Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study: Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(6):818-825. Published online November 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0171

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Abstract PDF: Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Cardiovascular Risk/Epidemiology
Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD: Ga Young Heo, Hee Byung Koh, Hyung Woo Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Jayoun Kim, Soo Wan Kim, Yeong Hoon Kim, Su Ah Sung, Kook-Hwan Oh, Seung Hyeok Han; Diabetes Metab J. 2023;47(4):535-546. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0112

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Background
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.

Citations

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The Beneficial Effect of Glycemic Control against Adverse Outcomes in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease
Dong-Hwa Lee
Diabetes & Metabolism Journal.2023; 47(4): 484. CrossRef

Review

Metabolic Risk/Epidemiology
Gestational Diabetes Mellitus and Its Implications across the Life Span: Brandy Wicklow, Ravi Retnakaran; Diabetes Metab J. 2023;47(3):333-344. Published online February 8, 2023; DOI: https://doi.org/10.4093/dmj.2022.0348

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Gestational diabetes mellitus (GDM) has historically been perceived as a medical complication of pregnancy that also serves as a harbinger of maternal risk of developing type 2 diabetes mellitus (T2DM) in the future. In recent decades, a growing body of evidence has detailed additional lifelong implications that extend beyond T2DM, including an elevated risk of ultimately developing cardiovascular disease. Furthermore, the risk factors that mediate this lifetime cardiovascular risk are evident not only after delivery but are present even before the pregnancy in which GDM is first diagnosed. The concept thus emerging from these data is that the diagnosis of GDM enables the identification of women who are already on an enhanced track of cardiometabolic risk that starts early in life. Studies of the offspring of pregnancies complicated by diabetes now suggest that the earliest underpinnings of this cardiometabolic risk profile may be determined in utero and may first manifest clinically in childhood. Accordingly, from this perspective, GDM is now seen as a chronic metabolic disorder that holds implications across the life span of both mother and child.

Citations

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Inflammation and decreased cardiovagal modulation are linked to stress and depression at 36th week of pregnancy in gestational diabetes mellitus
Manoharan Renugasundari, Gopal Krushna Pal, Latha Chaturvedula, Nivedita Nanda, K. T. Harichandrakumar, Thiyagarajan Durgadevi
Scientific Reports.2023;[Epub] CrossRef
Women with gestational diabetes mellitus, controlled for plasma glucose level, exhibit maternal and fetal dyslipidaemia that may warrant treatment
Barbara J. Meyer, Colin Cortie, Marloes Dekker-Nitert, Helen L. Barrett, Dilys J. Freeman
Diabetes Research and Clinical Practice.2023; 204: 110929. CrossRef
Pregnancy diet to prevent gestational diabetes: study design and dietary assessments
Sylvia H. Ley
The American Journal of Clinical Nutrition.2023; 118(5): 847. CrossRef

Original Articles

Cardiovascular Risk/Epidemiology
Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus: Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong, on Behalf of the Committee of Practice Guideline of Korean Lipid and Atheroscelerosis; Diabetes Metab J. 2023;47(1):45-58. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2021.0344

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Background
There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data.
Methods
Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018.
Results
The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL.
Conclusion
For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

Citations

Citations to this article as recorded by

Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Diabetes & Metabolism Journal.2023; 47(1): 1. CrossRef
Optimal Low-Density Lipoprotein Cholesterol Level for Primary Prevention in Koreans with Type 2 Diabetes Mellitus
Ji Yoon Kim, Nam Hoon Kim
Diabetes & Metabolism Journal.2023; 47(1): 42. CrossRef
Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Journal of Lipid and Atherosclerosis.2023; 12(1): 12. CrossRef
2023 Clinical Practice Guidelines for Diabetes: Management of Cardiovascular Risk Factors
Ye Seul Yang
The Journal of Korean Diabetes.2023; 24(3): 135. CrossRef
2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
Diabetes & Metabolism Journal.2023; 47(5): 575. CrossRef
Management of Dyslipidemia in Patients with Diabetes Mellitus
Kyung Ae Lee
The Journal of Korean Diabetes.2023; 24(3): 111. CrossRef

