Diabetes & Metabolism Journal

Original Articles

Basic and Translational Research
Hepatocyte RAP1A Deletion Impairs Lipid Catabolism and Worsens Steatosis via Autophagy Activation: Xiujuan Wei, Yinxu Fu, Yu Fang, Xi Lin, Zhonggui Luo, Keyi Li, Kaiqiang Yang, Ting Fu, Liqin Jin, Jianxin Lyu, Qiongya Zhao; Received May 1, 2025 Accepted August 25, 2025 Published online November 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0388 [Epub ahead of print]

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Metabolic disorders such as obesity, type 2 diabetes mellitus, and fatty liver disease are often linked to excessive hepatic lipid accumulation. This study aimed to determine the role of Ras-related protein 1a (RAP1A) in regulating hepatic lipid metabolism and to elucidate how RAP1A impacts metabolic dysfunction-associated fatty liver disease progression. We focused on RAP1A’s influence on liver lipid homeostasis and its connection to metabolic health.
Methods
A liver-specific Rap1a knockout (LKO) mouse model was generated and fed a high-fat diet to induce obesity and steatosis. Metabolic phenotyping (body weight, adiposity, glucose tolerance, insulin sensitivity) and liver analyses (histology, triglyceride/ cholesterol content, and gene expression profiling) were performed. In parallel, cultured hepatocyte models (alpha mouse liver 12 [AML12] cells) with RAP1A knockdown or overexpression were used to assess cellular lipid accumulation, fatty acid oxidation, and mechanistic pathways. Mitochondrial function assays, autophagy analysis, and extracellular signal-regulated kinase (ERK) signaling evaluations were conducted, including interventions with an ERK activator and autophagy inhibitor to probe pathway involvement.
Results
LKO mice developed increased adiposity and hepatic steatosis with significantly elevated liver triglycerides, cholesterol, and lipid droplet accumulation, despite unchanged caloric intake. They also exhibited impaired glucose tolerance and insulin resistance, indicating pronounced metabolic dysfunction. RAP1A deficiency led to dysregulated hepatic lipid gene expression—mainly downregulating genes for fatty acid oxidation and lipid catabolism—consistent with exacerbated lipid accumulation. Hepatocytes lacking RAP1A showed similar lipid accumulation, reduced fatty acid oxidation capacity, and altered expression of lipid metabolic enzymes. Mechanistically, RAP1A-deficient livers and cells displayed activated autophagy, particularly mitophagy. RAP1A was found to localize to mitochondrial membranes, and its loss was associated with reduced ERK phosphorylation. Notably, pharmacological activation of the ERK pathway restored ERK phosphorylation and significantly alleviated triglyceride accumulation in RAP1A-knockdown hepatocytes, rescuing the expression of key lipid breakdown enzymes. Conversely, inhibition of excessive autophagy in RAP1A-deficient cells also partially normalized lipid levels. These findings demonstrate that loss of RAP1A triggers hepatic lipid accumulation and metabolic dysregulation through coordinated effects on lipid metabolism genes, mitophagy, and ERK signaling.
Conclusion
RAP1A is a critical regulator of hepatic lipid metabolism, safeguarding against diet-induced steatosis and metabolic dysfunction. Its absence leads to lipid buildup and impaired metabolic homeostasis via disruptions in lipid accumulation, mitochondrial function, autophagy, and ERK signaling.

Others
Dynamic Lipidomic Remodeling and Clinical Correlations after Sleeve Gastrectomy in Obese Subjects: Gakyung Lee, Yeong Chan Lee, Minkuk Park, Seong Min Kim, Ji-Hyeon Park, Dae Ho Lee; Received February 12, 2025 Accepted April 17, 2025 Published online August 14, 2025; DOI: https://doi.org/10.4093/dmj.2025.0120 [Epub ahead of print]

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Background
Sleeve gastrectomy (SG) is an effective and the most commonly performed surgical intervention for obesity. However, detailed studies on the underlying mechanisms, particularly those involving lipid metabolism, remain limited. This study aimed to identify novel pathways associated with the metabolic efficacy of SG by assessing alterations in the serum lipidomic profiles of obese subjects following surgery.
Methods
A prospective study of 50 obese participants undergoing laparoscopic SG was conducted at a tertiary medical center. Serum samples were collected before surgery and 6 months after SG. Lipidomic profiling was performed alongside comprehensive follow-up assessments. Statistical analyses explored lipidomic alterations and their correlations with changes in clinical parameters (Clinical trial registration No. KCT0003527 and KCT0009704).
Results
Participants experienced a 25% reduction in body weight 6 months after SG, with a marked reduction (>70%) in hepatic steatosis and insulin resistance, and a 2-fold increase in plasma oxyntomodulin levels. Lipidomic analysis revealed significant molecular shifts in lipid subclasses based on the fatty acyl composition of lipid species, showing a trend toward higher unsaturation and longer carbon chain lengths, as well as metabolic regulation in specific lipid pathways. Key findings included characteristic shifts within triacylglycerols and glycerophospholipids, which were significantly associated with changes in oxyntomodulin levels. Enhanced phosphatidylcholine-to-lysophosphatidylcholine conversion and upregulated ether lipid levels correlated with liver stiffness measures. Metabolic remodeling of sphingolipids—characterized by a decrease in ceramide/sphingomyelin levels and upregulation of the hexosylceramide pathway—emerged as an additional lipidomic signature after SG.
Conclusion
These findings highlight the complex lipidomic remodeling underlying the metabolic efficacy and therapeutic potential of SG.

Citations

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Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications
Xuan Trong Truong, Dae Ho Lee
Diabetes & Metabolism Journal.2025; 49(5): 964. CrossRef

Complications
Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study: Eun Roh, Ji Hye Heo, Han Na Jung, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm; Diabetes Metab J. 2025;49(5):1106-1115. Published online May 21, 2025; DOI: https://doi.org/10.4093/dmj.2024.0406

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Background
Remnant cholesterol (remnant-C) has been linked to the risk of various vascular diseases, but the association between remnant-C and end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) remains unclear.
Methods
Using a nationwide cohort, a total of 2,537,149 patients with T2DM without ESRD, who had participated in the national health screening in 2009, were enrolled and followed up until 2020. Low-density lipoprotein cholesterol (LDL-C) levels were assessed by the Martin-Hopkins method, and remnant-C was calculated as total cholesterol–LDL-C–high-density lipoprotein cholesterol.
Results
During a median follow-up period of 10.3 years, 26,246 patients with T2DM (1.03%) developed ESRD. Participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.12 (95% confidence interval [CI], 1.08 to 1.17), 1.20 (95% CI, 1.15 to 1.24), and 1.33 (95% CI, 1.26 to 1.41) in the second, third, and fourth quartile, compared with the lowest quartile, in multivariable-adjusted analyses. The positive association between remnant-C and ESRD remained consistent, irrespective of age, sex, presence of pre-existing comorbidities, and use of anti-dyslipidemic medications. The increased risk of ESRD was more pronounced in high-risk subgroups, including those with hypertension, chronic kidney disease, obesity, and a longer duration of diabetes.
Conclusion
These findings suggest that remnant-C profiles in T2DM have a predictive role for future progression of ESRD, independent of traditional risk factors for renal dysfunction.

Citations

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Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2025;49:1106-15)
Jun Hwa Hong
Diabetes & Metabolism Journal.2026; 50(1): 190. CrossRef

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; Diabetes Metab J. 2025;49(1):105-116. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0066

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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.

