Endocrinology and Metabolism

Volume 36(6); December 2021

Review Articles

Diabetes, Obesity and Metabolism
Serotonergic Regulation of Hepatic Energy Metabolism: Jiwon Park, Wooju Jeong, Chahyeon Yun, Hail Kim, Chang-Myung Oh; Endocrinol Metab. 2021;36(6):1151-1160. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1331

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The liver is a vital organ that regulates systemic energy metabolism and many physiological functions. Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease and end-stage liver failure. NAFLD is primarily caused by metabolic disruption of lipid and glucose homeostasis. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic amine with several functions in both the central and peripheral systems. 5-HT functions as a neurotransmitter in the brain and a hormone in peripheral tissues to regulate systemic energy homeostasis. Several recent studies have proposed various roles of 5-HT in hepatic metabolism and inflammation using tissue-specific knockout mice and 5-HT-receptor agonists/antagonists. This review compiles the most recent research on the relationship between 5-HT and hepatic metabolism, and the role of 5-HT signaling as a potential therapeutic target in NAFLD.

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Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone
Petra Baković, Maja Kesić, Darko Kolarić, Jasminka Štefulj, Lipa Čičin-Šain
International Journal of Molecular Sciences.2023; 24(3): 2169. CrossRef
Serotonin in the regulation of systemic energy metabolism
Joon Ho Moon, Chang‐Myung Oh, Hail Kim
Journal of Diabetes Investigation.2022; 13(10): 1639. CrossRef
Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A
Takashi Owaki, Kenya Kamimura, Masayoshi Ko, Itsuo Nagayama, Takuro Nagoya, Osamu Shibata, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Takeki Sato, Toru Setsu, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Shuji Terai
Disease Models & Mechanisms.2022;[Epub] CrossRef
Non-alcoholic fatty liver disease (NAFLD) and mental illness: Mechanisms linking mood, metabolism and medicines
Anwesha Gangopadhyay, Radwa Ibrahim, Karli Theberge, Meghan May, Karen L. Houseknecht
Frontiers in Neuroscience.2022;[Epub] CrossRef

Miscellaneous
Quality Matters as Much as Quantity of Skeletal Muscle: Clinical Implications of Myosteatosis in Cardiometabolic Health: Hong-Kyu Kim, Chul-Hee Kim; Endocrinol Metab. 2021;36(6):1161-1174. Published online December 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1348

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Although age-related changes in skeletal muscles are closely associated with decreases in muscle strength and functional decline, their associations with cardiometabolic diseases in the literature are inconsistent. Such inconsistency could be explained by the fact that muscle quality—which is closely associated with fatty infiltration of the muscle (i.e., myosteatosis)—is as important as muscle quantity in cardiometabolic health. However, muscle quality has been less explored compared with muscle mass. Moreover, the standard definition of myosteatosis and its assessment methods have not been established yet. Recently, some techniques using single axial computed tomography (CT) images have been introduced and utilized in many studies, as the mass and quality of abdominal muscles could be measured opportunistically on abdominal CT scans obtained during routine clinical care. Yet, the mechanisms by which myosteatosis affect metabolic and cardiovascular health remain largely unknown. In this review, we explore the recent advances in the assessment of myosteatosis and its changes associated with aging. We also review the recent literature on the clinical implication of myosteatosis by focusing on metabolic and cardiovascular diseases. Finally, we discuss the challenges and unanswered questions that need addressing to set myosteatosis as a therapeutic target for the prevention or treatment of cardiometabolic diseases.

