Rg3 Improves Mitochondrial Function and the Expression of Key Genes Involved in Mitochondrial Biogenesis in C2C12 Myotubes

Kim, Min Joo,Koo, Young Do,Kim, Min,Lim, Soo,Park, Young Joo,Chung, Sung Soo,Jang, Hak C.,Park, Kyong Soo Korean Diabetes Association 2016 Diabetes and Metabolism Journal Vol.40 No.5

<P><B>Background</B></P><P><I>Panax ginseng</I> has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of <I>P. ginseng</I>, on mitochondrial function and biogenesis in C2C12 myotubes.</P><P><B>Methods</B></P><P>C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.</P><P><B>Results</B></P><P>Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.</P><P><B>Conclusion</B></P><P>Our results suggest that Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis, leading to an improvement in insulin resistance in skeletal muscle. Rg3 may have the potential to be developed as an anti-hyperglycemic agent.</P>

Endothelial Function is Not Changed during Short-Term Withdrawal of Thyroxine in Patients with Differentiated Thyroid Cancer and Low Cardiovascular Risk

장혁재,김경원,최성희,임수,박경운,박도준,최동주,Hak C. Jang,조보연,박영주 연세대학교의과대학 2010 Yonsei medical journal Vol.51 No.4

Purpose: The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore,the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk. Materials and Methods: To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) & 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin. Results: During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p <0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism. Conclusion: Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular risk.

Hemoglobin A _1c as a Diagnostic Tool for Diabetes Screening and New-Onset Diabetes Prediction : A 6-year community-based prospective study

Choi, Sung Hee,Kim, Tae Hyuk,Lim, Soo,Park, Kyong Soo,Jang, Hak C.,Cho, Nam H. American Diabetes Association 2011 Diabetes care Vol.34 No.4

<P><B>OBJECTIVE</B></P><P>Various cutoff levels of hemoglobin A<SUB>1c</SUB> (A1C) have been suggested to screen for diabetes, although more consensus about the best level, especially for different ethnicities, is required. We evaluated the usefulness of A1C levels when screening for undiagnosed diabetes and as a predictor of 6-year incident diabetes in a prospective, population-based cohort study.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>A total 10,038 participants were recruited from the Ansung-Ansan cohort study. All subjects underwent a 75-g oral glucose tolerance test at baseline and at each biennial follow-up. Excluding subjects with a previous history of diabetes (<I>n</I> = 572), the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of the A1C cutoff. The Cox proportional hazards model was used to predict diabetes at 6 years.</P><P><B>RESULTS</B></P><P>At baseline, 635 participants (6.8%) had previously undiagnosed diabetes. An A1C cutoff of 5.9% produced the highest sum of sensitivity (68%) and specificity (91%). At 6 years, 895 (10.2%) subjects had developed incident diabetes. An A1C cutoff of 5.6% had the highest sum of sensitivity (59%) and specificity (77%) for the identification of subsequent 6-year incident diabetes. After multivariate adjustment, men with baseline A1C ≥5.6% had a 2.4-fold increased risk and women had a 3.1-fold increased risk of new-onset diabetes.</P><P><B>CONCLUSIONS</B></P><P>A1C is an effective and convenient method for diabetes screening. An A1C cutoff of 5.9% may identify subjects with undiagnosed diabetes. Individuals with A1C ≥5.6% have an increased risk for future diabetes.</P>

Improved Glycemic Control Without Hypoglycemia in Elderly Diabetic Patients Using the Ubiquitous Healthcare Service, a New Medical Information System

Lim, Soo,Kang, Seon Mee,Shin, Hayley,Lee, Hak Jong,Won Yoon, Ji,Yu, Sung Hoon,Kim, So-Youn,Yoo, Soo Young,Jung, Hye Seung,Park, Kyong Soo,Ryu, Jun Oh,Jang, Hak C. American Diabetes Association 2011 Diabetes care Vol.34 No.2

