Endocrinology and Metabolism

Original Articles

Lack of Association between Vitamin D Insufficiency and Cardiovascular or Fracture Risk: A UK Biobank Study: Yongin Cho, Jong Hyun Jhee, Jong Ho Jhee, Hye-Sun Park; Received June 2, 2025 Accepted August 1, 2025 Published online October 15, 2025; DOI: https://doi.org/10.3803/EnM.2025.2482 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Vitamin D deficiency has been linked to increased risks of fractures and cardiovascular (CV) events, but the clinical relevance of the ‘insufficiency’ range remains unclear. We investigated CV and fracture risks across vitamin D levels, with a focus on the insufficiency range.
Methods
Using UK Biobank data, we analyzed 375,044 participants aged 40 to 69 years. Vitamin D status was categorized as deficient (<50 nmol/L), insufficient (≥50 to <75 nmol/L), or sufficient (≥75 nmol/L). Outcomes included three-point major adverse cardiovascular events (3P-MACE; myocardial infarction, stroke, and CV mortality) and major osteoporotic fractures, assessed via hospital records, registries, and death certificates.
Results
The vitamin D-deficient group had an increased risk of CV events (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.11 to 1.24) and fractures (aHR, 1.09; 95% CI, 1.01 to 1.18) compared to the vitamin D-sufficient group. Within the deficient group, the severely deficient group (<30 nmol/L) exhibited a markedly higher risk (aHR, 1.29; 95% CI, 1.21 to 1.37 for 3PMACE; and aHR, 1.20; 95% CI, 1.10 to 1.32 for fractures). In contrast, the vitamin D-insufficient group (50 to 75 nmol/L) showed no significant increase in the risk of either outcome, with no clear benefit or harm observed. Spline curve analysis revealed a negative correlation between vitamin D levels and risk, which was observed only within the deficient range and not within the insufficient range.
Conclusion
Vitamin D deficiency is strongly associated with increased CV disease and fracture risks, whereas the insufficiency range shows no significant risk or benefit, raising questions about its clinical relevance.

Diabetes, obesity and metabolism
Safety and Effectiveness of Pravastatin in Korean Patients with Dyslipidemia Based on the Cardiovascular Risk Classification: Pooled Analysis of Four Observational Studies: In-Kyung Jeong, Hyuk-Sang Kwon, Dae Jung Kim, Sin Gon Kim; Endocrinol Metab. 2025;40(4):598-609. Published online April 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2200

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Background
Despite their efficacy, statin-related adverse events (AEs) may interfere with statin treatment and contribute to negative outcomes in patients with cardiovascular diseases. In this study, we evaluated the safety and effectiveness of pravastatin in Korea.
Methods
Pooled data were collected from four multicenter prospective observational studies conducted in Korea between 2011 and 2020. Finally, 7,334 and 2,022 participants were included in the safety and effectiveness analyses, respectively. Overall safety, particularly muscle-related, incidence of new-onset diabetes mellitus (DM), changes in fasting plasma glucose and hemoglobin A1c level, achievement of target low-density lipoprotein cholesterol (LDL-C) level, and changes in LDL-C level were analyzed.
Results
At week 24, after 20 or 40 mg pravastatin treatment, safety results showed that AEs and adverse drug reactions (ADRs) were 8.7% and 1.3%, respectively, and that muscle-related AEs and ADRs were 0.5% and 0.3%, respectively, with no statistically significant difference in risk factors for statin-associated muscle symptoms. No patients developed DM during the study period. Additionally, at week 24, the achievement rates of target LDL-C levels were 87.9%, 78.4%, 57.8%, and 11.6% in low-, moderate-, high-, and very high-risk groups, respectively.
Conclusion
This study found that 20 or 40 mg pravastatin had minimal side effects and was safe for use in real-world clinical settings in Korea. Specifically, these doses effectively achieved the target LDL-C levels in patients with dyslipidemia in low-, moderate-, and high-risk groups for atherosclerotic cardiovascular disease (ASCVD). These results demonstrate that pravastatin can be safely administered continuously to patients with low-, moderate-, and high-risk ASCVD in a real-world clinical setting.

Citations

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Head-to-head comparison of visceral adiposity indices (A Body Shape Index and Visceral Adiposity Index) with traditional anthropometrics: a community-based strategy for cardiovascular risk prediction in urban China
Guoliang Ma, Wenyan Wang, Lin Zhu, Wenting Li, Zhuanzhuan Fan, Weiyi Zhong, Wenjing Zang, Xin Hong, Kun Li
BMJ Open.2025; 15(12): e102918. CrossRef

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Association between the Triglyceride-Glucose Index and Cardiovascular Risk and Mortality across Different Diabetes Durations: A Nationwide Cohort Study: Jeongeun Kwak, Kyung-Do Han, Eun Young Lee, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Jeongmin Lee; Endocrinol Metab. 2025;40(4):548-560. Published online March 5, 2025; DOI: https://doi.org/10.3803/EnM.2024.2205

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Background
We aimed to assess the association between triglyceride-glucose (TyG) index and cardiovascular disease (CVD) risk and mortality in a large cohort of diabetes patients.
Methods
A retrospective cohort study of 1,090,485 participants from the Korean National Health Insurance Service database was conducted. Participants were stratified into TyG quartiles.
Results
Higher TyG index quartiles were significantly associated with an increased CVD risk and mortality risk. In fully adjusted models, participants in the highest TyG quartile (Q4) had an 18% higher risk of CVD (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.13 to 1.23) and a 16% higher risk of mortality (HR, 1.16; 95% CI, 1.11 to 1.23) compared to those in the lowest quartile (Q1). The association was particularly pronounced in patients with fasting glucose ≥126 mg/dL (CVD [HR, 1.33; 95% CI, 1.29 to 1.37], mortality [HR, 1.23; 95% CI, 1.20 to 1.26]; P for interaction <0.001). Patients with a diabetes duration of ≥10 years showed the strongest association between the TyG index and CVD risk (HR, 1.44; 95% CI, 1.38 to 1.50), while the mortality risk was particularly elevated in those with a diabetes duration of less than 5 years (HR, 1.23; 95% CI, 1.18 to 1.30). Subgroup analyses revealed stronger associations between TyG index and CVD risk in younger participants, non-obese individuals, and non-smokers.
Conclusion
The TyG index is a significant predictor of CVD and mortality in diabetic patients, particularly in those with poor glycemic control or longer disease duration.

