Publications by authors named "Gyuri Kim"

67 Publications

Low skeletal muscle mass is associated with the presence, incidence, and progression of coronary artery calcification.

Can J Cardiol 2021 Apr 9. Epub 2021 Apr 9.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address:

Background: Low skeletal muscle mass (SMM) is an emerging risk factor of cardiovascular disease (CVD). We investigated the association between SMM and coronary artery calcification (CAC).

Methods: We enrolled 19,728 adults free of CVD who underwent computed tomographic estimation of Agatston CAC scores for cross-sectional analysis. Among them, 5,401 subjects who had two and more follow-up CAC scores were included in longitudinal analysis. Relative SMM is presented using the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/body weight (kg) x 100]. CAC presence and incidence were defined as CAC score>0, and CAC progression was defined as √CAC score (follow-up) -√CAC score (baseline)>2.5.

Results: Among all the subjects (mean 53.4 years, 80.8% of men), the prevalence of CAC was 36.7%. The incidence of CAC was 17.4% during mean of 3.6 years, and the progression of CAC was 49.9% during mean 2.3 years. The lowest SMI quartile was significantly associated with an increased risk of CAC presence (adjusted odds ratio=2.75, 95% confidence interval [CI]= 2.45-3.05; P<0.001), incidence (adjusted hazard ratio [AHR]=1.99, 95% CI = 1.36-2.91; P<0.001) and progression (AHR 1.48, 95% CI=1.25-1.77; P<0.001), compared to the highest quartile. SMI as a continuous value was also significantly, inversely associated with CAC. SMI was the best parameter to be related to CAC among other quantitative indices such as height- or BMI- adjusted.

Conclusions: Low SMM is significantly associated with an elevated risk of CAC, independent of other cardiometabolic parameters.
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http://dx.doi.org/10.1016/j.cjca.2021.04.002DOI Listing
April 2021

Correction: Characterization of ferroptosis in kidney tubular cell death under diabetic conditions.

Cell Death Dis 2021 Apr 8;12(4):382. Epub 2021 Apr 8.

Institute of Kidney Disease Research, College of Medicine, Yonsei University, Seoul, South Korea.

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http://dx.doi.org/10.1038/s41419-021-03667-yDOI Listing
April 2021

Risk of early mortality and cardiovascular disease according to the presence of recently diagnosed diabetes and requirement for insulin treatment: A nationwide study.

J Diabetes Investig 2021 Mar 4. Epub 2021 Mar 4.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Aims/introduction: We estimated the hazards of cardiovascular diseases (CVDs) and early all-cause mortality in Korean adults according to the presence of recently diagnosed type 2 diabetes (type 2 diabetes for <5 years) and insulin use.

Materials And Methods: We used the Korean National Health Insurance Service-National Sample Cohort database (2002-2015) for this longitudinal population-based study. Among adults aged ≥40 years without baseline CVD, individuals without diabetes or with recently diagnosed type 2 diabetes were selected (N = 363,919). The hazard ratios (HRs) for myocardial infarction (MI), stroke, and all-cause mortality during follow-up were analyzed according to three groups categorized by the presence of type 2 diabetes and insulin use.

Results: Within a mean 7.8 years, there were 5,275 MIs, 7,220 strokes, and 15,834 deaths. The hazards for outcomes were higher in the insulin-treated type 2 diabetes group than in the non-diabetes group [HR (95% CI): 2.344 (1.870-2.938) for MI, 2.420 (1.993-2.937) for stroke, and 3.037 (2.706-3.407) for death], higher in the non-insulin-treated type 2 diabetes group than in the non-diabetes group [HR (95% CI): 1.284 (1.159-1.423) for MI, 1.435 (1.320-1.561) for stroke, and 1.135 (1.067-1.206) for death], and higher in the insulin-treated type 2 diabetes group than in the non-insulin-treated type 2 diabetes group [HR (95% CI): 1.914 (1.502-2.441) for MI, 1.676 (1.363-2.060) for stroke, and 2.535 (2.232-2.880) for death].

Conclusions: Recently diagnosed type 2 diabetes patients showed increased risks of incident CVDs and premature mortality, and insulin-treated group demonstrated an additional increase in the risks of these outcomes in adults with recently diagnosed type 2 diabetes, suggesting the need for intensified cardio-protective interventions for adults with insulin-treated type 2 diabetes.
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http://dx.doi.org/10.1111/jdi.13539DOI Listing
March 2021

Primary aldosteronism subtyping in the setting of partially successful adrenal vein sampling.

Ther Adv Endocrinol Metab 2021 13;12:2042018821989239. Epub 2021 Feb 13.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, (06351) 81 Irwon-ro, Gangnam-gu, Seoul, Republic of Korea.

Background And Aims: Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side.

Methods: Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden's index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side.

