Endocrinology and Metabolism

Original Articles

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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Abstract PDF Supplementary Material PubReader ePub: 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.

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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Abstract PDF Supplementary Material PubReader ePub: 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.

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study: Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park; Endocrinol Metab. 2021;36(3):628-636. Published online May 26, 2021; DOI: https://doi.org/10.3803/EnM.2020.948

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Background
To investigate the clinical characteristics of gestational diabetes mellitus (GDM) in Korea, using a nationwide database.
Methods
We analyzed 417,139 women who gave birth between 2011 and 2015 using the Korean National Health Information Database. They underwent the Korean National Health Screening Program within one year before pregnancy and were not prescribed drugs for diabetes nor diagnosed with diabetes mellitus before 280 days antepartum. Patients with GDM were defined as those who visited the outpatient clinic more than twice with GDM codes.
Results
The prevalence of GDM was 12.70% and increased with increasing maternal age, prepregnancy body mass index (BMI), waist circumference (WC), and fasting plasma glucose (FPG) (P for trend <0.05). As compared with those aged <25 years, the odds ratio for women with GDM aged ≥40 years were 4.804 (95% confidence interval [CI], 4.436 to 5.203) after adjustment for covariates. Women with prepregnancy BMI ≥30 kg/m² were at 1.898 times (95% CI, 1.736 to 2.075) greater risk for GDM than those with prepregnancy BMI <18.5 kg/m². Women with WC of ≥95 cm were at 1.158 times (95% CI, 1.029 to 1.191) greater risk for GDM than women with WC of less than 65 cm. High FPG, high income, smoking, and drinking were associated with an elevated risk of GDM.
Conclusion
The prevalence of GDM in Korean women increased up to 12.70% during 2011 to 2015. These data suggest the importance of GDM screening and prevention in high-risk groups in Korea.

Citations

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Relationships between triglyceride-glucose index and incident gestational diabetes mellitus: a prospective cohort study of a Korean population using publicly available data
Zihe Mo, Changchun Cao, Yong Han, Haofei Hu, Yongcheng He, Xin Zuo
Frontiers in Public Health.2024;[Epub] CrossRef
Glucose tolerance test with a single abnormal value as a predictor of type 2 diabetes mellitus: a multicenter retrospective study
Seon Ui Lee, Subeen Hong, Sae Kyung Choi, Su Mi Kim, Jae Eun Shin, Ki Cheol Kil, Yeon Hee Kim, Jeong Ha Wie, Yun Sung Jo, Hyun Sun Ko
Scientific Reports.2024;[Epub] CrossRef
Exploring the influence of microbiota on gestational diabetes and its potential as a biomarker
Suresh Bokoliya, Stephanie McClellan, Yanjiao Zhou, Nini Fan
Frontiers in Bacteriology.2024;[Epub] CrossRef
Serum afamin levels in predicting gestational diabetes mellitus and preeclampsia: A systematic review and meta-analysis
Ying Yuan, Wenyin He, Xuejiao Fan, Junyu Liang, Zhen Cao, Lei Li
Frontiers in Endocrinology.2023;[Epub] CrossRef
Smoking during pregnancy and gestational diabetes mellitus: a systematic review and meta-analysis
Kleoniki I. Athanasiadou, Stavroula A. Paschou, Evgenia Papakonstantinou, Vasiliki Vasileiou, Fotini Kanouta, Paraskevi Kazakou, Katerina Stefanaki, Georgia N. Kassi, Theodora Psaltopoulou, Dimitrios G. Goulis, Eleni Anastasiou
Endocrine.2023; 82(2): 250. CrossRef
Association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of gestational diabetes mellitus: a second analysis based on data from a prospective cohort study
Yun You, Haofei Hu, Changchun Cao, Yong Han, Jie Tang, Weihua Zhao
Frontiers in Endocrinology.2023;[Epub] CrossRef
Effects of early standardized management on the growth trajectory of offspring with gestational diabetes mellitus at 0–5 years old: a preliminary longitudinal study
Bingbing Guo, Jingjing Pei, Yin Xu, Yajie Wang, Xinye Jiang
Scientific Reports.2023;[Epub] CrossRef
The Benefits Of Continuous Glucose Monitoring In Pregnancy
Jee Hee Yoo, Jae Hyeon Kim
Endocrinology and Metabolism.2023; 38(5): 472. CrossRef
Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications
Joon Ho Moon, Hak Chul Jang
Diabetes & Metabolism Journal.2022; 46(1): 3. CrossRef
Current Trends of Big Data Research Using the Korean National Health Information Database
Mee Kyoung Kim, Kyungdo Han, Seung-Hwan Lee
Diabetes & Metabolism Journal.2022; 46(4): 552. CrossRef
Maternal Gestational Diabetes Influences DNA Methylation in the Serotonin System in the Human Placenta
Jae Yen Song, Kyung Eun Lee, Eun Jeong Byeon, Jieun Choi, Sa Jin Kim, Jae Eun Shin
Life.2022; 12(11): 1869. CrossRef
Fetal Abdominal Obesity Detected At 24 to 28 Weeks of Gestation Persists Until Delivery Despite Management of Gestational Diabetes Mellitus (Diabetes Metab J 2021;45:547-57)
Kyung-Soo Kim
Diabetes & Metabolism Journal.2021; 45(6): 966. CrossRef