Citations

Citations to this article as recorded by

Preoperative triglyceride–glucose index as a metabolic predictor of surgical site infection after posterior lumbar fusion
Yu Hua, Shaoxing Li, Yuan Jiang, Jinwang Liu
Journal of Orthopaedic Surgery.2026;[Epub] CrossRef
Combined effect of triglyceride-glucose index and glucose disposal rate on cardio-cerebrovascular disease
Hongfei Yang, Chao Sun, Ya Li, You Zhou, Rui Wang, Yingxue Li, Marwan Salih Al-Nimer
PLOS One.2026; 21(2): e0342154. CrossRef
The Triglyceride-Glucose Index: A Practical Tool for Enhanced Cardiovascular Risk Stratification in Type 2 Diabetes
Jang Won Son
Endocrinology and Metabolism.2025; 40(4): 545. CrossRef
The association between triglyceride-glucose index and all-cause/cardiovascular mortality in patients with different glucose metabolism statuses
Jiajun Liu, Jinhua Kang, Pengpeng Liang, Zhangxiao Song, Guiyun Li, Xueshan Jin, Hongyan Wu
Cardiovascular Diabetology.2025;[Epub] CrossRef
Standardized Triglyceride-Glucose and Plasma Atherogenic Indices as Predictors of Diabetic Nephropathy and Coronary Artery Disease in Patients with Type 1 Diabetes Mellitus
Nazif Yalçın, Nizameddin Koca
European Journal of Therapeutics.2025;[Epub] CrossRef

Diabetes, obesity and metabolism
Prevalence of Mortality and Vascular Complications in Older Patients with Diabetes in Korea: Kwang Joon Kim, Jeongmin Lee, Yang Sun Park, Yong-ho Lee, Kyeong Hye Park, Hee-Won Jung, Chang Oh Kim, Man Young Park, Hun-Sung Kim, Bong-Soo Cha; Endocrinol Metab. 2025;40(3):448-458. Published online February 18, 2025; DOI: https://doi.org/10.3803/EnM.2024.2173

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Background
This study investigated the prevalence of diabetes mellitus (DM) and impaired fasting glucose, as well as their management and comorbidities among older Korean adults.
Methods
Data from 269,447 individuals aged 65 years and older from the Korean National Health Insurance Service between 2000 and 2019 were analyzed to evaluate trends in DM prevalence, healthcare utilization, mortality, and complications.
Results
Among 269,447 individuals, 18.6% (n=50,159/269,447) were diagnosed with DM and 27.0% (n=72,670/269,447) had impaired fasting glucose. The DM group had the highest body mass index, waist circumference, and prevalence of current smokers (P<0.001) but not the highest hypertension prevalence. From 2010 to 2019, the prevalence of DM and impaired fasting glucose increased from 15.5% to 21.9% and from 26.0% to 30.6%, respectively. Cancer-related mortality in DM was 1.15 times higher than in those with normal glucose tolerance (P<0.001), and cardiovascular disease-related mortality was 1.32 times higher (P<0.001); all mortalities were higher in female participants. Myocardial infarction (hazard ratio [HR], 1.34; P<0.001), stroke (HR, 1.24; P<0.001), and heart failure (HR, 1.13; P<0.001) were significantly higher in those with DM.
Conclusion
This is the first study to investigate the prevalence of DM and related complications in older individuals based on longterm representative data in Korea. These results highlight the necessity for targeted interventions to enhance management and outcomes in this population.

Citations

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Efficacy and safety of switching to ezetimibe 10 mg/rosuvastatin 2.5 mg in Korean patients with type 2 diabetes mellitus and dyslipidaemia: A multicentre, prospective study (EROICA study)
Sangmo Hong, Won J. Kim, Sungrae Kim, Jung H. Park, Eun S. Kang, Min K. Moon, Jae T. Kim, Ji‐Oh Mok, Ki Y. Lee, Cheol‐Young Park, Chang B. Lee
Diabetes, Obesity and Metabolism.2026; 28(2): 906. CrossRef

Hypothalamus and pituitary gland Big Data Articles (National Health Insurance Service Database)
Sex-Specific Cardiovascular Risks and Mortality in Patients with Panhypopituitarism: A Nationwide Cohort Study: Seung Shin Park, Hyunmook Jeong, Chang Ho Ahn, Min Jeong Park, Yong Hwy Kim, Kwangsoo Kim, Jung Hee Kim; Endocrinol Metab. 2025;40(3):469-483. Published online February 11, 2025; DOI: https://doi.org/10.3803/EnM.2024.2176

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Background
Panhypopituitarism is a condition of combined deficiency of multiple pituitary hormones, which requires lifelong hormone replacement therapy. Hormone deficiency or inadequate hormone replacement may contribute to cardiovascular disease. Here, we aimed to investigate the burden of cardiovascular, cerebrovascular diseases and mortality in patients with panhypopituitarism.
Methods
A total of 5,714 patients with panhypopituitarism were enrolled in the Korean National Health Insurance Service database from 2003 to 2020. Panhypopituitarism was defined according to the International Classification of Diseases, 10th Revision (ICD- 10) codes for hypopituitarism, pituitary adenoma, or craniopharyngioma and the continuous prescription of thyroid hormone and glucocorticoids. The risks of all-cause mortality, coronary artery disease (CAD), heart failure (HF), ischemic stroke, and intracranial hemorrhage were compared between patients with panhypopituitarism and age-, sex-, and index year-matched controls.
Results
The mean age of patients with panhypopituitarism and matched controls was 55.1 years, and men accounted for 51.5%. Patients with panhypopituitarism showed significantly higher all-cause mortality compared to matched controls after adjustment for covariates (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.95 to 2.43 in men and HR, 3.09; 95% CI, 2.78 to 3.44 in women). Additionally, there were higher risks of CAD, HF, ischemic stroke, and intracranial hemorrhage in both sexes, except for CAD in men.
Conclusion
Patients with panhypopituitarism have elevated risks of cardiovascular and cerebrovascular diseases as well as increased mortality. These risks are particularly prominent for all-cause mortality in women. Therefore, proactive monitoring for cardiovascular and cerebrovascular complications is required in patients with panhypopituitarism.

Citations

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Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions
Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2026; 41(1): 86. CrossRef

Thyroid
Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk: Nawoda Hewage, Udaya Wijesekara, Rasika Perera; Endocrinol Metab. 2024;39(6):864-876. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.2015

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Background
We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes.
Methods
This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese).
Results
The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk.
Conclusion
SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

Citations

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Increased Serum Lipopolysaccharide Levels are Related to a Higher Prevalent Risk of Subclinical Hypothyroidism
Xuan An, Xiaoyi Wang, Jin Zhang, Mingtong Xu, Muchao Wu, Suraiya Saleem
International Journal of Endocrinology.2025;[Epub] CrossRef
Incidence of Subclinical Hypothyroidism in Obese Adults and Its Metabolic Implications: A Prospective Cohort Study
Umer Jameel, Obaidullah Durrani, Ahmad Munib, Amanullah Khan
Cureus.2025;[Epub] CrossRef

