Publications by authors named "Eun-Jung Rhee"

224 Publications

Best Achievements in Clinical Medicine in Diabetes and Dyslipidemia in 2020.

Endocrinol Metab (Seoul) 2021 Feb 24;36(1):41-50. Epub 2021 Feb 24.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Over the last two decades, our understanding of diabetes and treatment strategies have evolved tremendously, from scientific, mechanistic, and human perspectives. The categories of anti-diabetic medications expanded from a few to numerous, enabling clinicians to personalize diabetes care and treatment. Thanks to rapid growth in the field of science and medical engineering, newer treatment options are coming to the market with various advantages and disadvantages to be aware of. Therefore, clinicians should rapidly adopt new trends based on guidelines and data from many clinical trials in the field of diabetes. In the treatment of dyslipidemia, trends and guidelines are changing every year, and novel therapies are being developed. In this review, we would like to summarize the major achievements in clinical medicine in 2020 in the field of diabetes mellitus and dyslipidemia.
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http://dx.doi.org/10.3803/EnM.2021.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937849PMC
February 2021

Dose-Dependent Effect of Smoking on Risk of Diabetes Remains after Smoking Cessation: A Nationwide Population-Based Cohort Study in Korea.

Diabetes Metab J 2021 Mar 4. Epub 2021 Mar 4.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: This study aimed to evaluate the dose-dependent effects of smoking on risk of diabetes among those quitting smoking.

Methods: We analyzed clinical data from a total of 5,198,792 individuals age 20 years or older who received health care check-up arranged by the national insurance program of Korea between 2009 and 2016 using the Korean National Health Insurance Service database. Cumulative smoking was estimated by pack-years. Smokers were classified into four categories according to the amount of smoking: light smokers (0.025 to 5 smoking pack-years), medium smokers (5 to 14 smoking pack-years), heavy smokers (14 to 26 smoking pack-years), and extreme smokers (more than 26 smoking pack-years).

Results: During the study period, 164,335 individuals (3.2% of the total population) developed diabetes. Compared to sustained smokers, the risk of diabetes was significantly reduced in both quitters (hazard ratio [HR], 0.858; 95% confidence interval [CI], 0.838 to 0.878) and nonsmokers (HR, 0.616; 95% CI, 0.606 to 0.625) after adjustment for multiple risk factors. The risk of diabetes gradually increased with amount of smoking in both quitters and current smokers. The risk of diabetes in heavy (HR, 1.119; 95% CI, 1.057 to 1.185) and extreme smokers (HR, 1.348; 95% CI, 1.275 to 1.425) among quitters was much higher compared to light smokers among current smokers.

Conclusion: Smoking cessation was effective in reducing the risk of diabetes regardless of weight change. However, there was a potential dose-dependent association between smoking amount and the development of diabetes. Diabetes risk still remained in heavy and extreme smokers even after smoking cessation.
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http://dx.doi.org/10.4093/dmj.2020.0061DOI Listing
March 2021

New Model for Predicting the Presence of Coronary Artery Calcification.

J Clin Med 2021 Jan 25;10(3). Epub 2021 Jan 25.

Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Korea.

Coronary artery calcification (CAC) is a feature of coronary atherosclerosis and a well-known risk factor for cardiovascular disease (CVD). As the absence of CAC is associated with a lower incidence rate of CVD, measurement of a CAC score is helpful for risk stratification when the risk decision is uncertain. This was a retrospective study with an aim to build a model to predict the presence of CAC (i.e., CAC score = 0 or not) and evaluate the discrimination and calibration power of the model. Our data set was divided into two set (80% for training set and 20% for test set). Ten-fold cross-validation was applied with ten times of interaction in each fold. We built prediction models using logistic regression (LRM), classification and regression tree (CART), conditional inference tree (CIT), and random forest (RF). A total of 3,302 patients from two cohorts (Soonchunhyang University Cheonan Hospital and Kangbuk Samsung Health Study) were enrolled. These patients' ages were between 40 and 75 years. All models showed acceptable accuracies (LRM, 70.71%; CART, 71.32%; CIT, 71.32%; and RF, 71.02%). The decision tree model using CART and CIT showed a reasonable accuracy without complexity. It could be implemented in real-world practice.
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http://dx.doi.org/10.3390/jcm10030457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865676PMC
January 2021

Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study (Diabetes Metab J 2020;44:737-46).