<P><B>OBJECTIVE</B></P><P>To improve quality and efficiency of care for elderly patients with type 2 diabetes, we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare (u-healthcare<B>)</B> service, which is an individualized health management system using advanced medical information technology.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>We conducted a 6-month randomized, controlled clinical trial involving 144 patients aged >60 years. Participants were randomly assigned to receive routine care (control, <I>n</I> = 48), to the self-monitored blood glucose (SMBG, <I>n</I> = 47) group, or to the u-healthcare group (<I>n</I> = 49). The primary end point was the proportion of patients achieving A1C <7% without hypoglycemia at 6 months. U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient’s mobile phone. Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server. Once the data are transferred to the server, an automated system, the CDSS rule engine, generates and sends patient-specific messages by mobile phone.</P><P><B>RESULTS</B></P><P>After 6 months of follow-up, the mean A1C level was significantly decreased from 7.8 ± 1.3% to 7.4 ± 1.0% (<I>P</I> < 0.001) in the u-healthcare group and from 7.9 ± 1.0% to 7.7 ± 1.0% (<I>P</I> = 0.020) in the SMBG group, compared with 7.9 ± 0.8% to 7.8 ± 1.0% (<I>P</I> = 0.274) in the control group. The proportion of patients with A1C <7% without hypoglycemia was 30.6% in the u-healthcare group, 23.4% in the SMBG group (23.4%), and 14.0% in the control group (<I>P <</I> 0.05).</P><P><B>CONCLUSIONS</B></P><P>The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients.</P>

Association of Dietary Quality Indices with Glycemic Status in Korean Patients with Type 2 Diabetes

( Ji Young Kim ),( Young Yun Cho ),( Young Mi Park ),( Cheong Min Sohn ),( Mi Yong Rha ),( Moon Kyu Lee ),( Hak C. Jang ) 한국임상영양학회 2013 Clinical Nutrition Research Vol.2 No.2

The present study was performed to evaluate the relationship between dietary quality indices including the Diet Quality Index- International (DQI-I), Alternate Healthy Eating Index (AHEI), and Healthy Diet Indicator (HDI) and glycemic status in Korean patients with type 2 diabetes. A total of 110 consecutive outpatients with type 2 diabetes who visited 2 university hospitals in Seoul and Seongnam from April 2004 to November 2006 were enrolled as subjects. At the time of enrollment, anthropometric parameters, dietary habits, experience of exercise, and metabolic parameters were obtained. Experienced registered dietitians collected one-day dietary intake using the 24-hour recall method. The mean scores for DQI-I, AHEI, and HDI were 68.9 ± 8.2, 39.4 ± 8.9, and 5.0 ± 1.3, respectively. After adjustment for age, body mass index, and energy intake, DQI-I and HDI were found to have a significant correlation with hemoglobin A1c (HbA1c) (r = .0.21, p < 0.05; r = .0.28, p < 0.05), fasting plasma glucose (r = .0.21, p < 0.05; r = .0.23, p < 0.05), and postprandial 2-h glucose (r = .0.30, p < 0.05; r = .0.26, p < 0.05, respectively). However, AHEI did not have a significant correlation with HbA1c. In conclusion, the DQI-I and HDI may be useful tools in assessing diet quality and adherence to dietary recommendations in Korean patients with type 2 diabetes. Future research is required to determine whether the dietary quality indices have predictive validity for dietary and glycemic changes following diet education in a clinical setting.

Finding Genetic Risk Factors of Gestational Diabetes

Kwak, Soo Heon,Jang, Hak C.,Park, Kyong Soo Korea Genome Organization 2012 Genomics & informatics Vol.10 No.4

Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy that is suspected to have a strong genetic predisposition. It is associated with poor perinatal outcome, and both GDM women and their offspring are at increased risk of future development of type 2 diabetes mellitus (T2DM). During the past several years, there has been progress in finding the genetic risk factors of GDM in relation to T2DM. Some of the genetic variants that were proven to be significantly associated with T2DM are also genetic risk factors of GDM. Recently, a genome-wide association study of GDM was performed and reported that genetic variants in CDKAL1 and MTNR1B were associated with GDM at a genome-wide significance level. Current investigations using next-generation sequencing will improve our insight into the pathophysiology of GDM. It would be important to know whether genetic information revealed from these studies could improve our prediction of GDM and the future development of T2DM. We hope further research on the genetics of GDM would ultimately lead us to personalized genomic medicine and improved patient care.