Diabetes, obesity and metabolism
Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE): Nam Hoon Kim, Juneyoung Lee, Suk Chon, Jae Myung Yu, In-Kyung Jeong, Soo Lim, Won Jun Kim, Keeho Song, Ho Chan Cho, Hea Min Yu, Kyoung-Ah Kim, Sang Soo Kim, Soon Hee Lee, Chong Hwa Kim, Soo Heon Kwak, Yong‐ho Lee, Choon Hee Chung, Sihoon Lee, Heung Yong Jin, Jae Hyuk Lee, Gwanpyo Koh, Sang-Yong Kim, Jaetaek Kim, Ju Hee Lee, Tae Nyun Kim, Hyun Jeong Jeon, Ji Hyun Lee, Jae-Han Jeon, Hye Jin Yoo, Hee Kyung Kim, Hyeong-Kyu Park, Il Seong Nam-Goong, Seongbin Hong, Chul Woo Ahn, Ji Hee Yu, Jong Heon Park, Keun-Gyu Park, Chan Ho Park, Kyong Hye Joung, Ohk-Hyun Ryu, Keun Yong Park, Eun-Gyoung Hong, Bong-Soo Cha, Kyu Chang Won, Yoon-Sok Chung, Sin Gon Kim; Endocrinol Metab. 2024;39(5):722-731. Published online August 22, 2024; DOI: https://doi.org/10.3803/EnM.2024.1995

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Background
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Citations

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Ezetimibe attenuates diabetic retinopathy via NRF2-mediated suppression of inflammation and oxidative stress
Lei Cheng, Shan Cheng, Ran Zhu, Guoxu Xu
Journal of Diabetes and its Complications.2026; 40(2): 109250. CrossRef
Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review
Jakub Michal Zimodro, Manfredi Rizzo, Ioanna Gouni-Berthold
Pharmaceuticals.2025; 18(2): 147. CrossRef
Fenofibrate therapy and risk of heart failure outcomes in patients with Type 2 diabetes: a propensity-matched cohort study
Ji Yoon Kim, Nam Hoon Kim, Jiyoon Lee, Dong-Hoon Kim, Sin Gon Kim
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(7): 620. CrossRef
Beyond lipids: fenofibrate in diabetic retinopathy and nephropathy
Mengying Liu, Seok Ting Lim, Weihua Song, Thomas M. Coffman, Xiaomeng Wang
Trends in Pharmacological Sciences.2025;[Epub] CrossRef
Differential Pre‐ and Post‐Treatment Effects of Low‐Dose Antidyslipidemic Drugs on Gentamicin‐Induced Acute Nephrotoxicity in the Rat: A Histopathological and Biochemical Study
Pitchai Balakumar, Sultan Alshahrani, Noohu Abdulla Khan, Rajavel Varatharajan, K. M. Sundram
Journal of Applied Toxicology.2025;[Epub] CrossRef

Miscellaneous
Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress: Marie Rhee, Joonyub Lee, Eun Young Lee, Kun-Ho Yoon, Seung-Hwan Lee; Endocrinol Metab. 2024;39(3):511-520. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2023.1915

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Background
This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.
Methods
Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay.
Results
Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression.
Conclusion
Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

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Biochemical Pharmacology.2026; 244: 117615. CrossRef
Lipid dysregulation in renal cancer: Drivers of tumor growth and determinants of treatment-induced toxicity
Mohammed Alnukhali, Alessia Fornoni, Alan Pollack, Anis Ahmad
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A Review of Emerging Biomarkers Connecting Diabetes and Ischemic Stroke: Implications for Early Detection and Risk Stratification
Nadia Hussain, Azza Ramadan, Amal Hussain Ibrahim Al Haddad, Zina Alfahl, Kenneth Lo
Journal of Diabetes Research.2026;[Epub] CrossRef
Roles of Catecholamines and Inflammation in Endothelial Dysfunction: a Study Using Takotsubo Syndrome Patient-specific hiPSC-ECs
Guoqiang Yang, Luyi Zhong, Jiayue Wang, Chenyu Yang, Lukas Cyganek, Nazha Hamdani, Xiaobo Zhou, Xuehui Fan, Ibrahim El-Battrawy, Ibrahim Akin
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Jason S. Irei, Kai Hirayama, William A. Boisvert
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Association between triglyceride glucose index-related indices and kidney stones in adults based on NHANES 2007–2020
Ming Liu, Ping Yang, Yunpeng Gou
Frontiers in Endocrinology.2025;[Epub] CrossRef
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Hashum Sum, Alison C. Brewer
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Molecular Immunology.2025; 181: 66. CrossRef
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Hygerta Berisha, Reham Hattab, Laura Comi, Claudia Giglione, Silvia Migliaccio, Paolo Magni
Nutrients.2025; 17(5): 776. CrossRef
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Miscellaneous
Prediction of Cardiovascular Complication in Patients with Newly Diagnosed Type 2 Diabetes Using an XGBoost/GRU-ODE-Bayes-Based Machine-Learning Algorithm: Joonyub Lee, Yera Choi, Taehoon Ko, Kanghyuck Lee, Juyoung Shin, Hun-Sung Kim; Endocrinol Metab. 2024;39(1):176-185. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1739

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Background
Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea.
Methods
To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset.
Results
The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036).
Conclusion
GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.

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Norma Latif Fitriyani, Muhammad Syafrudin, Nur Chamidah, Marisa Rifada, Hendri Susilo, Dursun Aydin, Syifa Latif Qolbiyani, Seung Won Lee
Mathematics.2025; 13(13): 2194. CrossRef
Development and validation of a machine learning model for cardiovascular disease risk prediction in type 2 diabetes patients
Chunming Xu, Fachao Shi, Wenlong Ding, Cunming Fang, Caoyang Fang
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Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study: Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun; Endocrinol Metab. 2023;38(6):770-781. Published online November 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1726

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Background
Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m², and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

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Association of Serum Gamma-Glutamyltransferase with In-hospital Heart Failure in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
An-Cheng Hou, Jian-Tong Hou, Wei-Ning Zhou, Yan-Jin Wei, Zhi-Hong Ou, Cun-Fei Liu
Reviews in Cardiovascular Medicine.2025;[Epub] CrossRef
The J-shaped relationship between the gamma-glutamyltransferase to high-density lipoprotein cholesterol ratio and mortality risk in U.S. adults
Shujuan Qiu, Chunlei Li, Zhentao Guo
Preventive Medicine Reports.2025; 52: 102958. CrossRef
Association between the levels of gamma-glutamyl transpeptidase and the risk of stroke: systematic review and meta-analysis
Gustavo Adolfo Vásquez-Tirado, Stefany M. Nieto-Rivera, Claudia Vanessa Quispe-Castañeda, Edinson Dante Meregildo-Rodríguez, Leslie Jacqueline Liñán-Díaz, Wilson Marcial Guzmán-Aguilar
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Serum gamma-glutamyl transferase level is associated with the risk of pancreatic cystic neoplasms: A nationwide retrospective cohort study
Min Woo Lee, Jin Myung Park, In Rae Cho, Kwang Hyun Chung, Bong Seong Kim, Jin Ho Choi, Woo Hyun Paik, Ji Kon Ryu, Kyungdo Han, Sang Hyub Lee
World Journal of Gastroenterology.2025;[Epub] CrossRef
Interplay of serum biomarkers bilirubin and γ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus
Ebtesam Abdullah Al-Suhaimi, Abdullah Ahmed Al-Rubaish
World Journal of Diabetes.2024; 15(6): 1074. CrossRef

