Earticle

제2형 당뇨병은 고혈당이 특징인 대사성 분비 장애로 여러 합병증을 야기하는 질병이며, 장기적인 치료가 필요 하기 때문에 매년 많은 의료비를 지출한다. 이를 해결하기 위해 많은 연구들이 있어왔지만, 기존의 연구들은 한 시점에 서의 데이터를 학습시켜 예측함으로써 정확도가 높지 않았다. 그래서 본 연구는 제2형 당뇨병 발생 예측에 대한 정확도 를 높이기 위하여 RNN을 이용한 모델을 제안하였다. 본 모델을 개발하기 위해 한국인유전체역학조사 지역사회 코호트 (안산·안성) 데이터를 이용하였으며, 시간의 흐름에 따른 데이터들을 모두 학습시켜 당뇨병 발생 예측모델을 만들었다. 예측 모델의 성능을 검증하기 위해 기존의 기계 학습 방법인 LR, k-NN, SVM과 정확도를 비교하였다. 비교한 결과 제안한 예측모델의 accuracy는 0.92, AUC는 0.92로 다른 기계 학습 방법보다 높은 정확도를 보였다. 따라서 본 연구 에서 제안한 제2형 당뇨병 발생 예측 모델을 활용하여 발병을 조기 예측함으로써 생활습관 개선 및 혈당조절을 통해 당뇨병 발병을 예방하고 늦출 수 있을 것이다.

Type 2 diabetes mellitus(T2DM) is included in metabolic disorders characterized by hyperglycemia, which causes many complications, and requires long-term treatment resulting in massive medical expenses each year. There have been many studies to solve this problem, but the existing studies have not been accurate by learning and predicting the data at specific time point. Thus, this study proposed a model using RNN to increase the accuracy of prediction of T2DM. This work propose a T2DM prediction model based on Korean Genome and Epidemiology study(Ansan, Anseong Korea). We trained all of the data over time to create prediction model of diabetes. To verify the results of the prediction model, we compared the accuracy with the existing machine learning methods, LR, k-NN, and SVM. Proposed prediction model accuracy was 0.92 and the AUC was 0.92, which were higher than the other. Therefore predicting the onset of T2DM by using the proposed diabetes prediction model in this study, it could lead to healthier lifestyle and hyperglycemic control resulting in lower risk of diabetes by alerted diabetes occurrence.

대사증후군은 심혈관질환의 주된 위험인자이며 심혈관질환을 개선하기 위해 규칙적인 운동을 실시해 야 한다는 근거는 매우 많이 존재한다. 또한 유산소 운동의 적용이 대사증후군 관리에 효과적이라는 연 구도 많이 존재한다. 따라서 대사증후군 지표 개선에 필수적으로 여겨지는 운동프로그램의 효율성을 높 이기 위해서 임상적 적용 사례를 알아보고 운동처방의 실제 적용과 효과 및 안전성 등을 고찰 해보고자 하였다. 대사증후군에 해당하는 지표들에 대한 운동의 효과를 분석한 연구들을 살펴본 결과 위험 부담 없이 효과적으로 운동을 실시하기 위해서 대사증후군 운동 프로그램이 매우 중요한 역할을 차지하고 있음을 알 수 있었다. 저항성 운동뿐만 아니라 유산소 운동은 대사 증후군 환자에서 중요한 관리 방법 이며, 비 약물로 치료 할 수 있는 중요한 방법 중 하나이다. 많은 선행 연구들을 통해 대사증후군에 대한 유산소 운동의 효과가 입증이 되었으며, 특히 세부적으로 비만, 당뇨, 고혈압, 이상지질혈증 등을 개선하는데 있 어서 유산소 운동은 임상적으로 큰 의미를 가지고 있음을 알 수 있다. 그리고 대사증후군의 발병은 주로 노인층임을 감안할 때 저항성 운동보다 유산소 운동처방으로 접근하였을 때가 가장 적합할 것으로 생각 된다. 외국의 사례를 바탕으로 우리나라에서도 대사증후군 환자들에게 보다 체계적인 운동의 적용이 필요하 며, 효율적인 접근을 위하여 우리나라 상황에 맞는 다양한 대사증후군 운동 프로그램에 대한 심도 깊은 연구가 이루어져야 할 것이다.

