Diabetes & Metabolism Journal

Sulwon Lecture 2021

Basic Research
Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c): Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim; Diabetes Metab J. 2022;46(3):402-413. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0092

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Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPR^mt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

Citations

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Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
Peptides.2024; 172: 171147. CrossRef
Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
Se Hee Min, Gil Myoung Kang, Jae Woo Park, Min-Seon Kim
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Roles of Myokines and Muscle-Derived Extracellular Vesicles in Musculoskeletal Deterioration under Disuse Conditions
Jie Zhang, Yunfang Gao, Jiangwei Yan
Metabolites.2024; 14(2): 88. CrossRef
Antifragility and antiinflammaging: Can they play a role for a healthy longevity?
Fabiola Olivieri, Francesco Prattichizzo, Fabrizia Lattanzio, Anna Rita Bonfigli, Liana Spazzafumo
Ageing Research Reviews.2023; 84: 101836. CrossRef
MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
Yuejun Zheng, Zilin Wei, Tianhui Wang
Frontiers in Endocrinology.2023;[Epub] CrossRef
MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria
Zewei Zhang, Dongmei Chen, Kaili Du, Yaping Huang, Xingzhe Li, Quwen Li, Xiaoting Lv
Mitochondrion.2023; 71: 76. CrossRef
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
Byung Soo Kong, Changhan Lee, Young Min Cho
Diabetes & Metabolism Journal.2023; 47(3): 315. CrossRef
MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake—A Preliminary Study
Remigiusz Domin, Michał Pytka, Mikołaj Żołyński, Jan Niziński, Marcin Rucinski, Przemysław Guzik, Jacek Zieliński, Marek Ruchała
International Journal of Molecular Sciences.2023; 24(19): 14951. CrossRef
Unique Properties of Apicomplexan Mitochondria
Ian M. Lamb, Ijeoma C. Okoye, Michael W. Mather, Akhil B. Vaidya
Annual Review of Microbiology.2023; 77(1): 541. CrossRef

Original Article

Cardiovascular Risk/Epidemiology
Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry: Gyung-Min Park, Chang Hoon Lee, Seung-Whan Lee, Sung-Cheol Yun, Young-Hak Kim, Yong-Giun Kim, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Dong Hyun Yang, Joon-Won Kang, Tae-Hwan Lim, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Hong-Kyu Kim, Jaewon Choe, Sang-Gon Lee; Diabetes Metab J. 2020;44(3):470-479. Published online November 22, 2019; DOI: https://doi.org/10.4093/dmj.2019.0073

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Background

There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.

Methods

We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively.

Results

Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; P=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; P=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; P<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; P<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (P=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (P=0.023).

Conclusion

Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.

Citations

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Differential Impact of Degree of Hypertension on Subclinical Coronary Atherosclerosis in Asymptomatic Subjects With and Without Diabetes Mellitus
Hyun Woo Park, Sangyong Jo, Kyung Sun Park, Hyeji Lee, Young-Jee Jeon, Sangwoo Park, Soe Hee Ann, Yong-Giun Kim, Seong Hoon Choi, Woon Jung Kwon, Young-Rak Cho, Jon Suh, Gyung-Min Park
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Exosomal MALAT1 Derived from High Glucose-Treated Macrophages Up-Regulates Resistin Expression via miR-150-5p Downregulation
Kou-Gi Shyu, Bao-Wei Wang, Wei-Jen Fang, Chun-Ming Pan, Chiu-Mei Lin
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Comparison of Framingham risk score and pooled cohort equations for the prediction of coronary atherosclerosis in patients who meet the target LDL-C level of Korean dyslipidemia guideline
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Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study
Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim
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Frequency and Significance of Right Bundle Branch Block and Subclinical Coronary Atherosclerosis in Asymptomatic Individuals
Hyeji Lee, Young-Jee Jeon, Byung Ju Kang, Tae Young Lee, Eun Ji Park, Sangwoo Park, Soe Hee Ann, Yong-Giun Kim, Yongjik Lee, Seong Hoon Choi, Gyung-Min Park
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The association between glucose-related variables and plaque morphology in patients with ST-segment elevated myocardial infarction
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Corrigendum