Diabetes, obesity and metabolism
Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study: Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Sang Min Lee, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki Won Oh, Sung Rae Cho, Young-Hoon Jeong, Eun-Jung Rhee; Endocrinol Metab. 2023;38(5):568-577. Published online October 10, 2023; DOI: https://doi.org/10.3803/EnM.2023.1770

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Background
Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.
Methods
We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.
Results
The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.
Conclusion
CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

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Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies
Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi
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Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

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Diabetes, Obesity and Metabolism
Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients: Ja Young Jeon, Shin Han-Bit, Bum Hee Park, Nami Lee, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, Seung Jin Han; Endocrinol Metab. 2023;38(1):139-145. Published online February 6, 2023; DOI: https://doi.org/10.3803/EnM.2022.1594

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Background
Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients.
Methods
We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model.
Results
Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE.
Conclusion
Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

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Kidney transplantation beyond immunosuppression: shifting the focus from graft survival to patient health
Gabriella Moroni, Francesco Reggiani, Claudio Ponticelli
Frontiers in Immunology.2026;[Epub] CrossRef
Computed tomography-based intermuscular adipose tissue analysis and its role in predicting post-kidney transplantation diabetes mellitus
Yang Feng, Yuechen Shi, Kexin Ma, Jiaming Xiao, Ming Liu, Yuqing Yi, Xiaoyu Zhang, Ke Wang, Zhenming Gao
Asian Journal of Surgery.2025; 48(1): 221. CrossRef
Prognostic impact of post-transplant diabetes mellitus in kidney allograft recipients: a meta-analysis
Mehmet Kanbay, Dimitrie Siriopol, Mustafa Guldan, Lasin Ozbek, Ahmet U Topcu, Ianis Siriopol, Katherine Tuttle
Nephrology Dialysis Transplantation.2025; 40(3): 554. CrossRef
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Vijaykumar D. Nimbarte, Shreya S. Sonak, Sharda Ishwarkar
Critical Reviews in Immunology.2025; 45(4): 43. CrossRef
Stratifying Post‐Transplant Diabetes: Prognostic Impact of Insulin Dependence and Treatment Duration
Beatriz Rodríguez‐Cubillo, Alejandro Morales, Rómulo Katsu, Yunaika Díaz Enamorado, M. Ángeles Moreno de la Higuera, Natividad Calvo Romero, María Muñiz, Arianne S. Aiffil, Cristina Riaza, Pilar Matía, Isabel Pérez‐Flores, Raquel Jiménez Ortego, Marina Pu
Clinical Transplantation.2025;[Epub] CrossRef
Management of Type 2 and Post-Transplant Diabetes in Kidney Transplant Recipients: A Single-Center Clinical Experience with GLP-1 Receptor Agonists and SGLT-2 Inhibitors
Ricardo E. T. Navarrete, Joana C. Freitas, Isabel Fonseca, Ana Cunha, Joao Roberto Sa, La Salete Martins
Diabetology.2025; 6(12): 158. CrossRef
Effect of post-transplant diabetes mellitus on cardiovascular events and mortality: a single‐center retrospective cohort study
Uğur Ünlütürk, Tolga Yıldırım, Merve Savaş, Seda Hanife Oğuz, Büşra Fırlatan, Deniz Yüce, Nesrin Damla Karakaplan, Cemile Selimova, Rahmi Yılmaz, Yunus Erdem, Miyase Bayraktar
Endocrine.2024; 85(2): 695. CrossRef
Prevalence of new-onset diabetes mellitus after kidney transplantation: a systematic review and meta-analysis
Qiufeng Du, Tao Li, Xiaodong Yi, Shuang Song, Jing Kang, Yunlan Jiang
Acta Diabetologica.2024; 61(7): 809. CrossRef
Safety and efficacy of semaglutide in post kidney transplant patients with type 2 diabetes or Post-Transplant diabetes
Moeber Mohammed Mahzari, Omar Buraykan Alluhayyan, Mahdi Hamad Almutairi, Mohammed Abdullah Bayounis, Yazeed Hasan Alrayani, Amir A. Omair, Awad Saad Alshahrani
Journal of Clinical & Translational Endocrinology.2024; 36: 100343. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2022;37(5):759-769. Published online October 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1515

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Background
This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death.
Methods
This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]–4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed.
Results
A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321).
Conclusion
Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

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Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study
Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Cardiovascular Diabetology.2023;[Epub] CrossRef

Review Article

Diabetes, Obesity and Metabolism
Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia: Joon Ho Moon, Kyuho Kim, Sung Hee Choi; Endocrinol Metab. 2022;37(4):575-586. Published online August 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.402

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High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

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Original Article

Diabetes, Obesity and Metabolism
High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging: Patcharapong Pantiya, Chanisa Thonusin, Natticha Sumneang, Benjamin Ongnok, Titikorn Chunchai, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Busarin Arunsak, Natthaphat Siri-Angkul, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn; Endocrinol Metab. 2022;37(4):630-640. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1430; Correction in: Endocrinol Metab 2025;40(4):657

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Background
High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.
Methods
Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.
Results
The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.
Conclusion
The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

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Review Articles

Adrenal Gland
Long-Term Outcomes of Congenital Adrenal Hyperplasia: Anna Nordenström, Svetlana Lajic, Henrik Falhammar; Endocrinol Metab. 2022;37(4):587-598. Published online July 8, 2022; DOI: https://doi.org/10.3803/EnM.2022.1528

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A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

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Diabetes, Obesity and Metabolism
Extra-Glycemic Effects of Anti-Diabetic Medications: Two Birds with One Stone?: Eun-Jung Rhee; Endocrinol Metab. 2022;37(3):415-429. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.304

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The world is suffering from a rapid increase in the number of people with diabetes due to the increased prevalence of obesity and lengthened life span. Since the development of insulin thanks to the efforts of Prof. Banting and Dr. Best in 1922, for which they won the Nobel Prize, remarkable developments in anti-diabetic medications have dramatically lengthened the lifespan of patients with diabetes. However, the control rate of hyperglycemia in patients with diabetes remains unsatisfactory, since glycemic control requires both medication and lifestyle modifications to slow the deterioration of pancreatic beta-cell function and prevent diabetic complications. From the initial “triumvirate” to the “ominous octet,” and now the “egregious eleven,” the number of organs recognized as being involved in hyperglycemia and diabetes has increased with the development of anti-diabetic medications. Recent unexpected results from outcome trials of anti-diabetic medications have enabled anti-diabetic medications to be indicated for the prevention of chronic kidney disease and heart failure, even in patients without diabetes. In this review, I would like to summarize the extra-glycemic effects of anti-diabetic medications.

