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Original Article
Drug/Regimen
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee
Received March 8, 2023  Accepted June 28, 2023  Published online May 20, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0077    [Epub ahead of print]
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AbstractAbstract PDF
Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
Review
Metabolic Risk/Epidemiology
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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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.
Original Article
Guideline/Fact Sheet
Dyslipidemia Fact Sheet in South Korea, 2022
Eun-Sun Jin, Jee-Seon Shim, Sung Eun Kim, Jae Hyun Bae, Shinae Kang, Jong Chul Won, Min-Jeong Shin, Heung Yong Jin, Jenny Moon, Hokyou Lee, Hyeon Chang Kim, In-Kyung Jeong, on Behalf of the Committee of Public Relation of the Korean Society of Lipid and Atherosclerosis
Diabetes Metab J. 2023;47(5):632-642.   Published online August 2, 2023
DOI: https://doi.org/10.4093/dmj.2023.0135
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  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022.
Methods
We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020.
Results
In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia—more than one out of three conditions (low-density lipoprotein cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein cholesterol [HDL-C] [men and women] <40 mg/dL)—was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-HDL-cholesterolemia in women changed from <40 to <50 mg/dL.
Conclusion
Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.

Citations

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  • Oxidative Balance Score and New-Onset Type 2 Diabetes Mellitus in Korean Adults without Non-Alcoholic Fatty Liver Disease: Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) Cohort
    Mid-Eum Moon, Dong Hyuk Jung, Seok-Jae Heo, Byoungjin Park, Yong Jae Lee
    Antioxidants.2024; 13(1): 107.     CrossRef
  • Comparison of metabolic and neurological comorbidities in Asian patients with psoriasis and atopic dermatitis
    Hee Joo Yang, Mi Young Lee, Jeong Hyeon Lee, Chang Jin Jung, Woo Jin Lee, Chong Hyun Won, Mi Woo Lee, Joon Min Jung, Sung Eun Chang
    Scientific Reports.2024;[Epub]     CrossRef
  • Effect of Adding Apolipoprotein B Testing on the Prevalence of Dyslipidemia and Risk of Cardiovascular Disease in the Korean Adult Population
    Rihwa Choi, Sang Gon Lee, Eun Hee Lee
    Metabolites.2024; 14(3): 169.     CrossRef
  • Body Weight Variability and Risk of Suicide Mortality: A Nationwide Population-Based Study
    Jeongmin Lee, Jin-Hyung Jung, Dong Woo Kang, Min-Hee Kim, Dong-Jun Lim, Hyuk-Sang Kwon, Jung Min Lee, Sang-Ah Chang, Kyungdo Han, Seung-Hwan Lee, Fuquan Zhang
    Depression and Anxiety.2024; 2024: 1.     CrossRef
  • Exploring Utilization and Establishing Reference Intervals for the Apolipoprotein B Test in the Korean Population
    Rihwa Choi, Sang Gon Lee, Eun Hee Lee
    Diagnostics.2023; 13(20): 3194.     CrossRef
Review
Complications
Dyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview
Sang Heon Suh, Soo Wan Kim
Diabetes Metab J. 2023;47(5):612-629.   Published online July 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0067
  • 3,446 View
  • 441 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Dyslipidemia is a potentially modifiable cardiovascular risk factor. Whereas the recommendations for the treatment target of dyslipidemia in the general population are being more and more rigorous, the 2013 Kidney Disease: Improving Global Outcomes clinical practice guideline for lipid management in chronic kidney disease (CKD) presented a relatively conservative approach with respect to the indication of lipid lowering therapy and therapeutic monitoring among the patients with CKD. This may be largely attributed to the lack of high-quality evidence derived from CKD population, among whom the overall feature of dyslipidemia is considerably distinctive to that of general population. In this review article, we cover the characteristic features of dyslipidemia and impact of dyslipidemia on cardiovascular outcomes in patients with CKD. We also review the current evidence on lipid lowering therapy to modify the risk of cardiovascular events in this population. We finally discuss the association between dyslipidemia and CKD progression and the potential strategy to delay the progression of CKD in relation to lipid lowering therapy.