Citations

Citations to this article as recorded by

J-shaped association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and heart failure: a cross-sectional study
Ping Lv, Chenze Zhao, Yu Shan
European Journal of Medical Research.2026;[Epub] CrossRef
Remnant cholesterol inflammatory index, calculated from residual cholesterol to C-reactive protein ratio, and stroke outcomes: a retrospective study using the National institutes of health stroke scale and modified Rankin scale
Yanmei Yu, Yiming Zhang, Chunyan Zhu, Tingting Duan, Zichen Rao
Lipids in Health and Disease.2025;[Epub] CrossRef
Association of outcome with non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in hospitalized patients with congestive heart failure: a retrospective analysis
Lina Yu, Lianhong Xie
Journal of Cardiothoracic Surgery.2025;[Epub] CrossRef

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; Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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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.

Citations

Citations to this article as recorded by

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)
Hongbing Wan, Xiuxiu Xu, Dasong Yi, Kexin Shuai
Expert Opinion on Drug Safety.2025; 24(3): 305. CrossRef
Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases
Biao Qu, Zheng Li, Wei Hu
World Journal of Diabetes.2025;[Epub] CrossRef

Review

Metabolic Risk/Epidemiology
Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism: Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan; Diabetes Metab J. 2024;48(3):354-372. Published online April 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0277

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Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

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Original Article

Metabolic Risk/Epidemiology
Biologically Informed Polygenic Scores for Brain Insulin Receptor Network Are Associated with Cardiometabolic Risk Markers and Diabetes in Women: Jannica S. Selenius, Patricia P. Silveira, Mikaela von Bonsdorff, Jari Lahti, Hannu Koistinen, Riitta Koistinen, Markku Seppälä, Johan G. Eriksson, Niko S. Wasenius; Diabetes Metab J. 2024;48(5):960-970. Published online March 25, 2024; DOI: https://doi.org/10.4093/dmj.2023.0039

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Background
To investigate associations between variations in the co-expression-based brain insulin receptor polygenic score and cardiometabolic risk factors and diabetes mellitus.
Methods
This cross-sectional study included 1,573 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Cardiometabolic markers included body composition, waist circumference, circulating lipids, insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 1 and 3 (IGFBP-1 and -3). Glucose and insulin levels were measured during a standardized 2-hour 75 g oral glucose tolerance test and impaired glucose regulation status was defined by the World Health Organization 2019 criteria. Analyzes were adjusted for population stratification, age, smoking, alcohol consumption, socioeconomic status, chronic diseases, birth weight, and leisure-time physical activity.
Results
Multinomial logistic regression indicated that one standard deviation increase in hePRS-IR was associated with increased risk of diabetes mellitus in all participants (adjusted relative risk ratio, 1.17; 95% confidence interval, 1.01 to 1.35). In women, higher hePRS-IR was associated with greater waist circumference and higher body fat percentage, levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, insulin, and IGFBP-1 (all P≤0.02). The mePRS-IR was associated with decreased IGF-1 level in women (P=0.02). No associations were detected in men and studied outcomes.
Conclusion
hePRS-IR is associated with sex-specific differences in cardiometabolic risk factor profiles including impaired glucose regulation, abnormal metabolic markers, and unfavorable body composition in women.

Citations

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A mesocorticolimbic insulin receptor gene co-expression network moderates the association between early life adversity and food approach eating behaviour style in childhood
Angela Marcela Jaramillo-Ospina, Roberta Dalle Molle, Sachin Patel, Shona Kelly, Irina Pokhvisneva, Carolina de Weerth, Patrícia Pelufo Silveira
Appetite.2025; 204: 107762. CrossRef
Early adversity and the comorbidity between metabolic disease and psychopathology
Ameyalli Gómez‐Ilescas, Patricia Pelufo Silveira
The Journal of Physiology.2025;[Epub] CrossRef
Brain insulin receptor gene network shapes risk for metabolic disease after early-life stress in women
Angela Marcela Jaramillo-Ospina, Guillaume Elgbeili, Sachin Patel, Irina Pokhvisneva, Patricia Pelufo Silveira
Communications Biology.2025;[Epub] CrossRef

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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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.

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Original Articles

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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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.

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Current Status of Continuous Glucose Monitoring Use in South Korean Type 1 Diabetes Mellitus Population–Pronounced Age-Related Disparities: Nationwide Cohort Study
Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim
Diabetes & Metabolism Journal.2025; 49(5): 1040. CrossRef
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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.

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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

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Abstract PDF PubReader 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

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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

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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.

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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
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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
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Ye Seul Yang
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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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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

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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.

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Cardiovascular Risk/Epidemiology
Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus: Takayoshi Sasako, Toshimasa Yamauchi, Kohjiro Ueki; Diabetes Metab J. 2023;47(2):185-197. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0325

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In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

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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

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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 Articles

Metabolic Risk/Epidemiology
Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study: He Gao, Jinying Yang, Wenfei Pan, Min Yang; Diabetes Metab J. 2022;46(2):307-318. Published online March 7, 2022; DOI: https://doi.org/10.4093/dmj.2020.0287

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Abstract PDF Supplementary Material PubReader ePub

Background
Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference.
Methods
Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes.
Results
According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes.
Conclusion
IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

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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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450 Download
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Abstract PDF Supplementary Material PubReader 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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Review

Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression: Dae-Seok Kim, Philipp E. Scherer; Diabetes Metab J. 2021;45(6):799-812. Published online November 22, 2021; DOI: https://doi.org/10.4093/dmj.2021.0077

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Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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Original Article

Metabolic Risk/Epidemiology
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus: So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim; Diabetes Metab J. 2022;46(1):140-148. Published online August 9, 2021; DOI: https://doi.org/10.4093/dmj.2021.0023

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Background
To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM).
Methods
We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age.
Results
Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m². The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles.
Conclusion
In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.

Citations

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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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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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Abstract PDF PubReader ePub

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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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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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.

Citations

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Obesity and Metabolic Syndrome
Comparison of Competitive Models of Metabolic Syndrome Using Structural Equation Modeling: A Confirmatory Factor Analysis: Karimollah Hajian-Tilaki; Diabetes Metab J. 2018;42(5):433-441. Published online October 22, 2018; DOI: https://doi.org/10.4093/dmj.2018.0010

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Background

The purpose of this study was to apply the structural equation modeling (SEM) to compare the fitness of different competing models (one, two, and three factors) of the metabolic syndrome (MetS) in Iranian adult population.

Methods

Data are given on the cardiometabolic risk factors of 841 individuals with nondiabetic adults from a cross-sectional population-based study of glucose, lipids, and MetS in the north of Iran. The three conceptual hypothesized models (single factor, two correlated factors, and three correlated latent factors) were evaluated by using confirmatory factor analysis with the SEM approach. The summary statistics of correlation coefficients and the model summary fitting indexes were calculated.

Results

The findings show that a single-factor model and a two-correlated factor model had a poorer summary fitting index compared with a three-correlated factor model. All fitting criteria met the conceptual hypothesized three-correlated factor model for both sexes. However, the correlation structure between the three underlying constructs designating the MetS was higher in women than in men.

Conclusion

These results indicate the plausibility of the pathophysiology and etiology of MetS being multifactorial, rather than a single factor, in a nondiabetic Iranian adult population.