Clinical Study
Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study: Jong Dai Kim, Dong-Mee Lim, Keun-Young Park, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Won-Young Lee, Ki Won Oh; Endocrinol Metab. 2020;35(3):610-617. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.721

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Background
It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes.
Methods
Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis.
Results
The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=–0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006).
Conclusion
Transferrin is positively associated with incident type 2 diabetes in Koreans.

Citations

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Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes
Xingyue Wang, You Wang, Junjie Hou, Hongyang Liu, Rong Zeng, Xiangyu Li, Mei Han, Qingrun Li, Linong Ji, Desi Pan, Weiping Jia, Wen Zhong, Tao Xu
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Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes
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Association between systemic iron status and β-cell function and insulin sensitivity in patients with newly diagnosed type 2 diabetes
Yao Qin, Yiting Huang, Yuxiao Li, Lu Qin, Qianying Wei, Xin Chen, Chuanhui Yang, Mei Zhang
Frontiers in Endocrinology.2023;[Epub] CrossRef
Association of Body Iron Metabolism with Type 2 Diabetes Mellitus in Chinese Women of Childbearing Age: Results from the China Adult Chronic Disease and Nutrition Surveillance (2015)
Jie Feng, Xiaoyun Shan, Lijuan Wang, Jiaxi Lu, Yang Cao, Lichen Yang
Nutrients.2023; 15(8): 1935. CrossRef
Serum Level of Ceruloplasmin, Angiotensin-Converting Enzyme and Transferrin as Markers of Severity in SARS-CoV-2 Infection in Patients with Type 2 Diabetes
Patricia-Andrada Reștea, Ștefan Țigan, Laura Grațiela Vicaș, Luminița Fritea, Eleonora Marian, Tunde Jurca, Annamaria Pallag, Iulius Liviu Mureșan, Corina Moisa, Otilia Micle, Mariana Eugenia Mureșan
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Clinical Study
Serum Adiponectin and Progranulin Level in Patients with Benign Thyroid Nodule or Papillary Thyroid Cancer: Hyemi Kwon, Se Eun Park, Ji-Sup Yun, Cheol-Young Park; Endocrinol Metab. 2020;35(2):396-406. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.396