Citations

Citations to this article as recorded by  
  • Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Control Trials
    Jafar Karami, Bahman Razi, Danyal Imani, Saeed Aslani, Mahdi Pakjoo, Mahdieh Fasihi, Keyhan Mohammadi, Amirhossein Sahebkar
    Current Pharmaceutical Design.2024; 30(5): 362.     CrossRef
Original Article
Cardiovascular Risk/Epidemiology
Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus
Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong, on Behalf of the Committee of Practice Guideline of Korean Lipid and Atheroscelerosis
Diabetes Metab J. 2023;47(1):45-58.   Published online January 26, 2023
DOI: https://doi.org/10.4093/dmj.2021.0344
  • 3,096 View
  • 265 Download
  • 4 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data.
Methods
Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018.
Results
The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL.
Conclusion
For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

Citations

Citations to this article as recorded by  
  • Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Diabetes & Metabolism Journal.2023; 47(1): 1.     CrossRef
  • Optimal Low-Density Lipoprotein Cholesterol Level for Primary Prevention in Koreans with Type 2 Diabetes Mellitus
    Ji Yoon Kim, Nam Hoon Kim
    Diabetes & Metabolism Journal.2023; 47(1): 42.     CrossRef
  • Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
    Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
    Journal of Lipid and Atherosclerosis.2023; 12(1): 12.     CrossRef
  • 2023 Clinical Practice Guidelines for Diabetes: Management of Cardiovascular Risk Factors
    Ye Seul Yang
    The Journal of Korean Diabetes.2023; 24(3): 135.     CrossRef
  • 2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
    Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
    Diabetes & Metabolism Journal.2023; 47(5): 575.     CrossRef
  • Management of Dyslipidemia in Patients with Diabetes Mellitus
    Kyung Ae Lee
    The Journal of Korean Diabetes.2023; 24(3): 111.     CrossRef
  • Significant Gap Between Guidelines and Practice in the Management of LDL Cholesterol: Insight From the Survey of the Korean Society of Myocardial Infarction
    Sang Yeub Lee, Kyung Hoon Cho, Jang Hoon Lee, Young Joon Hong, Jin yong Hwang, Myung Ho Jeong, Weon Kim
    Journal of Korean Medical Science.2023;[Epub]     CrossRef
Reviews
Guideline/Fact Sheet
Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon, on Behalf of Committee of Clinical Practice Guideline, Korean Diabetes Association and Clinical Practice Guideline Committee, Korean Society of Lipid and Atherosclerosis
Diabetes Metab J. 2023;47(1):1-9.   Published online January 20, 2023
DOI: https://doi.org/10.4093/dmj.2022.0448
  • 3,748 View
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  • 3 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
Dyslipidemia in patients with diabetes is an important treatment target as a modifiable risk factor for cardiovascular disease (CVD). Although the primary treatment goal for dyslipidemia is to control low-density lipoprotein cholesterol (LDL-C), achieving this goal remains suboptimal according to recent studies. It is important to set the target goal for LDL-C control based on an accurate risk assessment for CVD. Here, we summarize the latest evidence on lipid management in patients with diabetes and present a consensus of the Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis on the treatment goals of LDL-C according to the duration of diabetes, presence of CVD, target organ damage, or major cardiovascular risk factors. In patients with type 2 diabetes mellitus (T2DM) and CVD, an LDL-C goal of <55 mg/dL and a reduction in LDL-C level by 50% or more from the baseline is recommended. For the primary prevention of CVD in patients with T2DM with a duration of diabetes ≥10 years, major cardiovascular risk factors, or target organ damage, an LDL-C goal of <70 mg/dL is recommended. In patients with T2DM with a duration of diabetes <10 years and no major cardiovascular risk factors, an LDL-C goal of <100 mg/dL is recommended.

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  • Clinical Characteristics of Patients With Statin Discontinuation in Korea: A Nationwide Population-Based Study
    Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
    Journal of Lipid and Atherosclerosis.2024; 13(1): 41.     CrossRef
  • 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 & Metabolism Journal.2024; 48(2): 184.     CrossRef
  • Dyslipidemia Fact Sheet in South Korea, 2022
    Eun-Sun Jin, Jee-Seon Shim, Sung Eun Kim, Jae Hyun Bae, Shinae Kang, Jong Chul Won, Min-Jeong Shin, Heung Yong Jin, Jenny Moon, Hokyou Lee, Hyeon Chang Kim, In-Kyung Jeong
    Diabetes & Metabolism Journal.2023; 47(5): 632.     CrossRef
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    Min Kyong Moon
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    Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
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    Kyung Ae Lee
    The Journal of Korean Diabetes.2023; 24(3): 111.     CrossRef
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    Ye Seul Yang
    The Journal of Korean Diabetes.2023; 24(3): 135.     CrossRef
  • Dyslipidemia Fact Sheet in South Korea, 2022
    Eun-Sun Jin, Jee-Seon Shim, Sung Eun Kim, Jae Hyun Bae, Shinae Kang, Jong Chul Won, Min-Jeong Shin, Heung Yong Jin, Jenny Moon, Hokyou Lee, Hyeon Chang Kim, In-Kyung Jeong
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Drug/Regimen
New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi
Diabetes Metab J. 2022;46(4):517-532.   Published online July 27, 2022
DOI: https://doi.org/10.4093/dmj.2022.0198
Correction in: Diabetes Metab J 2022;46(5):817
  • 10,411 View
  • 873 Download
  • 26 Web of Science
  • 28 Crossref
AbstractAbstract PDFPubReader   ePub   
Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

