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Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review
Chaicharn Deerochanawong, Sin Gon Kim, Yu-Cheng Chang
Diabetes Metab J. 2024;48(2):184-195.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2023.0168
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  • 492 Download
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.

Citations

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  • Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT
    Eu Jeong Ku, Bongseong Kim, Kyungdo Han, Seung-Hwan Lee, Hyuk-Sang Kwon
    Cardiovascular Diabetology.2024;[Epub]     CrossRef
  • The role of DGAT1 and DGAT2 in tumor progression via fatty acid metabolism: A comprehensive review
    Leisheng Wang, Shiwei Xu, Mengzhen Zhou, Hao Hu, Jinyou Li
    International Journal of Biological Macromolecules.2024; 278: 134835.     CrossRef
Original Articles
Drug/Regimen
Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Ji Eun Jun, In-Kyung Jeong, Jae Myung Yu, Sung Rae Kim, In Kye Lee, Kyung-Ah Han, Sung Hee Choi, Soo-Kyung Kim, Hyeong Kyu Park, Ji-Oh Mok, Yong-ho Lee, Hyuk-Sang Kwon, So Hun Kim, Ho-Cheol Kang, Sang Ah Lee, Chang Beom Lee, Kyung Mook Choi, Sung-Ho Her, Won Yong Shin, Mi-Seung Shin, Hyo-Suk Ahn, Seung Ho Kang, Jin-Man Cho, Sang-Ho Jo, Tae-Joon Cha, Seok Yeon Kim, Kyung Heon Won, Dong-Bin Kim, Jae Hyuk Lee, Moon-Kyu Lee
Diabetes Metab J. 2020;44(1):78-90.   Published online June 20, 2019
DOI: https://doi.org/10.4093/dmj.2018.0265
  • 10,440 View
  • 218 Download
  • 7 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.

Methods

This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.

Results

After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.

Conclusion

The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Citations

Citations to this article as recorded by  
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    Rehab H. Werida, Aalaa Ramzy, Youssri Nassief Ebrahim, Maged Wasfy Helmy
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    Frontiers in Nutrition.2022;[Epub]     CrossRef
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    Jong Shin Woo, Soon Jun Hong, Dong Hoon Cha, Kee Sik Kim, Moo Hyun Kim, Jun-Won Lee, Myung Ho Jeong, Jin-Ok Jeong, Jun-Hee Lee, Doo Soo Jeon, Eun Joo Cho, Soon Kil Kim, Jun Kwan, Chang Gyu Park, Hae Young Lee, Taek Jong Hong, Jinho Shin, Ho Joong Youn, Do
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    Jeongseon Kim, Tung Hoang, Ji-Myung Kim, So Young Bu, Jeong-Hwa Choi, Eunju Park, Seung-Min Lee, Eunmi Park, Ji Yeon Min, In Seok Lee, So Young Youn, Jee-Young Yeon
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Epidemiology
Dietary Sodium Intake in People with Diabetes in Korea: The Korean National Health and Nutrition Examination Survey for 2008 to 2010
Myung Shin Kang, Chong Hwa Kim, Su Jin Jeong, Tae Sun Park
Diabetes Metab J. 2016;40(4):290-296.   Published online June 23, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.4.290
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  • 17 Web of Science
  • 19 Crossref
AbstractAbstract PDFPubReader   
Background

Diabetics are likely to receive advice from their physicians concerning lifestyle changes. To understand how much sodium is consumed by diabetics in Korea, we compared the average daily sodium intake between diabetics and non-diabetics after controlling for confounding factors.

Methods

We obtained the sodium intake data for 13,957 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES), 2008 to 2010, which consisted of a health interview and behavioral and nutritional surveys. The KNHANES uses a stratified, multistage, probability-sampling design, and weighting adjustments were conducted to represent the entire population.

Results

Our analysis revealed that, overall, diabetics tended to have lower sodium intake (4,910.2 mg) than healthy individuals (5,188.2 mg). However, both diabetic and healthy individuals reported higher sodium intake than is recommended by the World Health Organization (WHO). Stratified subgroup analyses revealed that the sodium intake (4,314.2 mg) among newly diagnosed diabetics was higher among women when compared to patients with known diabetes (3,812.5 mg, P=0.035). Female diabetics with cardiovascular disease had lower average sodium intake compared to those without cardiovascular disease after adjusting for sex, age, body mass index, and total energy intake (P=0.058). Sodium intake among male diabetics with hypercholesterolemia (P=0.011) and female diabetics with hypertriglyceridemia (P=0.067) tended to be higher than that among those who without dyslipidemia.

Conclusion

The average sodium intake of diabetics in Korea was higher than the WHO recommends. Sodium intake in newly diagnosed diabetics was significantly higher than that in non-diabetics and previously diagnosed diabetics among females. Prospective studies are needed to identify the exact sodium intake.