Corrigendum: Figure Correction. Primary Cilia as a Signaling Platform for Control of Energy Metabolism: Min-Seon Kim; Diabetes Metab J. 2018;42(4):354-354. Published online August 21, 2018; DOI: https://doi.org/10.4093/dmj.2018.0115

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Review

Pathophysiology
Primary Cilia as a Signaling Platform for Control of Energy Metabolism: Do Kyeong Song, Jong Han Choi, Min-Seon Kim; Diabetes Metab J. 2018;42(2):117-127. Published online April 19, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.117

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Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.

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MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R
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Original Articles

Others
Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial: Kyung-Wan Min, Bon Jeong Ku, Ji-Hyun Lee, Min-Seon Kim, Kyu-Jeung Ahn, Moon-Kyu Lee, Satoshi Kokubo, Satoshi Yoshida, Hyun-Ji Cho, Bong-Soo Cha; Diabetes Metab J. 2017;41(2):135-145. Published online January 11, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.2.135

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Background

This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.

Methods

This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea.

Results

Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection.

Conclusion

Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.

Citations

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Add-on therapy with dapagliflozin in routine outpatient care of type 2 diabetes patients from Turkey: a retrospective cohort study on HbA1c, body weight, and blood pressure outcomes
Derun Taner Ertugrul, Erdal Kan, Cigdem Bahadir Tura, Haci Bayram Tugtekin, Hayati Ayakta, Mehmet Celebioglu, Ceren Yılmaz, Onur Utebay, Ilhan Yetkin, Eren Gurkan, Kerem Sezer, Ramazan Gen, Suleyman Ozcaylak, Yildiz Okuturlar, Mehmet Coskun, Nilgun Govec
International Journal of Diabetes in Developing Countries.2022; 42(1): 147. CrossRef
SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients

André J Scheen
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Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial
Eugene Han, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Journal of Clinical Medicine.2020; 9(1): 259. CrossRef
Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials
Atsunori Kashiwagi, Marina V. Shestakova, Yuichiro Ito, Masahiro Noguchi, Wim Wilpshaar, Satoshi Yoshida, John P. H. Wilding
Diabetes Therapy.2019; 10(6): 2201. CrossRef
Mechanistic effects of SGLT2 inhibition on blood pressure in diabetes
Habib Yaribeygi, Stephen L. Atkin, Amirhossein Sahebkar
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2019; 13(2): 1679. CrossRef
Ipragliflozin as an add-on therapy in type 2 diabetes mellitus patients: An evidence-based pharmacoeconomics evaluation
Hongmei Wang, Gaoqiong Yao, Xi Chen, Jing Ouyang, Jiadan Yang
Diabetes Research and Clinical Practice.2019; 157: 107867. CrossRef
Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea
Eugene Han, Ari Kim, Sung Jae Lee, Je-Yon Kim, Jae Hyeon Kim, Woo Je Lee, Byung-Wan Lee
Diabetes Therapy.2018; 9(4): 1689. CrossRef
A phase 3 randomized placebo-controlled trial to assess the efficacy and safety of ipragliflozin as an add-on therapy to metformin in Russian patients with inadequately controlled type 2 diabetes mellitus
Marina V. Shestakova, John P.H. Wilding, Wim Wilpshaar, Reiner Tretter, Valeria L. Orlova, Andrey F. Verbovoy
Diabetes Research and Clinical Practice.2018; 146: 240. CrossRef
Efficacy and safety of ipragliflozin as an add‐on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial
Kyung‐Ah Han, Suk Chon, Choon Hee Chung, Soo Lim, Kwan‐Woo Lee, SeiHyun Baik, Chang Hee Jung, Dong‐Sun Kim, Kyong Soo Park, Kun‐Ho Yoon, In‐Kyu Lee, Bong‐Soo Cha, Taishi Sakatani, Sumi Park, Moon‐Kyu Lee
Diabetes, Obesity and Metabolism.2018; 20(10): 2408. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef
Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus
Min Kyong Moon, Kyu Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
The Korean Journal of Internal Medicine.2017; 32(6): 974. CrossRef
Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon, Kyu-Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
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Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea: Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee; Diabetes Metab J. 2015;39(2):126-131. Published online March 9, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.126

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Background

Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.