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Original Article
Metabolic Risk/Epidemiology
Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin Yun, In-Kyung Jeong, Jin-Hye Cha, Juneyoung Lee, Ho Chan Cho, Sung Hee Choi, SungWan Chun, Hyun Jeong Jeon, Ho-Cheol Kang, Sang Soo Kim, Seung-Hyun Ko, Gwanpyo Koh, Su Kyoung Kwon, Jae Hyuk Lee, Min Kyong Moon, Junghyun Noh, Cheol-Young Park, Sungrae Kim
Diabetes Metab J. 2022;46(3):464-475.   Published online March 3, 2022
DOI: https://doi.org/10.4093/dmj.2021.0088
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

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Reviews
Metabolic Risk/Epidemiology
Computed Tomography-Derived Myosteatosis and Metabolic Disorders
Iva Miljkovic, Chantal A. Vella, Matthew Allison
Diabetes Metab J. 2021;45(4):482-491.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2020.0277
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The role of ectopic adipose tissue infiltration into skeletal muscle (i.e., myosteatosis) for metabolic disorders has received considerable and increasing attention in the last 10 years. The purpose of this review was to evaluate and summarize existing studies focusing on computed tomography (CT)-derived measures of myosteatosis and metabolic disorders. There is consistent evidence that CT-derived myosteatosis contributes to dysglycemia, insulin resistance, type 2 diabetes mellitus, and inflammation, and, to some extent, dyslipidemia, independent of general obesity, visceral fat, and other relevant risk factors, suggesting that it may serve as a tool for metabolic risk prediction. Identification of which muscles should be examined, and the standardized CT protocols to be employed, are necessary to enhance the applicability of findings from epidemiologic studies of myosteatosis. Additional and longer longitudinal studies are necessary to confirm a role of myosteatosis in the development of type 2 diabetes mellitus, and examine these associations in a variety of muscles across multiple race/ethnic populations. Given the emerging role of myosteatosis in metabolic health, well-designed intervention studies are needed to investigate relevant lifestyle and pharmaceutical approaches.

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Drug/Regimen
Fibrates Revisited: Potential Role in Cardiovascular Risk Reduction
Nam Hoon Kim, Sin Gon Kim
Diabetes Metab J. 2020;44(2):213-221.   Published online April 23, 2020
DOI: https://doi.org/10.4093/dmj.2020.0001
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AbstractAbstract PDFPubReader   

Fibrates, peroxisome proliferator-activated receptor-α agonists, are potent lipid-modifying drugs. Their main effects are reduction of triglycerides and increase in high-density lipoprotein levels. Several randomized controlled trials have not demonstrated their benefits on cardiovascular risk reduction, especially as an “add on” to statin therapy. However, subsequent analyses by major clinical trials, meta-analyses, and real-world evidence have proposed their potential in specific patient populations with atherogenic dyslipidemia and metabolic syndrome. Here, we have reviewed and discussed the accumulated data on fibrates to understand their current status in cardiovascular risk management.

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Original Articles
Cardiovascular Risk/Epidemiology
Pre-existing Depression among Newly Diagnosed Dyslipidemia Patients and Cardiovascular Disease Risk
Jihoon Andrew Kim, Seulggie Choi, Daein Choi, Sang Min Park
Diabetes Metab J. 2020;44(2):307-315.   Published online November 1, 2019
DOI: https://doi.org/10.4093/dmj.2019.0002
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Whether depression before diagnosis of dyslipidemia is associated with higher cardiovascular disease (CVD) risk among newly diagnosed dyslipidemia patients is yet unclear.