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Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018: Eugene Han, Sun Ok Song, Hye Soon Kim, Kang Ju Son, Sun Ha Jee, Bong-Soo Cha, Byung-Wan Lee; Endocrinol Metab. 2022;37(3):466-474. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1440

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Background
Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate.
Methods
The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed.
Results
In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (p<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population.
Conclusion
The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes.

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Diabetes, Obesity and Metabolism
Comparative Study of Ex Vivo Antiplatelet Activity of Aspirin and Cilostazol in Patients with Diabetes and High Risk of Cardiovascular Disease: Sangmo Hong, Woo Je Lee, Cheol-Young Park; Endocrinol Metab. 2022;37(2):233-242. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1353

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Background
The role of aspirin in primary cardiovascular disease prevention in patients with diabetes remains controversial. However, some studies have suggested beneficial effects of cilostazol on cardiovascular disease in patients with diabetes. We prospectively investigated the antiplatelet effects of cilostazol compared with aspirin in patients with diabetes and cardiovascular risk factors.
Methods
We randomly assigned 116 patients with type 2 diabetes and cardiovascular risk factors but no evident cardiovascular disease to receive aspirin at a dose of 100 mg or cilostazol at a dose of 200 mg daily for 14 days. The primary efficacy outcome was antiplatelet effects of aspirin and cilostazol assessed with the VerifyNow system (aspirin response units [ARU]) and PFA-100 (closure time [CT]). Secondary outcomes were changes of clinical laboratory data (ClinicalTrials.gov Identifier: NCT02933788).
Results
After 14 days, there was greater decrease in ARU in aspirin (–28.9%±9.9%) compared cilostazol (–0.4%±7.1%, P<0.001) and was greater increase in CT in aspirin (99.6%±63.5%) compared cilostazol (25.7%±54.1%, P<0.001). The prevalence of aspirin resistance was 7.5% according to VerifyNow (defined by ARU ≥550) and 18.9% according to PFA-100 (CT <192 seconds). Compared with aspirin, cilostazol treatment was associated with increased high density lipoprotein cholesterol (7.1%±12.7% vs. 4.2%±18.0%, P=0.006) and decreased triglycerides (–9.4%±33.7% vs. 4.4%±17.57%, P=0.016). However, there were no significant changes in total and low density lipoprotein cholesterol, C-reactive protein level, and cluster of differentiation 40 ligand between cilostazol and aspirin groups.
Conclusion
Aspirin showed better antiplatelet effects assessed with VerifyNow and PFA-100 compared with cilostazol. However, there were favorable changes in atherogenic dyslipidemia only in the cilostazol.

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Namgok Lecture 2021

Diabetes, Obesity and Metabolism
The Influence of Obesity and Metabolic Health on Vascular Health: Eun-Jung Rhee; Endocrinol Metab. 2022;37(1):1-8. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2022.101

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The prevalence of obesity is rapidly increasing worldwide. Obesity should not be understood only as the accumulation of fat in the body, but instead as a phenomenon that exerts different effects on our health according to the place of fat deposition and its stability. Obesity is the starting point of most metabolic diseases, such as diabetes, hypertension, metabolic syndrome, sleep apnea, and eventually cardiovascular disease. There are different kinds of obesity, ranging from simple obesity to sarcopenic obesity. The main purpose of intervening to address obesity is to decrease the ultimate consequence of obesity—namely, cardiovascular disease. The main mechanism through which obesity, especially abdominal obesity, increases cardiovascular risk is the obesity-induced derangement of metabolic health, leading to the development of metabolic diseases such as diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, which are the main initiators of vascular damage. In this review, I discuss the influence of various types of obesity on the risk of metabolic diseases, and how these diseases increase cardiovascular disease risk.

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Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes: Seung-Hwan Lee, Kyungdo Han, Hyuk-Sang Kwon, Mee Kyoung Kim; Endocrinol Metab. 2021;36(5):1007-1015. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1218

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Background
Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods
Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results
The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for allcause mortality remained.
Conclusion
The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

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Diabetology & Metabolic Syndrome.2026;[Epub] CrossRef
Impact of cumulative exposure to a high TG to HDL-C ratio on type 2 diabetes risk in young adults
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Byeong Yun Ahn, Bokyung Kim, Sanghyun Park, Sang Gyun Kim, Kyungdo Han, Soo‐Jeong Cho
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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cardiovascular Outcomes of Obesity According to Menopausal Status: A Nationwide Population-Based Study: Bo Kyung Koo, Sang-Hyun Park, Kyungdo Han, Min Kyong Moon; Endocrinol Metab. 2021;36(5):1029-1041. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1197

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Background
We estimated the effect of obesity on the incidence of cardiovascular disease (CVD) and mortality in women according to menopausal status.
Methods
Women aged 40 to 69 years under routine health check-ups provided by the National Health Insurance Service in 2009 were followed up till 2018 (n=2,208,559).
Results
In premenopausal women, a significant increment of mortality rate was found in underweight and obesity class II (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.67; and HR, 1.25; 95% CI, 1.12 to 1.39) compared to normal body mass index (BMI); overweight and obesity class I did not affect mortality rate. In postmenopausal women, obesity as well as overweight status reduced the risk of mortality compared to normal BMI (HR, 0.86; 95% CI, 0.83 to 0.88; and HR, 0.84; 95% CI, 0.82 to 0.86). By contrast, there was a linear association between CVD and BMI above the normal range irrespective of menopausal status, which was attenuated in diabetic women.
Conclusion
The current study replicated the J-shaped relationship between BMI and mortality, being more prominent in the postmenopausal group. The risk of CVD was linearly increased as BMI was increased above the normal range irrespective of menopausal status.

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Review Article

Diabetes
Cardiorenal Protection in Diabetic Kidney Disease: Jason F. Lee, Ecaterina Berzan, Vikas S. Sridhar, Ayodele Odutayo, David Z.I. Cherney; Endocrinol Metab. 2021;36(2):256-269. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2021.987

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Over the last 5 years there have been many new developments in the management of diabetic kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially used for glycemic control, but more recent studies have now shown that their benefits extend to cardiovascular and kidney outcomes. The recent addition of data on the novel mineralocorticoid receptor antagonist (MRA) gives us another approach to further decrease the residual risk of diabetic kidney disease progression. In this review we describe the mechanism of action, key studies, and possible adverse effects related to these three classes of medications. The management of type 2 diabetes now includes an increasing number of medications for the management of comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors, GLP-1 RA and MRAs in patients with type 2 diabetes for heart and kidney protection.

