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저 HDL 콜레스테롤혈증이 관상동맥 질환에 미치는 영향: 4년의 전향적 지역 기반 코호트 연구
구보경 ( Bo Kyung Koo ),문민경 ( Min Kyong Moon ) 대한내과학회 2013 대한내과학회지 Vol.84 No.2
목적: 많은 역학 연구에서 낮은 HDL 콜레스테롤 농도가 관상동맥 질환의 위험을 높임이 보고되었으나, HDL 콜레스테롤이 직접적으로 관상동맥 질환 위험을 낮추는 역할을 하는지에 대해서는 아직 밝혀지지 않았다. 본 연구에서는 저 HDL 콜레스테롤혈증이 독립적으로 관상동맥 질환 발생을 높이는지를 전향적인 대규모 코호트에서 알아보고자 하였다. 방법: 안성, 안산 코호트는 한국인에서 만성 질환의 역학 연구를 위해 수립된, 대규모의 지역기반 전향적 코호트로서, 2000-2001년에 기초조사를 시작하였고 2년마다 추적 조사를 시행하였다. 본 연구는 3기까지의 총 4년의 조사 결과를 대상으로 분석을 시행하였다. HDL 콜레스테롤의 역할에 대한 교란변수를 제거하기 위해 기초 조사 당시 당뇨병이 있거나, 이전 관상동맥 질환 병력이 있는 대상자는 연구에서 제외하였다. 결과: 총 8,438명의 연구 대상자의 0.8%에서 4년간의 추적관찰 기간 동안 관상동맥 질환이 발생하였다. 관상동맥 질환이 발생한 경우는 그렇지 않은 대상자에 비해 나이가 많고(p<0.001), 체질량지수가 높았으며(p=0.003) 고혈압(p=0.005) 및 고중성지방혈증(p=0.045) 유병률이 높았다. Cox 회귀분석 결과 고중성지방혈증은 유의하게 추적관찰 기간 동안의 관상동맥 질환 위험도를 높였다(hazard ratio, 1.822; 95% confidence interval, 1.029-3.225). 기저 HDL 콜레스테롤 농도는 기저 중성지방 혈중 농도와 유의한 상관관계에 있었으나(r = (남자) 0.404, (여자) 0.460; p < 0.001), 향후의 관상 동맥 질환 위험도에 영향을 주지 못했다. 결론: 대규모 지역기반 코호트에서 저 HDL 콜레스테롤혈증은 독립적으로 4년 관상동맥 질환 위험을 높이지 않았다. Background/Aims: We investigated the effect of an isolated low high-density lipoprotein (HDL) cholesterol level on the risk of coronary artery disease (CAD) in a prospective cohort. Methods: The Ansung-Ansan cohort was established for inclusion in a prospective, large-scale, community-based epidemiologic study to investigate chronic diseases in Korea. The data from a baseline survey performed from 2000 to 2001 and two subsequent prospective biennial surveys were analyzed. We included subjects without diabetes mellitus or a history of CAD at the baseline. Results: Among 8,438 total subjects, 0.8% reported newly developed CAD events during 4 years of follow-up. The subjects who experienced CAD events were significantly older (p<0.001), had a higher body mass index (p=0.003), and had a higher prevalence of hypertension (p=0.005) and hypertriglyceridemia (p=0.045) at the baseline. However, there was no significant difference in the baseline HDL cholesterol level between subjects with or without CAD events. Furthermore, although the baseline triglyceride level was significantly correlated with the baseline HDL cholesterol level (r=-0.404 in men and -0.460 in women; p<0.001 in both), and Cox regression analysis showed that hypertriglyceridemia at the baseline was significantly associated with an increased hazard ratio for CAD events (hazard ratio, 1.822; 95% confidence interval, 1.029-3.225), low HDL cholesterolemia was not associated with a risk of CAD events. Conclusions: Low HDL cholesterolemia did not independently increase the subsequent 4 years` risk of CAD events in this community-based Korean cohort. (Korean J Med 2013;84:229-237)
ApoE 결손 생쥐에서 FXR 결핍과 피오글리타존이 동맥경화에 미치는 영향
박영주 ( Young Joo Park ),김민주 ( Min Joo Kim ),이관재 ( Kwan Jae Lee ),황지연 ( Ji Yeon Hwang ),이예나 ( Yen Na Lee ),안화영 ( Hwa Young Ahn ),최성희 ( Sung Hee Choi ),문민경 ( Min Kyong Moon ),임수 ( Soo Lim ),장학철 ( Hak C. 대한내과학회 2013 대한내과학회지 Vol.84 No.2