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Background
Obesity is associated with thyroid cancer risk. Adiponectin has insulin-sensitizing and anti-inflammatory effects, while progranulin is associated with inflammation and tumorigenesis. We investigated serum adiponectin and progranulin levels in patients with benign thyroid nodule (benign group) and papillary thyroid cancer (PTC; PTC group). The associations between these levels and the clinicopathological features of PTC were evaluated.
Methods
We included 157 patients who underwent thyroid surgery (17% of benign and 83% of PTC group). Clinicopathological features including size, lymph node metastasis, extrathyroidal extension (ETE), multifocality, American Thyroid Association risk stratification were evaluated.
Results
The age was 42.0 years, and 69% were female. Serum adiponectin and progranulin levels were 6.3 μg/mL and 101.5 ng/mL in the benign group and 5.4 μg/mL and 106.1 ng/mL in the PTC group, respectively (P=0.6 and P=0.4, respectively). Serum adiponectin levels showed no significant differences according to clinicopathological features of PTC. The proportions of patients with primary tumor size >1 cm were 3%, 5%, 8%, and 8% according to serum progranulin level quartiles, respectively (P=0.03). The proportions of patients with microscopic/gross ETE were 8%/0%, 9%/1%, 11%/1%, and 11%/2% according to serum progranulin level quartiles, respectively. Median serum progranulin level was significantly higher in patients with PTC >1 cm than in patients with papillary thyroid microcarcinoma (P=0.04, 115.3 ng/mL and 104.7 ng/mL, respectively).
Conclusion
Serum adiponectin and progranulin levels showed no significant difference between benign and PTC groups. Increased serum progranulin levels were significantly associated with PTC >1 cm and microscopic and gross ETE.

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Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancers—a systematic review
Lucas Fornari Laurindo, Andreline Franchi Sosin, Caroline Barbalho Lamas, Ricardo de Alvares Goulart, Jesselina Francisco dos Santos Haber, Claudia Rucco Penteado Detregiachi, Sandra Maria Barbalho
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Adiponectin Inhibits the Progression of Obesity-Associated Papillary Thyroid Carcinoma Through Autophagy
Changlin Li, Jiao Zhang, Gianlorenzo Dionigi, Nan Liang, Haixia Guan, Hui Sun
Endocrinology.2024;[Epub] CrossRef
Progranulin Oncogenic Network in Solid Tumors
Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. Iozzo, Antonio Giordano, Andrea Morrione
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Obesity and thyroid cancer risk
Lauren C. Burrage, Donald S.A. McLeod, Susan J. Jordan
Current Opinion in Endocrinology, Diabetes & Obesity.2023; 30(5): 244. CrossRef
Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma
Yanxu Dong, Hao Tan, Lidong Wang, Zhen Liu
Cancer Cell International.2023;[Epub] CrossRef
Obesity and Thyroid Cancer Risk: An Update
Fabiana Franchini, Giuseppe Palatucci, Annamaria Colao, Paola Ungaro, Paolo Emidio Macchia, Immacolata Cristina Nettore
International Journal of Environmental Research and Public Health.2022; 19(3): 1116. CrossRef
Obesity and Overweight Are Associated with Minimal Extrathyroidal Extension, Multifocality and Bilaterality of Papillary Thyroid Cancer
Krzysztof Kaliszewski, Dorota Diakowska, Marta Rzeszutko, Jerzy Rudnicki
Journal of Clinical Medicine.2021; 10(5): 970. CrossRef
Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity
Yuanyuan Zhou, Ying Yang, Taicheng Zhou, Bai Li, Zhanjian Wang
Aging and disease.2021; 12(2): 597. CrossRef

Endocrine Research
Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and Causes β-Cell Impairment via Mitochondrial Dysregulation: Seok-Woo Hong, Jinmi Lee, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2018;33(3):403-412. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.403

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Background

Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB).

Methods

We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels.

Results

Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused β-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved β-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends.

Conclusion

Altogether, these data suggest that S1P is an essential factor in the maintenance of β-cell function and survival through its regulation of mitochondrial action and PHB expression.