Citations

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Structural Equation Modelling for Predicting the Relative Contribution of Each Component in the Metabolic Syndrome Status Change
José E. Teixeira, José A. Bragada, João P. Bragada, Joana P. Coelho, Isabel G. Pinto, Luís P. Reis, Paula O. Fernandes, Jorge E. Morais, Pedro M. Magalhães
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Pathophysiology
The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly Measured Insulin Resistance: Maria Camila Pérez-Matos, Martha Catalina Morales-Álvarez, Freddy Jean Karlo Toloza, Maria Laura Ricardo-Silgado, Jose Oscar Mantilla-Rivas, Jairo Arturo Pinzón-Cortes, Maritza Perez-Mayorga, Elizabeth Jiménez, Edwin Guevara, Carlos O Mendivil; Diabetes Metab J. 2017;41(6):466-473. Published online November 27, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.6.466

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Background

Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles.

Methods

We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices.

Results

Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=−0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC).

Conclusion

In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

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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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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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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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Systematic Review on Efficacy, Effectiveness, and Safety of Pitavastatin in Dyslipidemia in Asia
Nam Xuan Vo, Huong Lai Pham, Tan Trong Bui, Tien Thuy Bui
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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
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Efficacy and Safety of High-Dose Atorvastatin in Moderate-to-High Cardiovascular Risk Postmenopausal Korean Women with Dyslipidemia
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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
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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

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Abstract PDF PubReader ePub

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.

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Reviews

Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia: Klaus G. Parhofer; Diabetes Metab J. 2015;39(5):353-362. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.353

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Glucose and lipid metabolism are linked to each other in many ways. The most important clinical manifestation of this interaction is diabetic dyslipidemia, characterized by elevated triglycerides, low high density lipoprotein cholesterol (HDL-C), and predominance of small-dense LDL particles. However, in the last decade we have learned that the interaction is much more complex. Hypertriglyceridemia and low HDL-C cannot only be the consequence but also the cause of a disturbed glucose metabolism. Furthermore, it is now well established that statins are associated with a small but significant increase in the risk for new onset diabetes. The underlying mechanisms are not completely understood but modulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA)-reductase may play a central role as genetic data indicate that mutations resulting in lower HMG CoA-reductase activity are also associated with obesity, higher glucose concentrations and diabetes. Very interestingly, this statin induced increased risk for new onset type 2 diabetes is not detectable in subjects with familial hypercholesterolemia. Furthermore, patients with familial hypercholesterolemia seem to have a lower risk for type 2 diabetes, a phenomenon which seems to be dose-dependent (the higher the low density lipoprotein cholesterol, the lower the risk). Whether there is also an interaction between lipoprotein(a) and diabetes is still a matter of debate.

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Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer
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Journal of Personalized Medicine.2023; 13(1): 157. CrossRef
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Metabolic Imaging and Molecular Biology Reveal the Interplay between Lipid Metabolism and DHA-Induced Modulation of Redox Homeostasis in RPE Cells
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The Scientific World Journal.2023; 2023: 1. CrossRef
Effect of saffron and fenugreek on lowering blood glucose: A systematic review with meta‐analysis
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The roles of dietary lipids and lipidomics in gut-brain axis in type 2 diabetes mellitus
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Canagliflozin protects diabetic cardiomyopathy by mitigating fibrosis and preserving the myocardial integrity with improved mitochondrial function
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Lipids in Health and Disease.2023;[Epub] CrossRef
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Triglyceride-Glucose Index as an Alternative Tool for Identifying Prediabetes and Insulin Resistance
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The effects of pomegranate peel added bread on anthropometric measurements, metabolic and oxidative parameters in individuals with type 2 diabetes: a double-blind, randomized, placebo-controlled study
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Triglyceride Glucose Index, its Modified Indices, and Triglyceride HDL-C Ratio as Predictor Markers of Insulin Resistance in Prediabetic Individuals
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Differentially Expressed Genes in Response to a Squalene-Supplemented Diet Are Accurate Discriminants of Porcine Non-Alcoholic Steatohepatitis
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Association of HDL Subfraction Profile with the Progression of Insulin Resistance
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The Role of Lipids in the Regulation of Immune Responses
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The Decrease in Serum Total Cholesterol and Low-Density Lipoprotein (LDL) Concentrations With the Initiation of Hemodialysis Despite a Concomitant Increase in Serum Albumin Concentrations
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Lipid Profile Paradox: Investigating Improved Lipid Levels in Diabetic Mellitus Patients with Foot Ulcer Infections—A Prospective Descriptive Study
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Variability, Mean, and Baseline Values of Metabolic Parameters in Predicting Risk of Type 2 Diabetes
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Glycemic Control and the Heart: The Tale of Diabetic Cardiomyopathy Continues
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The Role of Changes in Cumulative Lipid Parameter Burden in the Pathogenesis of Type 2 Diabetes Mellitus: A Cohort Study of People Aged 35–65 Years in Rural China
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Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 1831. CrossRef
Alternate-day fasting, a high-sucrose/caloric diet and praziquantel treatment influence biochemical and behavioral parameters during Schistosoma mansoni infection in male BALB/c mice
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Beneficial effects of monounsaturated fatty acid‐rich blended oils with an appropriate polyunsaturated/saturated fatty acid ratio and a low n‐6/n‐3 fatty acid ratio on the health of rats
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Hibiscus sabdariffa in Diabetes Prevention and Treatment—Does It Work? An Evidence-Based Review
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Statin therapy is not warranted for a person with high LDL-cholesterol on a low-carbohydrate diet
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Marek Skrzypski, Paweł A. Kołodziejski, Ewa Pruszyńska-Oszmałek, Tatiana Wojciechowicz, Paulina Janicka, Małgorzata Krążek, Emilian Małek, Mathias Z. Strowski, Krzysztof W. Nowak
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Biomolecules.2022; 12(10): 1535. CrossRef
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Minh Hoang Thi, Chung Dang Thanh, Thuan Huynh Quang
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Joint inference of physiological network and survival analysis identifies factors associated with aging rate
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Maiza Von Dentz, Gabriela Gambato, Andreza Ferrari, Roselei Claudete Fontana, Eliseu Rodrigues, Mirian Salvador, Marli Camassola, Matheus Parmegiani Jahn
Advances in Traditional Medicine.2021; 21(3): 453. CrossRef
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Diabetes, Lipids, and CV Risk
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The controversial role of glucose in the diabetic kidney
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The Changes of Cholesterol Profile at the Different Insulin Resistance Range in the Czech Republic
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Chronic Intake of Energy Drinks and Their Sugar Free Substitution Similarly Promotes Metabolic Syndrome
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Prevalence and Metabolic Predictors for Early Diagnosed Prediabetes in Women with Previous Gestational Diabetes: Observational Cohort Study
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High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies
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Emulsion Droplet Crystallinity Attenuates Short-Term Satiety in Healthy Adult Males: A Randomized, Double-Blinded, Crossover, Acute Meal Study
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Candidate Regulators of Dyslipidemia in Chromosome 1 Substitution Lines Using Liver Co-Expression Profiling Analysis
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Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium–Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity
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Hydroxyurea alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with βS haplotype and α-thalassemia
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Developmental Dioxin Exposure Alters the Methylome of Adult Male Zebrafish Gonads
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The association between exposure to different aspects of shift work and metabolic risk factors in health care workers, and the role of chronotype
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Raffia palm (Raphia hookeri G. Mann & H. Wendl) wine modulates glucose homeostasis by enhancing insulin secretion and inhibiting redox imbalance in a rat model of diabetes induced by high fructose diet and streptozotocin
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HDL-Cholesterol, Its Variability, and the Risk of Diabetes: A Nationwide Population-Based Study
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Aging and Hyperglycemia Intensify Dyslipidemia-Induced Oxidative Stress and Inflammation in Rats: Assessment of Restorative Potentials of ALA and EPA + DHA
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New Drugs for Treating Dyslipidemia: Beyond Statins: Chang Ho Ahn, Sung Hee Choi; Diabetes Metab J. 2015;39(2):87-94. Published online April 20, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.87

