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대한당뇨병학회> Diabetes and Metabolism Journal (DMJ)> Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease

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Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease

Eugene Han
  • : 대한당뇨병학회
  • : Diabetes and Metabolism Journal (DMJ) 46권4호
  • : 연속간행물
  • : 2022년 07월
  • : 564-566(3pages)
Diabetes and Metabolism Journal (DMJ)

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  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCOPUS
  • : 격월
  • : 2233-6079
  • : 2233-6087
  • : 학술지
  • : 연속간행물
  • : 1972-2022
  • : 2953


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1New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins

저자 : Kyuho Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 517-532 (16 pages)

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Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

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2Endoplasmic Reticulum Stress and Dysregulated Autophagy in Human Pancreatic Beta Cells

저자 : Seoil Moon , Hye Seung Jung

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 533-542 (10 pages)

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Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

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3Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics

저자 : Nam Hoon Kim , Nan Hee Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 543-551 (9 pages)

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Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

KCI등재 SCOPUS

4Current Trends of Big Data Research Using the Korean National Health Information Database

저자 : Mee Kyoung Kim , Kyungdo Han , Seung-hwan Lee

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 552-563 (12 pages)

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Recently, medical research using big data has become very popular, and its value has become increasingly recognized. The Korean National Health Information Database (NHID) is representative of big data that combines information obtained from the National Health Insurance Service collected for claims and reimbursement of health care services and results obtained from general health examinations provided to all Korean adults. This database has several strengths and limitations. Given the large size, various laboratory data, and questionnaires obtained from medical check-ups, their longitudinal nature, and long-term accumulation of data since 2002, carefully designed studies may provide valuable information that is difficult to obtain from other forms of research. However, consideration of possible bias and careful interpretation when defining causal relationships is also important because the data were not collected for research purposes. After the NHID became publicly available, research and publications based on this database have increased explosively, especially in the field of diabetes and metabolism. This article reviews the history, structure, and characteristics of the Korean NHID. Recent trends in big data research using this database, commonly used operational diagnosis, and representative studies have been introduced. We expect further progress and expansion of big data research using the Korean NHID.

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5Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease

저자 : Eugene Han

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 564-566 (3 pages)

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6Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus

저자 : Seung Eun Lee , Hyewon Nam , Han Seok Choi , Hoseob Kim , Dae-sung Kyoung , Kyoung-ah Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 567-577 (11 pages)

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Background: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Methods: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
Results: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
Conclusion: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

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7Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus

저자 : Soyeon Kang , Yong-moon Park , Dong Jin Kwon , Youn-jee Chung , Jeong Namkung , Kyungdo Han , Seung-hyun Ko

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 578-591 (14 pages)

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Background: Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated.
Methods: This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models.
Results: During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30-34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35-39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse.
Conclusion: Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

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8Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence

저자 : Se-a Kim , Hoyul Lee , Sung-mi Park , Mi-jin Kim , Yu-mi Lee , Young-ran Yoon , Hyun-kyung Lee , Hyo-bang Moon , In-kyu Lee , Duk-hee Lee

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 592-604 (13 pages)

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Background: Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.
Methods: Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p´-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells.
Results: The association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels.
Conclusion: The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

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9Effect of Different Types of Diagnostic Criteria for Gestational Diabetes Mellitus on Adverse Neonatal Outcomes: A Systematic Review, Meta-Analysis, and Meta-Regression

저자 : Fahimeh Ramezani Tehrani , Marzieh Saei Ghare Naz , Razieh Bidhendi-yarandi , Samira Behboudi-gandevani

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 605-619 (15 pages)

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Background: Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes.
Methods: Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel-Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg's test.
Results: A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar.
Conclusion: Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.