Citations

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Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology
Petr Ježek, Martin Jabůrek, Blanka Holendová, Hana Engstová, Andrea Dlasková
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Sphingolipids in mitochondria—from function to disease
Maryam Jamil, Lauren Ashley Cowart
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Sphingosine‐1‐phosphate in mitochondrial function and metabolic diseases
Meng Duan, Pan Gao, Sheng‐xi Chen, Petr Novák, Kai Yin, Xiao Zhu
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Involvement of miR‐27a‐3p in diabetic nephropathy via affecting renal fibrosis, mitochondrial dysfunction, and endoplasmic reticulum stress
Lina Wu, Qingzhu Wang, Feng Guo, Xiaojun Ma, Jiao Wang, Yanyan Zhao, Yushan Yan, Guijun Qin
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Sphingosine‐1‐phosphate in acute exercise and training
Katarzyna Hodun, Adrian Chabowski, Marcin Baranowski
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The Ethyl Acetate Extract From Celastrus orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB
Lide Tao, Zixin Yin, Tengyang Ni, Zewen Chu, Shihua Hao, Zeyu Wang, Masataka Sunagawa, Haibo Wang, Yanqing Liu
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Sphingosine 1-phosphate Stimulates Insulin Secretion and Improves Cell Survival by Blocking Voltage-dependent K+ Channels in β Cells
Zhihong Liu, Huanhuan Yang, Linping Zhi, Huan Xue, Zhihong Lu, Yanli Zhao, Lijuan Cui, Tao Liu, Shouan Ren, Peifeng He, Yunfeng Liu, Yi Zhang
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Sphingosine-1 Phosphate Lyase Regulates Sensitivity of Pancreatic Beta-Cells to Lipotoxicity
Yadi Tang, Thomas Plötz, Markus H. Gräler, Ewa Gurgul-Convey
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Sphingolipids and Mitochondrial Dynamic
Lais Brigliadori Fugio, Fernanda B. Coeli-Lacchini, Andréia Machado Leopoldino
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Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction
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Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage
Antonio Gil, Elisa Martín-Montañez, Nadia Valverde, Estrella Lara, Federica Boraldi, Silvia Claros, Silvana-Yanina Romero-Zerbo, Oscar Fernández, Jose Pavia, Maria Garcia-Fernandez
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WITHDRAWN: Ceramide and Sphingosine 1-Phosphate in adipose dysfunction
Zijian Fang, Susan Pyne, Nigel J. Pyne
Progress in Lipid Research.2019; : 100991. CrossRef
Dynamic of mitochondrial network, cristae, and mitochondrial nucleoids in pancreatic β-cells
Petr Ježek, Andrea Dlasková
Mitochondrion.2019; 49: 245. CrossRef
Sphingosine kinase 1 overexpression induces MFN2 fragmentation and alters mitochondrial matrix Ca2+ handling in HeLa cells
I. Pulli, C. Löf, T. Blom, M.Y. Asghar, T. Lassila, N. Bäck, K.-L. Lin, J.H. Nyström, K. Kemppainen, D.M. Toivola, E. Dufour, A. Sanz, H.M. Cooper, J.B. Parys, K. Törnquist
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Diabetes
Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells: Seok-Woo Hong, Jinmi Lee, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2018;33(1):105-113. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.105

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Background

The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear.

Methods

To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation.

Results

Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels.

Conclusion

Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus

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Diabetes
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study: Yu Hyun Kwon, Seul-Ki Kim, Jung Hwan Cho, Hyemi Kwon, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2018;33(1):55-61. Published online January 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.55

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Background

Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time.

Methods

A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal (<150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014.

Results

Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80).

Conclusion

In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.

Citations

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Response: The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55–61, Yu Hyun Kwon et al.)
Eun-Jung Rhee, Yu Hyun Kwon
Endocrinology and Metabolism.2018; 33(3): 425. CrossRef
The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study (Endocrinol Metab 2018;33:55–61, Yu Hyun Kwon et al.)
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Clinical Study
Changes in Body Composition According to Age and Sex among Young Non-Diabetic Korean Adults: The Kangbuk Samsung Health Study: Seul-Ki Kim, Yu-Hyun Kwon, Jung Hwan Cho, Da Young Lee, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2017;32(4):442-450. Published online November 21, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.442

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Background

Age-related decreases in lean mass represent a serious health problem. We aimed to analyze the risks of rapid decreases in lean mass by age and sex in relatively young Korean adults during a 4-year follow-up study.