Diabetes Metab J 2020 12 23;44(6):942-943. Epub 2020 Dec 23.

Department of Endocrinology and Metabolism, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.4093/dmj.2020.0266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801754PMC
December 2020

Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study.

Diabetes Metab J 2020 Dec 11. Epub 2020 Dec 11.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Previous studies have suggested that depression in patients with diabetes is associated with worse health outcomes. The aim of this study was to evaluate the risk of cardiovascular disease (CVD) and mortality in patients with diabetes with comorbid depression.

Methods: We examined the general health check-up data and claim database of the Korean National Health Insurance Service (NHIS) of 2,668,615 participants with type 2 diabetes mellitus who had examinations between 2009 and 2012. As NHIS database has been established since 2002, those who had been diagnosed with depression or CVD since 2002 were excluded. The 2,228,443 participants were classified into three groups according to the claim history of depression; normal group (n=2,166,979), transient depression group (one episode of depression, n=42,124) and persistent depression group (at least two episodes of depression, n=19,340). The development of CVD and mortality were analyzed from 2009 to 2017.

Results: Those with depression showed a significantly increased risk for stroke (transient depression group: hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.15 to 1.26) (persistent depression group: HR, 1.54; 95% CI, 1.46 to 1.63). Those with depression had an increased risk for myocardial infarction (transient depression group: HR, 1.25; 95% CI, 1.18 to 1.31) (persistent depression group: HR, 1.38; 95% CI, 1.29 to 1.49). The persistent depression group had an increased risk for all-cause mortality (HR, 1.66; 95% CI, 1.60 to 1.72).

Conclusion: Coexisting depression in patients with diabetes has a deleterious effect on the development of CVD and mortality. We suggest that more attention should be given to patients with diabetes who present with depressive symptoms.
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http://dx.doi.org/10.4093/dmj.2020.0008DOI Listing
December 2020

Clusterin Protects Lipotoxicity-Induced Apoptosis via Upregulation of Autophagy in Insulin-Secreting Cells.

Endocrinol Metab (Seoul) 2020 12 2;35(4):943-953. Epub 2020 Dec 2.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: There is a great need to discover factors that could protect pancreatic β-cells from apoptosis and thus prevent diabetes mellitus. Clusterin (CLU), a chaperone protein, plays an important role in cell protection in numerous cells and is involved in various cellular mechanisms, including autophagy. In the present study, we investigated the protective role of CLU through autophagy regulation in pancreatic β-cells.

Methods: To identify the protective role of CLU, mouse insulinoma 6 (MIN6) cells were incubated with CLU and/or free fatty acid (FFA) palmitate, and cellular apoptosis and autophagy were examined.

Results: Treatment with CLU remarkably upregulated microtubule-associated protein 1-light chain 3 (LC3)-II conversion in a doseand time-dependent manner with a significant increase in the autophagy-related 3 (Atg3) gene expression level, which is a mediator of LC3-II conversion. Moreover, co-immunoprecipitation and fluorescence microscopy experiments showed that the molecular interaction of LC3 with Atg3 and p62 was markedly increased by CLU. Stimulation of LC3-II conversion by CLU persisted in lipotoxic conditions, and FFA-induced apoptosis and dysfunction were simultaneously improved by CLU treatment. Finally, inhibition of LC3-II conversion by Atg3 gene knockdown markedly attenuated the cytoprotective effect of CLU.

Conclusion: Taken together, these findings suggest that CLU protects pancreatic β-cells against lipotoxicity-induced apoptosis via autophagy stimulation mediated by facilitating LC3-II conversion. Thus, CLU has therapeutic effects on FFA-induced pancreatic β-cell dysfunction.
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http://dx.doi.org/10.3803/EnM.2020.768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803614PMC
December 2020

Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults.