The purpose of this study was to investigate cases of metabolic syndrome to improve exercise efficiency and to examine the effect of exercise prescription. Metabolic syndrome refers to having three or more factors related to obesity, hypertension, diabetes, and dyslipidemia. Numerous studies have shown that exercise is effective in obesity, hypertension, diabetes, dyslipidemia and is an important method of non-drug therapy. Resistance exercise and aerobic exercise may be helpful in improving the metabolic syndrome index. However, considering that the elderly who have metabolic syndrome is an elderly person, it seems to be safer approach to aerobic exercise regimen. Based on the case of foreign countries, it is necessary to apply systematic exercise to patients with metabolic syndrome in Korea, and various and in-depth studies should be conducted for Korea.

Background: Diabetes is associated with cancer risk in the aging population. Observational studies have indicated the beneficial effects of metformin against breast cancer, making studies on the anticancer potential of antidiabetic drugs worthwhile. This study investigated cancer incidence in patients on antidiabetic monotherapy. Methods: Using National Health Insurance Service data (2002-2013), a retrospective cohort study that included type 2 diabetes mellitus (T2DM) patients was conducted. Study subjects were enrolled if they were ≥30 years old, on monotherapy for diabetes, and cancer-free. They were followed up for cancer occurrence or death, until December 31st, 2013. A Cox proportional hazard model analysis was conducted between metformin and sulfonylurea (including meglitinide) users, to determine cancer risk, with adjustment for age, gender, comorbidity index, dyslipidemia, hypertension, and T2DM duration. Results: The number of antidiabetic monotherapy-treated T2DM patients without a history of cancer was 9,554 (metformin, n = 5,825; sulfonylurea, n = 3,225; others, n = 504). During the follow-up period (mean, 2.04; IQR, 3.18 years), the cancer incidence rate was 5.48/100 and 5.45/100 patient-years for metformin and sulfonylurea, respectively. The hazard ratio (HR) for risk of cancer incidence in the metformin group was 0.74 (95% confidence interval [CI], 0.66-0.83; p < 0.0001), compared with sulfonylurea. Additionally, the HRs for risks of lung, liver, and stomach cancer were respectively 0.46 (95% CI, 0.31- 0.66; p < 0.0001), 0.41 (95% CI, 0.31-0.54; p < 0.0001), and 0.51 (95% CI, 0.35-0.73; p = 0.0003). Conclusion: Antidiabetic therapy with metformin reduces cancer risk by 26%, specifically for lung, liver, and stomach cancer.

본 연구의 목적은 8주 유산소 트레이닝이 제 2형 당뇨(T2DM)환자의 콜레스테롤과 신장기능에 미치는 영향을 규명하기 위함이다. 피험자는 총 4명(남 3, 여 1)이며 8주 유산소 걷기 트레이닝의 운동강도는 최대심박수($HR_{max}$)의 60~75%, 주당 3~5 회, 20~45 분간 실시되었으며 다음과 같은 결과를 얻었다. 신체적 특성 중 체지방률과 공복시 혈당은 8주 유산소 걷기 트레이닝 후 유의하게($p$ <0.05) 감소함을 나타냈고, 혈중지질인 총 콜레스테롤(TC)과 중성지방(TG)도 유의한 감소를 나타냈다. 그러나 신장기능[BUN, uric acids, creatinine]은 유의한 변화를 나타내지 못했다. 결과적으로 8주 유산소 트레이닝은 제 2형 당뇨(T2DM)와 당뇨병성 신증 환자의 1예에서 체지방률과 공복시혈당, 지질을 감소시키는데 영향을 미쳤지만 신장기능 증진에는 어떠한 영향도 미치지 못했다.

The purpose of this study was to examine the effect of 8 weeks of aerobic exercise on serum lipids and kidney function in middle-aged T2DM patients. Subjects participated in aerobic exercise training during 8 wk. They started with an exercise intensity of $HR_{max}$ 60-75%, 20~45 minutes per day, 3~5 times a week. The results were compared to the baseline after 8 weeks. After the 8-week aerobic exercise routine, the body fat percentage and fasting glucose were significantly decreased, and the total cholesterol (TC) andtriglycerides (TG) were significantly decreased. Additionally, kidney function (Blood Urea Nitrogen (BUN], uric acids, and creatinine) was not significantly changed. In conclusion, a regular 8-week aerobic exercise training routine may improve serum lipids; however, kidney function (BUN, uric acids, and creatinine) did not change in middle-age type 2 diabetes mellitus (T2DM) and T2DM in diabetic nephropathy patients.

