Diabetes & Metabolism Journal

Original Articles

Cardiovascular Risk/Epidemiology
Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression: Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim; Received February 10, 2024 Accepted May 13, 2024 Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0066 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus.
Methods
Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis.
Results
During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration.
Conclusion
Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Cardiovascular Risk/Epidemiology
Comparison of on-Statin Lipid and Lipoprotein Levels for the Prediction of First Cardiovascular Event in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jimi Choi, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2023;47(6):837-845. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0217

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Abstract PDF Supplementary Material PubReader ePub: Background
A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented.
Methods
From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C.
Results
MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL.
Conclusion
On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

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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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
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Exploring Utilization and Establishing Reference Intervals for the Apolipoprotein B Test in the Korean Population
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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

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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

2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang
Diabetes & Metabolism Journal.2024; 48(4): 546. 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
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

Cardiovascular Risk/Epidemiology
Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study: Junghyun Noh, Min Kyong Moon, 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):59-71. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2021.0320

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Background
To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline.
Methods
We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018.
Results
The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08–1.33), 1.27 (1.15–1.42), 1.39 (1.23–1.56), 1.69 (1.45–1.96), and 1.84 (1.49– 2.27) in very high-risk group, and 1.07 (1.02–1.13), 1.16 (1.10–1.21), 1.29 (1.22–1.36), 1.45 (1.36–1.55), and 1.73 (1.58–1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130–159, 160–189, and ≥190 mg/dL were 1.15 (1.11–1.20), 1.28 (1.22– 1.34), and 1.45 (1.36–1.54) in moderate-risk group and 1.07 (1.02–1.13), 1.20 (1.13–1.26), and 1.47 (1.37–1.57) in low-risk group.
Conclusion
We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

Citations

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Efficacy and Safety of a Single-Pill Triple Combination of Olmesartan, Amlodipine, and Rosuvastatin in Hypertensive Patients with Low-to-Moderate Cardiovascular Risk: A Multicenter, Randomized, Open-Label, Active-Control, Phase IV Clinical Trial
Byung Jin Kim, Kwang Soo Cha, Wook Hyun Cho, Eung Ju Kim, Seung-Hyuk Choi, Moo Hyun Kim, Sang-Hyun Kim, Jun-Bean Park, Seong-Mi Park, Il Suk Sohn, Kyu Hyung Ryu, In-Ho Chae
Journal of Cardiovascular Pharmacology and Therapeutics.2023;[Epub] CrossRef

Review

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

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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.

Citations

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Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study
Nam Hoon Kim, Ji Yoon Kim, Jimi Choi, Sin Gon Kim
European Heart Journal - Cardiovascular Pharmacotherapy.2024; 10(2): 118. CrossRef
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
Fenofibrate’s impact on cardiovascular risk in patients with diabetes: a nationwide propensity-score matched cohort study
Sangmo Hong, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
Cardiovascular Diabetology.2024;[Epub] CrossRef
The mediating effect of TyG and its derived indices in the association between OSAHS and atherosclerosis in patients with T2DM
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Cardiovascular Diabetology.2024;[Epub] 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
2023 Clinical Practice Guidelines for Diabetes
Min Kyong Moon
The Journal of Korean Diabetes.2023; 24(3): 120. 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
2023 Clinical Practice Guidelines for Diabetes: Management of Cardiovascular Risk Factors
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
Journal of Lipid and Atherosclerosis.2023; 12(3): 237. CrossRef

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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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.

Citations

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Risk factor control and cardiovascular events in patients with type 2 diabetes mellitus
Do Kyeong Song, Young Sun Hong, Yeon-Ah Sung, Hyejin Lee, Hidetaka Hamasaki
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Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial
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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
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
Management of Dyslipidemia in Patients with Diabetes Mellitus
Kyung Ae Lee
The Journal of Korean Diabetes.2023; 24(3): 111. CrossRef
Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes
Ji Eun Jun, You-Cheol Hwang, Kyu Jeong Ahn, Ho Yeon Chung, Geon-Ho Jahng, Soonchan Park, In-Kyung Jeong, Chang-Woo Ryu
Diabetes Research and Clinical Practice.2022; 191: 110067. CrossRef

Review

Cardiovascular Risk/Epidemiology
Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes: Min Jeong Park, Kyung Mook Choi; Diabetes Metab J. 2022;46(1):49-62. Published online January 27, 2022; DOI: https://doi.org/10.4093/dmj.2021.0316

