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Volume 31(1); March 2016
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Namgok Lecture 2015
Obesity and Metabolism
The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis
Kyung Mook Choi
Endocrinol Metab. 2016;31(1):1-6.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.1
  • 4,662 View
  • 63 Download
  • 38 Web of Science
  • 39 Crossref
AbstractAbstract PDFPubReader   

Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis.

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Close layer
Review Articles
Obesity and Metabolism
Understanding Metabolomics in Biomedical Research
Su Jung Kim, Su Hee Kim, Ji Hyun Kim, Shin Hwang, Hyun Ju Yoo
Endocrinol Metab. 2016;31(1):7-16.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.7
  • 6,486 View
  • 121 Download
  • 45 Web of Science
  • 42 Crossref
AbstractAbstract PDFPubReader   

The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced.

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Close layer
Small Heterodimer Partner and Innate Immune Regulation
Jae-Min Yuk, Hyo Sun Jin, Eun-Kyeong Jo
Endocrinol Metab. 2016;31(1):17-24.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.17
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AbstractAbstract PDFPubReader   

The nuclear receptor superfamily consists of the steroid and non-steroid hormone receptors and the orphan nuclear receptors. Small heterodimer partner (SHP) is an orphan family nuclear receptor that plays an essential role in the regulation of glucose and cholesterol metabolism. Recent studies reported a previously unidentified role for SHP in the regulation of innate immunity and inflammation. The innate immune system has a critical function in the initial response against a variety of microbial and danger signals. Activation of the innate immune response results in the induction of inflammatory cytokines and chemokines to promote anti-microbial effects. An excessive or uncontrolled inflammatory response is potentially harmful to the host, and can cause tissue damage or pathological threat. Therefore, the innate immune response should be tightly regulated to enhance host defense while preventing unwanted immune pathologic responses. In this review, we discuss recent studies showing that SHP is involved in the negative regulation of toll-like receptor-induced and NLRP3 (NACHT, LRR and PYD domains-containing protein 3)-mediated inflammatory responses in innate immune cells. Understanding the function of SHP in innate immune cells will allow us to prevent or modulate acute and chronic inflammation processes in cases where dysregulated innate immune activation results in damage to normal tissues.

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Bone Metabolism
Dual-Energy X-Ray Absorptiometry: Beyond Bone Mineral Density Determination
Yong Jun Choi
Endocrinol Metab. 2016;31(1):25-30.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.25
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AbstractAbstract PDFPubReader   

Significant improvements in dual-energy X-ray absorptiometry (DXA) concerning quality, image resolution and image acquisition time have allowed the development of various functions. DXA can evaluate bone quality by indirect analysis of micro- and macro-architecture of the bone, which and improve the prediction of fracture risk. DXA can also detect existing fractures, such as vertebral fractures or atypical femur fractures, without additional radiologic imaging and radiation exposure. Moreover, it can assess the metabolic status by the measurement of body composition parameters like muscle mass and visceral fat. Although more studies are required to validate and clinically use these parameters, it is clear that DXA is not just for bone mineral densitometry.

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Adrenal gland
In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use
Su Han Cho, Jang Hoe Kim, Wook Song
Endocrinol Metab. 2016;31(1):31-37.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.31
  • 3,359 View
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AbstractAbstract PDFPubReader   

Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies.

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Adrenal gland
How to Establish Clinical Prediction Models
Yong-ho Lee, Heejung Bang, Dae Jung Kim
Endocrinol Metab. 2016;31(1):38-44.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.38
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AbstractAbstract PDFPubReader   

A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice.

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Close layer
Adrenal gland
In Vivo Models for Incretin Research: From the Intestine to the Whole Body
Tae Jung Oh
Endocrinol Metab. 2016;31(1):45-51.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.45
  • 3,765 View
  • 51 Download
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AbstractAbstract PDFPubReader   

Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or β-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones.