Methods

To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.

Results

Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.

Conclusion

The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Citations

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Case report: Insulinomatosis: description of four sporadic cases and review of the literature
Delmar Muniz Lourenço, Maria Lucia Corrêa-Giannella, Sheila Aparecida Coelho Siqueira, Marcia Nery, Flavio Galvão Ribeiro, Elizangela Pereira de Souza Quedas, Manoel de Souza Rocha, Ramon Marcelino do Nascimento, Maria Adelaide Albergaria Pereira
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Review

Molecular Mechanisms of Appetite Regulation: Ji Hee Yu, Min-Seon Kim; Diabetes Metab J. 2012;36(6):391-398. Published online December 12, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.6.391

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Abstract PDF PubReader

The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

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Original Articles

Various Oscillation Patterns of Serum Fibroblast Growth Factor 21 Concentrations in Healthy Volunteers: Sang Ah Lee, Eunheiu Jeong, Eun Hee Kim, Mi-Seon Shin, Jenie Yoonoo Hwang, Eun Hee Koh, Woo Je Lee, Joong-Yeol Park, Min-Seon Kim; Diabetes Metab J. 2012;36(1):29-36. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.29

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Abstract PDF PubReader

Background

Fibroblast growth factor 21 (FGF21) was originally identified as a paroxysm proliferator activated receptor-α target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers.

Methods

Blood samples were collected from five non-obese (body mass index [BMI] ≤23 kg/m²) and five obese (BMI ≥25 kg/m²) healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured.

Results

The serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours). The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times, P<0.001). There was no difference in the total frequency or duration of oscillations between non-obese and obese subjects, but obese individuals had increased numbers of larger oscillations (amplitude ≥0.19 ng/mL).

Conclusion

Various oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.

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Metabolic Stress Index Including Mitochondrial Biomarker for Noninvasive Diagnosis of Hepatic Steatosis
Jae Seung Chang, Jhii-Hyun Ahn, Seong Hee Kang, Sang-Baek Koh, Jang-Young Kim, Soon Koo Baik, Ji Hye Huh, Samuel S. Lee, Moon Young Kim, Kyu-Sang Park
Frontiers in Endocrinology.2022;[Epub] CrossRef
Single-Arm 8-Week Ad Libitum Self-Prepared Paleo Diet Reduces Cardiometabolic Disease Risk Factors in Overweight Adults
Melissa M. Markofski, Kristofer Jennings, Chad Dolan, Natalie A. Davies, Emily C. LaVoy, Edward J. Ryan, Andres E. Carrillo
American Journal of Lifestyle Medicine.2021; 15(6): 690. CrossRef
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Mohamed Abou El Hassan, Edgard Delvin, Manal O. Elnenaei, Barry Hoffman
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Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity
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Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23
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Fibroblast Growth Factor 21: A Novel Metabolic Regulator
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MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21
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The Prevalence of Peripheral Arterial Disease in Korean Patients with Type 2 Diabetes Mellitus Attending a University Hospital: Ji Hee Yu, Jenie Yoonoo Hwang, Mi-Seon Shin, Chang Hee Jung, Eun Hee Kim, Sang Ah Lee, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee; Diabetes Metab J. 2011;35(5):543-550. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.543

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Background

Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD.

Methods

A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI ≤0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD.

Results

Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD.

Conclusion

The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.