Results: Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. of LIR >5.4 or <0.5 predicted unilateral PA with a sensitivity of 42.1% and a specificity of 98.6%. of RIR <0.5 or >7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity.

Conclusion: In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.
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http://dx.doi.org/10.1177/2042018821989239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887669PMC
February 2021

Association between Cigarette Smoking and Physical Fitness Level of Korean Adults and the Elderly.

Healthcare (Basel) 2021 Feb 9;9(2). Epub 2021 Feb 9.

Sports and Health Care Major, College of Humanities and Arts, Korea National University of Transportation, Chungju 27469, Korea.

Although previous studies have examined the relationship between smoking and physical fitness, they only considered current smoking status and the same fitness measurements regardless of age. This study investigated differences in physical fitness based on tobacco smoking habits. A total of 2830 non-elderly adults (NEA; 19-64 years) and 629 elderly (65-89 years) participated in the study, using data extracted from a Korean national database. One-way ANCOVA and ANOVA were conducted to analyze the results. The subjects were classified into three groups (smokers, those who had quit, and never-smokers). In NEA men, a significant difference was observed in 50-m dash ( = 0.003) and 20-m shuttle-run ( < 0.001), while in elderly men differences were only seen in sit-ups ( = 0.015). In the case of NEA and elderly women, no significant differences were observed in physical fitness levels ( > 0.05). The decreased fitness level due to smoking was more noticeable in men than in women, and in NEA more than in elderly persons. A non-smoking policy and customized training based on age or gender are necessary to increase fitness and improve health conditions.
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http://dx.doi.org/10.3390/healthcare9020185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914849PMC
February 2021

Characterization of ferroptosis in kidney tubular cell death under diabetic conditions.

Cell Death Dis 2021 Feb 8;12(2):160. Epub 2021 Feb 8.

Institute of Kidney Disease Research, College of Medicine, Yonsei University, Seoul, South Korea.

Kidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system X (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.
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http://dx.doi.org/10.1038/s41419-021-03452-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870666PMC
February 2021

The Association Between Continuous Glucose Monitoring-Derived Metrics and Cardiovascular Autonomic Neuropathy in Outpatients with Type 2 Diabetes.

Diabetes Technol Ther 2021 Apr 5. Epub 2021 Apr 5.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Continuous glucose monitoring (CGM)-derived metrics, including time in range (TIR), are attracting attention as new indicators, beyond hemoglobin A1c, of glycemic control and diabetes complications. This study investigated the associations between CGM-derived TIR, hyperglycemia, and hypoglycemia metrics and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. A total of 284 patients with type 2 diabetes who underwent CGM using GOLD™ (Medtronic MiniMed) for 3 days or iPro™2 (Medtronic MiniMed) for 6 days and autonomic function tests within 3 months based on outpatient data were recruited. The definition of CGM-derived metrics was subject to the most recent international consensus. CAN was defined as an abnormal result in two or more parasympathetic test, and the severity of CAN was estimated as the sum of the scores of the five cardiovascular autonomic function tests. A total of 84 patients (29.6%) were diagnosed with CAN, and the mean TIR was 57.0% ± 7.0%. A multiple logistic regression analysis revealed that the odds ratio (OR) of presence of CAN was 0.876 [95% confidence interval (CI): 0.79-0.98] per 10% increase in the TIR 70-180 mg/dL, after adjusting for age, sex, diabetes duration, any medications, and glycemic variability. A 10% increase in the TIR was significantly inversely associated with the severity of CAN (OR: 0.89, 95% CI: 0.81-0.98). Among the metrics of hyperglycemia, each 10% increase in a time above range (TAR) >180 mg/dL was also independently correlated with the presence of CAN (OR: 1.141, 97.5% CI: 1.01-1.29) and the severity of CAN (OR: 1.13, 97.5% CI: 1.01-1.26). A TIR 70-180 mg/dL and a TAR >180 mg/dL were significantly associated with CAN in outpatients with type 2 diabetes.
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http://dx.doi.org/10.1089/dia.2020.0599DOI Listing
April 2021

Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy.

Diabetes Metab J 2021 Feb 2. Epub 2021 Feb 2.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy.

Methods: This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed.

Results: The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV.

Conclusion: This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.
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http://dx.doi.org/10.4093/dmj.2019.0211DOI Listing
February 2021

Mean and visit-to-visit variability of glycemia and left ventricular diastolic dysfunction: A longitudinal analysis of 3025 adults with serial echocardiography.

Metabolism 2021 03 26;116:154451. Epub 2020 Nov 26.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Objective: We aimed to determine the mean glucose thresholds to increase the risk of left ventricular diastolic dysfunction (LVDD) and whether visit-to-visit variability of fasting plasma glucose (FPG) and glycated hemoglobin (A1C) could independently increase the risk in a cohort with serial echocardiography.