Diabetes Metab J 2020 Oct 21;44(5):783. Epub 2020 Oct 21.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4093/dmj.2020.0245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643593PMC
October 2020

Response: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601).

Diabetes Metab J 2020 10 21;44(5):781-782. Epub 2020 Oct 21.

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4093/dmj.2020.0221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643602PMC
October 2020

Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study.

Diabetes Metab J 2020 10 21;44(5):737-746. Epub 2020 Oct 21.

Department of Endocrinology and Metabolism, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea.

Methods: Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities.

Results: Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P<0.001) for ventilator use, and an aOR of 2.659 (95% CI, 1.896 to 3.729; P<0.001) for mortality.

Conclusion: Diabetes was associated with worse clinical outcomes in Korean patients with COVID-19, independent of other comorbidities. Therefore, patients with diabetes and COVID-19 should be treated with caution.
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http://dx.doi.org/10.4093/dmj.2020.0141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643598PMC
October 2020

Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study.

Endocrinol Metab (Seoul) 2020 09 22;35(3):610-617. Epub 2020 Sep 22.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes.

Methods: Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis.

Results: The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=-0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006).

Conclusion: Transferrin is positively associated with incident type 2 diabetes in Koreans.
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http://dx.doi.org/10.3803/EnM.2020.721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520588PMC
September 2020

2018 Guidelines for the Management of Dyslipidemia in Korea.

J Lipid Atheroscler 2019 Sep 7;8(2):78-131. Epub 2019 Aug 7.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.12997/jla.2019.8.2.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379116PMC
September 2019

Metformin, resveratrol, and exendin-4 inhibit high phosphate-induced vascular calcification via AMPK-RANKL signaling.

Biochem Biophys Res Commun 2020 09 13;530(2):374-380. Epub 2020 Aug 13.

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 03181, Republic of Korea. Electronic address:

Vascular calcification increases the risk of developing cardiovascular disease, and it is closely associated with metabolic disorders such as diabetes mellitus and non-alcoholic fatty liver disease. We investigated whether the activators of AMP-activated protein kinase (AMPK), metformin, resveratrol, and exendin-4, improved inorganic phosphate (Pi)-induced vascular calcification in rat vascular smooth muscle cells (VSMCs) and whether these effects were via AMPK. Pi increased calcium deposition in a dose-dependent manner, and metformin, resveratrol, and exendin-4 significantly decreased calcium deposition in the Pi-treated VSMCs. Moreover, metformin and exendin-4 increased the expression of a SMC marker gene, α-smooth muscle actin, and Ampk and reduced the receptor activator of nuclear factor kappa-Β ligand (Rankl)/osteoprotegerin ratio. Metformin, resveratrol, and exendin-4 reduced the expression of osteoblast differentiation-associated factors, such as runt-related transcription factor 2, bone morphogenic protein-2, p-small mothers against decapentaplegic 1/5/8, and Rankl. Inhibition of AMPK by siRNA adversely affected the anti-calcification effects of metformin, resveratrol, and exendin-4 and reversed the reduction of the expression of Rankl by metformin and exendin-4 in the Pi-treated VSMCs. These data suggest that metformin, resveratrol, and exendin-4 ameliorate Pi-induced vascular calcification by inhibiting osteoblast differentiation of VSMCs, which is mediated by AMPK.
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http://dx.doi.org/10.1016/j.bbrc.2020.07.136DOI Listing
September 2020

Serum lipoprotein(a) levels and insulin resistance have opposite effects on fatty liver disease.

Atherosclerosis 2020 09 30;308:1-5. Epub 2020 Jul 30.

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Background And Aims: High lipoprotein(a) [Lp(a)] levels are associated with increased risk of cardiovascular disease. However, the association between Lp(a) and fatty liver disease (FLD) remains controversial. Therefore, we analyzed the relationship between FLD and serum Lp(a) levels in Korean adults.