Citations

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Impaired Cardiovagal Activity as a Link Between Hyperglycemia and Arterial Stiffness in Adults With Type 2 Diabetes Mellitus Patients Among an Eastern Indian Population: A Cross-sectional Study
Nibedita Priyadarsini, Devineni Likhitha, Madumathy Ramachandran, Kishore Kumar Behera
Canadian Journal of Diabetes.2023;[Epub] CrossRef
The Predictability of Cystatin C for Peripheral Arterial Disease in Chinese Population with Type 2 Diabetes Mellitus
Luna Liu, Hai Wang, Jing Ning, Junming Han, Chunxiao Yu, Qingbo Guan, Hiroshi Okamoto
Journal of Diabetes Research.2022; 2022: 1. CrossRef
Atherectomy in Peripheral Artery Disease: Current and Future
Yohan Kwon, Jinoo Kim, Je-Hwan Won, Seong Ho Kim, Jeong-Eun Kim, Sung-Joon Park
Journal of the Korean Society of Radiology.2021; 82(3): 551. CrossRef
Peripheral arterial disease and its correlates in patients with type 2 diabetes mellitus in a teaching hospital in northern Nigeria: a cross-sectional study
Orighomisan Freda Agboghoroma, Fatai Momodu Akemokwe, Fabian H. Puepet
BMC Cardiovascular Disorders.2020;[Epub] CrossRef
The significance of ankle-brachial index in determining peripheral artery disease in patients with type 2 diabetes mellitus over 40 years of age and the relationship of peripheral artery disease with chronic complications of diabetes
Tuğçe Nur YİĞENOĞLU, Medine KEBAPÇI, Hülya ÖZEN
Journal of Health Sciences and Medicine.2020; 3(2): 115. CrossRef
Correlation of systemic arterial stiffness with changes in retinal and choroidal microvasculature in type 2 diabetes
Mirinae Kim, Rae-Young Kim, Joo-Young Kim, Young-Hoon Park
Scientific Reports.2019;[Epub] CrossRef
Abnormally Low or High Ankle-Brachial Index Is Associated With the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus
Mei-Yueh Lee, Pi-Jung Hsiao, Jiun-Chi Huang, Wei-Hao Hsu, Szu-Chia Chen, Jer-Ming Chang, Shyi–Jang Shin
Scientific Reports.2018;[Epub] CrossRef
Peripheral Arterial Disease in Type 2 Diabetes Is Associated with an Increase in Fibrinogen Levels
Qin-Fen Chen, Dan Cao, Ting-Ting Ye, Hui-Hui Deng, Hong Zhu
International Journal of Endocrinology.2018; 2018: 1. CrossRef
Association between peripheral arterial disease and diabetic foot ulcers in patients with diabetes mellitus type 2
M.Á. Tresierra-Ayala, A. García Rojas
Medicina Universitaria.2017; 19(76): 123. CrossRef
Factors associated with lower extremity atherosclerotic disease in Chinese patients with type 2 diabetes mellitus
Qingge Gao, Binbin He, Chaoyu Zhu, Yuanyuan Xiao, Li Wei, Weiping Jia
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Significant interarm blood pressure difference predicts cardiovascular risk in hypertensive patients
Su-A Kim, Jang Young Kim, Jeong Bae Park
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7^th Asian PAD Workshop