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Association of serum gamma-glutamyl transferase with myosteatosis assessed by muscle quality mapping using abdominal computed tomography
Han Na Jung, Yun Kyung Cho, Hwi Seung Kim, Eun Hee Kim, Min Jung Lee, Joong-Yeol Park, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
Clinical Imaging.2023; 93: 4. CrossRef
Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of cardiometabolic diseases in a Chinese natural population: A cross‐sectional study
Shi Zhang, Yaping Huang, Jing Li, Xincheng Wang, Xiaohe Wang, Minying Zhang, Yanju Zhang, Meiyang Du, Jingna Lin, Chunjun Li
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef
Association between hypertension and myosteatosis evaluated by abdominal computed tomography
Han Na Jung, Yun Kyung Cho, Hwi Seung Kim, Eun Hee Kim, Min Jung Lee, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
Hypertension Research.2023; 46(4): 845. CrossRef
Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
Jaime A. Gallo-Villegas, Juan C. Calderón
European Journal of Applied Physiology.2023; 123(5): 945. CrossRef
Muscle fat infiltration in chronic kidney disease: a marker related to muscle quality, muscle strength and sarcopenia
Carla Maria Avesani, Aline Miroski de Abreu, Heitor S. Ribeiro, Torkel B. Brismar, Peter Stenvinkel, Alice Sabatino, Bengt Lindholm
Journal of Nephrology.2023; 36(3): 895. CrossRef
IDF2022-1139 Association Between Dyslipidemia And Myosteatosis Using Visual Muscular Quality Map In Computed Tomography
H.S. Kim, H.N. Jung, Y.K. Cho, E.H. Kim, M.J. Lee, W.J. Lee, J.Y. Park, H.K. Kim, C.H. Jung
Diabetes Research and Clinical Practice.2023; 197: 110467. CrossRef
The role of skeletal muscle mass on cardiovascular disease risk: an emerging role on modulating lipid profile
Evangelia Damigou, Matina Kouvari, Demosthenes Panagiotakos
Current Opinion in Cardiology.2023;[Epub] CrossRef
Reference values for low muscle mass and myosteatosis using tomographic muscle measurements in living kidney donors
Lisa B. Westenberg, Marcel Zorgdrager, Tim D. A. Swaab, Marco van Londen, Stephan J. L. Bakker, Henri G. D. Leuvenink, Alain R. Viddeleer, Robert A. Pol
Scientific Reports.2023;[Epub] CrossRef
Association between sarcopenic obesity and poor muscle quality based on muscle quality map and abdominal computed tomography
Yun Kyung Cho, Han Na Jung, Eun Hee Kim, Min Jung Lee, Joong‐Yeol Park, Woo Je Lee, Hong‐Kyu Kim, Chang Hee Jung
Obesity.2023; 31(6): 1547. CrossRef
Assessment of Muscle Quantity, Quality and Function
Bo Kyung Koo
Journal of Obesity & Metabolic Syndrome.2022; 31(1): 9. CrossRef
Influence of cross‐sectional area and fat infiltration of paraspinal muscles on analgesic efficacy of epidural steroid injection in elderly patients
Hee Jung Kim, Miribi Rho, Kyung Bong Yoon, Minju Jo, Dong Woo Lee, Shin Hyung Kim
Pain Practice.2022; 22(7): 621. CrossRef
Sarcopenia, Obesity, Sarcopenic Obesity and Risk of Poor Nutritional Status in Polish Community-Dwelling Older People Aged 60 Years and Over
Marika Murawiak, Roma Krzymińska-Siemaszko, Aleksandra Kaluźniak-Szymanowska, Marta Lewandowicz, Sławomir Tobis, Katarzyna Wieczorowska-Tobis, Ewa Deskur-Śmielecka
Nutrients.2022; 14(14): 2889. CrossRef
Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation
Amedeo Lonardo, Alessandro Mantovani, Salvatore Petta, Amedeo Carraro, Christopher D. Byrne, Giovanni Targher
Nature Reviews Endocrinology.2022; 18(10): 638. CrossRef

Editorial

Thyroid
Diabetes and Hyperthyroidism: Is There a Causal Link?: Sang Yong Kim; Endocrinol Metab. 2021;36(6):1175-1177. Published online December 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.602