Methods

A total of 65,856 non-diabetic participants (59.5% men, mean age 39.1 years) in a health screening program were subjected to bioimpedance body composition analyses and metabolic parameter analyses at baseline and after 4 years. The participants were sub-divided according to age, and additionally to six groups by age and the degree of body weight change over the 4-year period. The actual changes in body weight, lean mass, and fat mass and the percent changes over the 4-year period were assessed.

Results

The percent change in lean mass decreased and the percent change of fat mass increased with increasing age in every age and sex group. However, the annual percent decrease in lean mass and percent increase in fat mass were significantly higher among women than among men (−0.26% vs. −0.15% and 0.34% vs. 0.42%, respectively; P<0.01). Participants who were older than 50 years and had a weight loss <−5% during the 4 years had significantly greater decreases in lean mass and smaller decreases in fat mass, compared to those who were younger than 50 years. An odds ratio analysis to determine the lowest quartile of the percent change in lean mass according to age group revealed that participants older than 60 years had a significantly increased risk of a rapid decrease in the lean mass percentage (2.081; 95% confidence interval, 1.678 to 2.581).

Conclusion

Even in this relatively young study population, the lean mass decreased significantly with age, and the risk of a rapid decrease in lean mass was higher among women than among men. Furthermore, the elderly exhibited a significantly more rapid decrease in lean mass, compared with younger participants.

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Clinical Study
Waist Circumference as a Marker of Obesity Is More Predictive of Coronary Artery Calcification than Body Mass Index in Apparently Healthy Korean Adults: The Kangbuk Samsung Health Study: Jongsin Park, Eun Seo Lee, Da Young Lee, Jihyun Kim, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(4):559-566. Published online December 20, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.559

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Background

We aimed to assess the risk for coronary artery calcification (CAC) according to groups subdivided by body mass index (BMI) and waist circumference (WC) in apparently healthy Korean adults.

Methods

Thirty-three thousand four hundred and thirty-two participants (mean age, 42 years) in a health screening program were divided into three groups according to BMI: <23 kg/m² (normal), 23 to 25 kg/m² (overweight), and >25 kg/m² (obese). In addition, the participants were divided into two groups according to WC. Coronary artery calcium score (CACS) was measured with multi-detector computed tomography in all participants. Presence of CAC was defined as CACS >0.

Results

When logistic regression analysis was performed with the presence of CAC as the dependent variable, the risk for CAC increased as BMI increased after adjusting for confounding variables (1.102 [95% confidence interval (CI), 1.000 to 1.216]; 1.284 [95% CI, 1.169 to 1.410]; in the overweight and obese groups vs. the normal weight group). When the participants were divided into six groups according to BMI and WC, the subjects with BMI and WC in the obese range showed the highest risk for CAC (1.321 [95% CI, 1.194 to 1.461]) and those with BMI in the overweight range and WC in the obese range showed the second highest risk for CAC (1.235 [95% CI, 1.194 to 1.461]).

Conclusion

Participants with obesity defined by both BMI and WC showed the highest risk for CAC. Those with BMIs in the overweight range but with WC in the obese range showed the second highest risk for CAC, suggesting that WC as a marker of obesity is more predictive of CAC than BMI.

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Articles inEndocrinology and Metabolismin 2016
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Clinical Study
Eligibility for Statin Treatment in Korean Subjects with Reduced Renal Function: An Observational Study: Byung Sub Moon, Jongho Kim, Ji Hyun Kim, Young Youl Hyun, Se Eun Park, Hyung-Geun Oh, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Kyu-Beck Lee, Hyang Kim, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(3):402-409. Published online August 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.402

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Background

The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults.