Methods: A total of 22,534 participants who underwent a routine health screening program at Kangbuk Samsung Hospital in 2010 and 2014 were enrolled. Anthropometric and biochemical parameters, including Lp(a), were measured. The presence of FLD was assessed using abdominal ultrasonography. Odds ratios (ORs) for the presence of FLD were analyzed in quartile groups of serum Lp(a) levels using logistic regression. We divided the participants into four groups according to the median values of Lp(a) and homeostasis model assessment for insulin resistance (HOMA-IR).

Results: Among the total study population, 3030 (13.4%) participants had fatty liver disease. The mean Lp(a) level was lower in subjects with FLD than in those without (70.0 vs 73.8 nmol/L, p < 0.001). The OR for FLD was the lowest in the fourth Lp(a) quartile group, using the first quartile group as the reference group after adjusting for confounding factors [0.815; 95% confidence interval (CI) 0.725-0.916]. When the OR for FLD was analyzed in four groups divided by the median values of Lp(a) and HOMA-IR, the low Lp(a)-high HOMA-IR group had the greatest OR for FLD, using the high Lp(a)-low HOMA-IR group as the reference (1.903; 95% CI 1.679-2.158).

Conclusions: Serum Lp(a) levels were inversely associated with the presence of FLD. Subjects with low Lp(a) and high insulin resistance (IR) showed higher risk of FLD than those with high Lp(a) and low IR, suggesting the opposite associations of Lp(a) and IR with FLD.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.07.020DOI Listing
September 2020

The Prevalence and Risk of Type 2 Diabetes in Adults with Disabilities in Korea.

Endocrinol Metab (Seoul) 2020 09 22;35(3):552-561. Epub 2020 Jul 22.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: People with disabilities are at risk of secondary conditions such as diabetes. The aim of this study was to evaluate the prevalence and risk of type 2 diabetes in South Korea, especially among people with all types of disabilities.

Methods: We conducted a cross-sectional study using data from the Korean National Health Insurance Service, with two disabilityfree controls matched for each participant with disabilities by age and sex. Information regarding the type, severity and grade of disabilities was obtained based on the National Disability Registry. Diagnosis of type 2 diabetes was defined according to the following criteria: presence of International Classification of Diseases, Tenth Revision, Clinical Modification codes E11, E12, E13, or E14 and claims for at least one oral anti-diabetic agent or insulin at baseline, or fasting glucose level ≥126 mg/dL.

Results: We included 1,297,806 participants with disabilities and 2,943,719 control. Out of 4,241,525 participants, 841,990 (19.9%) were diagnosed with diabetes. The prevalence of diabetes was higher in the disability group compared with individuals without disabilities (23.1% vs. 18.4%). The odds of having diabetes was higher in the disability group compared with the control group (adjusted odds ratio, 1.34; 95% confidence interval, 1.33 to 1.34). The results showed higher prevalence of diabetes in the mildly disabled group (23.2%) than in the severely disabled group (22.7%).

Conclusion: The prevalence and risk of diabetes were higher in people with disabilities compared with the general population. Physicians and public health authorities should focus on people with disabilities for proper diabetes management.
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http://dx.doi.org/10.3803/EnM.2020.653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520589PMC
September 2020

Protective effect of smoking cessation on subsequent myocardial infarction and ischemic stroke independent of weight gain: A nationwide cohort study.

PLoS One 2020 16;15(7):e0235276. Epub 2020 Jul 16.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Smoking cessation reduces the cardiovascular risk but increases body weight. We investigated the risk of subsequent myocardial infarction and ischemic stroke according to weight gain after smoking cessation, using a nationwide population based cohort. We enrolled 3,797,572 Korean adults aged over 40 years who participated in national health screenings between 2009 and 2010. Subjects who quit smoking were classified into three subgroups according to the weight change between baseline and 4 years prior. Myocardial infarctions and ischemic strokes were followed until the end of 2015. We compared the hazard ratios among smoking cessation subgroups, non-smokers, and current smokers. The mean changes in weight (1.5 ± 3.9 kg) of the smoking cessation group were higher than those of the other groups (p < 0.0001). A total of 31,277 and 46,811 subjects were newly diagnosed with myocardial infarction and ischemic stroke, respectively. Regardless of weight change, all subgroups of smoking cessation had significantly less risk than current smokers. The subgroup of smoking cessation with weight gain over 4kg showed the lowest risk for myocardial infarctions (hazard ratio 0.646, 95% confidence interval 0.583-0.714, p < 0.0001) and ischemic strokes (hazard ratio 0.648, 95% confidence interval 0.591-0.71, p < 0.0001) after multivariable adjustment. In conclusion, weight gain after smoking cessation did not adversely affect the cardiovascular protective effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235276PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365437PMC
September 2020