Cardiovascular Risk/Epidemiology
Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study: Junghyun Noh, Min Kyong Moon, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong, on Behalf of the Committee of Practice Guideline of Korean Lipid and Atheroscelerosis; Diabetes Metab J. 2023;47(1):59-71. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2021.0320

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

Citations

Citations to this article as recorded by

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

Reviews

Pathophysiology
Blood Pressure Target in Type 2 Diabetes Mellitus: Hyun-Jin Kim, Kwang-il Kim, on Behalf of the Policy Committee of Korean Society of Hypertension; Diabetes Metab J. 2022;46(5):667-674. Published online September 19, 2022; DOI: https://doi.org/10.4093/dmj.2022.0215

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The prevalence of diabetes mellitus continues to increase worldwide, and it is a well-established cardiovascular risk factor. Hypertension is also an important cardiovascular risk factor to be controlled and is common among patients with diabetes mellitus. Optimal blood pressure (BP) goals have been the subject of great debate in the management of hypertension among patients with diabetes mellitus. This review provides detailed results from randomized controlled trials and meta-analyses of clinical outcomes according to the target BP in patients with type 2 diabetes mellitus. In addition, the target BP in patients with diabetes mellitus recommended by different guidelines was summarized and presented. A target BP of <140/90 mm Hg is recommended for patients with hypertension and diabetes mellitus, and BP should be controlled to <130/80 mm Hg in patients with diabetes mellitus who have high-risk clinical features. We hope that this review will be helpful to clinicians and patients by promoting the understanding and appropriate application of BP control in the comprehensive management of patients with diabetes mellitus.

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Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease
María González-Amor, Beatriz Dorado, Vicente Andrés
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Effects of Diabetes and Voluntary Exercise on IgA Concentration and Polymeric Immunoglobulin Receptor Expression in the Submandibular Gland of Rats
Jaebum Park, Yuko Yamamoto, Kouki Hidaka, Satoko Wada-Takahashi, Shun-suke Takahashi, Toshiya Morozumi, Nobuhisa Kubota, Makiko Saita, Juri Saruta, Wakako Sakaguchi, Masahiro To, Tomoko Shimizu, Yuko Mikuni-Takagaki, Keiichi Tsukinoki
Medicina.2023; 59(4): 789. CrossRef
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Zachary Bloomgarden
Journal of Diabetes.2023; 15(7): 542. CrossRef
CARDIOPROTECTIVE AND METABOLIC EFFECTS OF ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH SUCH COMORBIDITIES AS ARTERIAL HYPERTENSION, TYPE 2 DIABETES MELLITUS, AND OBESITY
I. P. Dunaieva, N. O. Kravchun, І. A. Ilchenko
Bulletin of Problems Biology and Medicine.2023; 1(2): 211. CrossRef
Hypertensive Heart Failure
Filippos Triposkiadis, Pantelis Sarafidis, Alexandros Briasoulis, Dimitrios E. Magouliotis, Thanos Athanasiou, John Skoularigis, Andrew Xanthopoulos
Journal of Clinical Medicine.2023; 12(15): 5090. CrossRef
2023 Clinical Practice Guidelines for Diabetes
Min Kyong Moon
The Journal of Korean Diabetes.2023; 24(3): 120. CrossRef

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

Drug/Regimen
Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: Jong Ha Baek, Ye Seul Yang, Seung-Hyun Ko, Kyung Do Han, Jae Hyeon Kim, Min Kyong Moon, Jong Suk Park, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Jong Han Choi, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association; Diabetes Metab J. 2022;46(5):701-712. Published online June 3, 2022; DOI: https://doi.org/10.4093/dmj.2022.0002