Methods

Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m²; stage 2, eGFR 60 to 89 mL/min/1.73 m²; and stages 3 to 5, eGFR <60 mL/min/1.73 m². Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD) was calculated using the Framingham Risk Score (FRS) and Pooled Cohort Equation (PCE).

Results

There were 3,546 (18.9%) and 4,048 (21.5%) statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO) recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD) (κ value, 0.689 vs. 0.531). When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined.

Conclusions

The proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD.

Citations

Citations to this article as recorded by

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Honghong Ren, Lijun Zhao, Yutong Zou, Yiting Wang, Junlin Zhang, Yucheng Wu, Rui Zhang, Tingli Wang, Jiali Wang, Yitao Zhu, Ruikun Guo, Huan Xu, Lin Li, Mark E. Cooper, Fang Liu
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Seo Yeon Baik, Hyunah Kim, So Jung Yang, Tong Min Kim, Seung-Hwan Lee, Jae Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, Kun-Ho Yoon, Hun-Sung Kim
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Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea
Y. J. Jeong, H. Kim, S. J. Baik, T. M. Kim, S. J. Yang, S.-H. Lee, J.-H. Cho, H. Lee, H. W. Yim, I. Y. Choi, K.-H. Yoon, H.-S. Kim
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Eugene Han, Gyuri Kim, Ji-Yeon Lee, Yong-ho Lee, Beom Seok Kim, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
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Clinical Study
C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index: Jong-Dai Kim, Sung Ju Kang, Min Kyung Lee, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2016;31(2):320-327. Published online June 21, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.320

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Background

Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans.

Methods

This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline.

Results

Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014).

Conclusion

C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

Citations

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Clinical Study
The Relationship between 10-Year Cardiovascular Risk Calculated Using the Pooled Cohort Equation and the Severity of Non-Alcoholic Fatty Liver Disease: Jeong In Lee, Min Chul Kim, Byung Sub Moon, Young Seok Song, Eun Na Han, Hyo Sun Lee, Yoonjeong Son, Jihyun Kim, Eun Jin Han, Hye-Jeong Park, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(1):86-92. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.86

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Background

We investigated the association between the severity of non-alcoholic fatty liver disease (NAFLD) and the estimated 10-year risk of cardiovascular disease (CVD) calculated by Pooled Cohort Equation (PCE) and Framingham risk score (FRS).

Methods

A total of 15,913 participants (mean age, 46.3 years) in a health screening program were selected for analysis. The presence and severity of fatty liver was assessed by abdominal ultrasonogram. Subjects who drank alcohol more than three times a week were excluded from the study.

Results

Among the participants, 57.6% had no NAFLD, 35.4% had grade I, 6.5% had grade II, and 0.5% had grade III NAFLD. Mean estimated 10-year CVD risk was 2.59%, 3.93%, 4.68%, and 5.23% calculated using the PCE (P for trend <0.01) and 4.55%, 6.39%, 7.33%, and 7.13% calculated using FRS, according to NAFLD severity from none to severe (P for trend <0.01). The odds ratio for ≥7.5% estimated CVD risk calculated using the PCE showed a higher correlation with increasing severity of NAFLD even after adjustment for conventional CVD risk factors (1.52, 2.56, 3.35 vs. the no NAFLD group as a reference, P<0.01) compared with calculated risk using FRS (1.65, 1.62, 1.72 vs. no NAFLD group as a reference, P<0.01).

Conclusion

In our study of apparently healthy Korean adults, increasing severity of NAFLD showed a higher correlation with estimated 10-year CVD risk when calculated using the PCE than when calculated using FRS.