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10Prevalence of Diabetic Retinopathy in Undiagnosed Diabetic Patients: A Nationwide Population-Based Study

저자 : Han Na Jang , Min Kyong Moon , Bo Kyung Koo

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 620-629 (10 pages)

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Background: We investigated the prevalence of diabetic retinopathy (DR) in patients with undiagnosed diabetes through a nationwide survey, compared to those with known diabetes.
Methods: Among the participants of the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2017 to 2018, individuals aged ≥40 years with diabetes and fundus exam results were enrolled. Sampling weights were applied to represent the entire Korean population. Newly detected diabetes patients through KNHANES were classified under “undiagnosed diabetes.”
Results: Among a total of 9,108 participants aged ≥40 years, 951 were selected for analysis. Of them, 31.3% (standard error, ±2.0%) were classified under “undiagnosed diabetes.” The prevalence of DR in patients with known and undiagnosed diabetes was 24.5%±2.0% and 10.7%±2.2%, respectively (P<0.001). The DR prevalence increased with rising glycosylated hemoglobin (HbA1c) levels in patients with known and undiagnosed diabetes (P for trend=0.001 in both). Among those with undiagnosed diabetes, the prevalence of DR was 6.9%±2.1%, 8.0%±3.4%, 5.6%±5.7%, 16.7%±9.4%, and 42.6%±14.8% for HbA1c levels of <7.0%, 7.0%-7.9%, 8.0%-8.9%, 9.0%-9.9%, and ≥10.0% respectively. There was no difference in the prevalence of hypertension, dyslipidemia, hypertriglyceridemia, or obesity according to the presence or absence of DR.
Conclusion: About one-third of patients with diabetes were unaware of their diabetes, and 10% of them have already developed DR. Considering increasing the prevalence of DR according to HbA1c level was found in patients with undiagnosed diabetes like those with known diabetes, screening and early detection of diabetes and DR are important.

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1New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins

저자 : Kyuho Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 517-532 (16 pages)

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Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

KCI등재SCOUPUS

2Endoplasmic Reticulum Stress and Dysregulated Autophagy in Human Pancreatic Beta Cells

저자 : Seoil Moon , Hye Seung Jung

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 533-542 (10 pages)

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Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

KCI등재SCOUPUS

3Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics

저자 : Nam Hoon Kim , Nan Hee Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 543-551 (9 pages)

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Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

KCI등재SCOUPUS

4Current Trends of Big Data Research Using the Korean National Health Information Database

저자 : Mee Kyoung Kim , Kyungdo Han , Seung-hwan Lee

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 552-563 (12 pages)

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Recently, medical research using big data has become very popular, and its value has become increasingly recognized. The Korean National Health Information Database (NHID) is representative of big data that combines information obtained from the National Health Insurance Service collected for claims and reimbursement of health care services and results obtained from general health examinations provided to all Korean adults. This database has several strengths and limitations. Given the large size, various laboratory data, and questionnaires obtained from medical check-ups, their longitudinal nature, and long-term accumulation of data since 2002, carefully designed studies may provide valuable information that is difficult to obtain from other forms of research. However, consideration of possible bias and careful interpretation when defining causal relationships is also important because the data were not collected for research purposes. After the NHID became publicly available, research and publications based on this database have increased explosively, especially in the field of diabetes and metabolism. This article reviews the history, structure, and characteristics of the Korean NHID. Recent trends in big data research using this database, commonly used operational diagnosis, and representative studies have been introduced. We expect further progress and expansion of big data research using the Korean NHID.

KCI등재SCOUPUS

5Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease

저자 : Eugene Han

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 564-566 (3 pages)

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6Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus

저자 : Seung Eun Lee , Hyewon Nam , Han Seok Choi , Hoseob Kim , Dae-sung Kyoung , Kyoung-ah Kim

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 567-577 (11 pages)

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Background: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Methods: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
Results: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
Conclusion: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

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7Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus

저자 : Soyeon Kang , Yong-moon Park , Dong Jin Kwon , Youn-jee Chung , Jeong Namkung , Kyungdo Han , Seung-hyun Ko

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 578-591 (14 pages)

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Background: Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated.
Methods: This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models.
Results: During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30-34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35-39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse.
Conclusion: Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

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8Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence

저자 : Se-a Kim , Hoyul Lee , Sung-mi Park , Mi-jin Kim , Yu-mi Lee , Young-ran Yoon , Hyun-kyung Lee , Hyo-bang Moon , In-kyu Lee , Duk-hee Lee

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 592-604 (13 pages)

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Background: Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.
Methods: Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p´-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells.
Results: The association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels.
Conclusion: The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

