induce inflammation and distant organ damage. Conservative treatment options include fasting and insulin; limited evidence shows their comparable efficacy. Plasma exchange might provide more rapid lowering of triglycerides and amelioration of systemic effects of severe AP. Available data from controlled studies show only moderately faster lowering of triglycerides with apheresis (about 70% vs. 50% with conservative treatment within 24 h) and limited data from non-randomized studies show no improvement in clinical outcomes. New evidence is expected soon from ongoing large randomized trials. Until then, insulin may be used in mild HTG-AP and plasma exchange should be considered only in severe HTG-AP, especially if the decline of triglycerides with conservative treatment is slow, and in HTG-AP during pregnancy.
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Affiliation(s)
- Jakob Gubensek
- Department of Nephrology, University Medical Center Ljubljana, Zaloska cesta 7, 1000, Ljubljana, Slovenia.
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
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Izar MCDO, Santos Filho RDD, Assad MHV, Chagas ACP, Toledo Júnior ADO, Nogueira ACC, Souto ACCF, Lottenberg AMP, Chacra APM, Ferreira CEDS, Lourenço CM, Valerio CM, Cintra DE, Fonseca FAH, Campana GA, Bianco HT, Lima JGD, Castelo MHCG, Scartezini M, Moretti MA, Barreto NSF, Maia RE, Montenegro Junior RM, Alves RJ, Figueiredo RMM, Fock RA, Martinez TLDR. Brazilian Position Statement for Familial Chylomicronemia Syndrome - 2023. Arq Bras Cardiol 2023; 120:e20230203. [PMID: 37075362 PMCID: PMC10348387 DOI: 10.36660/abc.20230203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023] Open
Affiliation(s)
| | | | | | | | | | | | | | - Ana Maria Pitta Lottenberg
- Laboratório de Lípides (LIM 10) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
- Hospital Israelita Albert Einstein (HIAE), São Paulo, SP - Brasil
| | - Ana Paula Marte Chacra
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | | | - Cynthia Melissa Valerio
- Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE-RJ), Rio de Janeiro, RJ - Brasil
| | | | | | | | | | - Josivan Gomes de Lima
- Hospital Universitário Onofre Lopes da Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN - Brasil
| | | | | | - Miguel Antonio Moretti
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | | | - Renan Magalhães Montenegro Junior
- Complexo Hospitalar da Universidade Federal do Ceará (UFCE), Empresa Brasileira de Serviços Hospitalares (EBSERH), Fortaleza, CE - Brasil
| | - Renato Jorge Alves
- Hospital Santa Casa de Misericórdia de São Paulo, São Paulo, SP - Brasil
| | - Roberta Marcondes Machado Figueiredo
- Hospital Israelita Albert Einstein (HIAE), São Paulo, SP - Brasil
- Faculdade Israelita de Ciências da Saúde Albert Einstein (FICSAE), São Paulo, SP - Brasil
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Yang QY, Zhao Q, Hu JW. Incidence and clinical treatment of hypertriglyceridemic acute pancreatitis: A few issues. World J Clin Cases 2023; 11:479-481. [PMID: 36686359 PMCID: PMC9850974 DOI: 10.12998/wjcc.v11.i2.479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 11/16/2022] [Accepted: 01/03/2023] [Indexed: 01/12/2023] Open
Abstract
Hypertriglyceridemia is a well-recognized etiology of acute pancreatitis, and the incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased in frequency worldwide in response to lifestyle changes. It is crucial to identify hypertriglyceridemia as the cause of pancreatitis and initiate appropriate treatment. Insulin treatment produces effective lowering of triglycerides, but in our opinion, non-diabetic patients with HTG-AP require separate consideration to avoid hypoglycemia.