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Original Article

Clinical Study Big Data Articles (National Health Insurance Service Database)
Effect of Teneligliptin versus Sulfonylurea on Major Adverse Cardiovascular Outcomes in People with Type 2 Diabetes Mellitus: A Real-World Study in Korea: Da Hea Seo, Kyoung Hwa Ha, So Hun Kim, Dae Jung Kim; Endocrinol Metab. 2021;36(1):70-80. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.777

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Background
Results regarding the cardiovascular (CV) effects of dipeptidyl peptidase-4 (DPP-4) inhibitors are inconsistent. This study aimed to assess the effects of teneligliptin, a DPP-4 inhibitor, on the risk of major CV outcomes in type 2 diabetes mellitus (T2DM) patients compared to sulfonylurea.
Methods
From January 1, 2015 to December 31, 2017, we conducted a retrospective cohort study using the Korean National Health Insurance Service database. A total of 6,682 T2DM patients who were newly prescribed DPP-4 inhibitors or sulfonylurea were selected and matched in a 1:1 ratio by propensity score. The hazard ratios (HRs) for all-cause mortality, hospitalization for heart failure (HHF), all-cause mortality or HHF, myocardial infarction (MI), stroke, and hypoglycemia were assessed.
Results
During 641 days of follow-up, the use of teneligliptin was not associated with an increased risk of all-cause mortality (HR, 1.00; 95% confidence interval [CI], 0.85 to 1.19), HHF (HR, 0.99; 95% CI, 0.86 to 1.14), all-cause mortality or HHF (HR, 1.02; 95% CI, 0.90 to 1.14), MI (HR, 0.90; 95% CI, 0.68 to 1.20), and stroke (HR, 1.00; 95% CI, 0.86 to 1.17) compared to the use of sulfonylurea. However, it was associated with a significantly lower risk of hypoglycemia (HR, 0.68; 95% CI, 0.49 to 0.94) compared to sulfonylurea therapy.
Conclusion
Among T2DM patients, teneligliptin therapy was not associated with an increased risk of CV events including HHF, but was associated with a lower risk of hypoglycemia compared to sulfonylurea therapy.

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Review Article

Obesity and Metabolism
Metabolically Healthy and Unhealthy Normal Weight and Obesity: Norbert Stefan; Endocrinol Metab. 2020;35(3):487-493. Published online August 20, 2020; DOI: https://doi.org/10.3803/EnM.2020.301

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Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted.

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Original Articles

Clinical Study
Association of Body Mass Index with the Risk of Incident Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality: A Community-Based Prospective Study: Ji Cheol Bae, Nam H. Cho, Jae Hyeon Kim, Kyu Yeon Hur, Sang-Man Jin, Moon-Kyu Lee; Endocrinol Metab. 2020;35(2):416-424. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.416

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Background
Type 2 diabetes and cardiovascular disease (CVD) are the most important sequelae of obesity and the leading cause of death. We evaluated the association between body mass index (BMI) and the risk of incident type 2 diabetes, CVD, and all-cause mortality in a prospective study of a Korean population.
Methods
The shapes of the associations were modeled by restricted cubic splines regression analysis. After categorizing all subjects (n=8,900) into octiles based on their BMI levels, we estimated the hazard ratio (HR) for the association of categorized BMI levels with the risk of incident CVD and type 2 diabetes using a Cox’s proportional hazard analysis.
Results
The mean age of participants was 52 years and 48% were men. Of the subjects at baseline, 39.0% of men and 45.6% of women were classified as obese (BMI ≥25 kg/m²). Over a mean follow-up of 8.1 years, CVD events occurred in 509 participants; 436 died; and 1,258 subjects developed type 2 diabetes. The increased risk of incident diabetes began to be significant at BMI 23 to 24 kg/m² in both sexes (HR, 1.8). For CVD events, the risk began to increase significantly at BMI 26 to 28 kg/m² (HR, 1.6). We found a reverse J-shaped relationship between BMI and all-cause mortality, with an increased risk among individuals with BMI values in lower range (BMI <21 kg/m²).
Conclusion
These results suggest that the BMI cut-off points for observed risk were varied depending on the diseases and that the BMI classification of obesity need to be revised to reflect differential risk of obesity-related diseases.

Citations

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Effect of body mass index change on the development of diabetes mellitus
Masahiro Okano, Teruki Miyake, Shinya Furukawa, Osamu Yoshida, Yoshimasa Murakami, Ayumi Kanamoto, Masumi Miyazaki, Akihito Shiomi, Hironobu Nakaguchi, Yasunori Yamamoto, Yoshio Tokumoto, Masashi Hirooka, Teru Kumagi, Eiji Takesita, Yoshio Ikeda, Masanori
Endocrine Journal.2026; 73(2): 183. CrossRef
Predicting Metabolic and Cardiovascular Healthy from Nutritional Patterns and Psychological State Among Overweight and Obese Young Adults: A Neural Network Approach
Geovanny Genaro Reivan Ortiz, Laura Maraver-Capdevila, Roser Granero
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Hui Luo, Yesong Liu, Xue Tian, Yuhan Zhao, Lulu Liu, Zemeng Zhao, Lili Luo, Yanmin Zhang, Xiaozhong Jiang, Yeqiang Liu, Yanxia Luo, Anxin Wang
International Journal of Obesity.2024; 48(2): 263. CrossRef
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Anna Ramírez-Morros, Josep Franch-Nadal, Jordi Real, Queralt Miró-Catalina, Magdalena Bundó, Bogdan Vlacho, Didac Mauricio
Frontiers in Endocrinology.2024;[Epub] CrossRef
Research Progress on the Association and Mechanism between Obesity and Prostate Cancer
娜古丽·艾海提热
Advances in Clinical Medicine.2024; 14(04): 1941. CrossRef
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Ichiro Tatsuno, Laetitia Gerlier, Anamaria-Vera Olivieri, James Baker-Knight, Mark Lamotte
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Yaying Chen, Mengqian Guan, Ruiqi Wang, Xuewen Wang
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Body mass index at baseline directly predicts new-onset diabetes and to a lesser extent incident cardio-cerebrovascular events, but has a J-shaped relationship to all-cause mortality
Yoon-Jong Bae, Sang-Jun Shin, Hee-Taik Kang
BMC Endocrine Disorders.2022;[Epub] CrossRef
Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults
Chul Woo Ahn, Sungjae Shin, Seunghyun Lee, Hye-Sun Park, Namki Hong, Yumie Rhee
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M. L. Tang, Y. Q. Zhou, A. Q. Song, J. L. Wang, Y. P. Wan, R. Y. Xu, Carol Forsblom
Journal of Diabetes Research.2021; 2021: 1. CrossRef
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Manal Sabry Mohamed, Tarek Mohammed Youssef, Esraa Ebrahim Abdullah, Ahmed Elmetwally Ahmed
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Clinical Study
Subclinical Hypothyroidism Affects the Long-Term Outcomes of Patients Who Undergo Coronary Artery Bypass Grafting Surgery but Not Heart Valve Surgery: Hana Kim, Sung Hye Kong, Jae Hoon Moon, Sang Yoon Kim, Kay-Hyun Park, Jun Sung Kim, Joong Haeng Choh, Young Joo Park, Cheong Lim; Endocrinol Metab. 2020;35(2):308-318. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.308