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Statins have been shown to be very effective and safe in numerous randomized clinical trials, and became the implacable first-line treatment against atherogenic dyslipidemia. However, even with optimal statin treatment, 60% to 80% of residual cardiovascular risk still exists. The patients with familial hypercholesterolemia which results in extremely high level of low density lipoprotein cholesterol (LDL-C) level and the patients who are intolerant or unresponsive to statins are the other hurdles of statin treatment. Recently, new classes of lipid-lowering drugs have been developed and some of them are available for the clinical practice. The pro-protein convertase subtilisin/kexintype 9 (PCSK9) inhibitor increases the expression of low density lipoprotein (LDL) receptor in hepatocytes by enhancing LDL receptor recycling. The microsomal triglyceride transport protein (MTP) inhibitor and antisense oligonucleotide against apolipoprotein B (ApoB) reduce the ApoB containing lipoprotein by blocking the hepatic very low density lipoprotein synthesis pathway. The apolipoprotein A1 (ApoA1) mimetics pursuing the beneficial effect of high density lipoprotein cholesterol and can reverse the course of atherosclerosis. ApoA1 mimetics had many controversial clinical data and need more validation in humans. The PCSK9 inhibitor recently showed promising results of significant LDL-C lowering in familial hypercholesterolemia (FH) patients from the long-term phase III trials. The MTP inhibitor and antisesnse oligonucleotide against ApoB were approved for the treatment of homozygous FH but still needs more consolidated evidences about hepatic safety such as hepatosteatosis. We would discuss the benefits and concerns of these new lipid-lowering drugs anticipating additional benefits beyond statin treatment.

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Original Articles

The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes: Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang; Diabetes Metab J. 2014;38(3):211-219. Published online June 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.3.211

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Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

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Statin Discontinuation after Achieving a Target Low Density Lipoprotein Cholesterol Level in Type 2 Diabetic Patients without Cardiovascular Disease: A Randomized Controlled Study: Seung-Hwan Lee, Hyuk-Sang Kwon, Yong-Moon Park, Seung-Hyun Ko, Yoon-Hee Choi, Kun-Ho Yoon, Yu-Bae Ahn; Diabetes Metab J. 2014;38(1):64-73. Published online February 19, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.1.64

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Background

This study investigated the rate of relapse of dyslipidemia and the factors which could predict relapse following a short-term statin discontinuation after achieving a target low density lipoprotein cholesterol (LDL-C) level in type 2 diabetic patients without cardiovascular disease (CVD).

Methods

Ninety-nine subjects on rosuvastatin treatment and whose LDL-C level was lower than 100 mg/dL were randomly assigned to discontinue or maintain statin treatment at a 2:1 ratio. The subjects were followed-up after 10 weeks. A relapse of dyslipidemia was defined as a reascent of LDL-C level to greater than 100 mg/dL.

Results

The statin discontinuation group had a significant rate of relapse compared to the maintenance group (79% vs. 3%, respectively). Pretreatment and baseline lipid levels, their ratios, and hemoglobin A1c level were significantly different between the relapse and nonrelapse groups. The pretreatment and baseline lipid profiles and their ratios were independently associated with relapse. The pretreatment LDL-C level was the most useful parameter for predicting a relapse, with a cutoff of 123 mg/dL. During the follow-up period, no CVD event was noted.

Conclusion

The relapse rate of dyslipidemia was high when statins were discontinued in type 2 diabetic patients without CVD. Statin discontinuation should be considered carefully based on the pretreatment lipid profiles of patients.

Citations

Citations to this article as recorded by

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Visit-to-visit variability of lipid measurements and the risk of myocardial infarction and all-cause mortality: A prospective cohort study
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2018 Guidelines for the management of dyslipidemia
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Prevalence and Management of Dyslipidemia in Korea: Korea National Health and Nutrition Examination Survey during 1998 to 2010: Eun Roh, Seung-Hyun Ko, Hyuk-Sang Kwon, Nan Hee Kim, Jae Hyeon Kim, Chul Sik Kim, Kee-Ho Song, Jong Chul Won, Dae Jung Kim, Sung Hee Choi, Soo Lim, Bong-Yun Cha; Diabetes Metab J. 2013;37(6):433-449. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.433

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Background

Dyslipidemia is a major risk factor of cardiovascular disease. The aim of this study was to investigate the changing trends in the prevalence and management status of dyslipidemia among Korean adults.

Methods

The prevalence of dyslipidemia and the rates of awareness, treatment, and control of dyslipidemia were investigated in adults aged ≥20 years from the Korea National Health and Nutrition Surveys (KNHANES) 1998 to 2010. The updated National Cholesterol Education Program criteria was used, which define dyslipidemia as having one or more of the following lipid abnormalities: hypercholesterolemia (total cholesterol ≥240 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), hypertriglyceridemia (≥150 mg/dL), hyper-low density lipoprotein (LDL) cholesterolemia (≥160 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), and hypo-high density lipoprotein (HDL)-cholesterolemia (<40 mg/dL in men and <50 mg/dL in women).

Results

The number of participants was 6,921, 4,894, 5,312, 2,733, 6,295, 6,900, and 5,738 in KNHANES 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Age-standardized prevalence rates of dyslipidemia were 54.0%, 65.8%, 66.5%, 60.6%, 58.7%, 58.9%, and 59.0% in 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Hypertriglyceridemia and hypo-HDL-cholesterolemia were the two most frequent lipid abnormalities. The overall prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased by 1.36- and 1.35-fold in 2010 compared with 2007, respectively. Awareness, treatment, and control rates of dyslipidemia improved over the period of surveys in both sexes. In 2010, about 30% of dyslipidemic patients who received lipid-lowering treatment reached target levels.

Conclusion

Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.

Citations

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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

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Abstract PDF PubReader ePub

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.

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Original Article

Prevalence of Dyslipidemia among Korean Adults: Korea National Health and Nutrition Survey 1998-2005: Myung Ha Lee, Hyeon Chang Kim, Song Vogue Ahn, Nam Wook Hur, Dong Phil Choi, Chang Gyu Park, Il Suh; Diabetes Metab J. 2012;36(1):43-55. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.43

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Abstract PDF PubReader ePub

Background

Dyslipidemia is a disorder of lipid metabolism, including elevated total cholesterol, elevated triglyceride, elevated low density lipoprotein cholesterol (LDL-C), and decreased high density lipoprotein cholesterol (HDL-C). The objective of this study was to investigate recent changes in the prevalence of dyslipidemia and also the rates of awareness, treatment, and control of dyslipidemia among Korean adults.