Methods: This was a 3.5-year (range, 0.5-8.3) retrospective longitudinal cohort study of 3025 adults (age, 55.15 ± 7.6 years; without diabetes, n = 2755) with LV ejection fraction > 50% by serial echocardiography between 2006 and 2016. Mean, standard of deviation (SD) and coefficient of variation (CV) of FPG and A1C obtained from three consecutive measurements preceding the first echocardiography. The definition of LVDD in this study was primarily based on early peak mitral inflow velocity and early diastolic mitral annulus motion velocity.

Results: LVDD developed in 611/3025 subjects (20.2%). Cox proportional hazard models showed increased adjusted hazard ratios (HRs) for incident LVDD in the highest quartile of FPG-mean (HR 1.76, 95% confidence interval [CI]; 1.36-2.30), FPG-SD (HR 1.63, 95% CI; 1.27-2.09), FPG-CV (HR 1.47, 95% CI; 1.15-1.89), and A1C-mean (HR 1.83, 95% CI; 1.41-2.38) versus the lowest quartile, which was consistent even in subjects without diabetes. Mean glucose thresholds for the increased risk were below the lower limits for pre-diabetes.

Conclusions: In terms of mean glycemia, LVDD may be initiated in the earliest diabetic continuum, and such changes could be measurable within several years. Visit-to-visit variability of FPG, but not that of A1C, predicted accelerated development of LVDD.
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http://dx.doi.org/10.1016/j.metabol.2020.154451DOI Listing
March 2021

Mean and visit-to-visit variability of glycated hemoglobin, and the risk of non-alcoholic fatty liver disease.

J Diabetes Investig 2020 Nov 2. Epub 2020 Nov 2.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Aims/introduction: We aimed to determine whether mean and visit-to-visit glycated hemoglobin (HbA1c) variability independently increase the incidence of non-alcoholic fatty liver disease (NAFLD) across the diabetic continuum from normal glucose tolerance (NGT) to established diabetes.

Materials And Methods: In a longitudinal cohort study, 21,123 participants underwent five or more annual health screening checkups. Participants were categorized into diabetes (n = 1,635), prediabetes (n = 6,650) and NGT (n = 12,838) groups. Mean, standard deviation (SD) and coefficient of variation data on HbA1c were obtained from three consecutive measurements. The associations between those data and incident NAFLD were analyzed using Cox regressions.

Results: Over a median follow-up period of 57 months, 3,860 (18.3%) participants developed NAFLD. The risk of NAFLD increased continuously, with the mean HbA1c beginning at 4.9%, even in the NGT group. We found a significant association between increasing HbA1c variability and incident NAFLD (coefficient of variation, adjusted hazard ratio 1.14, 95% confidence interval 1.01-1.29; standard deviation, adjusted hazard ratio 1.19, 95% confidence interval 1.05-1.36) in the diabetes group, but not in the NGT or prediabetes group. Consistent findings were observed when NAFLD patients with a low possibility of fibrosis were excluded. The association between the coefficient of variation of HbA1c and incident NAFLD in the diabetes group was significant only in those with an increasing trend of post-baseline HbA1c (adjusted hazard ratio 1.24, 95% confidence interval 1.01-1.52).

Conclusions: Increased mean HbA1c levels elevated the risk of incident NAFLD, even with NGT. Increases in visit-to-visit variability of HbA1c independently elevated the risk of incident NAFLD, but only in the diabetes group.
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http://dx.doi.org/10.1111/jdi.13455DOI Listing
November 2020

Protective effect of a novel clinical-grade small molecule necrosis inhibitor against oxidative stress and inflammation during islet transplantation.

Am J Transplant 2021 04 10;21(4):1440-1452. Epub 2020 Nov 10.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Inhibition of mitochondrial reactive oxygen species (ROS) and subsequent damage-associated molecular patterns (DAMPs)-induced inflammatory responses could be a novel target in clinical islet transplantation. We investigated the protective effects of NecroX-7, a novel clinical-grade necrosis inhibitor that specifically targets mitochondrial ROS, against primary islet graft failure. Islets from heterozygote human islet amyloid polypeptide transgenic (hIAPP ) mice and nonhuman primates (NHPs) were isolated or cultured with or without NecroX-7 in serum-deprived medium. Supplementation with NecroX-7 during hIAPP mouse islet isolation markedly increased islet viability and adenosine triphosphate content, and attenuated ROS, transcription of c-Jun N-terminal kinases, high mobility group box 1, interleukin-1beta (IL-1 ), IL-6, and tumor necrosis factor-alpha. Supplementation of NecroX-7 during serum-deprived culture also protected hIAPP mouse and NHP islets against impaired viability, serum deprivation-induced ROS, proinflammatory response, and accumulation of toxic IAPP oligomer. Supplementation with NecroX-7 during isolation or serum-deprived culture of hIAPP mouse and NHP islets also improved posttransplant glycemia in the recipient streptozotocin-induced diabetic hIAPP mice and BALB/c-nu/nu mice, respectively. In conclusion, pretransplant administration of NecroX-7 during islet isolation and serum-deprived culture suppressed mitochondrial ROS injury, generation of DAMPs-induced proinflammatory responses, and accumulation of toxic IAPP oligomers ex vivo, and improved posttransplant glycemia in vivo.
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http://dx.doi.org/10.1111/ajt.16323DOI Listing
April 2021

Age at Diagnosis and the Risk of Diabetic Nephropathy in Young Patients with Type 1 Diabetes Mellitus.