Effects of Cardiovascular Risk Factor Variability on Health Outcomes.

Endocrinol Metab (Seoul) 2020 06 24;35(2):217-226. Epub 2020 Jun 24.

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Innumerable studies have suggested "the lower, the better" for cardiovascular risk factors, such as body weight, lipid profile, blood pressure, and blood glucose, in terms of health outcomes. However, excessively low levels of these parameters cause health problems, as seen in cachexia, hypoglycemia, and hypotension. Body weight fluctuation is related to mortality, diabetes, obesity, cardiovascular disease, and cancer, although contradictory findings have been reported. High lipid variability is associated with increased mortality and elevated risks of cardiovascular disease, diabetes, end-stage renal disease, and dementia. High blood pressure variability is associated with increased mortality, myocardial infarction, hospitalization, and dementia, which may be caused by hypotension. Furthermore, high glucose variability, which can be measured by continuous glucose monitoring systems or self-monitoring of blood glucose levels, is associated with increased mortality, microvascular and macrovascular complications of diabetes, and hypoglycemic events, leading to hospitalization. Variability in metabolic parameters could be affected by medications, such as statins, antihypertensives, and hypoglycemic agents, and changes in lifestyle patterns. However, other mechanisms modify the relationships between biological variability and various health outcomes. In this study, we review recent evidence regarding the role of variability in metabolic parameters and discuss the clinical implications of these findings.
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http://dx.doi.org/10.3803/EnM.2020.35.2.217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386100PMC
June 2020

Association Between Glycemic Status and the Risk of Parkinson Disease: A Nationwide Population-Based Study.

Diabetes Care 2020 09 1;43(9):2169-2175. Epub 2020 Jul 1.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Objective: Previous studies have suggested that diabetes increases the risk of Parkinson disease (PD); however, this has not been conclusively established. We analyzed the risk of PD based on baseline glucose tolerance status in a large-scale cohort representative of the general Korean population.

Research Design And Methods: This analysis was performed in a cohort of 15,168,021 adults aged ≥40 years who underwent health checkups under the National Health Insurance Service between January 2009 and December 2010. The clinical course of subjects was monitored until December 2016. Subjects were classified into the following groups: no diabetes, impaired fasting glucose (IFG), diabetes duration <5 years, and diabetes duration ≥5 years. We analyzed the adjusted hazard ratio of PD for each group.

Results: During the observation period of 49,076,148.74 person-years, PD occurred in 31,577 patients. Compared with the nondiabetes group, the adjusted hazard ratio was 1.038 (95% CI, 1.009-1.067) in the IFG group, 1.185 (95% CI, 1.143-1.229) in the diabetes duration <5 years group, and 1.618 (95% CI, 1.566-1.672) in the diabetes duration ≥5 years group. These results were consistent with those of the subgroup analysis, and the presence of diabetes further increased the risk of PD regardless of comorbidities such as cardiovascular, cerebrovascular, and chronic kidney diseases.

Conclusions: This population-based cohort study suggests that diabetes is an independent risk factor for PD.
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http://dx.doi.org/10.2337/dc19-0760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440896PMC
September 2020

Obesity Fact Sheet in Korea, 2019: Prevalence of Obesity and Abdominal Obesity from 2009 to 2018 and Social Factors.