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174 Download
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Background
The aim of this study was to determine the associations between subclinical hypothyroidism (SCH) and long-term cardiovascular outcomes after coronary artery bypass grafting (CABG) or heart valve surgery (HVS).
Methods
We retrospectively reviewed and compared all-cause mortality, cardiovascular mortality, and cardiovascular events in 461 patients who underwent CABG and 104 patients who underwent HVS.
Results
During a mean±standard deviation follow-up duration of 7.6±3.8 years, there were 187 all-cause deaths, 97 cardiovascular deaths, 127 major adverse cardiovascular events (MACE), 11 myocardial infarctions, one unstable angina, 70 strokes, 30 hospitalizations due to heart failure, 101 atrial fibrillation, and 33 coronary revascularizations. The incidence of all-cause mortality after CABG was significantly higher in patients with SCH (n=36, 55.4%) than in euthyroid patients (n=120, 30.3%), with a hazard ratio of 1.70 (95% confidence interval, 1.10 to 2.63; P=0.018) after adjustment for age, sex, current smoking status, body mass index, underlying diseases, left ventricular dysfunction, and emergency operation. Interestingly, low total triiodothyronine (T3) levels in euthyroid patients who underwent CABG were significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and MACE, but those associations were not observed in HVS patients. Both free thyroxine and thyroid-stimulating hormone levels in euthyroid patients were not related with any cardiovascular outcomes in either the CABG or HVS group.
Conclusion
SCH or low total T3 might be associated with a poor prognosis after CABG, but not after HVS, implying that preoperative thyroid hormonal status may be important in ischemic heart disease patients.

Citations

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Subclinical Hypothyroidism as a Risk for Coronary Artery Bypass Grafting
Ricardo Mendes Martins, Felipe José M. Pittella, Beatriz C. de Oliveira, Bernardo G. S. Lima, Caio C. Ferreira, Aline D. Pereira, Wolney A. Martins, Rubens A. C. Filho, Giovanna A. B. Lima, Muhammad Riaz
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Subclinical hypothyroidism and clinical outcomes after cardiac surgery: A systematic review and meta-analysis
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Impact of subclinical hypothyroidism on outcomes after coronary artery bypass grafting: a systematic review and meta-analysis
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Jiun-Yu Lin, Pei-Chi Kao, Yi-Ting Tsai, Chi-Hsiang Chung, Wu-Chien Chien, Chih-Yuan Lin, Chieh-Hua Lu, Chien-Sung Tsai
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Patrick Müller, Melvin Khee-Shing Leow, Johannes W. Dietrich
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Review Articles

Obesity and Metabolism
Effects of Cardiovascular Risk Factor Variability on Health Outcomes: Seung-Hwan Lee, Mee Kyoung Kim, Eun-Jung Rhee; Endocrinol Metab. 2020;35(2):217-226. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.217

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Innumerable studies have suggested “the lower, the better” for cardiovascular risk factors, such as body weight, lipid profile, blood pressure, and blood glucose, in terms of health outcomes. However, excessively low levels of these parameters cause health problems, as seen in cachexia, hypoglycemia, and hypotension. Body weight fluctuation is related to mortality, diabetes, obesity, cardiovascular disease, and cancer, although contradictory findings have been reported. High lipid variability is associated with increased mortality and elevated risks of cardiovascular disease, diabetes, end-stage renal disease, and dementia. High blood pressure variability is associated with increased mortality, myocardial infarction, hospitalization, and dementia, which may be caused by hypotension. Furthermore, high glucose variability, which can be measured by continuous glucose monitoring systems or self-monitoring of blood glucose levels, is associated with increased mortality, microvascular and macrovascular complications of diabetes, and hypoglycemic events, leading to hospitalization. Variability in metabolic parameters could be affected by medications, such as statins, antihypertensives, and hypoglycemic agents, and changes in lifestyle patterns. However, other mechanisms modify the relationships between biological variability and various health outcomes. In this study, we review recent evidence regarding the role of variability in metabolic parameters and discuss the clinical implications of these findings.

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Calcium and Cardiovascular Disease: Ian R. Reid, Sarah M. Birstow, Mark J. Bolland; Endocrinol Metab. 2017;32(3):339-349. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.339

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Circulating calcium is a risk factor for vascular disease, a conclusion arising from prospective studies involving hundreds of thousands of participants and extending over periods of up to 30 years. These associations may be partially mediated by other cardiovascular risk factors such as circulating lipid levels, blood pressure, and body mass index, but there appears to be a residual independent effect of serum calcium. Polymorphisms of the calcium-sensing receptor associated with small elevations of serum calcium are also associated with cardiovascular disease, suggesting that calcium plays a causative role. Trials of calcium supplements in patients on dialysis and those with less severe renal failure demonstrate increased mortality and/or acceleration of vascular disease, and meta-analyses of trials in those without overt renal disease suggest a similar adverse effect. Interpretation of the latter trials is complicated by a significant interaction between baseline use of calcium supplements and the effect of randomisation to calcium in the largest trial. Restriction of analysis to those who are calcium-naive demonstrates a consistent adverse effect. Observational studies of dietary calcium do not demonstrate a consistent adverse effect on cardiovascular health, though very high or very low intakes may be deleterious. Thus, obtaining calcium from the diet rather than supplements is to be encouraged.

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Endocrinology and Metabolism.2018; 33(4): 485. CrossRef

Original Article

Clinical Study
Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes: Hye Won Lee, A Ra Jo, Dong Won Yi, Yang Ho Kang, Seok Man Son; Endocrinol Metab. 2016;31(4):577-585. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.577

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Background

Nonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD) event in Korean patients with type 2 diabetes mellitus (T2DM).

Methods

Laboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events.

Results

Nonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR) and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m², and albuminuria.

Conclusion

The results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.

Citations

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European Journal of Medical Research.2021;[Epub] CrossRef
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Soluble Dipeptidyl Peptidase-4 Levels Are Associated with Decreased Renal Function in Patients with Type 2 Diabetes Mellitus
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Diabetes & Metabolism Journal.2019; 43(1): 97. CrossRef
STORIA NATURALE DELLA MALATTIA RENALE NEL DIABETE E TRATTAMENTO DELL’IPERGLICEMIA NEI PAZIENTI CON DIABETE DI TIPO 2 E RIDOTTA FUNZIONE RENALE

il Diabete.2019;[Epub] CrossRef
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Won-Young Lee
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Nonalbuminuric Renal Insufficiency: Can It Be a Novel Category of Diabetic Nephropathy?
Masami Tanaka, Hiroshi Itoh
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Review Article

Obesity and Metabolism
Diabetes Drugs and Cardiovascular Safety: Ji Cheol Bae; Endocrinol Metab. 2016;31(2):239-244. Published online June 10, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.239

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Abstract PDF PubReader

Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

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Original Article

Clinical Study
Characterization of Patients with Type 2 Diabetes according to Body Mass Index: Korea National Health and Nutrition Examination Survey from 2007 to 2011: Dong-Hwa Lee, Kyong Yeun Jung, Kyeong Seon Park, Kyoung Min Kim, Jae Hoon Moon, Soo Lim, Hak Chul Jang, Sung Hee Choi; Endocrinol Metab. 2015;30(4):514-521. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.514

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Background

The present study aimed to investigate the clinical characteristics of type 2 diabetes mellitus (T2DM) in Korean adults according to body mass index (BMI) and to analyze the association with cardiovascular disease (CVD).