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Reply to “Hyperthyroidism in patients with asthma”
Shuo-Yan Gau, Jing-Yang Huang, Su-Boon Yong, James Cheng-Chung Wei
The Journal of Allergy and Clinical Immunology: In Practice.2023; 11(2): 668. CrossRef

Original Articles

Calcium & Bone Metabolism Big Data Articles (National Health Insurance Service Database)
10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea: Yeon-Hee Baek, Sun Wook Cho, Han Eol Jeong, Ju Hwan Kim, Yunji Hwang, Jeffrey L. Lange, Ju-Young Shin; Endocrinol Metab. 2021;36(6):1178-1188. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1215

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Background
In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.
Methods
BMD was classified as normal (T-score ≥–1.0 standard deviation [SD]), osteopenia (T-score <–1.0 SD and >–2.5 SD), and osteoporosis (T score ≤–2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.
Results
Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.
Conclusion
Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

Citations

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Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Chronic airway disease as a major risk factor for fractures in osteopenic women: Nationwide cohort study
Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim
Frontiers in Endocrinology.2023;[Epub] CrossRef
Biomimetic Porous Magnesium Alloy Scaffolds Promote the Repair of Osteoporotic Bone Defects in Rats through Activating the Wnt/β-Catenin Signaling Pathway
Yuanchao Zhu, Gaozhi Jia, Yifei Yang, Jian Weng, Su Liu, Mengwei Zhang, Geng Zhang, Haotian Qin, Yixiao Chen, Qi Yang, Guangyin Yuan, Fei Yu, Hui Zeng
ACS Biomaterials Science & Engineering.2023;[Epub] CrossRef
A Meaningful Journey to Predict Fractures with Deep Learning
Jeonghoon Ha
Endocrinology and Metabolism.2022; 37(4): 617. CrossRef
The Efficacy of Selective Estrogen Receptor Modulators Monotherapies in Postmenopausal Women with Osteopenia
Kyung Wook Kim, Young Il Kim, Ki-Choul Kim
Journal of Bone Metabolism.2022; 29(3): 185. CrossRef
Correlation of Psoas Muscle Index with Fragility Vertebral Fracture: A Retrospective Cross-Sectional Study of Middle-Aged and Elderly Women
Yihui Zhang, Yilihamu Dilixiati, Wei Jiang, Xiufeng Cao, Yuanyuan Chen, Hui Guo, Christian-Heinz Anderwald
International Journal of Endocrinology.2022; 2022: 1. CrossRef

Calcium & Bone Metabolism
Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study: Ye An Kim, Ji Won Yoon, Young Lee, Hyuk Jin Choi, Jae Won Yun, Eunsin Bae, Seung-Hyun Kwon, So Eun Ahn, Ah-Ra Do, Heejin Jin, Sungho Won, Do Joon Park, Chan Soo Shin, Je Hyun Seo; Endocrinol Metab. 2021;36(6):1189-1200. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1241

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Background
Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods
We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results
rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion
The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

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Recent Information on Vitamin D Deficiency in an Adult Korean Population Visiting Local Clinics and Hospitals
Rihwa Choi, Sung-Eun Cho, Sang Gon Lee, Eun Hee Lee
Nutrients.2022; 14(9): 1978. CrossRef
The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
Antioxidants.2022; 11(6): 1090. CrossRef
A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts
Young Lee, Ji Won Yoon, Ye An Kim, Hyuk Jin Choi, Byung Woo Yoon, Je Hyun Seo
Genes.2022; 13(9): 1553. CrossRef
Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health
Elina Hyppönen, Karani S. Vimaleswaran, Ang Zhou
Nutrients.2022; 14(20): 4408. CrossRef
On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
Leonidas H. Duntas, Krystallenia I. Alexandraki
Nutrients.2022; 14(23): 5032. CrossRef
The genetic and epigenetic contributions to the development of nutritional rickets
Innocent Ogunmwonyi, Adewale Adebajo, Jeremy Mark Wilkinson
Frontiers in Endocrinology.2022;[Epub] CrossRef