Methods

Dyslipidemia is defined according to the National Cholesterol Education Program-Adult Treatment Panel III as total cholesterol ≥240 mg/dL, LDL-C ≥160 mg/dL, HDL-C <40 mg/dL, and triglyceride ≥200 mg/dL. The prevalence of dyslipidemia was estimated for adults aged ≥20 years using the Korea National Health and Nutrition Survey (KNHANES) in 1998 (n=6,923), 2001 (n=4,882), and 2005 (n=5,323). Rates of awareness, treatment and control of dyslipidemia were calculated for adults aged ≥30 years using the KNHANES in 2005 (n=4,654).

Results

The prevalence of dyslipidemia (aged ≥20 years) increased from 32.4% in 1998 to 42.6% in 2001 and 44.1% in 2005. Compared with the KNHANES in 1998, the prevalence of dyslipidemia was 47% (95% confidence interval [CI], 35% to 59%) higher in 2001 and 61% (95% CI, 49% to 75%) higher in 2005. In 2005, only 9.5% of people with dyslipidemia were aware of the disease, 5.2% used lipid-lowering medication, and 33.2% of patients with treatment reached treatment goals.

Conclusion

The prevalence of dyslipidemia in Korea gradually increased between 1998 and 2005. These findings suggest that more intense efforts for the prevention and treatment of dyslipidemia may lead to further improvement in the management of dyslipidemia.

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Review

Glycosphingolipid Modification: Structural Diversity, Functional and Mechanistic Integration of Diabetes: Tadashi Yamashita; Diabetes Metab J. 2011;35(4):309-316. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.309

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Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes have typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin. GSLs are usually observed in many organs ubiquitously. However, GSLs, including over 400 derivatives, participate in diverse cellular functions. Several studies indicate that GSLs might have an effect on signal transduction related to insulin receptors and epidermal growth factor receptors. GSLs may modulate immune responses by transmitting signals from the exterior to the interior of the cell. Guillain-Barré syndrome is one of the autoimmune disorders characterized by symmetrical weakness in the muscles of the legs. The targets of the immune response are thought to be gangliosides, which are one group of GSLs. Other GSLs may serve as second messengers in several signaling pathways that are important to cell survival or programmed cell death. In the search for clear evidence that GSLs may play critical roles in various biological functions, many researchers have made genetically engineered mice. Before the era of gene manipulation, spontaneous animal models or chemical-induced disease models were used.

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Original Article

The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.: Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim; Korean Diabetes J. 2009;33(6):485-493. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.485

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BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

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The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
Journal of Atherosclerosis and Thrombosis.2024; 31(8): 1194. CrossRef
Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
Ki Won Oh
Korean Diabetes Journal.2009; 33(6): 464. CrossRef

Review

Non-drug Intervention in Lipid Management: Dietary Portfolio.: In Ju Kim; Korean Diabetes J. 2007;31(5):377-382. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.377

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Abstract PDF: Non-Pharmaceutical interventions are essential in lipid management. The NCEP recommends the following three tiered approach to lipid management: 1. Institution of therapeutic lifestyle changes (TLC); 2. Use of non-drug adjuncts, including viscous fibers and plant sterol/stanol products; and 3. Drug therapy when required to reach treatment goals. Even though non-drug approaches often receive minimal attention in clinical practice, the efficacy of non-drug therapies is not so small. Non-drug adjuncts are known to reduce LDL cholesterol as follows: 12.5% for 45 g of soy protein/d; 6% to 7% for 9 to 10 g of psyllium/d, with smaller reductions for other viscous fibers; 10% for 1 to 2 g of plant sterols/d and 1% for 10 g almonds/d. Recently, combining these foods in a single dietary portfolio decreased LDL cholesterol and CRP similarly to the extent which achieved by a usual dose of a statin. This dietary portfolio can be regarded as an effective non-drug approach to reduce the risk of cardiovascular disease.

Original Articles

The Correlation between Central Obesity and Glucose, Lipid Metabolism and Macrovascular Complication in Elderly Type 2 Diabetes.: Eui Dal Jung, Jihyun Lee, Ho Sang Shon; Korean Diabetes J. 2007;31(4):343-350. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.343

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Abstract PDF

BACKGROUND
Obesity is related to abnormal lipid metabolism and macrovascular complication and accumulated fat on the abdomen in elderly diabetic patients. The aim of this study was to compare elderly diabetic patients' body fat composition with middle-aged patients and evaluate the role of central obesity on glucose and lipid metabolism and macrovascular complications in elderly type 2 diabetic patients. METHODS: We defined elderly patients who are over 65 years old and who waist circumference is over than 90 cm in men and 85 cm in women and waist-hip ratio (WHR) was over than 0.90 in men and 0.85 in women defined central obesity. % body fat were measured a bioimpedence analysis using DSM (Direct Segmental Measurement by 8-point electrode) method (Inbody 3.0, Biospace, Seoul, Korea) in two hundred two type 2 diabetes. Laboratory parameters such as fasting blood glucose, HbA1c, and lipid profile were included in this study and also investigated the macrovascular complication. RESULTS: 1) The ninety-five elderly diabetic patients, compared with middle-aged diabetic patients, were similar BMI and % of body fat but significantly increased waist circumference (P < 0.05) and WHR (P < 0.001). 2) In pearson's correlations, waist circumference was correlated with BMI (r = 0.927, P < 0.001), WHR (r = 0.851, P < 0.001), % body fat (r = 0.519, P < 0.001), total cholesterol (r = 0.255, P < 0.05), triglyceride (r = 0.365, P < 0.001), and LDL-cholesterol (r = 0.271, P < 0.05) in elderly diabetic patients. And WHR was also correlated with BMI (r = 0.744, P < 0.001), waist circumference (r = 0.851, P < 0.001), % body fat (r = 0.425, P < 0.001), total cholesterol (r = 0.372, P < 0.001), triglyceride (r = 0.408, P < 0.001), and LDL-cholesterol (r = 0.386, P < 0.001). 3) The obese elderly diabetic patients had increased triglyceride, total cholesterol and LDL-cholesterol but not related with macrovascular complication compared with lean elderly patients. CONCLUSION: In elderly type 2 diabetic patients are more central obesity although the same weight compared with middle-aged patients. Waist circumference and WHR were highly correlated with body fat composition and lipid profile in elderly diabetes. In obese elderly patients have abnormal lipid profile but not more macrovascular complication.

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Potential Benefits of Acupuncture and Herbs for Obesity‐Related Chronic Inflammation by Adipokines
Ji-Youn Kim, Seon-Eun Baek, Rehna Paula Ginting, Min-Woo Lee, Jeong-Eun Yoo, Yuan Xu
Evidence-Based Complementary and Alternative Medicine.2020;[Epub] CrossRef
A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006 - The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus -
Soo Lim, Dae Jung Kim, In-Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun-Gyu Park, Seung Hyun Ko, Yu-Bae Ahn, Inkyu Lee
Korean Diabetes Journal.2009; 33(1): 48. CrossRef

Effects of PPAR-alpha and-gamma Agonists on Fatty Acid Metabolism of Muscle Cells in Hyperlipidemic and Hyperglycemic Conditions.: Yong jik Lee, Zheng Shan Zhao, Soo Kyung Kim, Hae Jin Kim, Wan Sub Shim, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(5):324-335. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.324