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Affiliation(s)
- Qun-Ying Yang
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Qian Zhao
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
| | - Jian-Wen Hu
- Department of Gastroenterology, Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, China
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8
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He W, Cai W, Yang X, Camilleri G, Zheng X, Wang Q, Li Y, Mukherjee R, Huang W, Sutton R. Insulin or blood purification treatment for hypertriglyceridaemia-associated acute pancreatitis: A systematic review and meta-analysis. Pancreatology 2022; 22:846-857. [PMID: 35981949 DOI: 10.1016/j.pan.2022.07.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 06/11/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES Hypertriglyceridaemia increases risks from acute pancreatitis (HTG-AP) over other aetiologies, but optimal management for HTG-AP remains undefined. We performed a systematic review and meta-analysis of studies of insulin-based treatment (IT) versus blood purification treatment (BPT) for HTG-AP. METHODS Searches were conducted to identify randomised trials and observational studies published between 1946 and 2022 that compared IT and BPT for HTG-AP reporting baseline and post-treatment serum triglyceride (TG) levels with clinical outcomes. The primary outcome was serum TG reduction (Δ-TG) from baseline while secondary outcomes included complications, length of stay, adverse events, and cost. RESULTS Fifteen (1 randomised, 2 prospective case-controlled, and 12 retrospective cohort) studies were analysed comprising 909 cases with HTG-AP. Pooled results demonstrated IT was significantly less efficient than BPT in Δ-TG at 24 h (WMD -666.06, 95% CI -1130.18 to -201.94, P = 0.005; 12 studies), at 48 h (WMD -672.60, 95% CI -1233.44 to -111.77; 8 studies), and overall Δ-TG by day 7 (WMD -385.81, 95% CI -711.07 to -60.54; 8 studies) (both P = 0.02). IT, however, was associated with significantly fewer adverse events (OR 0.09, 95% CI 0.03 to 0.27, P < 0.0001; 7 studies) and significantly reduced cost (WMD -2.50, 95% CI -3.61 to -1.39, P < 0.00001; 3 studies). Other secondary outcomes were not significantly different between the two regimens (all P ≥ 0.11). In subgroup analysis Δ-TG at 24 h and overall Δ-TG became insignificant, while other results were unaffected. CONCLUSION Our findings support the general use of IT for inpatient management of HTG-AP, restricting BPT to those predicted or found to respond poorly to IT.
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Affiliation(s)
- Wenhua He
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China; Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Wenhao Cai
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Xinmin Yang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Georgette Camilleri
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Xi Zheng
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Qiqi Wang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Yuying Li
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Rajarshi Mukherjee
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China; West China Biobanks and Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, China.
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
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Grisham JM, Tran AH, Ellery K. Hypertriglyceridemia-induced acute pancreatitis in children: A mini-review. Front Pediatr 2022; 10:931336. [PMID: 36110119 PMCID: PMC9469503 DOI: 10.3389/fped.2022.931336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/28/2022] [Indexed: 11/24/2022] Open
Abstract
Severe hypertriglyceridemia (HTG) is a known metabolic cause of acute pancreatitis (AP) in pediatric patients. The incidence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is less well established in pediatric compared to adult patients. Studies in adults suggest that higher risk of AP occurs when triglyceride levels (TG) are >1,000 mg/dL. Most common etiologies for severe HTG in pediatric patients are either from primary hypertriglyceridemia, underlying genetic disorders of lipid and TG metabolism, or secondary hypertriglyceridemia, separate disease or exposure which affects TG metabolism. Most common theories for the pathophysiology of HTG-AP include hydrolysis of TG by pancreatic lipase to free fatty acids leading to endothelial and acinar cell damage and ischemia, as well as hyperviscosity related to increased chylomicrons. Though there are varying reports of HTG-AP severity compared to other causes of AP, a steadily growing body of evidence suggests that HTG-AP can be associated with more severe course and complications. Therapeutic interventions for HTG-AP typically involve inpatient management with dietary restriction, intravenous fluids, and insulin; select patients may require plasmapheresis. Long term interventions generally include dietary modification, weight management, control of secondary causes, and/or antihyperlipidemic medications. Though some therapeutic approaches and algorithms exist for adult patients, evidence-based management guidelines have not been well established for pediatric patients.