목적: Farnesoid X receptor (FXR)와 peroxisome proliferatoractivated receptor (PPAR)는 둘 다 지질 대사와 동맥경화에 중요한 역할을 담당하고 있어 이들의 상호작용에 대해 알아 보고자 하였다. 방법: 아포지질단백질 E가 결손된(ApoE-/-) 생쥐에 추가로 FXR을 결손시켜 ApoE-/-FXR-/- 생쥐를 만들었다. 생쥐는 ApoE-/-군, ApoE-/-FXR-/-군, ApoE-/-FXR-/-+ pioglitazone군, 3군으로 나누어 12주간 고지방 고콜레스테롤 식이를 먹였고 ApoE-/-FXR-/-+ pioglitazone군은 pioglitazone을 하루에 몸무게 kg당 20mg을 식이에 섞어 투여하였다. 이후 체중, 혈당, 혈청 지질 농도, 간효소치를 측정하였다. 대동맥에서 Oil red O 염색을 통해 동맥경화반을 평가하였다. 결과: 세 군 사이에 체중과 혈당에는 차이가 없었다. ApoE-/-FXR-/-군은 ApoE-/-군에 비하여 모든 종류의 지질 농도와 간 효소치가 유의하게 증가하였다(p<0.01). ApoE-/-FXR-/-+ pioglitazone군은 ApoE-/-FXR-/-군에 비하여 HDL 콜레스테롤과(55±4mg/dL vs. 28±2mg/dL, p<0.01) LDL 콜레스테롤이(797±26mg/dL vs. 682±47mg/dL, p=0.04) 유의하게 감소 하였다. 동맥경화반은 ApoE-/-군, ApoE-/-FXR-/-군, ApoE-/-FXR-/-+ pioglitazone군에서 각각 2.7±0.2%, 7.7±1.2%, 18.6±1.0%로 증가하였다. ApoE-/-FXR-/- 생쥐에서 pioglitazone의 투여는 유의하게 동맥경화를 증가시켰다(p=0.02) 결론: 본 연구에서 ApoE-/-FXR-/- 생쥐에서 pioglitazone의 투여는 동맥경화반의 발생을 증가시켜 FXR이 억제된 상태에서 PPARγ의 활성화는 동맥경화에 나쁜 영향을 미칠 수 있음을 시사하였다. Background/Aims: Both the farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) play important roles in lipid metabolism and atherosclerosis. We investigated the interaction between FXR and PPARγ. Methods: Apolipoprotein E knockout (ApoE-/-) mice and FXR knockout (FXR-/-) mice were crossed to generate ApoE-/-FXR-/-mice. The mice were divided into ApoE-/-, ApoE-/-FXR-/-, and ApoE-/-FXR-/-+ pioglitazone groups. All mice were fed a high-fat, high-cholesterol diet for 12 weeks. The ApoE-/-FXR-/-+ pioglitazone group was also treated with pioglitazone, 20 mg/kg body weight. Body weight, blood glucose level, lipid profile, and liver enzyme levels were measured. To evaluate atherosclerotic lesions, the aorta was stained with Oil red O. Results: There were no differences in body weight or blood glucose level among the three groups. The serum lipid concentration and liver enzyme levels increased in the ApoE-/-FXR-/- group compared with the ApoE-/- group (p<0.01). The ApoE-/-FXR-/-+ pioglitazone group had lower high-density lipoprotein (HDL) (55±4 vs. 28± 2mg/dL, p<0.01) and low-density lipoprotein (LDL) (797±26 vs. 682±47mg/dL, p=0.04) cholesterol than the ApoE-/-FXR-/- group. The respective percentages of aortic atherosclerotic plaques in the ApoE-/-, ApoE-/-FXR-/-, and ApoE-/-FXR-/-+ pioglitazone groups were 2.7±0.2%, 7.7±1.2%, and 18.6±1.0%. In ApoE-/-FXR-/- mice, the administration of pioglitazone significantly increased the number of atherosclerotic lesions (p=0.02). Conclusions: Pioglitazone increased the number of atherosclerotic plaques in ApoE-/-FXR-/- mice. This suggests that when FXR is inhibited, the activation of PPARγ can aggravate atherosclerosis. (Korean J Med 2013;84:238-244)
제2형 당뇨병 환자에서 장기간의 Sodium-glucose Cotransporter 2 억제제 치료가 신장기능에 미치는 효과
백종하 ( Jong Ha Baek ),오태정 ( Tae Jung Oh ),문주영 ( Ju-young Moon ),김태희 ( Taehee Kim ),고승현 ( Seung Hyun Ko ),문민경 ( Min Kyong Moon ),김현정 ( Hyun Jung Kim ),이동원 ( Dong Won Lee ),허규연 ( Kyu Yeon Hur ) 대한내과학회 2020 대한내과학회지 Vol.95 No.4
Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)
전이성 신세포암에서 Everolimus 사용 후 유발된 당뇨병성 케톤산증 1예
김이경 ( Lee Kyung Kim ),안창호 ( Chang Ho Ahn ),이지은 ( Jie Eun Lee ),정찬현 ( Chan Hyeon Jung ),구보경 ( Bo Kyung Koo ),문민경 ( Min Kyong Moon ) 대한내과학회 2014 대한내과학회지 Vol.86 No.6