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Abstract PDF

BACKGROUND
Studies for the regulation of fatty acid metabolism are deficient relatively in skeletal muscle and heart. The investigations in pathological conditions for malonyl-CoA decarboxylase (MCD) and for the relation of MCD and PPAR-alpha.-gamma agonists are insufficient in particular. METHODS: In the current study, fully differentiated H9c2 muscle cells were exposed to pathological conditions such as hyperlipidemic (0.1 mM Palmitate) and hyperglycemic (16.5 mM Glucose) condition with 5 uM PPAR-gamma agonist (rosiglitazone) and 10 uM PPAR-alpha agonist (WY14,643) and then experiments such as MCD activity assay, MCD real-time RT-PCR, MCD reporter gene assay, MCD Western blotting, PPAR-alpha Western blotting, and palmitate oxidation test were carried out. RESULTS: Only PPAR-alpha agonist increased MCD activity. In the result of real-time RT-PCR, both PPAR-alpha and PPAR-gamma agonists elevated MCD mRNA expression in hyperlipidemic condition. MCD protein expression was decreased in hyperlipidemic condition, however, increased in rosiglitazone, or WY14,643 treated conditions. Rosiglitazone, and WY14,643 treated groups showed incresed MCD protein expression in hyperglycemic condition. Hyperlipidemic control group and PPAR-alpha.-gamma agonists treated groups presented about 3.8 times more increased palmitate oxidation level than normolipidemic control group in hyperlipidemic condition. PPAR-alpha agonist treated group showed 49% more increased palmitate oxidation rate than hyperlipidemic control group in primary cultured rat skeletal muscle cells. The amount of palmitate oxidation from differentiated H9c2 muscle cells that had overexpressed PPAR-alpha structural genes was more increased than control group. CONCLUSION: This study suggests that PPAR-alpha agonist ameliorates the defects induced by hyperlipidemic condition through the regulation of MCD. In summary, a closely reciprocal relation among PPAR-alpha agonist, MCD, and fatty acid oxidation existed distinctly in hyperlipidemic condition, but not in hyperglycemic condition.

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Dhienda C. Shahannaz, Tadahisa Sugiura, Brandon E. Ferrell
BioChem.2025; 5(3): 23. CrossRef
Beneficial effect of Combination with Korean Red Ginseng and Morus alba in metabolic syndrome
Yun Jung Lee, Hye Yoom Kim, Jung Joo Yoon, So Min Lee, You Mee Ahn, Joung Hyun Kho, Min Chul Kho, Ho Sub Lee, Kyung Min Choi, Dae Gill Kang
The Korea Journal of Herbology.2012; 27(6): 99. CrossRef
Effects of Mixed Extract from Lycium chinense, Cordyceps militaris, and Acanthopanax senticosus on Glucose-Regulating Enzymes of HepG2 in Hyperglycemic Conditions
Dae-Jung Kim, Jeong-Mi Kim, Tae-Hyuk Kim, Jong-Mi Baek, Hyun-Sook Kim, Myeon Choe
Journal of the Korean Society of Food Science and Nutrition.2010; 39(9): 1257. CrossRef

Efficacy Evaluation of Atorvastatin in Korean Hyperlipidemic Patients with Type 2 Diabetes Mellitus.: Dong Seop Choi, Duk Kyu Kim, Doo Man Kim, Seong Yeon Kim, Moon Suk Nam, Yong Soo Park, Ho Sang Shon, Chul Woo Ahn, Kwan Woo Lee, Ki Up Lee, Moon Kyu Lee, Choon Hee Chung, Bong Yeon Cha; Korean Diabetes J. 2006;30(4):292-302. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.292

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Abstract PDF

BACKGROUND
NCEP ATP III Guideline recommends aggressive treatments of diabetic dyslipidemia, recognizing diabetes mellitus as CHD risk equivalents. This study was conducted to evaluate the effectiveness and safety of atorvastatin in hyperlipidemic patients with Type 2 diabetes mellitus through post-marketing drug use investigation of atorvastatin. METHODS: An open, multi-center, non-comparison, titrated dosage study was conducted in hyperlipidemic patients, who were treated with atorvastatin at first visiting hospitals from Mar. 2004 to Sep. 2004. 96 endocrinologists participated from 66 centers in this study. Total 2,182 hyperlipidemic patients were enrolled and 1,514 patients among them were accompanied by diabetes mellitus. Efficacy was evaluated at later than 4-week treatment by % change of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from baseline. Percent of patients reaching LDL-cholesterol level less than 100 mg/dL was also analyzed. The adverse events incidence and abnormalities of clinical laboratory values were evaluated for safety monitoring. RESULTS: Total cholesterol, triglycerides, and LDL-cholesterol level were reduced by 26.6%, 12.0%, and 34.8%, respectively, in diabetic hyperlipidemic patients after atorvastatin treatment. The patients with LDL-cholesterol level of less than 100 mg/dL were increased from 2.8% to 52.6%. Atorvastatin was considered to be safe because adverse drug reactions were reported in 32 patients (1.5%) of total 2,182 patients. CONCLUSION: Atorvastatin was effective and safe in hyperlipidemic patients with type 2 diabetes mellitus.

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Nahyun Cho, Jungah Uhm, Changsop Yang, Hiroshi Miyashita, Hobin Moon, Jungtae Leem
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Korean Diabetes Journal.2008; 32(3): 215. CrossRef

Randomized Controlled Trial

The Effect of Green Tea Polyphenol on Plasma Glucose, Lipid Levels and Antioxidant Systems in Type 2 Diabetic Patients.: Ji Hye Suk, Mi Kyung Kim, Jae Won Ju, Ji Sook Han, Jeong Hyun Park; Korean Diabetes J. 2006;30(3):217-225. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.217

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Abstract PDF

BACKGROUND
Green-tea polyphenol (GTP) is a well known antioxidant with favorable effect on blood glucose and lipid level in animal models. We were to investigate the effects of GTP on plasma glucose, lipid and antioxidant systems in patients with type 2 diabetes. METHODS: We recruited non-complicated type 2 diabetic patients with stable glycemic control by oral hypoglycemic agents. Subjects were randomly assigned to GTP group or placebo group for 12 weeks. Fasting plasma glucose (FPG), HbA1c, C-peptide, lipid levels, liver function test, renal function test, urine microalbumin, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were measured at baseline and after 12 weeks of treatment. RESULTS: At baseline, there were no significant differences in age, body mass index, duration of diabetes, dietary status, HbA1c, total cholesterol, LDL cholesterol, and HDL cholesterol levels between GTP and placebo group. However, FPG levels and triglyceride levels were significantly different between GTP and placebo group at baseline. In both of GTP and placebo group, there were no significant change after 12 weeks of treatment in FPG, HbA1c, total cholesterol, LDL cholesterol, triglyceride, levels of MDA, and GSHPx activities. SOD activities significantly increased after 12 weeks of treatment in both of GTP and placebo group. The increase of SOD activities were significantly higher in GTP group than in placebo group (P = 0.01). CONCLUSIONS: Supplementation of green tea polyphenol increased antioxidant activity in type 2 diabetic patients. The effect on plasma glucose and lipid level was not significant but should be confirmed in further large scaled studies.