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Despite strenuous efforts to reduce cardiovascular disease (CVD) risk by improving cardiometabolic risk factors, such as glucose and cholesterol levels, and blood pressure, there is still residual risk even in patients reaching treatment targets. Recently, researchers have begun to focus on the variability of metabolic variables to remove residual risks. Several clinical trials and cohort studies have reported a relationship between the variability of metabolic parameters and CVDs. Herein, we review the literature regarding the effect of metabolic factor variability and CVD risk, and describe possible mechanisms and potential treatment perspectives for reducing cardiometabolic risk factor variability.

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Original Articles

Cardiovascular Risk/Epidemiology
Mean and Variability of Lipid Measurements and Risk for Development of Subclinical Left Ventricular Diastolic Dysfunction: Jiyun Park, Mira Kang, Jiyeon Ahn, Min Young Kim, Min Sun Choi, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Jeong Hoon Yang, Sang-Man Jin; Diabetes Metab J. 2022;46(2):286-296. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0080

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Background
Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population.
Methods
This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram.
Results
Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents.
Conclusion
The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

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Guideline/Fact Sheet
Diabetes Fact Sheets in Korea, 2020: An Appraisal of Current Status: Chan-Hee Jung, Jang Won Son, Shinae Kang, Won Jun Kim, Hun-Sung Kim, Hae Soon Kim, Mihae Seo, Hye-Jung Shin, Seong-Su Lee, Su Jin Jeong, Yongin Cho, Seung Jin Han, Hyang Mi Jang, Mira Rho, Shinbi Lee, Mihyun Koo, Been Yoo, Jung-Wha Moon, Hye Young Lee, Jae-Seung Yun, Sun Young Kim, Sung Rae Kim, In-Kyung Jeong, Ji-Oh Mok, Kun Ho Yoon; Diabetes Metab J. 2021;45(1):1-10. Published online January 13, 2021; DOI: https://doi.org/10.4093/dmj.2020.0254

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Background
This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data.
Methods
This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated.
Results
In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes.
Conclusion
The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

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Metabolic Risk/Epidemiology
Intra-Abdominal Fat and High Density Lipoprotein Cholesterol Are Associated in a Non-Linear Pattern in Japanese-Americans: Sun Ok Song, You-Cheol Hwang, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko; Diabetes Metab J. 2020;44(2):277-285. Published online March 10, 2020; DOI: https://doi.org/10.4093/dmj.2019.0008

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Abstract PDF PubReader

Background

We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots.

Methods

We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials.

Results

Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm², and 1.67±0.43 mg/dL, 74.4±46.6 cm² and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: β=−0.1012, P<0.001; IAF²: β=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (β=−0.4919, P=0.001).

Conclusion

HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.

Citations

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Metabolic Risk/Epidemiology
Metabolic Health, Obesity, and the Risk of Developing Open-Angle Glaucoma: Metabolically Healthy Obese Patients versus Metabolically Unhealthy but Normal Weight Patients: Younhea Jung, Kyungdo Han, Hae-Young L. Park, Seung Hoon Lee, Chan Kee Park; Diabetes Metab J. 2020;44(3):414-425. Published online December 23, 2019; DOI: https://doi.org/10.4093/dmj.2019.0048

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Background

This study sought to investigate the associations between metabolic health status, obesity, and incidence of primary open-angle glaucoma (POAG).

Methods

In this nationwide, population-based, longitudinal prospective cohort study conducted using the Korean National Health Insurance System, we categorized all subjects based on presence and severity of metabolic syndrome and obesity. Insurance claims data were used to identify POAG development. Then, Cox regression was applied to calculate the hazard of developing POAG in people with various components of metabolic syndrome, obesity, or their combination.

Results

Of the total 287,553 subjects, 4,970 (1.3%) developed POAG. High fasting glucose, blood pressure, and total cholesterol levels were all associated with increased risk of developing POAG. Regarding obesity level, people with body mass index (BMI) greater than 30 kg/m² were more likely to develop POAG than those with normal BMI. Also, people with greater number of metabolic syndrome components showed a greater POAG incidence. People who are metabolically unhealthy and obese (adjusted hazard ratio [HR], 1.574; 95% confidence interval [CI], 1.449 to 1.711) and those who are metabolically unhealthy nonobese (MUNO: adjusted HR, 1.521; 95% CI, 1.405 to 1.645) but not those who are metabolically healthy obese (MHO: adjusted HR, 1.019; 95% CI, 0.907 to 1.144) had an increased hazard of developing POAG compared with metabolically healthy nonobese (MHNO) subjects.