Case Reports : A Case of Gastric Cancer Initially Presenting with Polydipsia

Seung Suk Han,Hae Sung Kim,Hak C. Jang,Il Soon Whang,Hy Sook Kim,Hye Sun Kim,Kyung Sang Lee 대한내과학회 2004 The Korean Journal of Internal Medicine Vol.19 No.4

Metastatic brain tumors from gastric cancer are extremely rare. A 61-year-old Korean woman, initially presenting with polydipsia and polyuria, was found to have metastatic lesions in the brain by MRI. We performed several diagnostic procedures to determin

Active incomplete biliary cirrhosis in an old female Japanese macaque

Bokyeong Ryu,Kyung-Yeon Eo,Ja-Jun Jang,Ji Min Lee,Hanseul Oh,Ukjin Kim,Jin Kim,Hyun-Ho Lee,Young-Mok Jung,C-Yoon Kim,Jae-Hak Park 한국실험동물학회 2018 한국실험동물학회 학술발표대회 논문집 Vol.2018 No.1

임신성 당뇨병 환자의 식습관 및 식이섭취에 관한 환자-대조군 연구

지선경(Ji Sun-Kyung),장학철(Jang Hak C),최혜미(Choi Haymie) 韓國營養學會 2008 Journal of Nutrition and Health Vol.41 No.1

임신성 당뇨병의 발병에 영향을 미치는 식이 인자를 알아보고자 컴퓨터용 식품섭취빈도조사지와 설문지 등을 이용하여 임신성 당뇨병의 환자군-대조군 연구를 시행한 결과는 다음과 같다. 임신성 당뇨병군이 대조군보다 연령과 BMI가 높았고, 당뇨병의 가족력이 많았다. 임신전의 식습관은 임신성 당뇨병군이 대조군보다 1일 식사횟수가 적었고, 식사 시간이 불규칙하고 식사속도가 빨랐으며 채식을 적게 하고 기름진 음식을 싫어하는 경향이었으며, 식습관점수가 낮았다. 식품섭취빈도법으로 조사한 영양소 섭취량에서는 임신성 당뇨병군이 대조군보다 탄수화물의 섭취량이 유의적으로 많았고 단백질의 에너지 섭취비율이 유의적으로 낮았다. 지방의 섭취량에는 두 군 간에 차이가 없었으며 임신성 당뇨병군이 대조군보다 단백질과 칼슘, 인, 비타민 B₁의 영양밀도가 유의적으로 낮았다. 두 그룹 간에 섭취량에 유의적 차이를 보이는 식품 중 쌀, 중국국수, 돼지고기 등은 임신성 당뇨병군에서 대조군보다 많이 섭취하였고, 옥수수, 오정어채, 큰멸치, 수박, 포도, 복숭아, 밤, 땅콩, 호상 요구르트, 치즈, 검정콩, 당근 등은 대조군에서 섭취량이나 섭취빈도가 많았다. 두 군 사이에 섭취량에 유의적 차이를 보이는 음식 중 온면, 시루떡, 햄버거, 돼지고기편육, 삶은 계란 등은 임신성 당뇨병군에서 섭취량이 많았고, 전병, 두부조림, 오징어채무침, 깍두기, 야채샐러드, 김치국, 과일샐러드, 콩밥, 콩조림, 토마토쥬스 등은 대조군에서 섭취량이나 섭취빈도가 많았다. 특히 쌀의 경우에는 임신성 당뇨병군이 대조군보다 섭취량은 많았으나 섭취빈도는 적어 임신성 당뇨병군에서 1회의 섭취분량이 많았던 것으로 생각할 수 있다. 영양소 중에서는 탄수화물이나 에너지의 섭취량이 많을 때 임신성 당뇨병의 odds ratio가 증가하였고, 식품이나 음식은 쌀, 국수, 돼지고기, 온면, 시루떡, 햄버거, 삶은 계란, 돼지고기편육 등의 섭취량이 많을 때 임신성 당뇨병의 odds ratio가 증가하였다. 상관관계의 분석결과 에너지 섭취량, 탄수화물 섭취량 등이 혈액의 포도당농도와 상관관계가 있는 것으로 나타났다. 이상으로 본 연구 결과를 종합해 볼 때 임신성 당뇨병에 영향을 미치는 식이 인자는 지방보다는 탄수화물의 섭취량으로 생각되어지며 단백질을 포함한 식사의 질과 바람직하지 않은 식습관이 영향을 미칠 수 있음을 생각해 볼 수 있다. Gestational diabetes mellitus (GDM) is defined as glucose intolerance discovered or onset during pregnancy and attention is needed because of increased risk of perinatal morbidties and higher incidence of diabetes afterward. This study was performed to identify dietary factors associated with the development of gestational diabetes mellitus (GDM). Developed food frequency questionnaire containing 192 food items were used to assess nutritional status of 246 control subjects and 104 GDM subjects. Food habits of subjects were examined in the questionnaire. The more irregularity and less variety of meal were found in GDM group compared to control group and GDM group tended to eat rapidly and do not like vegetables and greasy foods. Total score of food habits in GDM was lower than control group, which suggests that GDM group have undesirable food habits. Mean daily energy and carbohydrate intakes of GDM group were higher than those of control group, and percent energy from protein was significantly higher in control. Nutrient density of protein, calcium, phosphorus and vitamin B₁ of GDM group was significantly lower than those of control group. Therefore dietary quality of GDM group was lower than that of control group. Odds ratio for GDM was high when energy and carbohydrate intakes were high. And when the intakes of rice, noodle, shiruduk, hamburger, boiled egg, steamed pork shank were high, the odds ratio for GDM was high. These results indicate that the amount and frequencies of several foods and dish items were related with the occurrence of GDM subjects. On the whole, GDM subjects consumed more cereals and less vegetables and less legumes. From these results, pregnant women with GDM tended to have unhealthy food habits, and carbohydrate intake was important dietary factors on the onset of GDM. (Korean J Nutr 2008; 41(1): 41~53)