Calcium & Bone Metabolism
Computed Tomography-Derived Skeletal Muscle Radiodensity Is an Early, Sensitive Marker of Age-Related Musculoskeletal Changes in Healthy Adults: Yeon Woo Jung, Namki Hong, Joon Chae Na, Woong Kyu Han, Yumie Rhee; Endocrinol Metab. 2021;36(6):1201-1210. Published online December 13, 2021; DOI: https://doi.org/10.3803/EnM.2021.1206

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Background
A decrease in computed tomography (CT)-derived skeletal muscle radiodensity (SMD) reflects age-related ectopic fat infiltration of muscle, compromising muscle function and metabolism. We investigated the age-related trajectory of SMD and its association with vertebral trabecular bone density in healthy adults.
Methods
In a cohort of healthy adult kidney donors aged 19 to 69 years (n=583), skeletal muscle index (SMI, skeletal muscle area/height2), SMD, and visceral-to-subcutaneous fat (V/S) ratio were analyzed at the level of L3 from preoperative CT scans. Low bone mass was defined as an L1 trabecular Hounsfield unit (HU) <160 HU.
Results
L3SMD showed constant decline from the second decade (annual change –0.38% and –0.43% in men and women), whereas the decline of L3SMI became evident only after the fourth decade of life (–0.37% and –0.18% in men and women). One HU decline in L3SMD was associated with elevated odds of low bone mass (adjusted odds ratio, 1.07; 95% confidence interval, 1.02 to 1.13; P=0.003), independent of L3SMI, age, sex, and V/S ratio, with better discriminatory ability compared to L3SMI (area under the receiver-operating characteristics curve 0.68 vs. 0.53, P<0.001). L3SMD improved the identification of low bone mass when added to age, sex, V/S ratio, and L3SMI (category-free net reclassification improvement 0.349, P<0.001; integrated discrimination improvement 0.015, P=0.0165).
Conclusion
L3SMD can be an early marker for age-related musculoskeletal changes showing linear decline throughout life from the second decade in healthy adults, with potential diagnostic value for individuals with low bone mass.

Citations

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A review of radiological definitions of sarcopenia in cancer
James W. Wang, Jiarong Chen, Alison H. McGregor, Matthew Williams
JCSM Clinical Reports.2023; 8(2): 36. CrossRef

Calcium & Bone Metabolism
Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment: Eunhee Jang, Jeonghoon Ha, Ki-Hyun Baek, Moo Il Kang; Endocrinol Metab. 2021;36(6):1211-1218. Published online December 8, 2021; DOI: https://doi.org/10.3803/EnM.2021.1248

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Background
Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.
Methods
We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.
Results
After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (–11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).
Conclusion
Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

Citations

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Fracture risk and assessment in adults with cancer
Carrie Ye, William D. Leslie
Osteoporosis International.2023; 34(3): 449. CrossRef
Short-Term Impact of Hematopoietic Stem Cell Transplantation in Leukemia Patients on Bone Bio Markers, Electrolytes and Blood Profile
Rhythm Joshi, Zehva Khan, Aakriti Garg, Dinesh Bhurani, Nidhi B Agarwal, Ubada Aqeel, Mohd Ashif Khan
OBM Transplantation.2023; 07(02): 1. CrossRef

Calcium & Bone Metabolism
Comparison of Two DXA Systems, Hologic Horizon W and GE Lunar Prodigy, for Assessing Body Composition in Healthy Korean Adults: Seung Shin Park, Soo Lim, Hoyoun Kim, Kyoung Min Kim; Endocrinol Metab. 2021;36(6):1219-1231. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1274