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Close layer
Mechanisms of Vascular Calcification: The Pivotal Role of Pyruvate Dehydrogenase Kinase 4
Jaechan Leem, In-Kyu Lee
Endocrinol Metab. 2016;31(1):52-61.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.52
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  • 65 Download
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AbstractAbstract PDFPubReader   

Vascular calcification, abnormal mineralization of the vessel wall, is frequently associated with aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Vascular calcification is a key risk factor for many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. Vascular calcification was long considered to be a passive degenerative process, but it is now recognized as an active and highly regulated process similar to bone formation. However, despite numerous studies on the pathogenesis of vascular calcification, the mechanisms driving this process remain poorly understood. Pyruvate dehydrogenase kinases (PDKs) play an important role in the regulation of cellular metabolism and mitochondrial function. Recent studies show that PDK4 is an attractive therapeutic target for the treatment of various metabolic diseases. In this review, we summarize our current knowledge regarding the mechanisms of vascular calcification and describe the role of PDK4 in the osteogenic differentiation of vascular smooth muscle cells and development of vascular calcification. Further studies aimed at understanding the molecular mechanisms of vascular calcification will be critical for the development of novel therapeutic strategies.

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Editorial
Thyroid
Differentiated Thyroid Cancer in Asians
Bo Hyun Kim
Endocrinol Metab. 2016;31(1):62-63.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.62
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PDFPubReader   
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Original Articles
Clinical Study
Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption
Han Seok Choi, Kwang Joon Kim, Yumie Rhee, Sung-Kil Lim
Endocrinol Metab. 2016;31(1):64-71.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.64
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AbstractAbstract PDFPubReader   
Background

γ-Glutamyl transferase (GGT) is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD) in Korean adults.

Methods

A total of 462 subjects (289 men and 173 women), who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated.

Results

As serum GGT levels increased from the lowest tertile (tertile 1) to the highest tertile (tertile 3), BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women), hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002).

Conclusion

Serum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship.

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Clinical Study
Well-Differentiated Thyroid Cancer: The Philippine General Hospital Experience
Tom Edward N. Lo, Abigail T. Uy, Patricia Deanna D. Maningat
Endocrinol Metab. 2016;31(1):72-79.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.72
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  • 48 Download
  • 20 Web of Science
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AbstractAbstract PDFPubReader   
Background

Well-differentiated thyroid cancer (WDTC) is the most common form of thyroid malignancy. While it is typically associated with good prognosis, it may exhibit higher recurrence and mortality rates in selected groups, particularly Filipinos. This paper aims to describe the experience of a Philippine Hospital in managing patients with differentiated thyroid cancer.

Methods

We performed a retrospective cohort study of 723 patients with WDTC (649 papillary and 79 follicular), evaluating the clinicopathologic profiles, ultrasound features, management received, tumor recurrence, and eventual outcome over a mean follow-up period of 5 years.

Results

The mean age at diagnosis was 44±13 years (range, 18 to 82), with a majority of cases occurring in the younger age group (<45 years). Most tumors were between 2 and 4 cm in size. The majority of papillary thyroid cancers (PTCs, 63.2%) and follicular thyroid cancers (FTCs, 54.4%) initially presented as stage 1, with a greater proportion of FTC cases (12.7% vs. 3.7%) presenting with distant metastases. Nodal metastases at presentation were more frequent among patients with PTC (29.9% vs. 7.6%). A majority of cases were treated by complete thyroidectomy, followed by radioactive iodine therapy and thyroid stimulating hormone suppression, resulting in a disease-free state. Excluding patients with distant metastases at presentation, the recurrence rates for papillary and FTC were 30.1% and 18.8%, respectively.

Conclusion

Overall, PTC among Filipinos was associated with a more aggressive and recurrent behavior. FTC among Filipinos appeared to behave similarly with other racial groups.

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Close layer
Clinical Study
Effects of Short-Term Exenatide Treatment on Regional Fat Distribution, Glycated Hemoglobin Levels, and Aortic Pulse Wave Velocity of Obese Type 2 Diabetes Mellitus Patients
Ju-Young Hong, Keun-Young Park, Byung-Joon Kim, Won-Min Hwang, Dong-Ho Kim, Dong-Mee Lim
Endocrinol Metab. 2016;31(1):80-85.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.80
  • 4,618 View
  • 42 Download
  • 26 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   
Background

Most type 2 diabetes mellitus patients are obese and have obesity related vascular complications. Exenatide treatment is well known for both decreasing glycated hemoglobin levels and reduction in body weight. So, this study aimed to determine the effects of exenatide on body composition, glycated hemoglobin levels, and vascular stiffness in obese type 2 diabetes mellitus patients.

Methods

For 1 month, 32 obese type 2 diabetes mellitus patients were administered 5 µg of exenatide twice daily. The dosage was then increased to 10 µg. Patients' height, body weight, glycated hemoglobin levels, lipid profile, pulse wave velocity (PWV), body mass index, fat mass, and muscle mass were measured by using Inbody at baseline and after 3 months of treatment.