Diabetes Metab J 2021 Jan 10;45(1):46-54. Epub 2020 Jul 10.

Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The aim of this study was to evaluate characteristics and risk of diabetic complications according to age at diagnosis among young adults with type 1 diabetes mellitus (T1DM).

Methods: A total of 255 T1DM patients aged less than 40 years were included. Patients were categorized into three groups (<20, 20 to 29, and 30 to 40 years) according to age at diagnosis. Diabetic nephropathy (DN) was defined when spot urine-albumin creatinine ratio was 300 mg/g or more and/or estimated glomerular filtration ratio (eGFR) level was 60 mL/min/1.73 m2 or less.

Results: Median age at diagnosis was 25 years and disease duration was 14 years. Individuals diagnosed with T1DM at childhood/adolescent (age <20 years) had lower stimulated C-peptide levels. They received more intensive insulin treatment with higher total daily insulin doses compared to older onset groups. The prevalence of DN was higher in the childhood/adolescent-onset group than in older onset groups (25.3% vs. 15.3% vs. 9.6%, P=0.022). The eGFR was inversely associated with disease duration whilst the degree of decrease was more prominent in the childhood/adolescent-onset group than in the later onset group (aged 30 to 40 years; P<0.001). Childhood/adolescent-onset group was independently associated with the risk of DN compared to the older onset group (aged 30 to 40 years; odds ratio, 3.47; 95% confidence interval, 1.45 to 8.33; P=0.005).

Conclusion: In individuals with childhood/adolescent-onset T1DM, the reduction in renal function is more prominent with disease duration. Early age-onset T1DM is an independent risk of DN.
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http://dx.doi.org/10.4093/dmj.2019.0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850868PMC
January 2021

Validation of the effectiveness of a digital integrated healthcare platform utilizing an AI-based dietary management solution and a real-time continuous glucose monitoring system for diabetes management: a randomized controlled trial.

BMC Med Inform Decis Mak 2020 07 10;20(1):156. Epub 2020 Jul 10.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: Despite the numerous healthcare smartphone applications for self-management of diabetes, patients often fail to use these applications consistently due to various limitations, including difficulty in inputting dietary information by text search and inconvenient and non-persistent self-glucose measurement by home glucometer. We plan to apply a digital integrated healthcare platform using an artificial intelligence (AI)-based dietary management solution and a continuous glucose monitoring system (CGMS) to overcome those limitations. Furthermore, medical staff will be performing monitoring and intervention to encourage continuous use of the program. The aim of this trial is to examine the efficacy of the program in patients with type 2 diabetes mellitus (T2DM) who have HbA1c 53-69 mmol/mol (7.0-8.5%) and body mass index (BMI) ≥ 23 mg/m.

Methods: This is a 48-week, open-label, randomized, multicenter trial consisting of patients with type 2 diabetes. The patients will be randomly assigned to three groups: control group A will receive routine diabetes care; experimental group B will use the digital integrated healthcare platform by themselves without feedback; and experimental group C will use the digital integrated healthcare platform with continuous glucose monitoring and feedback from medical staff. There are five follow-up measures: baseline and post-intervention at weeks 12, 24, 36, and 48. The primary end point is change in HbA1c from baseline to six months after the intervention.

Discussion: This trial will verify the effectiveness of a digital integrated healthcare platform with an AI-driven dietary solution and a real-time CGMS in patients with T2DM.

Trial Registration: Clinicaltrials.gov NCT04161170, registered on 08 November 2019. https://clinicaltrials.gov/ct2/show/NCT04161170?term=NCT04161170&draw=2&rank=1.
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http://dx.doi.org/10.1186/s12911-020-01179-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353748PMC
July 2020

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Endocrinol Metab (Seoul) 2020 06 24;35(2):272-287. Epub 2020 Jun 24.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.
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http://dx.doi.org/10.3803/EnM.2020.35.2.272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386113PMC
June 2020

Relationship between low skeletal muscle mass, sarcopenic obesity and left ventricular diastolic dysfunction in Korean adults.

