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1.
Journal of the Korean Medical Association ; : 432-438, 2023.
Article in Korean | WPRIM | ID: wpr-1001683

ABSTRACT

Emerging evidence suggests that controlling both glycemic variability and hemoglobin A1c is necessary to prevent complications associated with diabetes mellitus. Hence, continuous glucose monitoring (CGM) is crucial for effectively managing diabetes.Current Concepts: There are two primary types of CGM. Retrospective CGM only allows the reviewal of glycemic data after the monitoring period, whereas personal CGM allows real-time monitoring. Personal CGM can be further categorized into real-time CGM and intermittently scanned CGM. To interpret CGM data, time in range (TIR) is considered the standard parameter. A TIR of 70–180 mg/dL for more than 70% of the period has been established as a typical target for both type 1 and type 2 diabetes. Other parameters such as time below range, time above range, coefficient of variation, and glucose management indicator should also be reviewed. Importantly, numerous clinical studies have demonstrated the efficacy of CGM in both type 1 and type 2 diabetes.Discussion and Conclusion: A wealth of clinical evidence supports the application of CGM in diabetes, confirming its effectiveness across various treatment stages. CGM has emerged as a compelling therapeutic option in instances when other treatment choices remain limited. With a growing body of clinical evidence, the widespread adoption of CGM in diabetes management appears inevitable. However, challenges related to user comfort, cost, the need for extensive data interpretation, and necessary system improvements remain unaddressed. Further research is required to validate the appropriate usage and frequency of CGM through costeffectiveness analyses.

2.
Endocrinology and Metabolism ; : 568-577, 2023.
Article in English | WPRIM | ID: wpr-1000325

ABSTRACT

Background@#Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. @*Methods@#We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. @*Results@#The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. @*Conclusion@#CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

3.
Diabetes & Metabolism Journal ; : 71-80, 2022.
Article in English | WPRIM | ID: wpr-914214

ABSTRACT

Background@#To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12. @*Results@#Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014). @*Conclusion@#The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

4.
Endocrinology and Metabolism ; : 74-83, 2022.
Article in English | WPRIM | ID: wpr-924968

ABSTRACT

Background@#Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA). @*Methods@#HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting. @*Results@#Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9-39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation. @*Conclusion@#These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.

5.
Diabetes & Metabolism Journal ; : 439-450, 2022.
Article in English | WPRIM | ID: wpr-924931

ABSTRACT

Background@#Prevailing insulin regimens for glycemic control in hospitalized patients have changed over time. We aimed to determine whether the current basal-bolus insulin (BBI) regimen is superior to the previous insulin regimen, mainly comprising split-mixed insulin therapy. @*Methods@#This was a single tertiary center, retrospective observational study that included non-critically ill patients with type 2 diabetes mellitus who were treated with split-mixed insulin regimens from 2004 to 2007 (period 1) and with BBI from 2008 to 2018 (period 2). Patients from each period were analyzed after propensity score matching. The mean difference in glucose levels and the achievement of fasting and preprandial glycemic targets by day 6 of admission were assessed. The total daily insulin dose, incidence of hypoglycemia, and length of hospital stay were also evaluated. @*Results@#Among 244 patients from each period, both fasting glucose (estimated mean±standard error, 147.4±3.1 mg/dL vs. 129.4±3.2 mg/dL, P<0.001, day 6) and preprandial glucose (177.7±2.8 mg/dL vs. 152.8±2.8 mg/dL, P<0.001, day 6) were lower in period 2 than in period 1. By day 6 of hospital admission, 42.6% and 67.2% of patients achieved a preprandial glycemic target of <140 mg/dL in periods 1 and 2, respectively (relative risk, 2.00; 95% confidence interval, 1.54 to 2.59), without an increased incidence of hypoglycemia. Length of stay was shorter in period 2 (10.23±0.26 days vs. 8.70±0.26 days, P<0.001). @*Conclusion@#BBI improved glycemic control in a more efficacious manner than a split-mixed insulin regimen without increasing the risk of hypoglycemia in a hospital setting.

6.
Endocrinology and Metabolism ; : 1016-1028, 2021.
Article in English | WPRIM | ID: wpr-914263

ABSTRACT

Background@#Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD. @*Methods@#We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI). @*Results@#After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m2. The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4). @*Conclusion@#Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

7.
Diabetes & Metabolism Journal ; : 813-839, 2021.
Article in English | WPRIM | ID: wpr-914185

ABSTRACT

Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

8.
Endocrinology and Metabolism ; : 885-894, 2021.
Article in English | WPRIM | ID: wpr-898202

ABSTRACT

Background@#There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function. @*Methods@#Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively. @*Results@#Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed. @*Conclusion@#PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

9.
Endocrinology and Metabolism ; : 845-854, 2021.
Article in English | WPRIM | ID: wpr-898188

ABSTRACT

Background@#Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes. @*Methods@#We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years. @*Results@#On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53). @*Conclusion@#Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

10.
Endocrinology and Metabolism ; : 885-894, 2021.
Article in English | WPRIM | ID: wpr-890498

ABSTRACT

Background@#There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function. @*Methods@#Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively. @*Results@#Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed. @*Conclusion@#PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.

11.
Endocrinology and Metabolism ; : 845-854, 2021.
Article in English | WPRIM | ID: wpr-890484

ABSTRACT

Background@#Weight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes. @*Methods@#We examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years. @*Results@#On dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53). @*Conclusion@#Regardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

12.
Endocrinology and Metabolism ; : 1-9, 2020.
Article | WPRIM | ID: wpr-832413

ABSTRACT

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.