Results

After 3 months of treatment, glycated hemoglobin levels decreased significantly (P=0.007). Triglyceride, total cholesterol, and low density lipoprotein levels decreased, while aspartate aminotransferase and alanine aminotransferase levels were no change. Body weight, and fat mass decreased significantly (P=0.002 and P=0.001, respectively), while interestingly, muscle mass did not decrease (P=0.289). In addition to, Waist-to-hip ratio and aortic PWV decreased significantly (P=0.006 and P=0.001, respectively).

Conclusion

Effects of short term exenatide use in obese type 2 diabetes mellitus with cardiometabolic high risk patients not only reduced body weight without muscle mass loss, body fat mass, and glycated hemoglobin levels but also improved aortic PWV in accordance with waist to hip ratio.

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    Qiuhe Ji
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Close layer
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
  • 4,392 View
  • 39 Download
  • 21 Web of Science
  • 23 Crossref
AbstractAbstract PDFPubReader   
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.

Citations

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    Dana Kablawi, Faisal Aljohani, Chiara Saroli Palumbo, Sophie Restellini, Alain Bitton, Gary Wild, Waqqas Afif, Peter L Lakatos, Talat Bessissow, Giada Sebastiani
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    Adriana Cervo, Giada Sebastiani, Jovana Milic, Thomas Krahn, Sergio Mazzola, Salvatore Petta, Antonio Cascio, Giovanni Guaraldi, Giovanni Mazzola
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    Grazia Pennisi, Vito Di Marco, Carola Buscemi, Giovanni Mazzola, Cristiana Randazzo, Federica Spatola, Antonio Craxì, Silvio Buscemi, Salvatore Petta
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    Jiwon Kim, Minyoung Lee, Soo Yeon Kim, Ji-Hye Kim, Ji Sun Nam, Sung Wan Chun, Se Eun Park, Kwang Joon Kim, Yong-ho Lee, Joo Young Nam, Eun Seok Kang
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Close layer
Clinical Study
High Levels of Serum DPP-4 Activity Are Associated with Low Bone Mineral Density in Obese Postmenopausal Women
Sang-Wook Kim, Eun-Hee Cho
Endocrinol Metab. 2016;31(1):93-99.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.93
  • 3,333 View
  • 38 Download
  • 10 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women.

Methods

We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] ≥25 kg/m2) and non-obese (BMI <25 kg/m2) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups.

Results

A total of 124 postmenopausal women was enrolled, with a mean age of 59.9±7.1 years. The mean BMI of the study patients was 24.4±2.8 kg/m2. Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=−0.288, P=0.038) with BMD of the spine in obese postmenopausal women.

Conclusion

This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women.

Citations

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    Eun-Hee Cho, Sang-Wook Kim
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    Qiwen Li, Yunshu Wu, Ning Kang
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Close layer
Clinical Study
Low Prevalence of Somatic TERT Promoter Mutations in Classic Papillary Thyroid Carcinoma
Min Ji Jeon, Won Gu Kim, Soyoung Sim, Seonhee Lim, Hyemi Kwon, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2016;31(1):100-104.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.100
  • 4,161 View
  • 31 Download
  • 16 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   
Background

Transcriptional activating mutations of telomerase reverse transcriptase (TERT) are associated with more aggressive thyroid cancer. We evaluated the significance of TERT promoter mutations in Korean patients with classic papillary thyroid cancer (PTC).

Methods

Genomic DNA was isolated from four thyroid cancer cell lines and 35 fresh-frozen PTC tissues. TERT promoter mutations (C228T and C250T) and the BRAF V600E mutation were evaluated by polymerase chain reaction amplification and direct sequencing.

Results

The CC228229TT mutation in the TERT promoter was detected in BCPAP cells and the C250T mutation was found in 8505C cells. No TERT promoter mutation was observed in Cal-62 or ML-1 cells. The C228T mutation was found in only 1 of 35 (2.8%) PTCs and no C250T mutations were detected in any of the study subjects. The BRAF V600E mutation was found in 20 of 35 (57.1%) PTCs. One patient with the C228T TERT mutation also harbored the BRAF V600E mutation and developed a recurrence.

Conclusion

The prevalence of somatic TERT promoter mutations was low in Korean patients with classic PTC. Therefore, the prognostic role of TERT promoter mutations might be limited in this patient cohort.

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Endocrinol Metab : Endocrinology and Metabolism