Diabetes Metab Res Rev 2021 Jan 1;37(1):e3363. Epub 2020 Jul 1.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background: Heart failure with preserved ejection fraction is an emerging global health issue attributed to an ageing population. However, the association between low skeletal muscle mass, sarcopenic obesity, and left ventricular diastolic dysfunction remains unclear. In the current study, we aimed to investigate the relationship between low skeletal muscle mass, sarcopenic obesity, and diastolic dysfunction in a large cohort of Korean adults.

Methods: We conducted a cross-sectional study of 31 258 subjects who underwent health examinations at Samsung Medical Centre's Health Promotion Centre in Seoul, Republic of Korea. Relative skeletal muscle mass was calculated using the skeletal muscle mass index [SMI (%) = appendicular skeletal muscle mass (kg)/body weight (kg) × 100], which was estimated by bioelectrical impedance analysis. Cardiac structure and function were evaluated by echocardiography.

Results: Amongst the 31 258 subjects, 3058 (9.78%) were determined to have diastolic dysfunction. The odds ratio (OR) of diastolic dysfunction was 1.56 [95% confidence interval (CI): 1.31-1.85; p for trend <0.001] for the lowest SMI tertile relative to the highest SMI tertile following multivariable adjustment. Furthermore, the risk of diastolic dysfunction was much higher in the sarcopenic obesity (OR: 1.70, 95% CI: 1.44-1.99), followed by in the obesity-only (OR: 1.40, 95% CI: 1.21-1.62), and sarcopenia-only (OR: 1.32, 95% CI: 1.08-1.61) when compared with the nonobese, nonsarcopenic group. These results remained consistent amongst the elderly (age ≥ 65 years).

Conclusions: Our findings demonstrate that lower skeletal muscle mass and sarcopenic obesity are strongly associated with diastolic dysfunction in middle-aged and older adults.
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http://dx.doi.org/10.1002/dmrr.3363DOI Listing
January 2021

Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study).

Diabetes Obes Metab 2020 09 29;22(9):1527-1536. Epub 2020 May 29.

Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi, South Korea.

Aim: To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes.

Materials And Methods: In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92).

Results: After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks.

Conclusion: In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes.
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http://dx.doi.org/10.1111/dom.14061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496811PMC
September 2020

Effects of low skeletal muscle mass and sarcopenic obesity on albuminuria: a 7-year longitudinal study.

Sci Rep 2020 04 1;10(1):5774. Epub 2020 Apr 1.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

We aimed to identify the association between low skeletal muscle, sarcopenic obesity, and the incidence of albuminuria in the general population using a longitudinal study. Data from 29,942 subjects who underwent two or more routine health examinations from 2006 to 2013 were retrospectively reviewed. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight-adjusted appendicular skeletal muscle mass estimated by bioelectrical impedance analysis. The cumulative incidence of albuminuria was 981 (3.3%) during the 7-year follow-up period. The hazard ratio of incident albuminuria was 1.44 (95% CI: 1.22-1.71, p for trend <0.001) in the lowest SMI tertile relative to the highest SMI tertile after multivariable adjustment. After additionally adjusting for general and central obesity, the hazard ratio was 1.35 (95% CI: 1.13-1.61, p for trend = 0.001) and 1.30 (95% CI: 1.08-1.56, p for trend = 0.003), respectively. Furthermore, the risk of developing albuminuria was much higher in the sarcopenic obesity group (HR: 1.49, 95% CI: 1.21-1.81, p for trend <0.001) compared to the other groups. Sarcopenic obesity, as well as low skeletal muscle, may lead to albuminuria in general populations.
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http://dx.doi.org/10.1038/s41598-020-62841-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113302PMC
April 2020

Impact of Skeletal Muscle Mass on Metabolic Health.

Endocrinol Metab (Seoul) 2020 03;35(1):1-6

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Skeletal muscle is regarded as an endocrine and paracrine organ. Muscle-derived secretory proteins, referred to as myokines, mediate interactions between skeletal muscle mass and other organs such as the liver, adipose tissue, pancreas, bone, and the cardiovascular system. As individuals age, reduced levels of physical activity and sarcopenia (loss of skeletal muscle mass and strength) are associated with physical frailty and disability. Recently, several studies have suggested that the loss of skeletal muscle mass may contribute to metabolic disease. Therefore, herein, we focus on the relationships between skeletal muscle mass and metabolic diseases, including metabolic syndrome and non-alcoholic fatty liver disease.
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http://dx.doi.org/10.3803/EnM.2020.35.1.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090295PMC
March 2020

Association Between Continuous Glucose Monitoring-Derived Time in Range, Other Core Metrics, and Albuminuria in Type 2 Diabetes.

