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A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Young Min, Sungrae Kim
Diabetes Metab J. 2022;46(6):855-865.   Published online March 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0264
  • 7,177 View
  • 299 Download
  • 6 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice.
Methods
In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled.
Results
Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42.
Conclusion
Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Citations

Citations to this article as recorded by  
  • Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
    Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697.     CrossRef
  • Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
    Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703.     CrossRef
  • Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
    Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747.     CrossRef
  • Lobeglitazone

    Reactions Weekly.2023; 1948(1): 262.     CrossRef
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    Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
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    Balamurugan M, Sarumathy S, Robinson R
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  • Oldies but Goodies: Thiazolidinedione as an Insulin Sensitizer with Cardioprotection
    Eun-Hee Cho
    Diabetes & Metabolism Journal.2022; 46(6): 827.     CrossRef
Obesity and Metabolic Syndrome
Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys
Soo In Choi, Dawn Chung, Jung Soo Lim, Mi Young Lee, Jang Yel Shin, Choon Hee Chung, Ji Hye Huh
Diabetes Metab J. 2017;41(1):51-59.   Published online December 21, 2016
DOI: https://doi.org/10.4093/dmj.2017.41.1.51
  • 4,422 View
  • 42 Download
  • 35 Web of Science
  • 36 Crossref
AbstractAbstract PDFPubReader   
Background

The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations.

Methods

A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry.

Results

The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001).

Conclusion

The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.

Citations

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Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community
Jae Hyun Kim, Gun Woo Kim, Mi Young Lee, Jang Yel Shin, Young Goo Shin, Sang Baek Koh, Choon Hee Chung
Diabetes Metab J. 2012;36(1):37-42.   Published online February 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.1.37
  • 3,956 View
  • 35 Download
  • 11 Crossref
AbstractAbstract PDFPubReader   
Background

Recently, the measurement of glycated hemoglobin (HbA1c) was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM). In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population.

Methods

We analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes.

Results

The mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1%) and 1,302 DM patients (12.9%). A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%).

Conclusion

Our results suggest that the optimal HbA1c level for DM screening is 5.95%.

Citations

Citations to this article as recorded by  
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Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model
Mi Young Lee, Myoung Sook Shim, Bo Hwan Kim, Soon Won Hong, Ran Choi, Eun Young Lee, Soo Min Nam, Gun Woo Kim, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Diabetes Metab J. 2011;35(2):130-137.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.130
  • 3,863 View
  • 65 Download
  • 15 Crossref
AbstractAbstract PDFPubReader   
Background

While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.

Methods

Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9).

Results

At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.

Conclusion

These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

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Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women.
Jang Hyun Koh, Mi Young Lee, Soo Min Nam, Joong Kyung Sung, Pil Moon Jung, Jin Kyu Noh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Korean Diabetes J. 2008;32(3):243-251.   Published online June 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.3.243
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AbstractAbstract PDF
BACKGROUND
Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.