Methods

The study population consisted of 72,235 newly diagnosed dyslipidemia patients during 2003 to 2012 from the National Health Insurance Service–Health Screening Cohort of South Korea. Newly diagnosed dyslipidemia patients were then detected for pre-existing depression within 3 years before dyslipidemia diagnosis. Starting from 2 years after the diagnosis date, patients were followed up for CVD until 2015. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated by Cox proportional hazards regression.

Results

Compared to dyslipidemia patients without depression, those with depression had higher risk for CVD (aHR, 1.24; 95% CI, 1.09 to 1.41). Similarly, pre-existing depression was associated with increased risk for stroke (aHR, 1.27; 95% CI, 1.06 to 1.53). The risk for CVD among depressed dyslipidemia patients for high (aHR, 1.42; 95% CI, 1.06 to 1.90), medium (aHR, 1.17; 95% CI, 0.91 to 1.52), and low (aHR, 1.25; 95% CI, 1.05 to 1.50) statin compliance patients tended to be increased compared to patients without pre-existing dyslipidemia. The risk-elevating effect of depression on CVD tended to be preserved regardless of subgroups of smoking, alcohol consumption, physical activity, and body mass index.

Conclusion

Dyslipidemia patients with pre-existing depression had increased risk for CVD. Future studies that determine CVD risk after management of depression among dyslipidemia patients are needed.

Citations

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Epidemiology
Association between Change in Alcohol Consumption and Metabolic Syndrome: Analysis from the Health Examinees Study
Seulggie Choi, Kyuwoong Kim, Jong-Koo Lee, Ji-Yeob Choi, Aesun Shin, Sue Kyung Park, Daehee Kang, Sang Min Park
Diabetes Metab J. 2019;43(5):615-626.   Published online April 23, 2019
DOI: https://doi.org/10.4093/dmj.2018.0128
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

The association between change in alcohol intake and metabolic syndrome is unclear.

Methods

This retrospective cohort consisted of 41,368 males and females from the Health Examinees-GEM study. Participants were divided into non-drinkers (0.0 g/day), light drinkers (male: 0.1 to 19.9 g/day; female: 0.1 to 9.9 g/day), moderate drinkers (male: 20.0 to 39.9 g/day; female: 10.0 to 19.9 g/day), and heavy drinkers (male: ≥40.0 g/day; female: ≥20.0 g/day) for each of the initial and follow-up health examinations. Logistic regression analysis was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for developing metabolic syndrome according to the change in alcohol consumption between the initial and follow-up health examinations. Adjusted mean values for the change in waist circumference, fasting serum glucose (FSG), blood pressure, triglycerides, and high density lipoprotein cholesterol (HDL-C) levels were determined according to the change in alcohol consumption by linear regression analysis.

Results

Compared to persistent light drinkers, those who increased alcohol intake to heavy levels had elevated risk of metabolic syndrome (aOR, 1.45; 95% CI, 1.09 to 1.92). In contrast, heavy drinkers who became light drinkers had reduced risk of metabolic syndrome (aOR, 0.61; 95% CI, 0.44 to 0.84) compared to persistent heavy drinkers. Increased alcohol consumption was associated with elevated adjusted mean values for waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels (all P<0.05). Reduction in alcohol intake was associated with decreased waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels among initial heavy drinkers (all P<0.05).

Conclusion

Heavy drinkers who reduce alcohol consumption could benefit from reduced risk of metabolic syndrome.

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Complications
Lipid Abnormalities in Type 2 Diabetes Mellitus Patients with Overt Nephropathy
Sabitha Palazhy, Vijay Viswanathan
Diabetes Metab J. 2017;41(2):128-134.   Published online January 11, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.2.128
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AbstractAbstract PDFPubReader   
Background

Diabetic nephropathy is a major complication of diabetes and an established risk factor for cardiovascular events. Lipid abnormalities occur in patients with diabetic nephropathy, which further increase their risk for cardiovascular events. We compared the degree of dyslipidemia among type 2 diabetes mellitus (T2DM) subjects with and without nephropathy and analyzed the factors associated with nephropathy among them.

Methods

In this retrospective study, T2DM patients with overt nephropathy were enrolled in the study group (n=89) and without nephropathy were enrolled in the control group (n=92). Both groups were matched for age and duration of diabetes. Data on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), urea and creatinine were collected from the case sheets. TG/HDL-C ratio, a surrogate marker for small, dense, LDL particles (sdLDL) and estimated glomerular filtration rate (eGFR) were calculated using equations. Multivariate analysis was done to determine the factors associated with eGFR.