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Effect of Young Barley Leaf Powder on Glucose Control in the Diabetic Rats
Hee-Kyoung Son, Yu-Mi Lee, Yong-Hyun Park, Jae-Joon Lee
The Korean Journal of Community Living Science.2016; 27(1): 19. CrossRef

Original Articles

The long term effects of rosiglitazone on serum lipid concentration and body weight.: Wan Sub Shim, Mi Young Do, Soo Kyung Kim, Hae Jin Kim, Kyu Yeon Hur, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(1):17-24. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.17

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Abstract PDF: BACKGROUND
Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentration and low density lipoprotein (LDL) particle size, it has adverse effects on the increment of total cholesterol (TC) and LDL cholesterol (LDL-C), and body weight in some studies. Such adverse effects of rosiglitazone on the serum lipid profiles and body weight seem to be attributed to the fact that most studies with rosiglitazone are limited to a short period of follow up. The aim of this study was to evaluate the long term effects of rosiglitazone on the serum lipid levels and body weight. MATERIALS AND METHODS: We prospectively evaluated fasting serum glucose, HbA1c, TC, LDL-C, triglyceride, HDL-C and body weight at baseline and every three months after rosiglitazone usage (4mg/d) in 202 type 2 diabetic patients. RESULTS: TC levels had increased maximally at 3 months and thereafter decreased, but were significantly higher at 18 months than those at baseline. LDL-C levels from the first 3 months to 12 months were significantly higher than those at baseline, but after 15 months, LDL-C concentration was not significantly different from the basal LDL-C concentration. HDL-C levels had increased after first 3 months and the increment of HDL-C concentration were maintained. The increment of HDL-C was more prominent in patients with low basal HDL-C concentration than in patients with high basal HDL-C concentration. Body weight from 3 months to 18 months were higher than that at baseline, but after 3 months, body weight did not increase furthermore significantly. CONCLUSIONS: The adverse effects on lipid concentration and body weight of rosiglitazone may attenuate after long term usage of rosiglitazone.

Increasing Trends of Metabolic Syndrome in Korea -Based on Korean National Health and Nutrition Examination Surveys-.: Soo Lim, Eun Jung Lee, Bo Kyeong Koo, Sung Il Cho, Kyong Soo Park, Hak Chul Jang, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2005;29(5):432-439. Published online September 1, 2005

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Abstract PDF: BACKGOUND: The number of individuals with metabolic syndrome is increasing in Asian as well as in Western countries. The aim of this study was to compare the prevalence and patterns of metabolic syndrome as determined by the 1998 and 2001 Korean National Health and Nutrition Examination Surveys(KNHANES). METHODS: A total of 6,907 and 4,536 Koreans aged over 20 years participated in the KNHANES in 1998 and 2001, respectively. A stratified multistage probability sampling design and weighting adjustments were made to obtain a representative Korean population. The working definition of the National Cholesterol Education Program-Adult Treatment Panel III was used to define metabolic syndrome. The International Obesity Task Force criteria for the Asian-Pacific population were used to determine waist circumference criteria. RESULTS: The age-adjusted prevalence of metabolic syndrome significantly increased from 22.5 to 24.1% between 1998 and 2001(P<0.01). Of the five components composing metabolic syndrome, low HDL-cholesterolemia showed the highest increase(32.6%) over this period, followed by hypertriglyceridemia and abdominal obesity, with 15.9% and 4.3% increases, respectively. In contrast, the number of subjects with high blood pressure or elevated fasting glucose levels were reduced(37.1-->33.1% and 18.9-->15.4%, respectively, both P<0.01). CONCLUSION: Dyslipidemia and abdominal obesity were primarily responsible for the increase in metabolic syndrome in Korea over the period 1998 to 2001. Changes to diet patterns and a reduction in physical activity are likely to have contributed to the rapid increase in metabolic syndrome in Korea; therefore, national strategies will be needed to counteract this increase.

Mitochondrial DNA 5178 C>A Polymorphism is Associated with Serum Lipid Levels.: Hyeon Jae Kim, Min Young Cho, Min Kim, Ku Cheol Park, Goo Jun Kang, Cheol Hak Jang, Yeon Seong Kim, Kyu Hong Lee, Soo Kyong Park; Korean Diabetes J. 2004;28(6):501-510. Published online December 1, 2004

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Abstract PDF: BACKGROUND
The mitochondrial DNA 5178 C>A polymorphism (Mt5178A) has been reported to the be associated with longevity, serum lipid levels and acute myocardial infarction in Japanese population. However, most of the studies on this subject have been confined to the Japanese population, and there have been fewer studies that tried to prove the association between Mt5178A polymorphism and type 2 diabetes or diabetic macrovascular complication. METHODS: The mt5178A polymorphism was genotyped in 658 type 2 diabetic patients and 334 non-diabetic controls subjects, and information on all the subjects' coronary heart disease and cerebrovascular disease was obtained from chart records. The anthropometric parameters, fasting blood glucose, insulin and lipid profiles were then measured. RESULTS: The frequency of the Mt5178A genotype in the control group (109/334; 32.6%) was not different from that found in the type 2 diabetic patients (223/658; 33.9%). The prevalence of cerebrovascular disease and coronary heart disease in the type 2 diabetic patients was not different between the Mt5178A genotype and the Mt5178C genotype. However, after adjustments for age and the body mass index, the HDL cholesterol concentration in men carrying the Mt5178A genotype was significantly higher than the HDL cholesterol concentration in men carrying the Mt5178C genotype (P = 0.007). The triglyceride concentration in women carrying the Mt5178A genotype was significantly lower than that in women carrying the Mt5178C genotype (P = 0.007). In addition, the frequency of the Mt5178A genotype in the control group increased with advanced age (P = 0.002). CONCLUSION: We could not find the association between Mt5178A and type 2 diabetes or diabetic macrovascular complication. However, the Mt5178 C>A polymorphism is associated with serum lipid levels and its frequency is increased with advanced age

Case Report

A Case of Primary Antiphospholipid Syndrome in a Patient with Diabetes Presenting as Foot Ulcer.: Chul Sik Kim, Dae Hoon Song, Jina Park, Jong Suk Park, Joo Young Nam, Young Kim, Hee Jung Yoon, Dol Mi Kim, Soo Jee Yoon, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2003;27(2):165-171. Published online April 1, 2003

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Abstract PDF: Antiphospholipid syndrome is a disorder characterized by recurrent vascular thrombosis, pregnancy loss and thrombocytopenia, and the presence of the lupus anticoagulant or a positive anticardiolipin test. A link of antiphospholipid syndrome to diabetes mellitus has not been established. There have been no reports of large artery thrombosis associated with antiphospholipid syndrome or diabetes mellitus. We present a case of an adult with large artery thrombosis, elevated anticardiolipin antibodies and lupus anticoagulant associated with diabetes. The patient was managed by successful primary percutaneous transluminal angioplasty and stent implantation, with accompanying anticoagulation therapy. To our knowledge, this is the first case where the occluded large artery was treated with primary stent implantation in primary antiphospholipid syndrome with diabetes mellitus

Original Articles

Effect of Red Ginseng Extract on Lipid Peroxidation in Streptozotocin-induced Diabetic Rats.: Hee Jong Jin, Sung Hee Ihm, Ja Hei Ihm; Korean Diabetes J. 2001;25(5):374-383. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus is postulated to be associated with increased oxidative stress and lipid peroxidation which may contribute to vascular complications. Recently ginseng (Panax) has been shown to have an antioxidant effect by enhancing nitric oxide synthesis in endothelial cells and by directly scavenging hydroxyl radicals. It is unknown whether ginseng might act as an antioxidant against lipid peroxidation in diabetes. METHODS: We studied the in vitro effect of red ginseng extract on lipid peroxidation employing phospholipid liposome and low-density lipoprotein (LDL) as a model system. To investigate the in vivo effect on lipid peroxidation in diabetes, we administered red ginseng extract (1 g/L in drinking water) to streptozotocin (STZ)- induced diabetic rats for 12 weeks and measured lipid peroxidation products in plasma, liver, kidneys and heart. RESULTS: The Fe(3+)- or Cu(2+)- mediated lipid peroxidation in phospholipid liposome and LDL, measured by the concentration of TBARS, was inhibited in the presence of red ginseng extract. MDA level in plasma measured by HPLC was higher in STZ-induced diabetic rats than in control rats. Plasma MDA level was lower by 41% in red ginseng-treated diabetic rats than in untreated diabetic rats. Tissue MDA levels measured by TBA method in liver, kidneys and heart were higher in STZ-induced diabetic rats than in control rats. In red ginseng-treated diabetic rats tissue MDA levels were lower by 14~30% than in untreated diabetic rats. CONCLUSION: We observed that red ginseng extract has an effect in inhibiting lipid peroxidation both in vitro and in STZ-induced diabetic rats. These results suggest that red ginseng might have a beneficial effect in diabetes as an antioxidant against lipid peroxidation and diabetic vascular complications.