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Background
To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).
Methods
Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.
Results
Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.
Conclusion
The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

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Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis
Teja Chakrala, Roshni O. Prakash, Justin Kim, Hanzhi Gao, Umar Ghaffar, Jaymin Patel, Alex Parker, Bhagwan Dass
American Heart Journal Plus: Cardiology Research and Practice.2023; 28: 100286. CrossRef
Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea
Joonyub Lee, Seung-Hwan Lee, Kun-Ho Yoon, Jae Hyoung Cho, Kyungdo Han, Yeoree Yang
Scientific Reports.2023;[Epub] CrossRef
Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus
Young Sang Lyu, Seok Oh, Jin Hwa Kim, Sang Yong Kim, Myung Ho Jeong
Cardiovascular Diabetology.2023;[Epub] CrossRef
Effectiveness and safety of sodium–glucose cotransporter 2 inhibitors in Asian populations
Kyoung Hwa Ha, Dae Jung Kim
Journal of Diabetes Investigation.2023;[Epub] CrossRef
Severe hypoglycemia as a risk factor for cardiovascular outcomes in patients with type 2 diabetes: is it preventable?
Seung-Hyun Ko
Cardiovascular Prevention and Pharmacotherapy.2022; 4(3): 106. CrossRef
Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis
Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon
Endocrinology and Metabolism.2022; 37(5): 759. CrossRef

Cardiovascular Risk/Epidemiology
Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study: You-Bin Lee, Minji Koo, Eunjin Noh, Soon Young Hwang, Jung A Kim, Eun Roh, So-hyeon Hong, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo; Diabetes Metab J. 2022;46(5):722-732. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0225

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Background
We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults.
Methods
The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616).
Results
During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up.
Conclusion
Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

Citations

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The relationship of low-density lipoprotein cholesterol and all-cause or cardiovascular mortality in patients with type 2 diabetes: a retrospective study
Chin-Huan Chang, Shu-Tin Yeh, Seng-Wei Ooi, Chung-Yi Li, Hua-Fen Chen
PeerJ.2023; 11: e14609. CrossRef
ERCC1 polymorphism and its expression associated with ischemic stroke in Chinese population
Xiao-Dong Deng, Jian-Lin Ke, Tai-Yu Chen, Qin Gao, Zhuo-Lin Zhao, Wei Zhang, Huan Liu, Ming-Liang Xiang, Li-Zhen Wang, Ying Ma, Yun Liu
Frontiers in Neurology.2023;[Epub] CrossRef
New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi
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Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon
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Review

Cardiovascular Risk/Epidemiology
Management of Cardiovascular Risk in Perimenopausal Women with Diabetes: Catherine Kim; Diabetes Metab J. 2021;45(4):492-501. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0262

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Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of coronary heart disease events increases in postmenopausal women with diabetes. Randomized studies have conflicted regarding the beneficial impact of estrogen therapy upon intermediate cardiovascular disease markers and events. Therefore, estrogen therapy is not currently recommended for indications other than symptom management. However, for women at low risk of adverse events, estrogen therapy can be used to minimize menopausal symptoms. The risk of adverse events can be estimated using risk engines for the calculation of cardiovascular risk and breast cancer risk in conjunction with screening tools such as mammography. Use of estrogen therapy, statins, and anti-platelet agents can be guided by such calculators particularly for younger women with diabetes. Risk management remains focused upon lifestyle behaviors and achieving optimal levels of cardiovascular risk factors, including lipids, glucose, and blood pressure. Use of pharmacologic therapies to address these risk factors, particularly specific hypoglycemic agents, may provide some additional benefit for risk prevention. The minimal benefit for women with limited life expectancy and risk of complications with intensive therapy should also be considered.

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Determination of the Level of Cardiovascular Risk in 172,282 Spanish Working Women
Ángel Arturo López-González, María Albaladejo Blanco, Cristina Vidal Ribas, Pilar Tomás-Gil, Pere Riutord Sbert, José Ignacio Ramírez-Manent
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Zeyu Liu, Bi Deng, Qin Huang, Ruxin Tu, Fang Yu, Jian Xia, Jie Feng
Frontiers in Public Health.2023;[Epub] CrossRef
Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications
Joon Ho Moon, Hak Chul Jang
Diabetes & Metabolism Journal.2022; 46(1): 3. CrossRef
Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus
Soyeon Kang, Yong-Moon Park, Dong Jin Kwon, Youn-Jee Chung, Jeong Namkung, Kyungdo Han, Seung-Hyun Ko
Diabetes & Metabolism Journal.2022; 46(4): 578. CrossRef
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Original Articles

Cardiovascular Risk/Epidemiology
Metabolic Syndrome Severity Score for Predicting Cardiovascular Events: A Nationwide Population-Based Study from Korea: Yo Nam Jang, Jun Hyeok Lee, Jin Sil Moon, Dae Ryong Kang, Seong Yong Park, Jerim Cho, Jang-Young Kim, Ji Hye Huh; Diabetes Metab J. 2021;45(4):569-577. Published online January 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0103

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Background
Recently, a metabolic syndrome severity score (MS score) using a dataset of the Korea National Health and Nutrition Examination Surveys has been developed. We aimed to determine whether the newly developed score is a significant predictor of cardiovascular (CV) events among the Korean population.
Methods
From the Korean National Health Insurance System, 2,541,364 (aged 40 to 59 years) subjects with no history of CV events (ischemic stroke or myocardial infarction [MI]), who underwent health examinations from 2009 to 2011 and were followed up until 2014 to 2017, were identified. Cox proportional hazard model was employed to investigate the association between MS score and CV events. Model performance of MS score for predicting CV events was compared to that of conventional metabolic syndrome diagnostic criteria (Adult Treatment Program III [ATP-III]) using the Akaike information criterion and the area under the receiver operating characteristic curve.
Results
Over a median follow-up of 6 years, 15,762 cases of CV events were reported. MS score at baseline showed a linear association with incident CV events. In the multivariable-adjusted model, the hazard ratios (95% confidence intervals) comparing the highest versus lowest quartiles of MS score were 1.48 (1.36 to 1.60) for MI and 1.89 (1.74 to 2.05) for stroke. Model fitness and performance of the MS score in predicting CV events were superior to those of ATP-III.
Conclusion
The newly developed age- and sex-specific continuous MS score for the Korean population is an independent predictor of ischemic stroke and MI in Korean middle-aged adults even after adjusting for confounding factors.

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Cardiovascular risk/Epidemiology
Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2021;45(3):379-389. Published online December 11, 2020; DOI: https://doi.org/10.4093/dmj.2020.0008

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Background
Previous studies have suggested that depression in patients with diabetes is associated with worse health outcomes. The aim of this study was to evaluate the risk of cardiovascular disease (CVD) and mortality in patients with diabetes with comorbid depression.
Methods
We examined the general health check-up data and claim database of the Korean National Health Insurance Service (NHIS) of 2,668,615 participants with type 2 diabetes mellitus who had examinations between 2009 and 2012. As NHIS database has been established since 2002, those who had been diagnosed with depression or CVD since 2002 were excluded. The 2,228,443 participants were classified into three groups according to the claim history of depression; normal group (n=2,166,979), transient depression group (one episode of depression, n=42,124) and persistent depression group (at least two episodes of depression, n=19,340). The development of CVD and mortality were analyzed from 2009 to 2017.
Results
Those with depression showed a significantly increased risk for stroke (transient depression group: hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.15 to 1.26) (persistent depression group: HR, 1.54; 95% CI, 1.46 to 1.63). Those with depression had an increased risk for myocardial infarction (transient depression group: HR, 1.25; 95% CI, 1.18 to 1.31) (persistent depression group: HR, 1.38; 95% CI, 1.29 to 1.49). The persistent depression group had an increased risk for all-cause mortality (HR, 1.66; 95% CI, 1.60 to 1.72).
Conclusion
Coexisting depression in patients with diabetes has a deleterious effect on the development of CVD and mortality. We suggest that more attention should be given to patients with diabetes who present with depressive symptoms.

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Review

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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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 Article

Metabolic Risk/Epidemiology
Sex-, Age-, and Metabolic Disorder-Dependent Distributions of Selected Inflammatory Biomarkers among Community-Dwelling Adults: So Mi Jemma Cho, Hokyou Lee, Jee-Seon Shim, Hyeon Chang Kim; Diabetes Metab J. 2020;44(5):711-725. Published online April 16, 2020; DOI: https://doi.org/10.4093/dmj.2019.0119

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Background

Inflammatory cytokines are increasingly utilized to detect high-risk individuals for cardiometabolic diseases. However, with large population and assay methodological heterogeneity, no clear reference currently exists.

Methods

Among participants of the Cardiovascular and Metabolic Diseases Etiology Research Center cohort, of community-dwelling adults aged 30 to 64 without overt cardiovascular diseases, we presented distributions of tumor necrosis factor (TNF)-α and -β, interleukin (IL)-1α, -1β, and 6, monocyte chemoattractant protein (MCP)-1 and -3 and high sensitivity C-reactive protein (hsCRP) with and without non-detectable (ND) measurements using multiplex enzyme-linked immunosorbent assay. Then, we compared each markers by sex, age, and prevalence of type 2 diabetes mellitus, hypertension, and dyslipidemia, using the Wilcoxon Rank-Sum Test.

Results

In general, there were inconsistencies in direction and magnitude of differences in distributions by sex, age, and prevalence of cardiometabolic disorders. Overall, the median and the 99th percentiles were higher in men than in women. Older participants had higher TNF-α, high sensitivity IL-6 (hsIL-6), MCP-1, hsCRP, TNF-β, and MCP-3 median, after excluding the NDs. Participants with type 2 diabetes mellitus had higher median for all assayed biomarkers, except for TNF-β, IL-1α, and MCP-3, in which the medians for both groups were 0.00 due to predominant NDs. Compared to normotensive group, participants with hypertension had higher TNF-α, hsIL-6, MCP-1, and hsCRP median. When stratifying by dyslipidemia prevalence, the comparison varied significantly depending on the treatment of NDs.

Conclusion

Our findings provide sex-, age-, and disease-specific reference values to improve risk prediction and diagnostic performance for inflammatory diseases in both population- and clinic-based settings.

Citations

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Review

Basic Research
Histone Deacetylase 9: Its Role in the Pathogenesis of Diabetes and Other Chronic Diseases: Siqi Hu, Eun-Hee Cho, Ji-Young Lee; Diabetes Metab J. 2020;44(2):234-244. Published online March 24, 2020; DOI: https://doi.org/10.4093/dmj.2019.0243

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As a member of the class IIa histone deacetylases (HDACs), HDAC9 catalyzes the deacetylation of histones and transcription factors, commonly leading to the suppression of gene transcription. The activity of HDAC9 is regulated transcriptionally and post-translationally. HDAC9 is known to play an essential role in regulating myocyte and adipocyte differentiation and cardiac muscle development. Also, recent studies have suggested that HDAC9 is involved in the pathogenesis of chronic diseases, including cardiovascular diseases, osteoporosis, autoimmune disease, cancer, obesity, insulin resistance, and liver fibrosis. HDAC9 modulates the expression of genes related to the pathogenesis of chronic diseases by altering chromatin structure in their promotor region or reducing the transcriptional activity of their respective transcription factors. This review summarizes the current knowledge of the regulation of HDAC9 expression and activity. Also, the roles of HDAC9 in the pathogenesis of chronic diseases are discussed, along with potential underlying mechanisms.

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