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Background
Dual-energy X-ray absorptiometry (DXA) is the most widely used method for evaluating muscle masses. The aim of this study was to investigate the agreement between muscle mass values assessed by two different DXA systems.
Methods
Forty healthy participants (20 men, 20 women; age range, 23 to 71 years) were enrolled. Total and regional body compositional values for fat and lean masses were measured consecutively with two DXA machines, Hologic Horizon and GE Lunar Prodigy. Appendicular lean mass (ALM) was calculated as the sum of the lean mass of four limbs.
Results
In both sexes, the ALM values measured by the GE Lunar Prodigy (24.8±4.3 kg in men, 15.8±2.9 kg in women) were significantly higher than those assessed by Hologic Horizon (23.0±4.0 kg in men, 14.8±3.2 kg in women). Furthermore, BMI values or body fat (%), either extremely higher or lower levels, contributed greater differences between two systems. Bland-Altman analyses revealed a significant bias between ALM values assessed by the two systems. Linear regression analyses were performed to develop equations to adjust for systematic differences (men: Horizon ALM [kg]=0.915×Lunar Prodigy ALM [kg]+0.322, R²=0.956; women: Horizon ALM [kg]=1.066×Lunar Prodigy ALM [kg]–2.064, R²=0.952).
Conclusion
Although measurements of body composition including muscle mass by the two DXA systems correlated strongly, significant differences were observed. Calibration equations should enable mutual conversion between different DXA systems.

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Total and regional appendicular skeletal muscle mass prediction from dual-energy X-ray absorptiometry body composition models
Cassidy McCarthy, Grant M. Tinsley, Anja Bosy-Westphal, Manfred J. Müller, John Shepherd, Dympna Gallagher, Steven B. Heymsfield
Scientific Reports.2023;[Epub] CrossRef
Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa
Mícheál Ó Breasail, Ramatoulie Janha, Ayse Zengin, Camille Pearse, Landing Jarjou, Ann Prentice, Kate A. Ward
Calcified Tissue International.2023; 112(5): 573. CrossRef

Diabetes, Obesity and Metabolism
The Leg Fat to Total Fat Ratio Is Associated with Lower Risks of Non-Alcoholic Fatty Liver Disease and Less Severe Hepatic Fibrosis: Results from Nationwide Surveys (KNHANES 2008–2011): Hyun Min Kim, Yong-ho Lee; Endocrinol Metab. 2021;36(6):1232-1242. Published online November 23, 2021; DOI: https://doi.org/10.3803/EnM.2021.1087

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Background
The prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased worldwide. The aim of this study was to investigate whether there is an independent relationship between regional fat distribution, especially leg fat mass, and the presence of NAFLD using nationally representative data in Korea.
Methods
This cross-sectional study analyzed data from 14,502 participants in the Korea National Health and Nutrition Examination Survey 2008 to 2011. Total fat mass, leg fat mass, and appendicular skeletal muscle mass were measured by dual-energy X-ray absorptiometry. Validated NAFLD prediction models and scoring systems for hepatic fibrosis were used.
Results
The leg fat to total fat (LF/TF) ratio showed a negative relationship with many factors, including body mass index, waist circumference, blood pressure, fasting blood glucose, and liver enzyme levels. When the LF/TF ratio and indices of hepatic steatosis were stratified by quartiles, the LF/TF ratio showed a negative correlation with the scoring systems that were used. The LF/TF ratio showed better accuracy in predicting NAFLD than total fat mass or leg fat mass alone. After adjusting for various traditional and lifestyle factors, a low LF/TF ratio remained a risk factor for NAFLD. Among NAFLD subjects, the LF/TF ratio showed a negative relationship with hepatic fibrosis.
Conclusion
A lower LF/TF ratio was markedly associated with a higher risk of hepatic steatosis and advanced hepatic fibrosis using various predictive models in a Korean population. Therefore, the LF/TF ratio could be a useful anthropometric parameter to predict NAFLD or advanced hepatic fibrosis.