Cigarette smoking is an independent risk factor for type 2 diabetes: a four-year community-based prospective study

Cho, Nam H.,Chan, Juliana C. N.,Jang, Hak Chul,Lim, Soo,Kim, Hyung L.,Choi, Sung Hee Blackwell Publishing Ltd 2009 Clinical endocrinology Vol.71 No.5

<P>Summary</P><P>Objectives </P><P>We investigated the association between smoking and its additive effects with insulin resistance and &bgr;-cell function on the incidence of type 2 diabetes in a prospective population-based cohort study.</P><P>Design and method </P><P>A total of 10 038 subjects were recruited from rural and urban areas. All subjects underwent 75 g oral glucose tolerance tests and full biochemical assessments at baseline and during 4-year follow-up period. The final analysis was limited to 4041 men due to the low smoking rates in women.</P><P>Results </P><P>The ex- and heavy current smokers had the highest incidence of diabetes of 12·5% and 11·1% respectively, compared with never-smokers (7·9%) during 4 years. After multivariate adjustment by Cox-proportional hazard model, ex- and current smokers reveal a relative risk of 1·60 (95% CI: 1·07–2·39), 2·06 (1·35–3·16, for <20 cigarettes/day) and 2·41 (1·48–3·93, for ≥20 cigarettes/day) respectively compared with never smokers. The risk of new onset diabetes was the highest in those with low homeostasis model assessment for beta cell function (HOMA-&bgr;) and high homeostasis model assessment for insulin resistance (HOMA-IR) group in both smokers and never smokers.</P><P>Conclusions </P><P>Smoking is an independent risk factor for type 2 diabetes mellitus and showed synergistic interaction with the status of low insulin secretion and high insulin resistance for developing diabetes. Given the high rates of smoking and growing burden of diabetes in the world, cessation of smoking should be considered as one of the key factors for diabetes prevention and treatment programmes.</P>