Results

Dyslipidemia was present among 56.52% of control subjects and 75.28% of nephropathy subjects (P=0.012). The percentage of subjects with atherogenic dyslipidemia (high TG+low HDL-C+sdLDL) was 14.13 among controls and 14.61 among nephropathy subjects. Though serum creatinine was not significantly different, mean eGFR value was significantly lower among nephropathy patients (P=0.002). Upon multivariate analysis, it was found that TC (P=0.007) and HDL-C (P=0.06) were associated with eGFR among our study subjects.

Conclusion

Our results show that dyslipidemia was highly prevalent among subjects with nephropathy. Regular screening for dyslipidemia may be beneficial in controlling the risk for adverse events among diabetic nephropathy patients.

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Clinical Care/Education
Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus
Sung Hye Kong, Bo Kyung Koo, Min Kyong Moon
Diabetes Metab J. 2017;41(1):23-30.   Published online December 16, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.1.23
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AbstractAbstract PDFPubReader   
Background

There has been evidences of ethnic differences in the low density lipoprotein cholesterol (LDL-C) lowering effect of statin. We aimed to evaluate the efficacy of moderate-intensity statins in the treatment of dyslipidemia among Korean patients with type 2 diabetes mellitus (T2DM).

Methods

We analyzed a retrospective cohort that consisted of Korean patients with T2DM aged 40 to 75 years who had been prescribed any of the moderate-intensity statins (atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, or pravastatin 40 mg). Among them, only patients with baseline lipid profiles before starting statin treatment were selected, and changes in their lipid profiles before and 6 months after statin therapy were analyzed.

Results

Following the first 6 months of therapy, the overall LDL-C reduction was −47.4% (interquartile range, −56.6% to −34.1%). In total, 92.1% of the participants achieved an LDL-C level of <100 mg/dL, 38.3% had a 30% to 50% reduction in their LDL-C levels, and 42.3% had a reduction in their LDL-C levels greater than 50%. The response rates of each drug for achieving a LDL-C level <100 mg/dL were 81.7%, 93.1%, 95.0%, 95.0%, 96.5%, and 91.7% for treatment with atorvastatin doses of 10 or 20 mg, rosuvastatin 5 or 10 mg, pitavastatin 2 mg, and pravastatin 40 mg, respectively.

Conclusion

In conclusion, the use of moderate-intensity statins reduced LDL-C levels less than 100 mg/dL in most of the Korean patients studied with T2DM. The efficacies of those statins were higher than expected in about 42% of Korean patients with T2DM.

Citations

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  • Effect of combining evolocumab with statin on carotid intraplaque neovascularization in patients with premature coronary artery disease (EPOCH)
    Yanyan Han, Ling Ren, Xiang Fei, Jingjing Wang, Tao Chen, Jun Guo, Qi Wang
    Atherosclerosis.2024; 391: 117471.     CrossRef
  • Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease
    Xiao-hong Zhou, Li-yun Cai, Wei-Hua Lai, Xue Bai, Yi-bin Liu, Qian Zhu, Guo-dong He, Ji-Yan Chen, Min Huang, Zhi-ling Zhou, Shi-long Zhong
    Frontiers in Pharmacology.2020;[Epub]     CrossRef
  • Efficacy and Safety of High-Dose Atorvastatin in Moderate-to-High Cardiovascular Risk Postmenopausal Korean Women with Dyslipidemia
    Jaecheol Moon, Soyeon Yoo, Gwanpyo Koh, Kyung-Wan Min, Hyun Ho Shin
    Journal of Lipid and Atherosclerosis.2020; 9(1): 162.     CrossRef
  • Effects of lowest-dose vs. highest-dose pitavastatin on coronary neointimal hyperplasia at 12-month follow-up in type 2 diabetic patients with non-ST elevation acute coronary syndrome: an optical coherence tomography analysis
    Jung Wook Lim, Han Saem Jeong, Soon Jun Hong, Hyo Jeong Kim, Young Chan Kim, Bong Gyun Kang, Su Min Jeon, Jae Young Cho, Seung Hoon Lee, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu
    Heart and Vessels.2019; 34(1): 62.     CrossRef
  • Effect of Statin Therapy on Outcomes of Patients With Acute Ischemic Stroke and Atrial Fibrillation
    Kang‐Ho Choi, Woo‐Keun Seo, Man‐Seok Park, Joon‐Tae Kim, Jong‐Won Chung, Oh Young Bang, Gyeong‐Moon Kim, Tae‐Jin Song, Bum Joon Kim, Sung Hyuk Heo, Jin‐Man Jung, Kyung‐Mi Oh, Chi Kyung Kim, Sungwook Yu, Kwang‐Yeol Park, Jeong‐Min Kim, Jong‐Ho Park, Jay Ch
    Journal of the American Heart Association.2019;[Epub]     CrossRef
  • Moderate-intensity versus high-intensity statin therapy in Korean patients with angina undergoing percutaneous coronary intervention with drug-eluting stents: A propensity-score matching analysis
    Mahn-Won Park, Gyung-Min Park, Seungbong Han, Yujin Yang, Yong-Giun Kim, Jae-Hyung Roh, Hyun Woo Park, Jon Suh, Young-Rak Cho, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Dae-Won Kim, Sung Ho Her, Sang-Gon Lee, George C.M. Siontis
    PLOS ONE.2018; 13(12): e0207889.     CrossRef
  • Letter: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30)
    Jae-Han Jeon
    Diabetes & Metabolism Journal.2017; 41(2): 150.     CrossRef
  • Response: Efficacy of Moderate Intensity Statins in the Treatment of Dyslipidemia in Korean Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2017;41:23-30)
    Sung Hye Kong, Bo Kyung Koo, Min Kyong Moon
    Diabetes & Metabolism Journal.2017; 41(2): 152.     CrossRef
Others
Effect of Atorvastatin on Growth Differentiation Factor-15 in Patients with Type 2 Diabetes Mellitus and Dyslipidemia
Ji Min Kim, Min Kyung Back, Hyon-Seung Yi, Kyong Hye Joung, Hyun Jin Kim, Bon Jeong Ku
Diabetes Metab J. 2016;40(1):70-78.   Published online February 19, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.1.70
  • 4,245 View
  • 33 Download
  • 5 Web of Science
  • 5 Crossref
AbstractAbstract PDFPubReader   
Background