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A greater ratio of thigh subcutaneous fat to lower abdominal fat is associated with protection against non-alcoholic fatty liver disease
Yebei Liang, Peizhu Chen, Siyu Chen, Dan Liu, Fusong Jiang, Zhijun Zhu, Keqing Dong, Li Wei, Xuhong Hou
JHEP Reports.2023; : 100730. CrossRef

Diabetes, Obesity and Metabolism
The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE^−/−FXR^−/− Mice: Yenna Lee, Bo-Rahm Kim, Geun-Hyung Kang, Gwan Jae Lee, Young Joo Park, Haeryoung Kim, Hak Chul Jang, Sung Hee Choi; Endocrinol Metab. 2021;36(6):1243-1253. Published online December 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1100

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Background
Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods
En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)^−/− and ApoE^−/−FXR^−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results
Compared with ApoE^−/− mice, ApoE^−/−FXR^−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE^−/−FXR^−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion
Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

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Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis
Min Yao, Ping Zhou, Yan-Yan Qin, Li Wang, Deng-Fu Yao
World Journal of Gastroenterology.2023; 29(12): 1765. CrossRef
Emerging Roles of Gut Microbial Modulation of Bile Acid Composition in the Etiology of Cardiovascular Diseases
Tess Yntema, Debby P. Y. Koonen, Folkert Kuipers
Nutrients.2023; 15(8): 1850. CrossRef
The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease
Alexandra C. Finney, Sandeep Das, Dhananjay Kumar, M. Peyton McKinney, Bishuang Cai, Arif Yurdagul, Oren Rom
Frontiers in Cardiovascular Medicine.2023;[Epub] CrossRef
Targeting PPARs for therapy of atherosclerosis: A review
Miao Miao, Xue Wang, Tian Liu, Yan-Jie Li, Wen-Qian Yu, Tong-Mei Yang, Shou-Dong Guo
International Journal of Biological Macromolecules.2023; : 125008. CrossRef
Cabernet sauvignon dry red wine ameliorates atherosclerosis in mice by regulating inflammation and endothelial function, activating AMPK phosphorylation, and modulating gut microbiota
Xinlong Cheng, Xue Han, Liangfu Zhou, Yasai Sun, Qian Zhou, Xuan Lin, Zhe Gao, Jie Wang, Wen Zhao
Food Research International.2023; 169: 112942. CrossRef
Whey protein hydrolysate alleviated atherosclerosis and hepatic steatosis by regulating lipid metabolism in apoE-/- mice fed a Western diet
Kai Wang, Zixin Fu, Xiaoyi Li, Hui Hong, Xin Zhan, Xiaohong Guo, Yongkang Luo, Yuqing Tan
Food Research International.2022; 157: 111419. CrossRef
Melatonin alleviates PM 2.5 ‐induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic reticulum stress
Zhou Du, Junjie Hu, Lisen Lin, Qingqing Liang, Mengqi Sun, Zhiwei Sun, Junchao Duan
Journal of Pineal Research.2022;[Epub] CrossRef
Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia
Joon Ho Moon, Kyuho Kim, Sung Hee Choi
Endocrinology and Metabolism.2022; 37(4): 575. CrossRef
The role of the gut microbiota in health and cardiovascular diseases
Lu Wang, Shiqi Wang, Qing Zhang, Chengqi He, Chenying Fu, Quan Wei
Molecular Biomedicine.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Association between Lung Function and New-Onset Diabetes Mellitus in Healthy Individuals after a 6-Year Follow-up: Hwa Young Lee, Juyoung Shin, Hyunah Kim, Seung-Hwan Lee, Jae-Hyoung Cho, Sook Young Lee, Hun-Sung Kim; Endocrinol Metab. 2021;36(6):1254-1267. Published online December 13, 2021; DOI: https://doi.org/10.3803/EnM.2021.1249