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  • Interaction between major dietary patterns and cardiorespiratory fitness on metabolic syndrome in Iranian adults: a cross-sectional study
    Hossein Shahinfar, Mahtab Ghanbari, Yahya Jalilpiran, Nastaran Payande, Mahshid Shahavandi, Nadia Babaei, Kurosh Djafarian, Cain C. C. Clark, Sakineh Shab-Bidar
    Nutrition Journal.2021;[Epub]     CrossRef
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    Jeong-Eun Yoo
    Journal of Korean Medicine for Obesity Research.2016; 16(2): 133.     CrossRef
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    A. D. Rodrigues, H. Theodoro, K. G. Mendes, V. M. Paniz, D. de Lorenzi, M. T. Anselmo Olinto
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  • Effects of Web-based Health Education on Blood Glucose and Blood Pressure Improvement in Postmenopausal Women with Impaired Fasting Blood Glucose
    Jeong-Ah Oh, Hee-Seung Kim, Min-Jeong Park, Hye-Sun Shim
    Journal of Korean Academy of Nursing.2011; 41(5): 724.     CrossRef
  • Prevalence of Metabolic Syndrome and Related Risk Factors of Elderly Residents in Andong Rural Area 2. Based on the Biochemical Measurements and Nutrient Intakes
    Hye-Sang Lee, Chong-Suk Kwon
    Journal of the Korean Society of Food Science and Nutrition.2010; 39(10): 1459.     CrossRef
  • The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
    Ho Chan Cho
    Korean Diabetes Journal.2010; 34(2): 111.     CrossRef
  • Prevalence of Metabolic Syndrome and Related Risk Factors of Elderly Residents in Andong Rural Area 1. Based on the Anthropometric Measurements and Health Behaviors
    Hye-Sang Lee, Chong-Suk Kwon
    Journal of the Korean Society of Food Science and Nutrition.2010; 39(4): 511.     CrossRef
The Effect of Rosiglitazone on Gluose Metabolism and Insulin Sensitivity in Non Obese Type 2 Diabetic Rat Models.
Mi Jin Kim, Eui Jong Chung, Byung Wook Ha, Ji Hoon Kim, Su Min Nam, Mi Young Lee, Jang Hyun Kho, Young Goo Shin, Choon Hee Chung
Korean Diabetes J. 2007;31(4):319-325.   Published online July 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.4.319
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BACKGROUND
In Korea, most of type 2 diabetic patients are non obese. We made non obese type 2 diabetic rat models, which were characterized by insulin resistance and insulin secretion defect. Our study aimed to investigate the effect of rosiglitazone on glucose metabolism and insulin sensitivity in non obese type 2 diabetic rat models. Furthermore, we may estimate the effect of rosiglitazone treatment in non obese type 2 diabetic patients in Korea. METHODS: 20 male newborn (12 hours old) Sprague-Dawley rats were made diabetes by streptozotocin (75 mg/kg, intraperitoneal injection). At 16 weeks old, diabetes were confirmed by intraperitoneal glucose tolerance test (IPGTT, 30% D/W, 2 kg/kg). After that, diabetic groups were divided into two groups. One group was fed on normal chow and rosiglitazone (3 mg/kg/day) and the other group was fed on normal chow for eight weeks. At the age of 24 weeks, we measured body weight (BW), plasma glucose, insulin, C-peptide levels. And we performed IPGTT and insulin tolerance test (ITT) in two groups. Thereafter, we determined the insulin content of pancreas and epididymal fat weight. RESULTS: Body weight was significantly higher in rosiglitazone group than control group. On IPGTT, plasma glucose, insulin and C-peptide levels were not significantly different between two groups. But, on insulin tolerance test, Kitt (%/min) values of rosiglitazone group were significantly higher than control group (2.7 vs. 1.8). The insulin content of pancreas and epididymal fat weight was not different between two groups. CONCLUSION: These results suggested that rosiglitazone improved insulin sensitivity in non obese type 2 diabetes rat models independent of glucose level.
Alcohol Consumption, Liver Enzymes, and Prevalence of Metabolic Syndrome in Korean Adult Men.
Soo Min Nam, Ho Yeol Yu, Mi Young Lee, Jang Hyun Koh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Korean Diabetes J. 2007;31(3):253-260.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.253
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AbstractAbstract PDF
BACKGROUND
Metabolic syndrome is associated with an increasing incidence of diabetes and cardiovascular disease. The relationship between the amount of alcohol consumption and the prevalence of metabolic syndrome is controversial. Our study was performed to evaluate the relationship between alcohol consumption and the prevalence of metabolic syndrome in Korean men. Also we examined the correlation of liver markers, including alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) with the development of metabolic syndrome. METHODS: We enrolled 1,775 Korean men (mean age 40.0 +/- 5.8 years) who were undergone health check-ups in our hospital. Each component of metabolic syndrome was measured by using the American Association of Clinical Endocrinologists (AACE) criteria. The subjects were divided into 4 subgroups according to the amount of alcohol consumption; Group 1: no consumption, 2 (mild): those consumed less than 200 g/week, 3 (moderate): those consumed 200~399 g/week, 4 (heavy): those consumed more than 400 g/week. RESULTS: The prevalence of metabolic syndrome was 24.6%. There were significant positive correlations between the amount of alcohol consumption blood pressure, triglyceride, fasting blood glucose, GGT levels and HDL cholesterol levels. But the odds ratios for metabolic syndrome were not significantly increased in subjects with moderate alcohol consumption. The odds ratios for the metabolic syndrome significantly increased in proportion to the increasing levels of ALT and GGT. CONCLUSION: Although alcohol consumption didn't increase the prevalence of metabolic syndrome, the amount of alcohol consumption had significant positive correlation with components of metabolic syndrome in Korean men, and elevated ALT and GGT levels could strongly associate with the prevalence of metabolic syndrome.