13.
Diabetes & Metabolism Journal ; : 737-746, 2020.
Article | WPRIM | ID: wpr-832371

ABSTRACT

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.

14.
Endocrinology and Metabolism ; : 132-141, 2020.
Article in English | WPRIM | ID: wpr-816620

ABSTRACT

BACKGROUND: Adrenal cortical carcinoma (ACC) is a rare cancer with a variable prognosis. Several prognostic factors of ACC have been previously reported, but a proteomic analysis has not yet been performed. This study aimed to investigate prognostic biomarkers for ACC using a proteomic approach.METHODS: We used reverse-phase protein array data from The Cancer Proteome Atlas, and identified differentially expressed proteins in metastatic ACCs. Multivariate Cox regression analysis adjusted by age and staging was used for survival analysis, and the C-index and category-free net reclassification improvement (cfNRI) were utilized to evaluate additive prognostic value.RESULTS: In 46 patients with ACC, cyclin B1, transferrin receptor (TfR1), and fibronectin were significantly overexpressed in patients with distant metastasis. In multivariate models, high expression of cyclin B1 and TfR1 was significantly associated with mortality (hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.02 to 36.7; and HR, 6.59; 95% CI, 1.14 to 38.2; respectively), whereas high fibronectin expression was not (HR, 3.92; 95% CI, 0.75 to 20.4). Combinations of high cyclin B1/high TfR1, high cyclin B1/high fibronectin, and high TfR1/high fibronectin were strongly associated with mortality ([HR, 13.72; 95% CI, 1.89 to 99.66], [HR, 9.22; 95% CI, 1.34 to 63.55], and [HR, 18.59; 95% CI, 2.54 to 135.88], respectively). In reclassification analyses, cyclin B1, TfR1, fibronectin, and combinations thereof improved the prognostic performance (C-index, 0.78 to 0.82–0.86; cfNRI, all P values <0.05).CONCLUSION: In ACC patients, the overexpression of cyclin B1, TfR1, and fibronectin and combinations thereof were associated with poor prognosis.


Subject(s)
Humans , Adrenocortical Carcinoma , Biomarkers , Cyclin B1 , Cyclins , Fibronectins , Mortality , Neoplasm Metastasis , Prognosis , Protein Array Analysis , Proteome , Proteomics , Receptors, Transferrin , Transferrin
15.
Endocrinology and Metabolism ; : 943-953, 2020.
Article in English | WPRIM | ID: wpr-898144

ABSTRACT

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.

16.
Endocrinology and Metabolism ; : 943-953, 2020.
Article in English | WPRIM | ID: wpr-890440

ABSTRACT

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.

17.
Journal of Korean Diabetes ; : 214-223, 2018.
Article in Korean | WPRIM | ID: wpr-726691

ABSTRACT

In hospitalized patients, hyperglycemia is frequently observed in patients with and without diabetes. Inpatient hyperglycemia worsens outcomes, potentially leading to infection, post-operative complications, and even death. Therefore, it is important to control blood glucose level in an inpatient setting. However, in these patients, it can be difficult to achieve adequate glycemic control due to the disease itself (e.g., infection), treatment drugs (e.g., corticosteroids), procedures requiring fasting, or enteral/parenteral nutrition therapy. In most cases, insulin therapy is required. We reviewed the insulin treatment regimens in hospitalized patients.


Subject(s)
Humans , Blood Glucose , Diabetes Mellitus , Fasting , Hyperglycemia , Inpatients , Insulin , Nutrition Therapy
18.
Journal of Korean Diabetes ; : 275-283, 2017.
Article in Korean | WPRIM | ID: wpr-726898

ABSTRACT

BACKGROUND: Dapagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, lowers blood glucose by reducing glucose reabsorption at the proximal renal tubule in an insulin-independent manner. We aimed to evaluate the efficacy and safety of dapagliflozin and to identify the risk factors of adverse drug events in patients with type 2 diabetes. METHODS: As an institutional pharmacovigilance review activity, we reviewed data from medical records of 455 patients with type 2 diabetes who received dapagliflozin therapy from July 2014 to August 2015 in Seoul National University Hospital. We analyzed the changes in laboratory data and examined the characteristics of dapagliflozin users who showed adverse effects. RESULTS: Mean changes in HbA1c and fasting serum glucose level from baseline to second visit were −0.42% (8.07 ± 1.51% to 7.65 ± 1.31%, P < 0.001) and −22.9 mg/dL (167.8 ± 48.5 mg/dL to 144.9 ± 37.6 mg/dL, P < 0.001), respectively. Adverse drug events observed during this study were lower urinary tract symptoms (7.7%), dehydration-related symptoms (6.1%), ketonuria (3.4%), hypoglycemia (3.4%), and urogenital infection (4.2%). Thiazide use, age, insulin use, number of anti-diabetic drugs, gender and history of urogenital infection were the risk factors for adverse drug events (P < 0.05). CONCLUSION: Dapagliflozin significantly improved hyperglycemia in patients with type 2 diabetes without serious adverse drug events. The incidences of adverse drug events were was similar to those ofthat in the previous studies.


Subject(s)
Humans , Blood Glucose , Diabetes Mellitus , Drug-Related Side Effects and Adverse Reactions , Fasting , Glucose , Hyperglycemia , Hypoglycemia , Incidence , Insulin , Ketosis , Kidney Tubules, Proximal , Lower Urinary Tract Symptoms , Medical Records , Pharmacovigilance , Risk Factors , Seoul
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