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
We analyzed hemoglobin A1c (HbA1c) levels and various lung function test results in healthy individuals after a 6-year follow-up period to explore the influence of lung function changes on glycemic control.
Methods
Subjects whose HbA1c levels did not qualify as diabetes mellitus (DM) and who had at least two consecutive lung function tests were selected among the people who visited a health promotion center. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC ratio, and forced expiratory flow 25% to 75% (FEF_25%−75%), were divided into four groups based on their baseline quantiles. To evaluate future DM onset risk in relation to lung function changes, the correlation between baseline HbA1c levels and changes in lung function parameters after a 6-year follow-up period was analyzed.
Results
Overall, 17,568 individuals were included; 0.9% of the subjects were diagnosed with DM. The individuals included in the quartile with FEV1/FVC ratio values of 78% to 82% had lower risk of DM than those in the quartile with FEV1/FVC ratio values of ≥86% after adjusting for age, sex, and body mass index (P=0.04). Baseline percent predicted FEV1, FVC, FEV1/FVC ratio, and FEF_25%−75%, and differences in the FEV1/FVC ratio or FEF_25%−75%, showed negative linear correlations with baseline HbA1c levels.
Conclusion
Healthy subjects with FEV1/FVC ratio values between 78% and 82% had 40% lower risk for future DM. Smaller differences and lower baseline FEV1/FVC ratio or FEF_25%−75% values were associated with higher baseline HbA1c levels. These findings suggest that airflow limitation affects systemic glucose control and that the FEV1/FVC ratio could be one of the factors predicting future DM risk in healthy individuals.

Citations

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Combined multi-omics analysis reveals oil mist particulate matter-induced lung injury in rats: Pathological damage, proteomics, metabolic disturbances, and lung dysbiosis
Huipeng Nie, Huanliang Liu, Yue Shi, Wenqing Lai, Xuan Liu, Zhuge Xi, Bencheng Lin
Ecotoxicology and Environmental Safety.2022; 241: 113759. CrossRef
Retrospective cohort analysis comparing changes in blood glucose level and body composition according to changes in thyroid‐stimulating hormone level
Hyunah Kim, Da Young Jung, Seung‐Hwan Lee, Jae‐Hyoung Cho, Hyeon Woo Yim, Hun‐Sung Kim
Journal of Diabetes.2022; 14(9): 620. CrossRef
Improving Machine Learning Diabetes Prediction Models for the Utmost Clinical Effectiveness
Juyoung Shin, Joonyub Lee, Taehoon Ko, Kanghyuck Lee, Yera Choi, Hun-Sung Kim
Journal of Personalized Medicine.2022; 12(11): 1899. CrossRef

Thyroid
Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves’ Disease: A Retrospective Multicenter Study: Jee Hee Yoon, Meihua Jin, Mijin Kim, A Ram Hong, Hee Kyung Kim, Bo Hyun Kim, Won Bae Kim, Young Kee Shong, Min Ji Jeon, Ho-Cheol Kang; Endocrinol Metab. 2021;36(6):1268-1276. Published online November 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.1227

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods
Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results
Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion
The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

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Outcomes of Surgical Treatment for Graves’ Disease: A Single-Center Experience of 216 Cases
Hanxing Sun, Hui Tong, Xiaohui Shen, Haoji Gao, Jie Kuang, Xi Chen, Qinyu Li, Weihua Qiu, Zhuoran Liu, Jiqi Yan
Journal of Clinical Medicine.2023; 12(4): 1308. CrossRef
Cancer and Mortality Risks of Graves’ Disease in South Korea Based on National Data from 2010 to 2019
Young Ju Choi, Kyungdo Han, Won Kyoung Cho, Min Ho Jung, Byung-Kyu Suh
Clinical Epidemiology.2023; Volume 15: 535. CrossRef
Risk and Prognosis of Thyroid Cancer in Patients with Graves’ Disease: An Umbrella Review
Marco Palella, Francesca Maria Giustolisi, Adriana Modica Fiascaro, Martina Fichera, Antonella Palmieri, Rossella Cannarella, Aldo E. Calogero, Margherita Ferrante, Maria Fiore
Cancers.2023; 15(10): 2724. CrossRef
Table of Contents

