- Diabetes, obesity and metabolism
- Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
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Nam Hoon Kim, Juneyoung Lee, Suk Chon, Jae Myung Yu, In-Kyung Jeong, Soo Lim, Won Jun Kim, Keeho Song, Ho Chan Cho, Hea Min Yu, Kyoung-Ah Kim, Sang Soo Kim, Soon Hee Lee, Chong Hwa Kim, Soo Heon Kwak, Yong‐ho Lee, Choon Hee Chung, Sihoon Lee, Heung Yong Jin, Jae Hyuk Lee, Gwanpyo Koh, Sang-Yong Kim, Jaetaek Kim, Ju Hee Lee, Tae Nyun Kim, Hyun Jeong Jeon, Ji Hyun Lee, Jae-Han Jeon, Hye Jin Yoo, Hee Kyung Kim, Hyeong-Kyu Park, Il Seong Nam-Goong, Seongbin Hong, Chul Woo Ahn, Ji Hee Yu, Jong Heon Park, Keun-Gyu Park, Chan Ho Park, Kyong Hye Joung, Ohk-Hyun Ryu, Keun Yong Park, Eun-Gyoung Hong, Bong-Soo Cha, Kyu Chang Won, Yoon-Sok Chung, Sin Gon Kim
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Endocrinol Metab. 2024;39(5):722-731. Published online August 22, 2024
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DOI: https://doi.org/10.3803/EnM.2024.1995
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Abstract
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- Background
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
- Calcium & bone metabolism
- Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019)
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Seong Hee Ahn, Eun Byeol Park, Seongha Seo, Yongin Cho, Da Hea Seo, So Hun Kim, Young Ju Suh, Seongbin Hong
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Endocrinol Metab. 2023;38(6):709-719. Published online November 7, 2023
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DOI: https://doi.org/10.3803/EnM.2023.1740
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults.
Methods This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability.
Results The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69–3.10; P=0.027–0.038), especially in daughters (OR, 2.04–4.64; P=0.029–0.034).
Conclusion HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.
- Calcium & Bone Metabolism
- Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia
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Seong Hee Ahn, Hee-Won Jung, Eunju Lee, Ji Yeon Baek, Il-Young Jang, So Jeong Park, Jin Young Lee, Eunah Choi, Yun Sun Lee, Seongbin Hong, Beom-Jun Kim
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Endocrinol Metab. 2022;37(3):487-496. Published online May 27, 2022
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DOI: https://doi.org/10.3803/EnM.2022.1428
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Abstract
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- Background
Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia.
Methods Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay.
Results The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025).
Conclusion Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.
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Citations
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Zhonghan Zhao, Kai Yan, Qiao Guan, Qiang Guo, Can Zhao Frontiers in Endocrinology.2024;[Epub] CrossRef - Musculoskeletal disorders and coronary artery disease —promising molecular markers: literature review
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Jingwen Tian, Minchul Song, Kyu Jeong Cho, Ho Yeop Lee, Sang Hyeon Ju, Jung Ryul Lim, Ha Thi Nga, Thi Linh Nguyen, Ji Sun Moon, Hyo Ju Jang, Jung-Mo Hwang, Hyon-Seung Yi Endocrinology and Metabolism.2024; 39(3): 521. CrossRef - Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue
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- Obesity and Metabolism
- Metformin-Associated Lactic Acidosis: Predisposing Factors and Outcome
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Min Ju Kim, Ju Young Han, Jun Young Shin, Shin Il Kim, Jeong Min Lee, Seongbin Hong, So Hun Kim, Moon Suk Nam, Yong Seong Kim
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Endocrinol Metab. 2015;30(1):78-83. Published online March 27, 2015
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DOI: https://doi.org/10.3803/EnM.2015.30.1.78
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- Background
Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. MethodsTo identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. ResultsSix patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. ConclusionRenal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment.
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- Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health
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Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim
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Received July 17, 2024 Accepted August 7, 2024 Published online October 24, 2024
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DOI: https://doi.org/10.3803/EnM.2024.2100
[Epub ahead of print]
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated.
Methods We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.
Results After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).
Conclusion These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.
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