Diabetes Technol Ther 2020 10 13;22(10):768-776. Epub 2020 Apr 13.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

As the use of continuous glucose monitoring (CGM) has increased, time in range (TIR) and other core CGM metrics are now emerging as the core metrics for clinical targets and assessing diabetic complications, beyond HbA1c. This study investigated the association between the CGM-derived TIR, hyperglycemia, hypoglycemia metrics, and albuminuria. A total of 866 subjects with type 2 diabetes who underwent 3 or 6 days of CGM and had urinary albumin-to-creatinine ratio (ACR) measurements were retrospectively reviewed. CGM metrics were defined according to the most recent international consensus. Albuminuria was defined as one or more of the ACR measurements being >30 mg/g. The overall prevalence of albuminuria was 36.6%. The prevalence of albuminuria was lower in subjects who achieved the target of TIR 70-180 mg/dL, time above range (TAR) >180 mg/dL, and TAR >250 mg/dL, as recommended by international consensus ( < 0.001). Multiple logistic regression analysis revealed that the odds ratio of having albuminuria was 0.94 (95% confidence interval: 0.88-0.99, for trend = 0.04) per 10% increase in TIR of 70-180 mg/dL, after adjusting for multiple factors, including glycemic variability. The results were similar for hyperglycemia metrics (TAR >250 mg/dL and TAR >180 mg/dL). TIR 70-180 mg/dL and hyperglycemia metrics are strongly associated with albuminuria in type 2 diabetes.
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http://dx.doi.org/10.1089/dia.2019.0499DOI Listing
October 2020

Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study.

Cardiovasc Diabetol 2019 11 16;18(1):157. Epub 2019 Nov 16.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.

Background: Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes.

Methods: We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline.

Results: During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490-1.893) for MI; 2.105 (1.901-2.330) for HF; 1.608 (1.411-1.833) for AF; 1.884 (1.762-2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138-2.718) for MI; 3.024 (2.730-3.350) for HF; 1.748 (1.534-1.993) for AF; 2.874 (2.689-3.073) for death].

Conclusions: In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.
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http://dx.doi.org/10.1186/s12933-019-0953-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858684PMC
November 2019

Anisotropic Silicification of Nanostructured Surfaces by Local Liquid-Phase Deposition.

Langmuir 2019 10 19;35(39):12656-12664. Epub 2019 Sep 19.

Department of Chemistry , Sookmyung Women's University , Seoul 04310 , Republic of Korea.

Exploration of the bioinspired silicification of artificial scaffolds is crucial to understanding and engineering the hierarchically complex and elaborate three-dimensional (3D) frustules of diatoms, which have high porosity and mechanical stability with related gas diffusion and storage properties. Herein, we report on the bioinspired silicification of the nanostructured surfaces of hexagonally close-packed silica bead (hc-SB) arrays using a liquid-phase deposition (LPD) method. This process, governed by the kinetics of silicification, was controlled using the concentration of the reactants and the reaction temperature and monitored in real time using a quartz-crystal microbalance, which allowed the investigation of the silicification on the surface during the LPD reaction. These heterogeneous LPD reactions on hc-SB arrays were optimized to mimic natural 3D hierarchical structures. Anisotropic silicification of the nanostructures occurred owing to differences in the energy and local concentration of silicic acid on the nanostructured surface. A 3D hierarchical pore network was realized via a heterogeneous LPD reaction by controlling the size, location, and arrangement of the SBs. We believe that our silicification process on nanostructured surfaces can lead to great improvements in the bioinspired morphogenesis-based engineering of 3D hierarchical structures.
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http://dx.doi.org/10.1021/acs.langmuir.9b01998DOI Listing
October 2019

Predictive factors for the development of diabetes in cancer patients treated with phosphatidylinositol 3-kinase inhibitors.

Cancer Chemother Pharmacol 2019 08 27;84(2):405-414. Epub 2019 Jun 27.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Purpose: Targeted therapy using phosphatidylinositol 3-kinase (PI3K) inhibitors is used to treat cancer such as lymphoma. In animal studies, its use raised concern about alteration of glucose metabolism. To date, clinical data are inconclusive; therefore, we investigated the incidence and clinical manifestations of diabetes in cancer patients treated with PI3K inhibitors.

Methods: In a retrospective review of diabetes-free patients with advanced solid tumors treated with PI3K inhibitor, we performed Cox regression to identify independent predictors for the development of diabetes.

Results: Of 38 patients (mean age: 54.5 years, 23.7% female) having a mean duration of follow-up of 238.5 days who initiated PI3K inhibitors, 55.3% developed diabetes during treatment (mean 29.1 days); among these, 28.6% experienced remission of diabetes after discontinuing PI3K inhibitors (mean 72.1 days). Patients with incident diabetes had higher anti-hypertensive medication use, higher HbA1c levels and fasting glucose at baseline, and longer duration of PI3K inhibitor use (P = 0.024, P = 0.005, P = 0.008, and P = 0.023, respectively). Previous steroid use and lower baseline HbA1c level were significantly associated with development of diabetes (HR = 8.41, 95% CI 1.89-37.33; HR = 2.16, 95% CI 1.09-4.25, respectively). Patients whose diabetes remitted after discontinuing PI3K inhibitors were younger (P = 0.035) and had lower fasting glucose levels during PI3K inhibitor treatment (P = 0.001) compared to those non-remitters.