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Association Between Impaired Vascular Endothelial Function and High Sensitivity C-reactive Protein, a Chronic Inflammatory Marker, in Patients with Type 2 Diabetes Mellitus.
Jang Yel Shin, Mi Young Lee, Jang Hyun Koh, Jang Young Kim, Young Goo Shin, Choon Hee Chung
Korean Diabetes J. 2005;29(5):469-478.   Published online September 1, 2005
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BACKGOUND: Eighty percents of diabetes-related mortalities are due to atherosclerotic vascular complications. The accelerated atherosclerosis in type 2 diabetic patients is partly due to the increased incidences of cardiovascular risk factors, such as hypertension, obesity, dyslipidemia, insulin resistance and oxidative stress. Endothelial dysfunction is known as an early marker of cardiovascular disease and a predictor of cardiovascular events. The flow mediated dilation (FMD) of the brachial artery has been documented as being reduced in type 2 diabetic patients. Inflammatory markers, such as C-reactive protein(CRP) and interleukin-6(IL-6), are associated with the risk of cardiovascular disease. Endothelial dysfunction has a direct correlation with the levels of CRP, which are elevated in patients with diabetes compared with non-diabetic subjects. In this study, the FMD in diabetic and non-diabetic subjects were compared, and the association of cardiovascular risk factors and endothelial function examined in type 2 diabetic patients. METHODS: 57 consecutive diabetic subjects and 29 non-diabetic subjects, aged 35 to 69(54.0+/-1.0 years), without proven macrovascular complications, were enrolled in this study. Cardiovascular risk factors, such as body weight, height, waist and hip circumference, fasting plasma glucose and insulin levels, lipid profiles, inflammatory and coagulation markers were measured. The FMD of the brachial artery and the intima-media thickness(IMT) of the carotid artery were determined using high-resolution B-mode ultrasound. RESULTS: The FMD values were significantly lower in the diabetic compared with the non-diabetic subjects(7.6+/-0.2% vs. 8.9+/-0.4%, P=0.004). The homocysteine levels were significantly higher in the diabetic than non-diabetic subjects(12.4+/-0.4micromol/L vs. 9.5+/-0.6micromol/L, P<0.0001). In diabetic subjects, the FMD was shown to be significantly negatively correlated with high sensitivity C-reactive protein(hsCRP)(P=0.006), fibrinogen(P=0.024) and homocysteine (P=0.038). A multiple regression analysis, after adjusted for age, sex, body mass index(BMI), hypertension, and smoking, showed that hsCRP(beta=-0.424, P=0.002) and fibrinogen(beta=-0.324, P=0.025) had significant inverse association with the FMD in diabetic subjects. CONCLUSION: Diabetic subjects have an impaired endothelial function compared with the non-diabetic subjects, and the vascular endothelial function has a significant negative correlation with hsCRP and fibrinogen. These findings suggest that hsCRP might be an independent predictor of endothelial dysfunction and atherosclerosis, and chronic inflammation might play a pivotal role in the impairment of the endothelial function in diabetic patients.
Self-Management and Health-Related Quality of Life in Adolescent and Adulthood Diabetic Patients.
Bong Suk Park, Gi Nam Jin, Youn Chung Choi, Ji Hee Chung, Kyoung Hoe Kim, Mi Young Lee, Jang Hyun Koh, Choon Hee Chung
Korean Diabetes J. 2005;29(3):254-261.   Published online May 1, 2005
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BACKGROUND