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6^th Asian PAD Workshop

Annals of Vascular Diseases.2015; 8(2): 135. CrossRef
Abnormally Low or High Ankle-Brachial Index Is Associated with Proliferative Diabetic Retinopathy in Type 2 Diabetic Mellitus Patients
Szu-Chia Chen, Pi-Jung Hsiao, Jiun-Chi Huang, Kun-Der Lin, Wei-Hao Hsu, Yu-Li Lee, Mei-Yueh Lee, Jer-Ming Chang, Shyi–Jang Shin, Xiao-Feng Yang
PLOS ONE.2015; 10(7): e0134718. CrossRef
Identification of peripheral arterial disease in diabetic patients and its association with quality of life, physical activity and body composition
Ana Tereza do Nascimento Sales, Guilherme Augusto de Freitas Fregonezi, Ana Gabriela Câmara Batista Silva, Cibele Teresinha Dias Ribeiro, Mario Emílio Teixeira Dourado-Junior, André Gustavo Pires Sousa, Fernando Augusto Lavezzo Dias
Jornal Vascular Brasileiro.2015; 14(1): 46. CrossRef
Chronic venous ulceration of leg associated with peripheral arterial disease: an underappreciated entity in developing country
Falguni Nag, Abhishek De, Avijit Hazra, Gobinda Chatterjee, Arghyaprasun Ghosh, Trupti V Surana
International Wound Journal.2014; 11(5): 546. CrossRef
Photoplethysmography and Continuous-Wave Doppler Ultrasound as a Complementary Test to Ankle–Brachial Index in Detection of Stenotic Peripheral Arterial Disease
Du Hyun Ro, Hyuk Ju Moon, Ji Hyeung Kim, Kyoung Min Lee, Sung Ju Kim, Dong Yeon Lee
Angiology.2013; 64(4): 314. CrossRef
Ankle brachial index as a predictor of subclinical atherosclerosis in the elderly
Ilker Tasci, Samet Verim, Hasan Kutsi Kabul, Aydogan Aydogdu
International Journal of Cardiology.2012; 160(2): 147. CrossRef
Low ankle-brachial index is an independent predictor of poor functional outcome in acute cerebral infarction
Jinkwon Kim, Dong Hyun Lee, Myoung-Jin Cha, Tae-Jin Song, Ji Hye Park, Hye Sun Lee, Chung Mo Nam, Hyo Suk Nam, Young Dae Kim, Ji Hoe Heo
Atherosclerosis.2012; 224(1): 113. CrossRef
Letter: The Prevalence of Peripheral Arterial Disease in Korean Patients with Type 2 Diabetes Mellitus Attending a University Hospital (Diabetes Metab J 2011;35:543-50)
Won Jun Kim, Cheol-Young Park
Diabetes & Metabolism Journal.2011; 35(6): 637. CrossRef

Homocysteine as a Risk Factor for Development of Microalbuminuria in Type 2 Diabetes: Eun-Hee Cho, Eun Hee Kim, Won Gu Kim, Eun Hui Jeong, Eun Hee Koh, Woo-Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee; Korean Diabetes J. 2010;34(3):200-206. Published online June 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.3.200

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Background

Kidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes.

Methods

A nested case-control study. Of 887 patients with type 2 diabetes who did not have microalbuminuria at baseline, 76 developed microalbuminuria during follow-up (mean, 36.0 ± 11.7 months; range, 18 to 76 months). The control group consisted of 152 age- and sex-matched subjects who did not develop microalbuminuria. Baseline plasma homocysteine concentrations were measured in stored samples.

Results

Baseline plasma homocysteine concentrations and mean HbA1C levels during follow-up were significantly higher in patients who developed microalbuminuria than in those who remained normoalbuminuric. Multivariate logistic regression analysis showed that baseline plasma homocysteine level and mean HbA1C were independent predictors of microalbuminuria in type 2 diabetes.

Conclusion

Hyperhomocysteinemia was associated with increased risk of microalbuminuria in patients with type 2 diabetes supporting the concept that hyperhomocysteinemia has an etiologic role in the pathogenesis of diabetic nephropathy.