신세포암, 유방암, 췌장의 신경내분비종 등의 치료에 사용이 증가하고 있는 mTOR 억제제인 everolimus의 치료 시고혈당, 고지질혈증 등의 대사 이상이 발생할 수 있음이 알려져 있으나 당뇨병성 케톤산증의 발생은 보고된 바 없다. 저자들은 전이성 신세포암에서 everolimus 투여 후 발생한 당뇨병성 케톤산증 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Everolimus, an inhibitor of the mammalian target of the rapamycin (mTOR) pathway, is widely used as an immunosuppressant for the prevention of organ rejection following transplant and to treat metastatic clear-cell type renal cell carcinoma (RCC), breast cancer, and pancreatic neuroendocrine tumors. Everolimus commonly induces metabolic abnormalities such as hyperglycemia, hypercholesterolemia, and hypertriglyceridemia due to concomitant increases in blood glucose levels via the induction of insulin resistance and a decrease in β cell function, which both lead to insulin deficiency. Although abnormal blood glucose levels are observed in more than 50% of patients treated with Everolimus, hyperglycemia exceeding 500 mg/dL is not common and there have been no reports of Everolimus-induced acute hyperglycemic crisis conditions. Here, a novel case of Everolimus-associated diabetic ketoacidosis (DKA) in a patient with RCC is reported. (Korean J Med 2014;86:761-765)
당뇨병 환자에서 기초 인슐린 주입량과 1일 인슐린 투여량의 상관관계
신원식,안종호,김태용,문민경,이홍규,김성연,박경수,조영민,임수 대한당뇨병학회 2000 Diabetes and Metabolism Journal Vol.24 No.5
Background: In patients who need insulin therapy, it is difficult to assess insulin requirements because of individual variability in insulin sensitivity and secretion. The aim of this study is to know that it is possible to achieve rapidly and efficiently normoglycemia based on insulin infusion algorithm and whether there is correlation between basal insulin requirements and daily administered total insulin dose. Methods: Total 34 patients were enrolled. Insulin infusion was begun at 2:00 p.m., and bedside blood glucose concentration was measured at hourly intervals. The rate of insulin infusion was adjusted according to blood glucose levels. We compared insulin requirements to maintain normoglycemia (basal insulin requirements) with daily administered total insulin dose. Results: At start, the mean blood glucose concentration was 14.9±4.7 mmol/L; by the first hour, it was 10.7±3.6 mmol/L; by the second hour, it was 7.4±3.1 mmol/L; when the infusion was discontinued, it was 5.7±1.0mmol/L. This algorithm successfully inducted normoglycemia in all patients within 3.5±1.8 h. There was significant correlation between basal insulin requirements and daily administered total insulin dosage. And, daily administered insulin dose had significant correlation with first hour glucose concentration, first hour insulin infusion rate, second hour glucose concentration, second hour insulin infusion rate, and glucose concentration at the end. Conclusions: We concluded that normoglycemia can be achieved rapidly and efficiently based on insulin infusion algorithm. The present study suggested that we could predict daily insulin requirements through basal insulin requirements that we measured.