The purposes of this study are to analyze the factors that influence selfmanagement and health-related QOL, and to provide useful informations to improve the QOL in adolescent and adult diabetic patients. METHODS: For this study, we interviewed 126 adolescent and adult diabetic patients who visited the Yonsei University Wonju Christian Hospital from March 4th, 2004 to April 5th, 2004. RESULTS: We examined the relationship between the socio-demographic characteristics and the health-related quality of life(QOL). There were statistically significant relationships between the QOL-and employment, years of education, income level and marriage status, but not between the health-related QOL and age and gender. Furthermore, there were no statistically significant relationships between the health-related QOL and smoking or drinking, nor between type 1 and 2 diabetic patients. The health-related QOL was significantly higher for an increased diabetes duration and for a greater number of symptoms, but the QOL was significantly lower in the presence of complications and hospital admission. The health-related QOL was lower when the preprandial blood glucose levels and HbA1c concentrations were higher, but it was higher when the hemoglobin and hematocrit levels were higher. Regarding the treatment methods, the health-related QOL was significantly lower for those patients who took insulin injection. The QOL was higher when the general self-management and diet therapy were well-controlled. Meanwhile, those subjects who had obtained medical informations from doctors, the media(including the internet and TV) and nurses in that order, they selected diet therapy as the hardest factor in the management of their diabetes. CONCLUSION: Adolescent and adult diabetic patients need continuous education and assistance to improve their health-related QOL and to keep from developing complications
Differential Activation of the Renal Renin-Angiotensin System Components in Diabetic Rats.
Woon Jung Kim, Mi Young Lee, Tae Hyung Kim, Eun Kyoung Yang, Won Jung Lee
Korean Diabetes J. 1998;22(2):218-230.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
The renin-angiotensin system(RAS) plays an important role in the physiologic regulation of the renal microcirculation and may contribute to the imbalance of resistances present at the preglomerular and postglomerular sites whirh are responsible for glomerular capillary hypertension, a major injurious factor in the diabetic kidney. Blockade of angiotensin(Ang II) with angiotensin converting enzyme(ACE) inhibitor or Ang II receptor antagonists reduces glomerular injury. However, the relationship between diabetes and the RAS is unclear. METHOD: To investigate changes of gene expression of the renal renin-angiotensin system in diabetic nephropathy, mRNA levels of the RAS components were determined with the methods of Northern blot and RT-PCR in streptozotocin-induced diabetic(STZ-D) rats. Sprague-Dawley rats(240~260 g) were made diabetic by double i.p. injections of 45 mg/kg STZ. Result: Plasma renin concentration increased significantly at the onset of diabetes, and then suppressed at 4 and 8 week sof diabetes. Changes in renal renin content and mRNA levels were in parallel with plasma renin concentration during 8 weeks of diabetes. Renal angiotensinogen mRNA levels of the STZ-D rats decreased initially and then returned to the baseline with the progression of diabetes. Gene expression of angiotensin II-AT1 receptor subtypes, AT1a and AT1b, was not significantly changed during 8 wk of diabetes. Plasma and renal ACE activity increased significantly at 4 and 8 wk of diabetes. CONCLUSION: Results of the present study show a marked decrease in renal renin mRNA levels and renin concentration, but significant increase in ACE activity in chronic diabetic rats. When considering renoprotective effect of ACE inhibitors and AT receptor antagonists, the present result may suggest an increased intrarenal generation of Ang II and its pathophysiologic role in diabetic nephropathy. However, further studies are required to clarify meanings of the differential activation of the renal renin-angiotensin system components in diabetic rats.

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