Citations

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Homocysteine and diabetes: Role in macrovascular and microvascular complications
Emir Muzurović, Ivana Kraljević, Mirsala Solak, Siniša Dragnić, Dimitri P. Mikhailidis
Journal of Diabetes and its Complications.2021; 35(3): 107834. CrossRef
Associations of Homocysteine with B Vitamins and Zinc in Serum Levels of Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study
Sadako MATSUI, Chika HIRAISHI, Ryo SATO, Takai KOJIMA, Kiyotaka ANDO, Kei FUJIMOTO, Hiroshi YOSHIDA
Journal of Nutritional Science and Vitaminology.2021; 67(6): 417. CrossRef
A risk scoring system for the decreased glomerular filtration rate in Chinese general population
Yan Gu, Min Chen, Bei Zhu, Xiaohua Pei, Zhenzhu Yong, Xiaona Li, Qun Zhang, Weihong Zhao
Journal of Clinical Laboratory Analysis.2020;[Epub] CrossRef
Relationship between plasma total homocysteine and the severity of renal function in Chinese patients with type 2 diabetes mellitus aged ≥75 years
Ning Ma, Ning Xu, Dong Yin, Weiwei Liu, Mengping Wu, Xingbo Cheng
Medicine.2020; 99(27): e20737. CrossRef
Correlation between serum homocysteine level and ulcerative colitis: A meta-analysis
Yifang Zhong, Feng Yan, Weixia Jie, Ying Zhou, Fang Fang
Pteridines.2019; 30(1): 114. CrossRef
The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis
A. M. Burdennyy, V. I. Loginov, T. M. Zavarykina, E. A. Braga, A. A. Kubatiev
Russian Journal of Genetics.2017; 53(5): 528. CrossRef
МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЕ НАРУШЕНИЯ ГЕНОВ ФОЛАТНОГО И ГОМОЦИСТЕИНОВОГО ОБМЕНА В ПАТОГЕНЕЗЕ РЯДА МНОГОФАКТОРНЫХ ЗАБОЛЕВАНИЙ, "Генетика"
А. М. Бурдённый, В.И. Логинов, Т.М. Заварыкина, Э.А. Брага, А.А. Кубатиев
Генетика.2017; (5): 526. CrossRef
Association Between Plasma Homocysteine and Microalbuminuria in Untreated Patients with Essential Hypertension: a Case-Control Study
Ze-min Kuang, Ying Wang, Shu-jun Feng, Long Jiang, Wen-li Cheng
Kidney and Blood Pressure Research.2017; 42(6): 1303. CrossRef
NMDA Receptors as Potential Therapeutic Targets in Diabetic Nephropathy: Increased Renal NMDA Receptor Subunit Expression in Akita Mice and Reduced Nephropathy Following Sustained Treatment With Memantine or MK-801
Hila Roshanravan, Eun Young Kim, Stuart E. Dryer
Diabetes.2016; 65(10): 3139. CrossRef
Association between homocysteine status and the risk of nephropathy in type 2 diabetes mellitus
Song Mao, Wei Xiang, Songming Huang, Aihua Zhang
Clinica Chimica Acta.2014; 431: 206. CrossRef
Prevalence and Determinants of Diabetic Nephropathy in Korea: Korea National Health and Nutrition Examination Survey
Jae Hee Ahn, Ji Hee Yu, Seung-Hyun Ko, Hyuk-Sang Kwon, Dae Jung Kim, Jae Hyeon Kim, Chul Sik Kim, Kee-Ho Song, Jong Chul Won, Soo Lim, Sung Hee Choi, Kyungdo Han, Bong-Yun Cha, Nan Hee Kim
Diabetes & Metabolism Journal.2014; 38(2): 109. CrossRef
Plasma Homocysteine level and its clinical correlation with type 2 diabetes mellitus and its complications
Satyendra Kumar Sonkar, Gyanendra Kumar Sonkar, Deepika Soni, Dheeraj Soni, Kauser Usman
International Journal of Diabetes in Developing Countries.2014; 34(1): 3. CrossRef
Genetic Predisposition for Development of Nephropathy in Type 2 Diabetes Mellitus
Ravindra Kumar, Raj Kumar Sharma, Sarita Agarwal
Biochemical Genetics.2013; 51(11-12): 865. CrossRef
Is C677T Polymorphism in Methylenetetrahydrofolate Reductase Gene a Risk Factor for Diabetic Nephropathy or Diabetes Mellitus in a Chinese Population?
Wen-peng Cui, Bing Du, Ye Jia, Wen-hua Zhou, Sheng-mao Liu, Ying-chun Cui, Fu-zhe Ma, Ping Luo, Li-ning Miao
Archives of Medical Research.2012; 43(1): 42. CrossRef
The role of coagulation and inflammation in the development of diabetic nephropathy in patients withdiabetes mellitus type 2
Yulia Valer'evna Khasanova, Alsu Asatovna Nelaeva, Anna Borisovna Galkina, Irina Vasil'evna Medvedeva
Diabetes mellitus.2012; 15(1): 31. CrossRef

Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients: Eun Hee Kim, Ji Hee Yu, Sang Ah Lee, Eui Young Kim, Won Gu Kim, Seung Hun Lee, Eun Hee Cho, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee; Korean Diabetes J. 2010;34(2):95-100. Published online April 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.2.95

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Abstract PDF PubReader

Background

Serum cystatin C level is a more sensitive marker of renal dysfunction than serum creatinine level. Serum cystatin C level was recently reported to predict the development of cardiovascular disease. This study was performed to evaluate whether the cystatin C level is associated with coronary artery disease (CAD), independent of diabetic nephropathy.

Methods

We conducted a case-control study to assess the relationship between serum cystatin C level and coronary artery disease in diabetic patients. Among 460 diabetic patients, 38 diabetic patients had CAD. The control group consisted of 38 diabetic patients who were matched to cases by age, sex, and presence/absence of diabetic nephropathy. Serum cystatin C level was measured in stored samples.

Results

Serum cystatin C level was significantly higher in patients with diabetic nephropathy, both in CAD and non-CAD patients. However, serum cystatin C level did not differ between CAD and non-CAD patients, regardless of diabetic nephropathy.

Conclusion

Serum cystatin C level is a marker of renal dysfunction, but not coronary artery disease, in diabetic patients.

Citations

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Higher Levels of Cystatin C in HIV/AIDS Patients with Metabolic Syndrome
Gordana Dragović, Danica Srdić, Khawla Al Musalhi, Ivan Soldatović, Jovana Kušić, Djordje Jevtović, Devaki Nair
Basic & Clinical Pharmacology & Toxicology.2018; 122(4): 396. CrossRef
The association between serum cystatin C and carotid intima–media thickness in metabolic syndrome patients with normal estimated glomerular filtration rate
Rong Huang, Jingli Gu, Qin Cao, Jiahua Ma, Weiwei Gu, Zhuping Fan
Clinica Chimica Acta.2015; 448: 170. CrossRef
Association of plasma cystatin C levels with angiographically documented coronary artery disease in patients of Indian origin
Aditya Batra, Aditya Kapoor, R.K. Sharma, Nitin Agrawal, Archana Sinha, Sudeep Kumar, Naveen Garg, Satyendra Tewari, Pravin K. Goel
Journal of Cardiology.2012; 59(2): 182. CrossRef
Cystatin C and asymptomatic coronary artery disease in patients with metabolic syndrome and normal glomerular filtration rate
Xie Qing, Wang Furong, Liu Yunxia, Zhang Jian, Wang Xuping, Gao Ling
Cardiovascular Diabetology.2012;[Epub] CrossRef
Response: Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients (Korean Diabetes J 2010;34:95-100)
Eun Hee Kim, Ki-Up Lee
Korean Diabetes Journal.2010; 34(3): 209. CrossRef
Serum Cystatin C as a Biomarker for Predicting Coronary Artery Disease in Diabetes
Jee-Young Oh
Korean Diabetes Journal.2010; 34(2): 84. CrossRef
Letter: Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients (Korean Diabetes J 2010;34:95-100)
Kyu-Chang Won
Korean Diabetes Journal.2010; 34(3): 207. CrossRef

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