Conclusions: Previous steroid use and lower baseline HbA1c level may be important predictors for developing diabetes in patients with advanced solid tumors treated with PI3K inhibitors, warranting close observation and careful intervention.
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http://dx.doi.org/10.1007/s00280-019-03889-0DOI Listing
August 2019

Risk of end-stage renal disease from chronic kidney disease defined by decreased glomerular filtration rate in type 1 diabetes: A comparison with type 2 diabetes and the effect of metabolic syndrome.

Diabetes Metab Res Rev 2019 11 11;35(8):e3197. Epub 2019 Jul 11.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: We estimated the end-stage renal disease (ESRD) risk of chronic kidney disease (CKD) in patients with type 1 diabetes (T1D). The ESRD risk of CKD in patients with T1D was compared with that of CKD in patients without diabetes and with type 2 diabetes (T2D). We also evaluated the predictive value of metabolic syndrome (MetS) for ESRD development in CKD patients with T1D.

Materials And Methods: The Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 were used. The risk of incident ESRD was analysed according to the presence and type of diabetes in CKD (defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m ) patients aged 20 years or older. Incident ESRD risk according to the presence of MetS was calculated among adult patients with CKD and T1D.

Results: During 10 701 375.84 person-years of follow-up, 43 693 cases of ESRD developed. Hazard ratios (HRs) for incident ESRD from CKD in the T1D group were 2.580 (95% confidence interval [CI], 2.336-2.849) and 9.267 (95% CI, 8.378-10.251) compared with T2D and nondiabetes groups, respectively. In CKD patients with T1D, the presence of MetS increased incident ESRD risk by an HR of 2.023 (95% CI, 1.501-2.727).

Conclusions: The presence of diabetes increases the risk for ESRD development from CKD. Furthermore, patients with T1D have a higher risk for ESRD incidence from CKD than do patients with T2D in a Korean population. MetS may be a useful predictor for ESRD in CKD patients with T1D.
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http://dx.doi.org/10.1002/dmrr.3197DOI Listing
November 2019

Multi-layer surface modification of pancreatic islets for magnetic resonance imaging using ferumoxytol.

Biomaterials 2019 09 23;214:119224. Epub 2019 May 23.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address:

Ferumoxytol is the only clinically available ultrasmall superparamagnetic iron oxide. However, the labeling efficacy of islet magnetic resonance imaging (MRI) using ferumoxytol is not suitable for use in clinical pancreatic islet transplantation (PIT). We evaluated the feasibility of pancreatic islet MRI using ferumoxytol through multi-layer surface modification. A four-layer nanoshield with poly (ethylene) glycol (PEG, 2 layers), ferumoxytol, and heparin was formed on the pancreatic islets. We compared pancreatic islet function, viability, and labeling efficacy of control, ferumoxytol alone-labeled, heparin-PEGylated, and ferumoxytol-heparin-PEGylated islets. With optimization of the ferumoxytol concentration during the ferumoxytol-heparin-PEGylation process, the labeling contrast in ex vivo MRI of ferumoxytol-heparin-PEGylated pancreatic islets was stronger than that of pancreatic islets labeled with ferumoxytol alone, without decreasing ex vivo islet viability or function. In a syngeneic mouse renal subcapsular PIT model, heparin-PEGylation and ferumoxytol-heparin-PEGylation delayed the revascularization of pancreatic islet grafts but did not impair glucose tolerance or revascularization of pancreatic islet grafts four weeks post-transplantation. Pancreatic islet visibility after labeling was also confirmed in a syngeneic mouse intraportal PIT model and in preliminary analysis of a non-human primate intraportal PIT model. In conclusion, multi-layer islet surface modification is a promising option for pancreatic islet MRI in intraportal PIT.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119224DOI Listing
September 2019

Prevention of Hepatocellular Carcinoma by Statins: Clinical Evidence and Plausible Mechanisms.

Semin Liver Dis 2019 May 25;39(2):141-152. Epub 2019 Mar 25.

Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University, Seoul, Republic of Korea.

Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are widely used to treat hypercholesterolemia for primary and secondary prevention of cardiovascular disease. Statins inhibit HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and modulate the downstream signaling of the mevalonate pathway. In addition to the primary effect, the antitumor effect of statins can be associated with mevalonate pathway-mediated and nonmevalonate pathway-mediated mechanisms, which improve endothelial function and lead to proapoptotic, antiproliferative, antiinflammatory, and antifibrotic properties. Statins are implicated in the improvement of metabolic status. Statins are orally available and safely and widely used for long-term treatment; they represent a novel approach for the prevention and treatment for hepatocellular carcinoma (HCC). Although several observational studies and experimental studies have revealed the preventive and therapeutic potential of statins for HCC treatment, further prospective interventional studies and randomized control trials are warranted to confirm these observations.
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http://dx.doi.org/10.1055/s-0039-1679956DOI Listing
May 2019

Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus.