J Obes Metab Syndr 2020 Jun;29(2):124-132

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The prevalence of obesity has rapidly increased in countries across the world in recent decades. The 2019 Obesity Fact Sheet released by the Korean Society for the Study of Obesity addressed the prevalence of obesity and abdominal obesity during the period of 2009 to 2018 and obesity-related social factors.

Methods: Data from the Korean National Health Insurance Service health checkup database between 2009 and 2018 and the Korea National Health and Nutrition Examination Survey between 2010 and 2017 were analyzed. The prevalence of obesity and abdominal obesity was calculated after standardizing for age and sex based on the 2010 population and housing census.

Results: From 2009 to 2018, the prevalence of obesity and abdominal obesity increased to 35.7% and 23.8%, respectively, in 2018. Upward trends in the prevalence of obesity and abdominal obesity was observed among both sexes and nearly all age groups. The prevalence of obesity and abdominal obesity was higher among individuals with lower education and household income levels. Among occupations, managers exhibited the highest prevalence of obesity and abdominal obesity. Further, the prevalence of obesity and abdominal obesity became higher among individuals working longer hours and split and night shift workers.

Conclusion: The 2019 Obesity Fact Sheet provides information on changes in obesity dynamics during the past decade and obesity-related social factors in the Korean adult population. This report might constitute a cornerstone by which to establish targets for future interventions for reversing the rise in the prevalence of obesity and reducing the burden of obesity in Korea.
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http://dx.doi.org/10.7570/jomes20058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338491PMC
June 2020

Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association.

Diabetes Metab J 2020 06 11;44(3):382-401. Epub 2020 May 11.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.

This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.
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http://dx.doi.org/10.4093/dmj.2020.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332334PMC
June 2020

Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults.

Diabetes Metab J 2020 08 20;44(4):592-601. Epub 2020 Apr 20.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status.

Methods: We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose [IFG], and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively.

Results: Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI <18.5 kg/m²) showed a 1.7-fold increased risk of HF, and those with BMI ≥30 kg/m² showed a 1.1-fold increased risk of HF, suggesting a J-shaped association with BMI. When similar analyses were performed for different glycemic statuses, the J-shaped association between BMI and HF risk was consistently observed in both groups with and without diabetes.

Conclusion: Participants with IFG and diabetes showed a significantly increased HF risk compared to normoglycemic participants. This increased risk of HF was mostly prominent in underweight and class II obese participants than in participants with normal weight.
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http://dx.doi.org/10.4093/dmj.2019.0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453986PMC
August 2020

Encountering COVID-19 as Endocrinologists.

Endocrinol Metab (Seoul) 2020 06 23;35(2):197-205. Epub 2020 Apr 23.

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.
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http://dx.doi.org/10.3803/EnM.2020.35.2.197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386104PMC
June 2020

Decreased Vagal Activity and Deviation in Sympathetic Activity Precedes Development of Diabetes.

Diabetes Care 2020 06 16;43(6):1336-1343. Epub 2020 Apr 16.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Objective: The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians.

Research Design And Methods: A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal intervals [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group.

Results: During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70-0.95], 0.76 [0.65-0.90], and 0.78 [0.67-0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21-1.65], 1.32 [1.13-1.53], and 1.31 [1.13-1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance.

Conclusions: Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes.
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http://dx.doi.org/10.2337/dc19-1384DOI Listing
June 2020

Increased Mortality Burden in Young Asian Subjects with Dysglycemia and Comorbidities.

J Clin Med 2020 Apr 7;9(4). Epub 2020 Apr 7.

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea.

Background: High blood glucose level has a linear relationship with all-cause mortality. However, the influence of glycemic abnormality on mortality differs by age group. We aimed to analyze all-cause mortality according to glycemic status, age groups, and comorbidities using a national health database.

Methods: The 6,330,369 participants who underwent Korean National Health Screening in 2009 were followed up until 2016, with a median follow-up of 7.3 years. All-cause mortality rates were analyzed according to glycemic status (normoglycemia, impaired fasting glucose [IFG], newly diagnosed diabetes, diabetes duration <5 years, diabetes duration ≥5 years), age groups (20-39, 40-65, and ≥65 years), and comorbidities using the Korean National Health Insurance System database.