Clinical Thyroidology.2022; 34(2): 48. CrossRef
Predisposition to and Prognosis of Thyroid Cancer May Not Be Affected by Graves’ Disease, But Some Questions Still Remain
Yanrui Huang, Haixia Guan
Clinical Thyroidology.2022; 34(2): 59. CrossRef
A Comparative Follow-Up Study of Patients with Papillary Thyroid Carcinoma Associated or Not with Graves’ Disease
Andrea Marongiu, Susanna Nuvoli, Andrea De Vito, Maria Rondini, Angela Spanu, Giuseppe Madeddu
Diagnostics.2022; 12(11): 2801. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes in Patients with Long-Standing Graves’ Disease: A Longitudinal Study: Eyun Song, Min Ji Koo, Eunjin Noh, Soon Young Hwang, Min Jeong Park, Jung A Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo; Endocrinol Metab. 2021;36(6):1277-1286. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1251

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies.
Methods
The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group.
Results
A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019).
Conclusion
The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Citations

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Prevalencia de diabetes en personas con disfunción tiroidea
Juan J. Díez, Pedro Iglesias
Medicina Clínica.2023; 160(8): 333. CrossRef
Control of Thyroid Dysfunction in Spanish Population Registered in the Primary Care Clinical Database: An Analysis of the Proportion of Patients with Thyrotropin Values Outside the Reference Range
Juan J. Díez, Pedro Iglesias
Hormone and Metabolic Research.2023; 55(03): 184. CrossRef
Prevalence of thyroid dysfunction and its relationship to income level and employment status: a nationwide population-based study in Spain
Juan J. Díez, Pedro Iglesias
Hormones.2023; 22(2): 243. CrossRef
Prevalence of diabetes in people with thyroid dysfunction
Juan J. Díez, Pedro Iglesias
Medicina Clínica (English Edition).2023; 160(8): 333. CrossRef
Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves’ Disease
Ho Yeop Lee, Byeong Chang Sim, Ha Thi Nga, Ji Sun Moon, Jingwen Tian, Nguyen Thi Linh, Sang Hyeon Ju, Dong Wook Choi, Daiki Setoyama, Hyon-Seung Yi
Endocrinology and Metabolism.2022; 37(6): 891. CrossRef
Diabetes and Hyperthyroidism: Is There a Causal Link?
Sang Yong Kim
Endocrinology and Metabolism.2021; 36(6): 1175. CrossRef

Adrenal Gland
Clinical and Molecular Characteristics of PRKACA L206R Mutant Cortisol-Producing Adenomas in Korean Patients: Insoon Jang, Su-jin Kim, Ra-Young Song, Kwangsoo Kim, Seongmin Choi, Jang-Seok Lee, Min-Kyeong Gwon, Moon Woo Seong, Kyu Eun Lee, Jung Hee Kim; Endocrinol Metab. 2021;36(6):1287-1297. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1217

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: Background
An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea.
Methods
We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues.
Results
The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis.
Conclusion
The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.

Miscellaneous
Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea: Hoon Sung Choi, Jin Taek Kim, Hong Kyu Lee, Wook Ha Park, Youngmi Kim Pak, Sung Woo Lee; Endocrinol Metab. 2021;36(6):1298-1306. Published online November 26, 2021; DOI: https://doi.org/10.3803/EnM.2021.1226

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Abstract PDF PubReader ePub Crossref - TDM

Background
Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels.
Methods
We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays.
Results
During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function.
Conclusion
Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

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An Interactive Online App for Predicting Diabetes via Machine Learning from Environment-Polluting Chemical Exposure Data
Rosy Oh, Hong Kyu Lee, Youngmi Kim Pak, Man-Suk Oh
International Journal of Environmental Research and Public Health.2022; 19(10): 5800. CrossRef

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