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Brief Report
Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy
Myung Won Lee, Jeong Kyung Park, Jae Won Hong, Kwang Joon Kim, Dong Yeob Shin, Chul Woo Ahn, Young Duk Song, Hong Keun Cho, Seok Won Park, Eun Jig Lee
Diabetes Metab J. 2013;37(3):207-211.   Published online June 14, 2013
DOI: https://doi.org/10.4093/dmj.2013.37.3.207
  • 4,682 View
  • 47 Download
  • 23 Crossref
AbstractAbstract PDFPubReader   

Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

Citations

Citations to this article as recorded by  
  • Diabetic cardiac autonomic neuropathy: insulin resistance, lipid profile, and omega-3 polyunsaturated fatty acids
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    Vitoria Melo, Thomas Silva, Thaissa Silva, Juliana Freitas, Joselita Sacramento, Mirian Vazquez, Edilene Araujo
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    Gediz Dogay Us, Sohail Mushtaq
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Randomized Controlled Trial
Effects of Adding omega-3 Fatty Acids to Simvastatin on Lipids, Lipoprotein Size and Subspecies in Type 2 Diabetes Mellitus with Hypertriglyceridemia.
Won Jun Kim, Chang Beom Lee, Cheol Young Park, Se Eun Park, Eun Jung Rhee, Won Young Lee, Ki Won Oh, Sung Woo Park, Dae Jung Kim, Hae Jin Kim, Seung Jin Han, Hong Keum Cho
Korean Diabetes J. 2009;33(6):494-502.   Published online December 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.6.494
  • 2,748 View
  • 38 Download
AbstractAbstract PDF
BACKGROUND
omega-3 fatty acids are known to improve lipid profiles, the distribution of lipoprotein subclasses, and secondary prevention against post-myocardial infarction. Rare reports have emerged of synergistic results of omega-3 fatty acids with simvastatin in cases of type 2 diabetes mellitus with hypertriglyceridemia. The purpose of this study was to determine the combined relationship of omega-3 fatty acids plus simvastatin on lipid, lipoprotein size and the types of subspecies. METHODS: This randomized, multi-center, comparison study evaluated eight weeks of combination therapy (omega-3 fatty acids (Omacor) 4 g/day plus simvastatin 20 mg/day) or monotherapy (simvastatin 20 mg/day) for at least six weeks in 62 diabetic patients. Subjects with a triglyceride concentration of more than 200 mg/dL were eligible for inclusion. RESULTS: No significant differences for omega-3 fatty acids + simvastatin versus simvastatin alone were observed for triglycerides (-22.7% vs. -14.3%, P = 0.292), HDL peak particle size (+2.8% vs. -0.4%, P = 0.076), LDL mean particle size (+0.4% vs -0.1%, P = 0.376) or LDL subspecies types, although the combination therapy showed a tendency toward lower triglycerides, larger HDL, and LDL particle sizes than did the monotherapy. There were no significant differences between the two groups in regard to HDL-C, LDL-C, or HbA1c levels. There were no serious adverse events and no abnormalities in the laboratory values associated with this study. CONCLUSION: omega-3 fatty acids were a safeform of treatment in hypertriglyceridemic patients with type 2 diabetes mellitus. But, regarding efficacy, a much larger sample size and longer-term follow-up may be needed to distinguish between the effects of combination therapy and monotherapy.
Case Reports
Acquired Generalized Lipodystrophy with Severe Insulin Resistant Diabetes Mellitus.
Jung Min Lee, Tae Seo Sohn, Hyun Shik Son
Korean Diabetes J. 2006;30(6):487-491.   Published online November 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.6.487
  • 1,810 View
  • 24 Download
AbstractAbstract PDF
Acquired generalized lipodystrophy is a rare disease, and often follows autoimmune disease, prodromal infection, HIV infection. The clinical characteristics are generalized absence of fat, insulin resistance, diabetes mellitus, absence of ketosis, elevated basal metabolic rate, severe hypertriglyceridemia, and hepatomegaly. Here we experience and report a case of 16-year-old female patient who has clinical features of acquired generalized lipodystrophy with severe insulin resistant diabetes mellitus without any prodromal states.
A Case of Severe Hypertriglyceridemia with Diabetic Ketoacidosis.
Dong Seop Choi, Jeong Heon Oh, Ie Byung Park, Jin Won Kim, Kyung Mook Choi, Yong Hyun Kim, Nan Hee Kim, Sang Jin Kim, Sei Hyun Baik
Korean Diabetes J. 1999;23(5):715-721.   Published online January 1, 2001
  • 1,165 View
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AbstractAbstract PDF
Severe hypertriglyceridemia exceeding 5.6 mmol/L in diabetic ketoacidosis occasionally occur in patients with type 1 diabetes mellitus. The pattern of dyslipidemia is usually Fredrickson classification type lV. But it also exists in type III and type V. However, extreme triglyceridemia, triglyceride level exceeds 22.6 mmol/L, occur rarely in the modern era of insulin therapy. And the pattern is usually Fredrickson type I. The severe hypertriglyceridemia in diabetic ketoacidosis is mainly due to lipoprotein lipase deficiency, and secondly to insulin deficiency. The severity usually improves with insulin replacement. In patients with extreme hypertriglyceri-demia, serum electrolyte values of the patients are fallaciously low, and it leads to the misinterpretation of biochemical results and to the inappropriate treatment. We reported a case of a 25 years old female patient with diabetic ketoacidosis and extreme hypertriglyceridemia. At admission, the color of her serum was milky, her plasma triglyceride concentration was 144.7 mmol/L (12864 mg/dL), cholesterol was 25.5 mmol/L (982 mg/dl), and HDL-cholesterol was 0.77 mmol/L (40 mg/dL). The biochemical values at admission could not be measured. Empirical therapy was administered with the use of insulin and fluid. After the initial treatment with insulin and fluid, plasma triglyceride declined rapidly and was nearly normal after 72 hours. We also measured fasting blood glucose concentration and lipid profiles from her father and two sisters. Their plasma glucose and lipid profiles were normal.

Diabetes Metab J : Diabetes & Metabolism Journal
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