본 연구에서는 12주 유산소 트레이닝 전에 비해 트레이닝 후, 간 기능을 나타내는 효소들이 모두 감소함을 나타냈으나 모두 통계적으로 유의한 차이는 나타내지 못했으며 이는 트레이닝이 간 기능에 영향을 미치지 못한 선행연구[5,15]들에서와 같은 결과를 나타냈다. 하지만 부분적으로 전체 대상자 13명 중 3명(23%)의 간 효소들 즉, 임상적 비정상을 나타낸 알부민(albumin), 토탈빌리루빈(total bilirubine), AST가 트레이닝 후, 정상적인 임상수치로 돌아와 규칙적인 12주 유산소 트레이닝이 제 2형 당뇨(T2DM) 환자의 간 효소에 통계적으로 유의한 차이는 나타내지 못했지만 임상적 판단 수치에 영향을 미친 것은 사실이다. 하지만 모든 비정상적인 간 기능 효소가 정상으로 회기한 것도 아니며 통계적으로 유의한 차이도 나지못했기 때문에 제 2형 당뇨환자(T2DM)의 간 기능 효소를 증진시키는 데 있어 운동 트레이닝의 효과는 성급히 판단하기 어려우며 운동 강도와 기간 등 좀 더 세분화고 다양한 연구가 필요하다고 생각된다.

The purpose of the this study was to examine the effects of 12 weeks of regular aerobic exercise training on hepatic enzymes in type 2 diabetes mellitus (T2DM) patients. The subjects consisted of 13 middle-aged male type 2 diabetes mellitus (T2DM) patients, all of whom had no other complications. Subjects participated in regular aerobic exercise training for 12 weeks, in which they started to exercise for $20{\sim}60$ min, at $60{\sim}80$% $HR_{max}$ (exercise intensity was increased gradually), per day, $3{\sim}5$ times a weeks. The results after 12 weeks were compared to baseline values. Weight and BMI, %body fat, and fasting glucose significantly decreased, and $_{peak}VO_{2}$, exercise time (ET) significantly increased after 12 weeks of aerobic exercise training. On the other hand, there were no significant differences in hepatic enzymes of Albumin, Total bilirubin, Alkaline phosphatate, AST, and ALT after training compared to baseline values. Conclusively, 12 weeks of aerobic exercise training may result in a decrease of insulin resistance factors (Weight, BMI, % body fat, fasting glucose) and an increase of aerobic capacity, but hepatic enzymes did not significantly decrease in middle age T2DM patients.

Objective: The aim of this study was to compare the effects of different doses of Geumnyeonyijin-tang (GNYJT) water extracts with those of metformin (250 mg/kg) in mild diabetic-obese mice. Methods and Results: The 48 mice were divided into 1 normal pellet diet (NFD) group and 5 high-fat diet (HFD) groups. At the end of 12 weeks of oral administration of metformin (250 mg/kg) or GNYJT water extracts (400, 200, or100 mg/kg), the effects were evaluated. The HFD control mice showed noticeable increases in body weight, adipose tissue density, fat pad weight of the periovarian and abdominal wall, and insulin, blood glucose, and HbA1c levels, with decreases in serum HDL levels. Increases in the periovarian and dorsal abdominal fat pad, regions of steatohepatitis, adipocyte hypertrophy, and hepatocyte hypertrophy were also discovered. The HFD group showed a decline in glucose levels and elevation of hepatic gluconeogenesis, suggesting an HFD-induced AMPK downregulation related to glucose dysregulation, as well as lipid metabolism related to obese insulin-resistant type II diabetes, dyslipidemia, and oxidative stress related diabetic hepatopathy (non-alcoholic fatty liver disease, NAFLD). Conclusion: Assessment of the key parameters for inhibition of diabetes and related complications in HFD-fed diabetic-obese mice demonstrated that GNYJT water extracts have favorable ameliorating effects. The effect of GNYJT was manifested through the stimulation of AMPK upregulation of related hepatic glucose enzyme activities and expression of lipid metabolism-related genes. Therefore, appropriate oral dosages of GNYJT could be promising as a new preventive candidate for controlling diabetes and related complications. Further screening of biologically active compounds, elucidation of detailed mechanisms, and more animal studies are warranted.

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca²⁺) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca²⁺ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.