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Kyung Mook Choi, Kyungdo Han, Sanghyun Park, Hye Soo Chung, Nam Hoon Kim, Hye Jin Yoo, Ji-A Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Yong Gyu Park, Seon Mee Kim
Scientific Reports.2018;[Epub] CrossRef
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Gyuri Kim, Suk‐Yong Jang, Eugene Han, Yong‐ho Lee, Se‐young Park, Chung Mo Nam, Eun Seok Kang
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Eun-Jung Rhee
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Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases
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Clinical Study
Association of Waist-Height Ratio with Diabetes Risk: A 4-Year Longitudinal Retrospective Study: Yoon Jeong Son, Jihyun Kim, Hye-Jeong Park, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee; Endocrinol Metab. 2016;31(1):127-133. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.127

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Abstract PDF PubReader

Background

Waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of various baseline adiposity indices, including WHtR, with the development of diabetes over 4 years of follow-up in apparently healthy Korean individuals.

Methods

A total of 2,900 nondiabetic participants (mean age, 44.3 years; 2,078 men) in a health screening program, who repeated the medical check-up in 2005 and 2009, were recruited. Subjects were divided into two groups according to development of diabetes after 4 years. The cut-off values of baseline body mass index (BMI), waist circumference (WC), and WHtR for the development of diabetes over 4 years were calculated. The sensitivity, specificity, and mean area under the receiver operator characteristic curve (AUROC) of each index were assessed. The odds ratio (OR) for diabetes development was analyzed for each of the three baseline adiposity indices.

Results

During the follow-up period, 101 new cases (3.5%) of diabetes were diagnosed. The cut-off WHtR value for diabetes development was 0.51. Moreover, WHtR had the highest AUROC value for diabetes development among the three adiposity indices (0.716, 95% confidence interval [CI], 0.669 to 0.763; 0.702, 95% CI, 0.655 to 0.750 for WC; 0.700, 95% CI, 0.651 to 0.750 for BMI). After adjusting for confounding variables, the ORs of WHtR and WC for diabetes development were 1.95 (95% CI, 1.14 to 3.34) and 1.96 (95% CI, 1.10 to 3.49), respectively. No significant differences were observed between the two groups regarding BMI.

Conclusion

Increased baseline WHtR and WC correlated with the development of diabetes after 4 years. WHtR might be a useful screening measurement to identify individuals at high risk for diabetes.