Results: At baseline, 712,901 (11.3%) subjects had diabetes. Compared with subjects without diabetes, those with diabetes at baseline showed increased mortality risk after adjustment for multiple risk factors (hazard ratio [HR] 1.613; 95% confidence interval [CI] 1.598,1.629), and those with IFG showed a significantly increased mortality risk compared with normoglycemic subjects (HR 1.053; 95% CI 1.042,1.064). Mortality risk associated with glycemic status decreased gradually from younger to older age groups and was consistently higher in those with diabetes with coronary heart disease, ischemic stroke or decreased renal function than those without comorbidities.

Conclusion: Compared with normoglycemic subjects, subjects with diabetes and IFG had an increased mortality risk and the mortality risk was higher in the younger age group than in the older age group. The presence of diabetes and comorbid diseases synergistically increased mortality risk.
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http://dx.doi.org/10.3390/jcm9041042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230603PMC
April 2020

Visceral-to-Subcutaneous Abdominal Fat Ratio Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis.

Endocrinol Metab (Seoul) 2020 03;35(1):165-176

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: We evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD.

Methods: This is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high.

Results: The multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects.

Conclusion: High VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.
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http://dx.doi.org/10.3803/EnM.2020.35.1.165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090310PMC
March 2020

Prevalence and Current Management of Cardiovascular Risk Factors in Korean Adults Based on Fact Sheets.

Authors:
Eun Jung Rhee

Endocrinol Metab (Seoul) 2020 03;35(1):85-94

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Korea is currently an aged society and is on the cusp of becoming a superaged society in a few years. The health burden of cardiovascular diseases increases with age, and the increasing prevalence of cardiovascular risk factors, such as obesity, hypertension, diabetes mellitus, and dyslipidemia, may be linked to increased population-level cardiovascular risk. In 2018, the prevalence of obesity in Korea was 35.7% (men, 45.4%; women, 26.5%) according to the Obesity Fact Sheet 2019, based on National Health Insurance Corporation medical checkup data. In 2016, the prevalence of diabetes was 14.4% in Koreans older than 30 years according to the Diabetes Fact Sheet published by the Korean Diabetes Association, based on data from the Korean National Health and Nutrition Examination Survey. The prevalence of hypertension in the total population of Korea in 2018 was 28.3% according to the Korean Hypertension Fact Sheet produced by the Korean Society of Hypertension. Lastly, the prevalence of dyslipidemia in 2018 was 40.5% according to the Dyslipidemia Fact Sheet published by the Korean Society of Lipid and Atherosclerosis. In this article, I would like to review the prevalence and current management of cardiovascular risk factors in Korea according to the fact sheets released by various associations.
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http://dx.doi.org/10.3803/EnM.2020.35.1.85DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090302PMC
March 2020

Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis.

Metabolism 2020 10 6;111S:154203. Epub 2020 Mar 6.

Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease and important unmet medical need. Current guidelines recommend, under specific restrictions, pioglitazone or vitamin E in patients with NASH and significant fibrosis, but the use of both remains off-label. We summarize evidence on medications for the treatment of nonalcoholic steatohepatitis (NASH), since NASH has been mainly associated with higher morbidity and mortality. Some of these medications are currently in phase 3 clinical trials, including obeticholic acid (a farnesoid X receptor agonist), elafibranor (a peroxisome proliferator activated receptor [PPAR]-α/δ dual agonist), cenicriviroc (a CC chemokine receptor antagonist), MSDC-0602 K (a PPAR sparing modulator), selonsertib (an apoptosis signal-regulating kinase-1 inhibitor) and resmetirom (a thyroid hormone receptor agonist). A significant research effort is also targeting PPARs and selective PPAR modulators, including INT131 and pemafibrate, with the expectation that novel drugs may have beneficial effects similar to those of pioglitazone, but without the associated adverse effects. Whether these and other medications could offer tangible therapeutic benefits, alone or in combination, apparently on a background of lifestyle modification, i.e. exercise and a healthy dietary pattern (e.g. Mediterranean diet) remain to be proven. In conclusion, major advances are expected for the treatment of NASH.
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http://dx.doi.org/10.1016/j.metabol.2020.154203DOI Listing
October 2020

Obesity Fact Sheet in Korea, 2018: Data Focusing on Waist Circumference and Obesity-Related Comorbidities.