Diabetes Metab J 2020 04 28;44(2):267-276. Epub 2019 Feb 28.

Huh's Diabetes Center and the 21st Century Diabetes and Vascular Research Institute, Seoul, Korea.

Background: Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods: We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results: LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, =0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; =0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; =0.002).

Conclusions: Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.
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http://dx.doi.org/10.4093/dmj.2019.0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188976PMC
April 2020

Risk of Incident Dementia According to Metabolic Health and Obesity Status in Late Life: A Population-Based Cohort Study.

J Clin Endocrinol Metab 2019 07;104(7):2942-2952

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Context: The risk for dementia among subjects who are obese with normal metabolic profiles, or called metabolically healthy obese (MHO), remains uninvestigated.

Objective: To determine the association between late-life metabolic health and obesity status and risk of incident dementia.

Design: Retrospective cohort study.

Setting: The National Health Insurance System, Republic of Korea.

Patients: A total of 12,296,863 adults >50 years old who underwent health examinations from 2009 to 2012 without baseline history of dementia.

Main Outcome Measure: Incident overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD).

Results: Among subjects ≥60 years old, 363,932 (6.4%) developed dementia during a median follow-up of 65 months (interquartile range 51 to 74 months). The MHO group showed the lowest incidence of overall dementia [hazard ratio (HR) 0.85; 95% CI, 0.84 to 0.86] and AD (HR 0.87; 95% CI, 0.86 to 0.88), but not VaD, compared with the metabolically healthy nonobese group. All components of metabolic syndrome except obesity significantly elevated the risk of dementia, and these associations were more pronounced in VaD. In particular, being underweight dramatically increased the risk of dementia.

Conclusions: The MHO phenotype in late life demonstrated lower risk of overall dementia and AD but not VaD. Additional studies in other populations are warranted to elucidate current results and may predict individuals most at risk for developing dementia.
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http://dx.doi.org/10.1210/jc.2018-01491DOI Listing
July 2019

Spontaneous ketonuria and risk of incident diabetes: a 12 year prospective study.

Diabetologia 2019 05 20;62(5):779-788. Epub 2019 Feb 20.

Department of Preventive Medicine, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea.

Aims/hypothesis: Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study.

Methods: We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12 year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0 mmol/l, post-load 2 h glucose ≥11.1 mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed.

Results: Over 12 years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1 h and 2 h glucose levels and a higher insulinogenic index despite comparable baseline values.

Conclusions/interpretation: The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.
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http://dx.doi.org/10.1007/s00125-019-4829-xDOI Listing
May 2019

Relationship Between Circulating Netrin-1 Concentration, Impaired Fasting Glucose, and Newly Diagnosed Type 2 Diabetes.

Front Endocrinol (Lausanne) 2018 23;9:691. Epub 2018 Nov 23.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

The protein netrin-1 has demonstrated anti-inflammatory, tissue regeneration, and immune modulation properties. Although inflammation is a major contributing factor in the development of insulin resistance and type 2 diabetes, little is known about a possible relationship between serum netrin-1 and type 2 diabetes. Therefore, we investigated the association between circulating levels of netrin-1 and glycometabolic parameters predictive of type 2 diabetes. Serum samples were collected from 41 normal controls, 85 subjects with impaired fasting glucose (IFG), and 92 subjects with newly diagnosed type 2 diabetes. Clinical and laboratory parameters were assessed and netrin-1 levels were measured by commercial enzyme-linked immunosorbent assay. Spearman correlation analyses and multivariable-adjusted regression analyses were conducted to examine the relationship between serum netrin-1 levels and glycometabolic parameters. Serum netrin-1 levels in subjects with type 2 diabetes or IFG were significantly higher compared to normal controls (441.0, 436.6, and 275.9 pg/mL, respectively; for trend < 0.001). Serum netrin-1 levels were significantly positively correlated with fasting glucose, HbA, and insulin resistance index (all s < 0.01). Serum netrin-1 levels were independently associated with IFG or type 2 diabetes (standardized β = 0.405, < 0.001) after adjusting for covariates and potential confounders. In addition, the receiver operating characteristic (ROC) analysis showed that serum netrin-1 levels could identify the presence of IFG and type 2 diabetes with the area under the ROC curve (AUC) of 0.784 ( < 0.001). Our results suggest that elevated serum netrin-1 levels are significantly associated with the presence of IFG and type 2 diabetes.
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http://dx.doi.org/10.3389/fendo.2018.00691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265472PMC
November 2018