Citations

Citations to this article as recorded by

Comparison of waist circumference and waist‐to‐height ratio as predictors of clustering of cardiovascular risk factors among middle‐aged people in rural Khanh Hoa, Vietnam
Rachana Manandhar Shrestha, Thuy Thi Phuong Pham, Shohei Yamamoto, Chau Que Nguyen, Ami Fukunaga, Phan Cong Danh, Masahiko Hachiya, Huy Xuan Le, Hung Thai Do, Tetsuya Mizoue, Yosuke Inoue
American Journal of Human Biology.2024;[Epub] CrossRef
Novel anthropometric indices for predicting type 2 diabetes mellitus
Erfan Sadeghi, Alireza Khodadadiyan, Seyed Ali Hosseini, Sayed Mohsen Hosseini, Ashraf Aminorroaya, Massoud Amini, Sara Javadi
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Body Composition and Cardiovascular Risk: A Study of Polish Military Flying Personnel
Agata Gaździńska, Stefan Gaździński, Paweł Jagielski, Paweł Kler
Metabolites.2023; 13(10): 1102. CrossRef
Cues of pregnancy decrease female physical attractiveness for males
Pavol Prokop, Martina Zvaríková, Milan Zvarík, Peter Fedor
Current Psychology.2022; 41(2): 697. CrossRef
Waist-to-height ratio has a stronger association with cardiovascular risks than waist circumference, waist-hip ratio and body mass index in type 2 diabetes
Jiang-Feng Ke, Jun-Wei Wang, Jun-Xi Lu, Zhi-Hui Zhang, Yun Liu, Lian-Xi Li
Diabetes Research and Clinical Practice.2022; 183: 109151. CrossRef
Diagnostic accuracy of anthropometric indices for discriminating elevated blood pressure in pediatric population: a systematic review and a meta-analysis
Jun-Min Tao, Wei Wei, Xiao-Yang Ma, Ying-Xiang Huo, Meng-Die Hu, Xiao-Feng Li, Xin Chen
BMC Pediatrics.2022;[Epub] CrossRef
The utilization of BMI in patients with high WHtR as to cardiovascular risk
Meliha Melin UYGUR
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Neha Rai, Hanjabam Barun Sharma, Renu Kumari, Jyotsna Kailashiya
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Katharina Lechner, Benjamin Lechner, Alexander Crispin, Peter E. H. Schwarz, Helene von Bibra
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Mostafa Q. Alshamiri, Faisal Mohd A Habbab, Saad Saeed AL-Qahtani, Khalil Abdullah Alghalayini, Omar Mohammed Al-Qattan, Fayez El-shaer, Anne Knowlton
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A simple cut-off for waist-to-height ratio (0·5) can act as an indicator for cardiometabolic risk: recent data from adults in the Health Survey for England
Sigrid Gibson, Margaret Ashwell
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Gebremedhin Gebreegziabiher, Tefera Belachew, Dessalegn Tamiru
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Quan Nguyen Minh, Minh Hoang Nguyen Vo
Integrated Blood Pressure Control.2020; Volume 13: 181. CrossRef
Relation between Baseline Height and New Diabetes Development: A Nationwide Population-Based Study
Eun-Jung Rhee, Jung-Hwan Cho, Hyemi Kwon, Se-Eun Park, Jin-Hyung Jung, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Won-Young Lee
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Issues in Measuring and Interpreting Diet and Its Contribution to Obesity
Rachael M. Taylor, Rebecca L. Haslam, Tracy L. Burrows, Kerith R. Duncanson, Lee M. Ashton, Megan E. Rollo, Vanessa A. Shrewsbury, Tracy L. Schumacher, Clare E. Collins
Current Obesity Reports.2019; 8(2): 53. CrossRef
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Jaeeun Myung, Kyung Yoon Jung, Tae Hyun Kim, Euna Han
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Clinical Study
Effect of Pitavastatin Treatment on ApoB-48 and Lp-PLA₂ in Patients with Metabolic Syndrome: Substudy of PROspective Comparative Clinical Study Evaluating the Efficacy and Safety of PITavastatin in Patients with Metabolic Syndrome: Hyo-Sun Lee, Chang Hee Jung, Sung Rae Kim, Hak Chul Jang, Cheol-Young Park; Endocrinol Metab. 2016;31(1):120-126. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.120

3,487 View
35 Download
6 Web of Science
6 Crossref

Abstract PDF PubReader

Background

Apolipoprotein (Apo) B-48 is an intestinally derived lipoprotein that is expected to be a marker for cardiovascular disease (CVD). Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a vascular-specific inflammatory marker and important risk predictor of CVD. The aim of this study was to explore the effect of pitavastatin treatment and life style modification (LSM) on ApoB-48 and Lp-PLA₂ levels in metabolic syndrome (MS) patients at relatively low risk for CVD, as a sub-analysis of a previous multi-center prospective study.

Methods

We enrolled 75 patients with MS from the PROPIT study and randomized them into two treatment groups: 2 mg pitavastatin daily+intensive LSM or intensive LSM only. We measured the change of lipid profiles, ApoB-48 and Lp-PLA₂ for 48 weeks.

Results

Total cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and ApoB-100/A1 ratio were significantly improved in the pitavastatin+LSM group compared to the LSM only group (P≤0.001). Pitavastatin+LSM did not change the level of ApoB-48 in subjects overall, but the level of ApoB-48 was significantly lower in the higher mean baseline value group of ApoB-48. The change in Lp-PLA₂ was not significant after intervention in either group after treatment with pitavastatin for 1 year.

Conclusion

Pitavastatin treatment and LSM significantly improved lipid profiles, ApoB-100/A1 ratio, and reduced ApoB-48 levels in the higher mean baseline value group of ApoB-48, but did not significantly alter the Lp-PLA₂ levels.

Citations

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Vivencio Barrios, Carlos Escobar
Future Cardiology.2016; 12(4): 449. CrossRef

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