J Obes Metab Syndr 2019 Dec 30;28(4):236-245. Epub 2019 Dec 30.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea.

Background: The global prevalence of obesity has increased steadily in recent years. Waist circumference (WC) reflects body composition better than body mass index. The Korean Society for the Study of Obesity released the 2018 Obesity Fact Sheet to address the incidence of obesity-related comorbidities according to WC levels.

Methods: Data from the Korean National Health Insurance Service health examination database from 2009 to 2016 were analyzed. Abdominal obesity was defined as a WC ≥90 cm in men and ≥85 cm in women. Incidence rates of comorbidities and all-cause mortality rates were calculated after standardizing by age and sex based on the 2010 census.

Results: From 2009 to 2015, the incidence rates of type 2 diabetes mellitus, hypertension, myocardial infarction, and ischemic stroke increased both in men and women. Individuals with the lowest WC levels had the highest all-cause mortality rates followed by those with the highest WC levels in men, women, and the total population. The incidence rates of total cancer increased as WC levels escalated between 2009 and 2016. In men, the incidence rates of colorectal, prostate, and liver cancers increased as WC levels increased. The incidence rates of thyroid, colorectal, and stomach cancers increased as WC levels rose in women. In addition, medical expenses continuously increased as WC increased in both men and women.

Conclusion: Based on the 2018 Obesity Fact Sheet, strategies for reducing the abdominal obesity and related comorbidities and medical expenses are a public health priority.
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http://dx.doi.org/10.7570/jomes.2019.28.4.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939699PMC
December 2019

Corrigenda: Table Correction. Nonalcoholic Fatty Liver Disease in Diabetes. Part I: Epidemiology and Diagnosis.

Diabetes Metab J 2019 Oct;43(5):731

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

This corrects the article on p. 31 in vol. 43, PMID: 30793550.
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http://dx.doi.org/10.4093/dmj.2019.0188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834842PMC
October 2019

Nonalcoholic Fatty Liver Disease and Diabetes: An Epidemiological Perspective.

Authors:
Eun Jung Rhee

Endocrinol Metab (Seoul) 2019 09;34(3):226-233

Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Nonalcoholic fatty liver disease (NAFLD) is thought to stem from the body's inability to store excess energy in adipocytes; as such, it is commonly viewed as the hepatic manifestation of metabolic syndrome. The pathogenesis of NAFLD involves ectopic fat accumulation, which also takes place in the liver, muscle and visceral fat. NAFLD is rapidly becoming more widespread in Korea, with an estimated prevalence of 30% in adults. Type 2 diabetes mellitus (T2DM) and NAFLD share insulin resistance as a common pathophysiological mechanism, and each of these two diseases affects the development of the other. Recent studies have suggested that NAFLD is often present as a comorbidity in T2DM patients. The mutual interrelationship between these conditions is shown by findings suggesting that T2DM can exacerbate NAFLD by promoting progression to nonalcoholic hepatosteatosis or fibrosis, while NAFLD causes the natural course of diabetic complications to worsen in T2DM patients. It remains unknown whether one disease is the cause of the other or vice versa. In this review, I would like to discuss current epidemiological data on the associations between NAFLD and T2DM, and how each disease affects the course of the other.
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http://dx.doi.org/10.3803/EnM.2019.34.3.226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769345PMC
September 2019

2018 Guidelines for the management of dyslipidemia in Korea.

Korean J Intern Med 2019 Sep 28;34(5):1171. Epub 2019 Aug 28.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3904/kjim.2019.188.e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718745PMC
September 2019