Proliferative Ability of Aortic Smooth Muscle Cells and Lipid Peroxidation of Red Blood Cell Membrane in Diabetic Rats.: Sae Young Park, Hyung Joon Yoo, Kyun Soo Kim, Hyun Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Sung Woo Park; Korean Diabetes J. 1999;23(6):785-792. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus is a known risk factor for atherosclerosis, and lipid peroxidation, expression of oxidative stress, is also known to related to diabetes mellitus. The purpose of this study was to investigate the proliferative behaviour of cultured vascular smooth muscle cells (VSMCs) and the alteration of lipid peroxidation in relation to the pathogenesis of diabetic atherosclerosis. METHODS: Seven streptozotocin-induced insulin dependent diabetic Sprague Dawley rats and 7 normal rats were studied. Using enzyme method, aortic VSMCs was cultured in diabetic rats. and proliferation was compared between normal and diabetic rat. The membrane lipid peroxidaton of erythrocytes was determined by measurement of malonyl- dialdehyde(MDA), an end-product of fatty acid peroxidation with thiobarbituric acid (TBA) reaction. MDA-TBA colored complex concentration was calculated with the extinction coefficient of MDA-TBA complex at 532nm = 1.56X105cm-lM-1. RESULT: 1. The proliferative ability of cultured VSMCs was much higher in diabetic rats than in nondiabetic ones (p<0.05). 2. Compared with normal control rats, MDA concentration of diabetic rats was significantly increased (p<0.05). CONCLUSION: We concluded that proliferation of cultured VSMCs is due to oxidative stress in diabetes mellitus as a result of the increased proliferative ability of cultured VSMCs combined with increased lipid pemxidation in diabetic rats.

The Relationship between Apolipoprotein E Phenotypes, Serum Lipid Metabolism, and Oxidative Stress in Korean Type 2 Diabetic Patients.: Soo Bong Choi, Sun Min Park; Korean Diabetes J. 1999;23(2):182-192. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The cause of type 2 diabetes mellitus (DM) is not known, but one of the causes may be the reduction of insulin secretion through the fibrosis formed with amyloid deposits in pancreatic beta cells. Amyloidogenesis in hippocampus is a characteristic feature in Alzheimers disease. Possession of the Apolipoprotein (Apo) E 4 allele (E4/2, FA/3 or E4/4) is a risk factor for the development of Alzheimers disease. However, it is controversial that Apo E polymophsim is associated with the etiopathology of type 2 DM. Both Alzheimers disease and type 2 DM has increased oxidative stress, which may be related to the formation of fibrosis. The purpose of this study was to investigate the distribution of Apo E phenotypes in type 2 diabetic subjects and healthy subjects, and to determine whether Apo E phenotypes influenced serum lipid profiles and glutathione peroxidase and superoxide dismutase activities of red blood cells in type 2 DM and healthy subjects. METHODS: Overnight fasting blood was collected from 84 type 2 diabetic patients and 85 healthy subjects. Apo E phenotypes was determined by the isoelectrofocusing method. Serum lipid profiles and supetoxide dismutase and glutathione peroxidase activ'ities of red blood cells (RBC) were measured. RESULTS: The frequency of Apo E 4 in the type 2 DM was higher than that in the control group (p<0,05). The serum total cholesterol and triglyceride levels of the type 2 DM were overall higher than in healthy subjects. Serum lipid profiles were not affected by Apo E phenotypes in healthy subjects. However, semm total cholesterol levels of type 2 diab diabetic patients with Apo E3/3 were signifcantly lower than those with Apo FA/3 (p<0.05), but serum HDL, cholesterol levels had an opposite tendency. Serum triglyceride levels of type 2 diabetic patients with Apo E3/2 were higher than those with Apo E4/3 (p<0.05), RBC superoxide dismutase and gluta,thione peroxidase activities in type 2 diabetic patients tended to be lower than those in the control group. These enzyme activities of type 2 diabetic patieints with Apo E3 were lowest among the Apo E phenotype groups (p<0.05). CONCLUSION: This result suggests that type 2 diabctic patients had more Apo E 4 allele than in healthy people. Antioxidant enzyme activities decrqased in type 2 diabetic patients with Apo E 4 allele. Serum lipid profiles of type 2 diabetic patients with Apo E 4 allele was an increased risk factor for cardiovascular disease.

Effects of Smoking on Plasma Lipid Metabolism in Patients with non-insulin Dependent Diabetes Mellitus.: Seon Min Jeon, Yeun Kyung Lee, Hye Sung Lee, Bo Wan Kim, Young Bok Park, Myung Sook Choi; Korean Diabetes J. 1997;21(4):457-468. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus has been identified as a risk factor in the development of coronary vascular disease. Smoking also has been known as an independent risk factor in the development of coronary artery disease, causing a dislipidemia. This study was carried out to examine the effects of smoking on plasma lipids and lipoproteins metabolism in patients with NIDDM and in normal healthy subjects among Korean population in Taegu. METHODS: The 80 patients with NIDDM and 60 normal subjects were suMivided into non-stnoker, ex-smoker, and smoker group. Antbropornetric assessments, mean intake of nutrients, and the levels of plasma lipids, Apo A-I, L,p(a), CETP activity, and antioxidant vitamins such as vitamin A, E were measured, RESULTS: WHR in non-smoker of patients with NIDDM was greater than that in non-smoker of normal control. There were no differences in the nutrient intakes among groups, but protein intake was even higher in smoker of NIDDM group than that of normal group. There were no smoking effect on total cholesterol, LDL-C, AI, Apo A-I, Lp(a) and lipid peroxide in plasma of two groups, but they were higher in NIDDM group than normal group. Plasma TG concentrations were higher in smoker group than other groups within normal group, HDL-C levels were lower in non-smoker group than other groups within NIDDM group. CETP activities were higher in smoker group than non-smoker within normal group. And CEPT activities in NIDDM group were mostly higher than those of normal group. Vit. A levels of non-smoker in normal group were higher than ex-smoker within same group, and were also higher than non-smoker in NIDDM group. Vit. E levels showed no difference within each group, but they were mostly lower in NIDDM group than normal group. CONCLUSION: It was concluded that smoking was not a major factor for changing lipid metabolism in NIDDM patients as well as normal subjects unlike others findings. Their abnormal lipid rnetabolism may be induced from other risk factors for NIDDM rather than smoking itself. However, present study was done only for a short period, thus more studies are needed for longer term to investigate the effects af smoking on lipid metabolism in NIDDM among Korean population.

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