Elevated serum levels of growth differentiation factor-15 (GDF-15) are associated with type 2 diabetes. Therefore, the effects of atorvastatin on metabolic parameters and GDF-15 levels in patients with type 2 diabetes and dyslipidemia were evaluated.

Methods

In this prospective randomized trial from February 2013 to March 2014, 50 consecutive type 2 diabetic patients with a low density lipoprotein cholesterol (LDL-C) levels ≥100 mg/dL were enrolled. The patients were divided into two groups based on the amount of atorvastatin prescribed, 10 mg/day (n=23) or 40 mg/day (n=27). The effect of atorvastatin on metabolic parameters, including lipid profiles and GDF-15 levels, at baseline and after 8 weeks of treatment were compared.

Results

The baseline metabolic parameters and GDF-15 levels were not significantly different between the two groups. After 8 weeks of treatment, the total cholesterol (TC) and LDL-C levels were significantly decreased in both groups. The mean changes in TC and LDL-C levels were more significant in the 40 mg atorvastatin group. The GDF-15 level was decreased in the 10 mg atorvastatin group, from 1,460.6±874.8 to 1,451.0±770.8 pg/mL, and was increased in the 40 mg atorvastatin group, from 1,271.6±801.0 to 1,341.4±855.2 pg/mL. However, the change in the GDF-15 level was not statistically significant in the 10 or 40 mg atorvastatin group (P=0.665 and P=0.745, respectively).

Conclusion

The GDF-15 levels were not significantly changed after an 8-week treatment with atorvastatin in type 2 diabetic patients.

Citations

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  • Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis
    Alexander Hodkinson, Dialechti Tsimpida, Evangelos Kontopantelis, Martin K Rutter, Mamas A Mamas, Maria Panagioti
    BMJ.2022; : e067731.     CrossRef
  • The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker
    Boel De Paepe
    International Journal of Molecular Sciences.2022; 23(21): 13180.     CrossRef
  • Biomarkers of subclinical atherosclerosis in patients with psoriasis
    Hannah Kaiser, Xing Wang, Amanda Kvist-Hansen, Martin Krakauer, Peter Michael Gørtz, Benjamin D. McCauley, Lone Skov, Christine Becker, Peter Riis Hansen
    Scientific Reports.2021;[Epub]     CrossRef
  • Growth differentiation factor-15 regulates oxLDL-induced lipid homeostasis and autophagy in human macrophages
    Kathrin Ackermann, Gabriel A. Bonaterra, Ralf Kinscherf, Anja Schwarz
    Atherosclerosis.2019; 281: 128.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal