1.2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung MOON ; Shinae KANG ; Jong Han CHOI ; Kyung Ae LEE ; Joon Ho MOON ; Suk CHON ; Dae Jung KIM ; Hyun Jin KIM ; Ji A SEO ; Mee Kyoung KIM ; Jeong Hyun LIM ; Yoon Ju SONG ; Ye Seul YANG ; Jae Hyeon KIM ; You-Bin LEE ; Junghyun NOH ; Kyu Yeon HUR ; Jong Suk PARK ; Sang Youl RHEE ; Hae Jin KIM ; Hyun Min KIM ; Jung Hae KO ; Nam Hoon KIM ; Chong Hwa KIM ; Jeeyun AHN ; Tae Jung OH ; Soo-Kyung KIM ; Jaehyun KIM ; Eugene HAN ; Sang-Man JIN ; Jaehyun BAE ; Eonju JEON ; Ji Min KIM ; Seon Mee KANG ; Jung Hwan PARK ; Jae-Seung YUN ; Bong-Soo CHA ; Min Kyong MOON ; Byung-Wan LEE
Diabetes & Metabolism Journal 2024;48(4):546-708
2.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 ;
Diabetes & Metabolism Journal 2023;47(1):59-71
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.
3.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 ;
Diabetes & Metabolism Journal 2023;47(1):45-58
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.
4.A Novel Role of Hyaluronic Acid and Proteoglycan Link Protein 1(HAPLN1) in Delaying Vascular Endothelial Cell Senescence
Dan ZHOU ; Ji Min JANG ; Goowon YANG ; Hae Chan HA ; Zhicheng FU ; Dae Kyong KIM
Biomolecules & Therapeutics 2023;31(6):629-639
Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.
5.Novel Effect of Hyaluronan and Proteoglycan Link Protein 1(HAPLN1) on Hair Follicle Cells Proliferation and Hair Growth
Hae Chan HA ; Dan ZHOU ; Zhicheng FU ; Moon Jung BACK ; Ji Min JANG ; In Chul SHIN ; Dae Kyong KIM
Biomolecules & Therapeutics 2023;31(5):550-558
Hair loss is a common condition that can have a negative impact on an individual’s quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.
6.2023 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 Jin KIM ; Hyun Min KIM ; Jung Hae KO ; Nam Hoon KIM ; Chong Hwa KIM ; Jeeyun AHN ; Tae Jung OH ; Soo-Kyung KIM ; Jaehyun KIM ; Eugene HAN ; Sang-Man JIN ; Won Suk CHOI ; Min Kyong MOON ; ;
Diabetes & Metabolism Journal 2023;47(5):575-594
In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.
7.Clinical Characteristics and Risk Factors for Mortality in Critical COVID-19 Patients Aged 50 Years or Younger During Omicron Wave in Korea:Comparison With Patients Older Than 50 Years of Age
Hye Jin SHI ; Jinyoung YANG ; Joong Sik EOM ; Jae-Hoon KO ; Kyong Ran PECK ; Uh Jin KIM ; Sook In JUNG ; Seulki KIM ; Hyeri SEOK ; Miri HYUN ; Hyun Ah KIM ; Bomi KIM ; Eun-Jeong JOO ; Hae Suk CHEONG ; Cheon Hoo JUN ; Yu Mi WI ; Jungok KIM ; Sungmin KYM ; Seungjin LIM ; Yoonseon PARK
Journal of Korean Medical Science 2023;38(28):e217-
Background:
The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group.
Methods:
We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality.
Results:
Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m 2 or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043–1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584–14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042–8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691–98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294–10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison.
Conclusion
Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.
8.Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea
Hye Jin SHI ; Eliel NHAM ; Bomi KIM ; Eun-Jeong JOO ; Hae Suk CHEONG ; Shin Hee HONG ; Miri HYUN ; Hyun ah KIM ; Sukbin JANG ; Ji-Young RHEE ; Jungok KIM ; Sungmin KIM ; Hyun Kyu CHO ; Yu Mi WI ; Shinhye CHEON ; Yeon-Sook KIM ; Seungjin LIM ; Hyeri SEOK ; Sook In JUNG ; Joong Sik EOM ; Kyong Ran PECK
Journal of Korean Medical Science 2022;37(22):e175-
Background:
Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea.
Methods:
We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics.
Results:
During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m 2 .Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092;95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients.Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group.The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m 2 ), and the one remaining patient died from a secondary infection.
Conclusion
About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.
9.A Novel Therapeutic Effect of a New Variant of CTLA4-Ig with Four Antennas That Are Terminally Capped with Sialic Acid in the CTLA4 Region
Yongwei PIAO ; So Yoon YUN ; Hee Soo KIM ; Bo Kyung PARK ; Hae Chan HA ; Zhicheng FU ; Ji Min JANG ; Moon Jung BACK ; In Chul SHIN ; Jong Hoon WON ; Dae Kyong KIM
Biomolecules & Therapeutics 2022;30(6):529-539
Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies.Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-beadassisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.
10.Preventive effect of dentifrice containing 1,450 ppm fluoride and sodium pyrophosphate
Min-Ji PARK ; Ja-Won CHO ; Hyun-Jun YOO ; Mi-Hae YUN ; Kyong-Hoon SHIN ; Young-Hoon PARK
Journal of Korean Academy of Oral Health 2022;46(2):63-69
Objectives:
This study aimed to evaluate the effects of a toothpaste containing sodium pyrophosphate and a high concentration (1,450 ppm) of fluoride on dental plaque, gingivitis index, and calculus index in a clinical trial.
Methods:
This study used an eight-week, randomized, double-blinded, controlled, comparative, parallel design. The participants, who voluntarily signed a consent form, were screened through visit evaluation if they met the selection/exclusion criteria. After a one-week run-in period, the selected participants were randomly assigned to either an experimental or control group in the order of their enrollment. Subsequently, the participants were asked to brush their teeth with the study toothpaste using the rolling method for 3 min, thrice daily, for 8 weeks. Oral examinations were performed at baseline and after 3 weeks, 4 weeks, and 8 weeks. Evaluation of papillary marginal attachment index (PMA index), Talbott’s gingival index, patient hygiene performance index (PHP index), Turesky plaque index, and calculus index were performed during the oral examination.
Results:
After 8 weeks, the PMA indices were 7.12 for the control group and 5.00 for experimental groups. In addition, the PHP index was 2.06 for the control group and 1.66 for the experimental group. Significant differences were observed between the control and experimental groups in all indice (P<0.05).
Conclusions
This study shows that using a toothpaste containing sodium fluoride, sodium pyrophosphate, tocopherol acetate, and dental-type silica improves dental plaque removal, reduces gingivitis, and inhibits calculus formation.

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