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Affiliation(s)
- John M. Grisham
- Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH, United States
| | - Andrew H. Tran
- The Heart Center, Nationwide Children's Hospital, Columbus, OH, United States
- Department of Pediatrics, The Ohio State University, Columbus, OH, United States
| | - Kate Ellery
- Division of Gastroenterology, Hepatology, and Nutrition, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States
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Gubensek J, Andonova M, Jerman A, Persic V, Vajdic-Trampuz B, Zupunski-Cede A, Sever N, Plut S. Comparable Triglyceride Reduction With Plasma Exchange and Insulin in Acute Pancreatitis - A Randomized Trial. Front Med (Lausanne) 2022; 9:870067. [PMID: 35492338 PMCID: PMC9039231 DOI: 10.3389/fmed.2022.870067] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
Background and Aims Both insulin and plasma exchange (PE) are used in hypertriglyceridemic acute pancreatitis (HTG-AP). Our aim was to compare the efficacy of both treatments. Methods A randomized, parallel group study performed in a tertiary hospital in 22 HTG-AP patients with non-severe prognosis and triglycerides between 15 and 40 mmol/L. Patients were randomized to daily PE or insulin infusion until triglycerides were <10 mmol/L. Primary outcome was % reduction in triglycerides within 24 h. Secondary outcomes were days needed to lower triglycerides <10 mmol/L, highest CRP and percentage of patients with a severe course of pancreatitis. Results There was a trend toward a greater decrease in triglycerides within the first 24 h in the PE group (67 ± 17% vs. 53 ± 17%, p = 0.07), but the absolute difference was modest [mean difference of 6 mmol/L (14% of initial value)]. Triglycerides fell below 10 mmol/L in a median (IQR) of 1 (1-2) and 2 (1-2) days, respectively (p = 0.25). Secondary outcomes related to disease severity were also comparable: highest CRP 229 vs. 211 mg/L (p = 0.69) and severe course of pancreatitis in 2/11 cases in both groups (p = 1.0). Regarding treatment complications, there was one mild hypoglycemia and one allergic reaction during PE. Survival was 100% in both groups. Conclusion There was no significant difference, but only a trend toward a greater decrease in triglycerides with PE, and the clinical course was also comparable. These results do not support universal use of PE in patients with HTG-AP. Clinical Trial Registration [ClinicalTrials.gov], identifier [NCT02622854].
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Affiliation(s)
- Jakob Gubensek
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Milena Andonova
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Alexander Jerman
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Vanja Persic
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Barbara Vajdic-Trampuz
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Ana Zupunski-Cede
- Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Nejc Sever
- Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Samo Plut
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia
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11
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Hypertriglyceridemia-Induced Pancreatitis and a Lipemic Blood Sample: A Case Report and Brief Clinical Review. J Emerg Nurs 2022; 48:455-459. [PMID: 35337668 DOI: 10.1016/j.jen.2022.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 02/09/2022] [Accepted: 02/11/2022] [Indexed: 11/23/2022]
Abstract
Hypertriglyceridemia is the third most common cause of acute pancreatitis after gallstones and long-term alcohol use. There are specific therapeutic options unique to hyperglyceridemia-induced pancreatitis, such as continuous insulin therapy and plasmapheresis, emphasizing the importance of identifying hypertriglyceridemia as the cause. Triglyceride levels > 1000 mg/dL may result in a visibly lipemic blood sample. Lipemic samples may interfere with laboratory equipment, resulting in erroneous levels or the inability to measure several serum blood tests. Consider hypertriglyceridemia as a cause for acute pancreatitis in the setting of a lipemic blood sample or when gallstones have been excluded.
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12
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Ibarra F, Loi K, Vu AW. Safety and Efficacy of Various Intravenous Insulin Infusion Rates in Patients With and Without Diabetes Presenting With Hypertriglyceridemia. Ann Pharmacother 2022; 56:1016-1022. [DOI: 10.1177/10600280211070102] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background The use of IV insulin infusions in the acute management of hypertriglyceridemia has only been evaluated in small observational studies and case reports. Objective To evaluate the safety and efficacy of IV insulin infusions in the acute management of hypertriglyceridemia. Methods This was a retrospective chart review of adult patients who received an IV insulin infusion for the acute management of hypertriglyceridemia. The primary efficacy and safety outcomes were the number of patients who achieved a triglyceride level <500 mg/dL and experienced hypoglycemia (<70 mg/dL), respectively. A subgroup analysis was performed to compare outcomes between patients with and without diabetes, in addition to the IV insulin infusion rate received. Results In the total population (n = 51), there were no statistically significant differences between the insulin intensity groups in the number of patients who achieved TG levels <500 mg/dL. Compared to patients with a past medical history of diabetes, more patients without a past medical history of diabetes achieved triglyceride levels <500 mg/dL (14% vs 53%, respectively, P < 0.001). The number of hypoglycemic events observed in patients with and without a past medical history of diabetes were 5 (14%) and 4 (27%), respectively ( P = 0.023). Conclusion and Relevance Our findings suggest that patients who present with lower initial TG levels are more likely to achieve TG levels <500 mg/dL. To minimize the risk of hypoglycemia providers should consider prescribing a concomitant dextrose infusion and limiting IV insulin infusion rates ≤ 0.075 units/kg/h.