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9Effect of Different Types of Diagnostic Criteria for Gestational Diabetes Mellitus on Adverse Neonatal Outcomes: A Systematic Review, Meta-Analysis, and Meta-Regression

저자 : Fahimeh Ramezani Tehrani , Marzieh Saei Ghare Naz , Razieh Bidhendi-yarandi , Samira Behboudi-gandevani

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 605-619 (15 pages)

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Background: Evidence supporting various diagnostic criteria for diagnose gestational diabetes mellitus (GDM) are consensus-based, needs for additional evidence related to outcomes. Therefore, the aim of this systematic-review and meta-analysis was to assess the impact of different GDM diagnostic-criteria on the risk of adverse-neonatal-outcomes.
Methods: Electronic databases including Scopus, PubMed, and Web of Sciences were searched to retrieve English original, population-based studies with the universal GDM screening approach, up to January-2020. GDM diagnostic criteria were classified in seven groups and International Association of the Diabetes and Pregnancy Study Groups (IADPSG) was considered as reference one. We used the Mantel-Haenszel method to calculate the pooled odds of events. The possibility of publication bias was examined by Begg's test.
Results: A total of 55 population-based studies consisting of 1,604,391 pregnant women with GDM and 7,770,855 non-GDM counterparts were included. Results showed that in all diagnostic-criteria subgroups, the risk of adverse neonatal outcomes including macrosomia, hyperbilirubinemia, respiratory distress syndrome, neonatal hypoglycemia, neonatal intensive care unit admission, preterm birth, and birth-trauma were significantly higher than the non-GDM counterparts were significantly higher than non-GDM counterparts. Meta-regression analysis revealed that the magnitude of neonatal risks in all diagnostic-criteria subgroups are similar.
Conclusion: Our results showed that the risk of adverse-neonatal-outcome increased among women with GDM, but the magnitude of risk was not different among those women who were diagnosed through more or less intensive strategies. These findings may help health-care-providers and policy-makers to select the most cost-effective approach for the screening of GDM among pregnant women.

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10Prevalence of Diabetic Retinopathy in Undiagnosed Diabetic Patients: A Nationwide Population-Based Study

저자 : Han Na Jang , Min Kyong Moon , Bo Kyung Koo

발행기관 : 대한당뇨병학회 간행물 : Diabetes and Metabolism Journal (DMJ) 46권 4호 발행 연도 : 2022 페이지 : pp. 620-629 (10 pages)

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Background: We investigated the prevalence of diabetic retinopathy (DR) in patients with undiagnosed diabetes through a nationwide survey, compared to those with known diabetes.
Methods: Among the participants of the Korean National Health and Nutrition Examination Surveys (KNHANES) from 2017 to 2018, individuals aged ≥40 years with diabetes and fundus exam results were enrolled. Sampling weights were applied to represent the entire Korean population. Newly detected diabetes patients through KNHANES were classified under “undiagnosed diabetes.”
Results: Among a total of 9,108 participants aged ≥40 years, 951 were selected for analysis. Of them, 31.3% (standard error, ±2.0%) were classified under “undiagnosed diabetes.” The prevalence of DR in patients with known and undiagnosed diabetes was 24.5%±2.0% and 10.7%±2.2%, respectively (P<0.001). The DR prevalence increased with rising glycosylated hemoglobin (HbA1c) levels in patients with known and undiagnosed diabetes (P for trend=0.001 in both). Among those with undiagnosed diabetes, the prevalence of DR was 6.9%±2.1%, 8.0%±3.4%, 5.6%±5.7%, 16.7%±9.4%, and 42.6%±14.8% for HbA1c levels of <7.0%, 7.0%-7.9%, 8.0%-8.9%, 9.0%-9.9%, and ≥10.0% respectively. There was no difference in the prevalence of hypertension, dyslipidemia, hypertriglyceridemia, or obesity according to the presence or absence of DR.
Conclusion: About one-third of patients with diabetes were unaware of their diabetes, and 10% of them have already developed DR. Considering increasing the prevalence of DR according to HbA1c level was found in patients with undiagnosed diabetes like those with known diabetes, screening and early detection of diabetes and DR are important.

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