1.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
2.Prevalence and Current Status of Cardiometabolic Risk Factors in Korean Adults Based on Fact Sheets 2024
Endocrinology and Metabolism 2025;40(2):174-184
Korea has entered ‘super-aged’ society in 2025 with the proportion of people 65 years or older exceeding 20% as of the end of the year 2024. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. According to data from 2022, the overall prevalence of obesity reached 38.4%, marking a continued upward trend, based on National Health Insurance medical checkup data. In the combined data of 2021 to 2022, the prevalence of diabetes was 15.5% in Koreans older than 30 years according to the Diabetes Fact Sheet 2024 published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2022 was 30% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2022 was 40.9% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations in 2024.
3.Association Between Childhood Trauma and Anhedonia-Related Symptoms: The Mediation Role of Trait Anhedonia and Circulating Proteins
Sang Jin RHEE ; Dongyoon SHIN ; Daun SHIN ; Yoojin SONG ; Eun-Jeong JOO ; Hee Yeon JUNG ; Sungwon ROH ; Sang-Hyuk LEE ; Hyeyoung KIM ; Minji BANG ; Kyu Young LEE ; Jihyeon LEE ; Yeongshin KIM ; Youngsoo KIM ; Yong Min AHN
Journal of Korean Medical Science 2025;40(18):e66-
Background:
Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators.
Methods:
This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms.
Results:
Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017).
Conclusion
Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.
4.Association Between Childhood Trauma and Anhedonia-Related Symptoms: The Mediation Role of Trait Anhedonia and Circulating Proteins
Sang Jin RHEE ; Dongyoon SHIN ; Daun SHIN ; Yoojin SONG ; Eun-Jeong JOO ; Hee Yeon JUNG ; Sungwon ROH ; Sang-Hyuk LEE ; Hyeyoung KIM ; Minji BANG ; Kyu Young LEE ; Jihyeon LEE ; Yeongshin KIM ; Youngsoo KIM ; Yong Min AHN
Journal of Korean Medical Science 2025;40(18):e66-
Background:
Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators.
Methods:
This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms.
Results:
Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017).
Conclusion
Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.
5.The prognostic role of lipoprotein(a) in cardiovascular disease
Cardiovascular Prevention and Pharmacotherapy 2025;7(1):9-12
Lipoprotein(a) (Lp(a)), is not a new entity; however, it has become an increasingly discussed and studied risk factor for atherosclerotic cardiovascular disease (CVD) and aortic valve stenosis. Recent guidelines recommend measuring Lp(a) levels throughout the lifetime in patients at high risk for CVD, as Lp(a) can serve as a signature marker for identifying individuals at elevated risk for CVD. Numerous genetic and epidemiological studies have underscored the significant causal role of Lp(a) in the incidence of CVD. Individuals with high Lp(a) levels face an increased risk for CVD, even with optimal low-density lipoprotein cholesterol lowering. Furthermore, Lp(a) levels are primarily determined by genetics and are not significantly reduced by lifestyle changes or certain medications. This review will discuss the characteristics, genetic factors, and epidemiological properties of Lp(a) in relation to CVD.
6.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
7.Prevalence and Current Status of Cardiometabolic Risk Factors in Korean Adults Based on Fact Sheets 2024
Endocrinology and Metabolism 2025;40(2):174-184
Korea has entered ‘super-aged’ society in 2025 with the proportion of people 65 years or older exceeding 20% as of the end of the year 2024. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. According to data from 2022, the overall prevalence of obesity reached 38.4%, marking a continued upward trend, based on National Health Insurance medical checkup data. In the combined data of 2021 to 2022, the prevalence of diabetes was 15.5% in Koreans older than 30 years according to the Diabetes Fact Sheet 2024 published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2022 was 30% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2022 was 40.9% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations in 2024.
8.Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon KIM ; Soo LIM ; In-Kyung JEONG ; Eun-Jung RHEE ; Jun Sung MOON ; Ohk-Hyun RYU ; Hyuk-Sang KWON ; Jong Chul WON ; Sang Soo KIM ; Sang Yong KIM ; Bon Jeong KU ; Heung Yong JIN ; Sin Gon KIM ; Bong-Soo CHA ;
Diabetes & Metabolism Journal 2025;49(2):225-234
Background:
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods:
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.
9.Prevalence and Current Status of Cardiometabolic Risk Factors in Korean Adults Based on Fact Sheets 2024
Endocrinology and Metabolism 2025;40(2):174-184
Korea has entered ‘super-aged’ society in 2025 with the proportion of people 65 years or older exceeding 20% as of the end of the year 2024. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. According to data from 2022, the overall prevalence of obesity reached 38.4%, marking a continued upward trend, based on National Health Insurance medical checkup data. In the combined data of 2021 to 2022, the prevalence of diabetes was 15.5% in Koreans older than 30 years according to the Diabetes Fact Sheet 2024 published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2022 was 30% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2022 was 40.9% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations in 2024.
10.Association Between Childhood Trauma and Anhedonia-Related Symptoms: The Mediation Role of Trait Anhedonia and Circulating Proteins
Sang Jin RHEE ; Dongyoon SHIN ; Daun SHIN ; Yoojin SONG ; Eun-Jeong JOO ; Hee Yeon JUNG ; Sungwon ROH ; Sang-Hyuk LEE ; Hyeyoung KIM ; Minji BANG ; Kyu Young LEE ; Jihyeon LEE ; Yeongshin KIM ; Youngsoo KIM ; Yong Min AHN
Journal of Korean Medical Science 2025;40(18):e66-
Background:
Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators.
Methods:
This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms.
Results:
Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017).
Conclusion
Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms.The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

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