Conclusion

Metabolic health status and obesity were significantly associated with increased risk of POAG incidence. MUNO subjects but not MHO subjects showed a higher risk of POAG development than did MHNO subjects, suggesting that metabolic status is more important than obesity in POAG.

Citations

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Epidemiology
Diabetes Fact Sheets in Korea, 2018: An Appraisal of Current Status: Bo-Yeon Kim, Jong Chul Won, Jae Hyuk Lee, Hun-Sung Kim, Jung Hwan Park, Kyoung Hwa Ha, Kyu Chang Won, Dae Jung Kim, Kyong Soo Park; Diabetes Metab J. 2019;43(4):487-494. Published online July 17, 2019; DOI: https://doi.org/10.4093/dmj.2019.0067

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Abstract PDF PubReader

Background

The objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older.

Methods

This study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%.

Results

In 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c <6.5%, blood pressure <140/85 mm Hg, and low density lipoprotein cholesterol <100 mg/dL. Only 8.4% of people with diabetes had good control of all three targets.

Conclusion

This study confirms that diabetes is as an important public health problem. Efforts should be made to increase awareness, detection, and comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

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Obesity and Metabolic Syndrome
Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension: You-Cheol Hwang, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko; Diabetes Metab J. 2019;43(1):114-122. Published online September 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0053

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Abstract PDF PubReader

Background

Recent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension.

Methods

A total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline.

Results

During 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension.

Conclusion

A higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

Citations

Citations to this article as recorded by

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Tong Chen, Shiquan Wu, Ling Feng, SiYu Long, Yu Liu, WenQian Lu, Wenya Chen, Guoai Hong, Li Zhou, Fang Wang, Yuechan Luo, Hequn Zou
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Yuqin Zhang, Shirui Chen, Jing Wei, Jie Jiang, Xiao Lin, Ying Wang, Chun Hao, Wenjing Wu, Zhupei Yuan, Jie Sun, Han Wang, Zhicheng Du, Wangjian Zhang, Yuantao Hao
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Complications
Risk Factors for the Development and Progression of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Advanced Diabetic Retinopathy: Kyung-Jin Yun, Hye Ji Kim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Hyun Baek, Young Jung Roh, Ki-Ho Song; Diabetes Metab J. 2016;40(6):473-481. Published online September 20, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.473

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Background

Some patients with type 2 diabetes mellitus (T2DM) do not develop diabetic kidney disease (DKD) despite the presence of advanced diabetic retinopathy (DR). We aimed to investigate the presence of DKD and its risk factors in patients with T2DM and advanced DR.

Methods

We conducted a cross-sectional study in 317 patients with T2DM and advanced DR. The phenotypes of DKD were divided into three groups according to the urine albumin/creatinine ratio (uACR, mg/g) and estimated glomerular filtration rate (eGFR, mL/min/1.73 m²): no DKD (uACR <30 and eGFR ≥60), non-severe DKD (uACR ≥30 or eGFR <60), and severe DKD (uACR ≥30 and eGFR <60). Mean systolic and diastolic blood pressure, mean glycosylated hemoglobin (HbA1c) level, and HbA1c variability (standard deviation [SD] of serial HbA1c values or HbA1c-SD) were calculated for the preceding 2 years.

Results

The prevalence of no DKD, non-severe DKD, and severe DKD was 37.2% (n=118), 37.0% (n=117), and 25.8% (n=82), respectively. HbA1c-SD and the triglyceride/high density lipoprotein cholesterol (TG/HDL-C) ratio correlated positively with uACR and negatively with eGFR. Multiple linear regression analyses showed that the HbA1c-SD and TG/HDL-C ratio were significantly related with eGFR. Multiple logistic regression analyses after adjusting for several risk factors showed that HbA1c-SD and the TG/HDL-C ratio were significant risk factors for severe DKD.

Conclusion

The prevalence of DKD was about 60% in patients with T2DM and advanced DR. HbA1c variability and TG/HDL-C ratio may affect the development and progression of DKD in these patients.

Citations

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