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Affiliation(s)
- Francisco Ibarra
- Department of Pharmacy Services, Community Regional Medical Center, Fresno, CA, USA
| | - Kaitlyn Loi
- Department of Pharmacy Services, Community Regional Medical Center, Fresno, CA, USA
| | - Ann W. Vu
- Department of Pharmacy Services, Community Regional Medical Center, Fresno, CA, USA
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13
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Gutierrez Alvarez A, Yachelevich N, Kohn B, Brar PC. Genotype - phenotype correlation in an adolescent girl with pathogenic variant in PPARƴ gene causing severe hypertriglyceridemia and early onset type 2 diabetes. Ann Pediatr Endocrinol Metab 2021; 26:284-289. [PMID: 34991302 PMCID: PMC8749027 DOI: 10.6065/apem.2142056.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 05/25/2021] [Indexed: 12/13/2022] Open
Abstract
Severe hypertriglyceridemia (HTG) (>885 mg/dl) can be caused by familial partial lipodystrophy Type 3 (FPLD 3), an autosomal dominant disorder caused by a loss of function of the peroxisome proliferator activated receptor gamma (PPARG), characterized by abnormal distribution of fat and metabolic derangements. A 16-year-old female (body mass index, BMI 23.5 kg/m2) was hospitalized twice for pancreatitis (TG level >2200 mg/dl). She was managed with bowel rest, insulin infusion, and plasmapheresis. On a low fat 10 g daily diet and fenofibrate 160 mg daily her fasting TG had decreased to 411 mg/dL (range 0-149). She had a normal leptin level. Panel testing of genes involved in triglyceride metabolism revealed a known pathogenic variant in PPARG gene (c.452A>G p.Tyr151Cys). A second variant detected in this gene, c.1003G>C (p.Val335Leu), is considered benign. HbA1C of 6.6% and two-hours oral glucose tolerance test confirmed Type 2 diabetes (T2DM). We outline the earliest description of T2DM in an adolescent with a pathogenic variant of PPARG. PPARG related FLPD 3 should be considered in lean children presenting with severe HTG and insulin resistance and treatment with PPARy agonists Thiazolidinediones should be considered.
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Affiliation(s)
- Ana Gutierrez Alvarez
- Division of Endocrinology and Diabetes, Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA
| | - Naomi Yachelevich
- Division of Clinical Genetics, Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA
| | - Brenda Kohn
- Division of Endocrinology and Diabetes, Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA
| | - Preneet Cheema Brar
- Division of Endocrinology and Diabetes, Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA,Address for correspondence: Preneet Cheema Brar Division of Endocrinology and Diabetes, Department of Pediatrics, New York University Grossman School of Medicine, 150 East 32nd street, L2, New York, NY 10016, USA
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14
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Abstract
Hypertriglyceridemia is one of the most common lipid abnormalities encountered in clinical practice. Many monogenic disorders causing severe hypertriglyceridemia have been identified, but in most patients triglyceride elevations result from a combination of multiple genetic variations with small effects and environmental factors. Common secondary causes include obesity, uncontrolled diabetes, alcohol misuse, and various commonly used drugs. Correcting these factors and optimizing lifestyle choices, including dietary modification, is important before starting drug treatment. The goal of drug treatment is to reduce the risk of pancreatitis in patients with severe hypertriglyceridemia and cardiovascular disease in those with moderate hypertriglyceridemia. This review discusses the various genetic and acquired causes of hypertriglyceridemia, as well as current management strategies. Evidence supporting the different drug and non-drug approaches to treating hypertriglyceridemia is examined, and an easy to adopt step-by-step management strategy is presented.
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Affiliation(s)
- Vinaya Simha
- Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA
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15
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Hartz JC, de Ferranti S, Gidding S. Hypertriglyceridemia in Diabetes Mellitus: Implications for Pediatric Care. J Endocr Soc 2018; 2:497-512. [PMID: 29850649 PMCID: PMC5961027 DOI: 10.1210/js.2018-00079] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 04/25/2018] [Indexed: 01/06/2023] Open
Abstract
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.
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Affiliation(s)
- Jacob C Hartz
- Boston Children’s Hospital, Department of Cardiology, Boston, Massachusetts
| | - Sarah de Ferranti
- Nemours Cardiac Center, A. I. DuPont Hospital for Children, Wilmington, Delaware
| | - Samuel Gidding
- Boston Children’s Hospital, Department of Cardiology, Boston, Massachusetts
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16
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Abstract
Hypertriglyceridemia is increasingly identified in children and adolescents, owing to improved screening and higher prevalence of childhood obesity. Hypertriglyceridemia can result from either increased triglyceride (TG) production or reduced TG clearance. The etiologic origin can be primary (genetic) or secondary, but it is often multifactorial. Management is challenging because of the interplay of genetic and secondary causes and lack of evidence-based guidelines. Lifestyle changes and dietary interventions are most important, especially in hypertriglyceridemia associated with obesity. Dietary restriction of fat remains the mainstay of management in primary hypertriglyceridemia. When fasting TG concentration is increased above 500 mg/dL (5.65 mmol/L), fibrates may be used to prevent pancreatitis. Omega-3 fatty acids are often used as an adjunctive therapy. When the fasting TG concentration is less than 500 mg/dL (5.65 mmol/L) and if the non-high-density lipoprotein cholesterol level is above 145 mg/dL (3.76 mmol/L), statin treatment can be considered.
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Affiliation(s)
- Badhma Valaiyapathi
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL
| | - Bhuvana Sunil
- Department of Pediatrics, Harlem Hospital Center, New York, NY
| | - Ambika P Ashraf
- Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, Children's of Alabama, University of Alabama at Birmingham, Birmingham, AL
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17
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Ashraf AP, Hurst AC, Garg A. Extreme hypertriglyceridemia, pseudohyponatremia, and pseudoacidosis in a neonate with lipoprotein lipase deficiency due to segmental uniparental disomy. J Clin Lipidol 2017; 11:757-762. [DOI: 10.1016/j.jacl.2017.03.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 03/23/2017] [Accepted: 03/26/2017] [Indexed: 12/23/2022]
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18
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Azofeifa G, Quesada S, Navarro L, Hidalgo O, Portet K, Pérez AM, Vaillant F, Poucheret P, Michel A. Hypoglycaemic, hypolipidaemic and antioxidant effects of blackberry beverage consumption in streptozotocin-induced diabetic rats. J Funct Foods 2016. [DOI: 10.1016/j.jff.2016.08.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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19
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Hepburn K, Brzozowska MM. Diabetic ketoacidosis and severe hypertriglyceridaemia as a consequence of an atypical antipsychotic agent. BMJ Case Rep 2016; 2016:bcr-2016-215413. [PMID: 27507689 DOI: 10.1136/bcr-2016-215413] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The atypical antipsychotic agent clozapine, although an effective treatment for schizophrenia, is linked with metabolic adverse effects. We report a case of diabetic ketoacidosis and very severe hypertriglyceridaemia associated with clozapine use, in a patient with type 2 diabetes mellitus, who was successfully treated with continuous insulin infusion and fluids. As clozapine proved to be the most efficacious in controlling the patient's psychotic symptoms, the patient has been continued on clozapine despite its known metabolic side effects. Importantly the patient has achieved satisfactory long-term lipid and glycaemic control. The current recommendations related to the metabolic care for patients treated with atypical antipsychotic agents as well as the mechanisms behind abnormal glucose and lipid regulation with clozapine therapy are discussed.
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Affiliation(s)
- Kirsten Hepburn
- Endocrinology Department, Sutherland Hospital, Caringbah, New South Wales, Australia
| | - Malgorzata Monika Brzozowska
- Endocrinology Department, Sutherland Hospital, Caringbah, New South Wales, Australia St George & Sutherland Hospital Clinical School, University of New South Wales, Sydney, New South Wales, Australia
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20
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Chang CT, Tsai TY, Liao HY, Chang CM, Jheng JS, Huang WH, Chou CY, Chen CJ. Double Filtration Plasma Apheresis Shortens Hospital Admission Duration of Patients With Severe Hypertriglyceridemia-Associated Acute Pancreatitis. Pancreas 2016; 45:606-12. [PMID: 26491906 DOI: 10.1097/mpa.0000000000000507] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVES 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. METHODS 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. RESULTS 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). CONCLUSIONS When applied to serum triglyceride in excess of 5000 mg/dL, DFPP removes oxidized and inflammatory lipoproteins, shortens hospitalization duration, and minimizes STAP recurrence.
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Affiliation(s)
- Chiz-Tzung Chang
- From the *College of Medicine, China Medical University; †Division of Nephrology, ‡L5 Research Center, §Division of Gastroenterology, ∥Proteomic Core Laboratory, China Medical University Hospital; and ¶Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
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21
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Valdivielso P, Ramírez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med 2014; 25:689-94. [PMID: 25269432 DOI: 10.1016/j.ejim.2014.08.008] [Citation(s) in RCA: 285] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 08/19/2014] [Accepted: 08/20/2014] [Indexed: 12/21/2022]
Abstract
Severe hypertriglyceridemia (HTG) is a well established and the most common cause of acute pancreatitis (AP) after alcohol and gall stone disease. It is alleged to account for up to 10% of all pancreatitis episodes. Studies suggest that in patients with triglyceride (TG) levels>1000 mg/dL (>11.3 mmol/L), hypertriglyceridemia-induced acute pancreatitis (HTGP-AP) occurs in approximately 15-20% of all subjects referred to Lipid Clinics. Until now, there is no clear evidence which patients with severe HTG will develop pancreatitis and which will not. Underlying pathophysiological concepts include hydrolysis of TG by pancreatic lipase and excessive formation of free fatty acids with inflammatory changes and capillary injury. Additionally hyperviscosity and ischemia may play a decisive role. The clinical features of HTG-AP patients are supposed to be no different from patients with AP of other etiologies. Yet, there are well-conducted studies suggesting that HTG-AP is associated with a higher severity and complication rate. Therapeutic measurements in HTG-AP include dietary modifications, different antihyperlipidemic agents, insulin and/or heparin treatment. The beneficial use of plasmapheresis is repeatedly reported and suggested in many studies. Yet, due to the lack of randomized and controlled trials, it is currently unknown if plasmapheresis may improve morbidity and mortality in the clinical setting of HTG-AP. Since there are no commonly accepted clinical guidelines in the management of HTG-AP, there is a definite need for an international, multicenter approach to this important subject.
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Affiliation(s)
- Pedro Valdivielso
- Department of Medicine and Dermatology, University of Malaga, Spain; Servicio de Medicina Interna, Hospital Virgen de la Victoria, Malaga, Spain
| | - Alba Ramírez-Bueno
- Servicio de Medicina Interna, Hospital Virgen de la Victoria, Malaga, Spain
| | - Nils Ewald
- Justus-Liebig-University Giessen, 35392 Giessen, Germany; General Hospital Luebbecke-Rahden, Department of Internal Medicine, 32312 Luebbecke, Germany.
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22
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Thuzar M, Shenoy VV, Malabu UH, Schrale R, Sangla KS. Extreme hypertriglyceridemia managed with insulin. J Clin Lipidol 2014; 8:630-634. [PMID: 25499946 DOI: 10.1016/j.jacl.2014.09.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 08/22/2014] [Accepted: 09/11/2014] [Indexed: 01/07/2023]
Abstract
Extreme hypertriglyceridemia can lead to acute pancreatitis and rapid lowering of serum triglycerides (TG) is necessary for preventing such life-threatening complications. However, there is no established consensus on the acute management of extreme hypertriglyceridemia. We retrospectively reviewed 10 cases of extreme hypertriglyceridemia with mean serum TG on presentation of 101.5 ± 23.4 mmol/L (8982 ± 2070 mg/dL) managed with insulin. Serum TG decreased by 87 ± 4% in 24 hours in those patients managed with intravenous insulin and fasting and 40 ± 8.4% in those managed with intravenous insulin alone (P = .0003). The clinical course was uncomplicated in all except 1 patient who subsequently developed a pancreatic pseudocyst. Thus, combination of intravenous insulin with fasting appears to be an effective, simple, and safe treatment strategy in immediate management of extreme hypertriglyceridemia.
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Affiliation(s)
- Moe Thuzar
- Department of Endocrinology and Diabetes, The Townsville Hospital, Queensland, Australia; University of Queensland, Australia.
| | - Vasant V Shenoy
- Department of Endocrinology and Diabetes, The Townsville Hospital, Queensland, Australia; James Cook University, Queensland, Australia
| | - Usman H Malabu
- Department of Endocrinology and Diabetes, The Townsville Hospital, Queensland, Australia; James Cook University, Queensland, Australia
| | - Ryan Schrale
- James Cook University, Queensland, Australia; Department of Cardiology, The Townsville Hospital, Queensland, Australia
| | - Kunwarjit S Sangla
- Department of Endocrinology and Diabetes, The Townsville Hospital, Queensland, Australia; James Cook University, Queensland, Australia.
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23
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TANG LINLIN, WANG LINGYAN, YE HUADAN, XU XUTING, HONG QINGXIAO, WANG HONGWEI, XU LEITING, BU SHIZHONG, ZHANG LINA, CHENG JIA, LIU PANPAN, YE MENG, MAI YIFENG, DUAN SHIWEI. BCL11A gene DNA methylation contributes to the risk of type 2 diabetes in males. Exp Ther Med 2014; 8:459-463. [PMID: 25009601 PMCID: PMC4079426 DOI: 10.3892/etm.2014.1783] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 05/06/2014] [Indexed: 12/17/2022] Open
Abstract
BCL11A is a critical modulator involved in hemoglobin switching. Recent studies have established an association between BCL11A gene polymorphisms and a risk of type 2 diabetes (T2D). The aim of the present study was to assess the correlation between BCL11A DNA methylation and T2D. A total of 48 T2D cases and 48 age- and gender-matched controls were recruited to evaluate BCL11A methylation using bisulfite pyrosequencing technology. Although no significant association was observed in BCL11A methylation between T2D patients and healthy controls (P=0.322), breakdown analysis by gender identified a significant association between BCL11A methylation and T2D in males (P=0.018). Notably, there was also a significant female-specific association between the mean BCL11A DNA methylation and triglyceride (TG) concentration (r=-0.34; P=0.019). The results indicated that BCL11A methylation contributed to the risk of T2D in males. In addition, BCL11A methylation may have an effect on the development of T2D by influencing TG metabolism. Thus, gender difference may provide new information to aid the understanding of T2D pathogenesis.
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Affiliation(s)
- LINLIN TANG
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
| | - LINGYAN WANG
- Bank of Blood Products, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
| | - HUADAN YE
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - XUTING XU
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - QINGXIAO HONG
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
| | - HONGWEI WANG
- Section of Endocrinology, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - LEITING XU
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
- Bank of Blood Products, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
| | - SHIZHONG BU
- Bank of Blood Products, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
| | - LINA ZHANG
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
- Bank of Blood Products, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
| | - JIA CHENG
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
| | - PANPAN LIU
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
| | - MENG YE
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
| | - YIFENG MAI
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
| | - SHIWEI DUAN
- Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University, Ningbo, Zhejiang 315211, P.R. China
- The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
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24
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Pang J, Chan DC, Watts GF. Origin and therapy for hypertriglyceridaemia in type 2 diabetes. World J Diabetes 2014; 5:165-75. [PMID: 24748930 PMCID: PMC3990315 DOI: 10.4239/wjd.v5.i2.165] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 03/08/2014] [Accepted: 03/17/2014] [Indexed: 02/05/2023] Open
Abstract
Hypertriglyceridaemia (HTG) is a risk factor for cardiovascular disease (CVD) in type 2 diabetes and is caused by the interaction of genes and non-genetic factors, specifically poor glycaemic control and obesity. In spite of statin treatment, residual risk of CVD remains high in type 2 diabetes, and this may relate to HTG and atherogenic dyslipidemia. Treatment of HTG emphasises correcting secondary factors and adverse lifestyles, in particular, diet and exercise. Pharmacotherapy is also required in most type 2 diabetic patients. Statins are the first-line therapy to achieve recommended therapeutic targets of plasma low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol. Fibrates, ezetimibe and n-3 fatty acids are adjunctive treatment options for residual and persistent HTG. Evidence for the use of niacin has been challenged by non-significant CVD outcomes in two recent large clinical trials. Further investigation is required to clarify the use of incretin-based therapies for HTG in type 2 diabetes. Extreme HTG, with risk of pancreatitis, may require insulin infusion therapy or apheresis. New therapies targeting HTG in diabetes need to be tested in clinical endpoint trials. The purpose of this review is to examine the current evidence and provide practical guidance on the management of HTG in type 2 diabetes.
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