Methods

We conducted a cross-sectional study of data from the Korea National Health and Nutrition Examination Survey from 2007 to 2011. A total of 3,370 patients with T2DM were divided into categories according to BMI. We conducted a comparison of the T2DM patient population composition by BMI category between different countries. We investigated the prevalence of awareness, treatment, and target control of T2DM according to BMI.

Results

Patients with T2DM had a higher BMI, and were more likely to have a history of CVD than healthy controls. For Korean adults with T2DM, 8% had BMI ≥30 kg/m². By contrast, the population of patients with T2DM and BMI ≥30 kg/m² was 72% in patients in the USA and 56% in the UK. The rate of recognition, treatment, and control has worsened in parallel with increasing BMI. Even in patients with BMI 25 to 29.9 kg/m², the prevalence of CVD or high risk factors for CVD was significantly higher than in patients with BMI 18.5 to 22.9 kg/m² (odds ratio, 2.07).

Conclusion

Korean patients with T2DM had lower BMI than those in Western countries. Higher BMI was associated with lower awareness, treatment, and control of diabetes, and a positive association was observed between CVD or high risk factors for CVD and BMI, even for patients who were overweight but not obese.

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Review Article

Thyroid
Subclinical Hypothyroidism and Cardiovascular Disease: Sunghwan Suh, Duk Kyu Kim; Endocrinol Metab. 2015;30(3):246-251. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.246

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Subclinical hypothyroidism (SCH) is a common disorder that is characterized by elevated thyroid-stimulating hormone levels in conjunction with free thyroxine concentrations within the normal reference range. Thyroid hormones are known to affect the heart and vasculature and, as a result, the impact of SCH on the cardiovascular (CV) system has recently become an important topic of research. Strong evidence points to a link between SCH and CV risk factors such as alterations in blood pressure, lipid levels, and atherosclerosis. Additionally, accumulating evidence indicates that SCH is associated with metabolic syndrome and heart failure. The present review proposes that SCH may be a potentially modifiable risk factor of CV disease and mortality. However, large-scale clinical trials with appropriate power investigating the risks and benefits of SCH treatment are required to determine whether these benefits can be achieved with levothyroxine therapy.

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Original Articles

Obesity and Metabolism
Apolipoprotein B Is Related to Metabolic Syndrome Independently of Low Density Lipoprotein Cholesterol in Patients with Type 2 Diabetes: Younghyup Lim, Soyeon Yoo, Sang Ah Lee, Sang Ouk Chin, Dahee Heo, Jae Cheol Moon, Shinhang Moon, Kiyoung Boo, Seong Taeg Kim, Hye Mi Seo, Hyeyoung Jwa, Gwanpyo Koh; Endocrinol Metab. 2015;30(2):208-215. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.208

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Background

Increased low density lipoprotein cholesterol (LDL-C) level and the presence of metabolic syndrome (MetS) are important risk factors for cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an independent predictor of the development of CVD especially in patients with T2DM. The aim of this study was to investigate the relationship between apoB and MetS in T2DM patients.

Methods

We analyzed 912 patients with T2DM. Fasting blood samples were taken for glycated hemoglobin, high-sensitivity C-reactive protein, total cholesterol, triglyceride (TG), high density lipoprotein cholesterol, LDL-C, and apoB. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria. We performed a hierarchical regression analysis with apoB as the dependent variable. Age, sex, the number of components of MetS and LDL-C were entered at model 1, the use of lipid-lowering medications at model 2, and the individual components of MetS were added at model 3.

Results

Seventy percent of total subjects had MetS. ApoB level was higher in subjects with than those without MetS (104.5±53.3 mg/dL vs. 87.7±33.7 mg/dL, P<0.01) even after adjusting for LDL-C. ApoB and LDL-C were positively correlated to the number of MetS components. The hierarchical regression analysis showed that the increasing number of MetS components was associated with higher level of apoB at step 1 and step 2 (β=0.120, P<0.001 and β=0.110, P<0.001, respectively). At step 3, TG (β=0.116, P<0.001) and systolic blood pressure (β=0.099, P<0.05) were found to significantly contribute to apoB.

Conclusion

In patients with T2DM, apoB is significantly related to MetS independently of LDL-C level. Of the components of MetS, TG, and systolic blood pressure appeared to be determinants of apoB.

Citations

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Obesity and Metabolism
Sex Factors in the Metabolic Syndrome as a Predictor of Cardiovascular Disease: Sunghwan Suh, Jongha Baek, Ji Cheol Bae, Kyoung-Nyoun Kim, Mi Kyoung Park, Duk Kyu Kim, Nam H. Cho, Moon-Kyu Lee; Endocrinol Metab. 2014;29(4):522-529. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.522

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Background

Metabolic syndrome (MetS) is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD.

Methods

A total of 8,898 subjects (4,241 males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up).

Results

The prevalence of MetS at baseline was 22.0% (932/4,241) and 29.7% (1,383/4,657) in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95% confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females) and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females). Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192). Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk.

Conclusion

MetS is a significant risk factor for the development of CVD although its impact varies between sexes.

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Review Article

Obesity and Metabolism
Metabolic and Cardiovascular Implications of a Metabolically Healthy Obesity Phenotype: Mi Hae Seo, Eun-Jung Rhee; Endocrinol Metab. 2014;29(4):427-434. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.427

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Metabolically healthy obesity (MHO) is a new concept in which an individual may exhibit an obese phenotype in the absence of any metabolic abnormalities. There are a number of definitions of MHO that utilize a variety of components. The findings of clinical and basic studies indicate that subjects with MHO do not exhibit an increased mortality, an increased risk of cardiovascular disease, or an increased risk of type 2 diabetes mellitus, as compared to normal-weight controls. Although these findings imply that metabolic health is a more important factor than obesity, several studies have shown that subjects with MHO have a similar risk of metabolic or cardiovascular diseases as those with metabolically unhealthy obesity. Thus, there is still debate regarding not only the implications of the MHO phenotype but its very existence. Accordingly, future studies should focus on developing a unified definition of MHO and distinguishing subjects who will be at a high risk for metabolic and cardiovascular diseases.

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