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Obesity and Metabolic Syndrome
Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats
Shan-Ji Piao, So Hun Kim, Young Ju Suh, Seong-Bin Hong, Seong Hee Ahn, Da Hae Seo, In-Sun Park, Moonsuk Nam
Diabetes Metab J. 2017;41(6):474-485.   Published online November 15, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.6.474
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AbstractAbstract PDFPubReader   
Background

Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals.

Methods

We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment.

Results

Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group.

Conclusion

Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.

Citations

Citations to this article as recorded by  
  • Impacts of an Exercise Intervention on the Health of Pancreatic Beta-Cells: A Review
    Shuang Zhang, Yaru Wei, Chunxiao Wang
    International Journal of Environmental Research and Public Health.2022; 19(12): 7229.     CrossRef
  • Molecular mechanisms by which aerobic exercise induces insulin sensitivity
    Habib Yaribeygi, Stephen L. Atkin, Luis E. Simental‐Mendía, Amirhossein Sahebkar
    Journal of Cellular Physiology.2019; 234(8): 12385.     CrossRef
Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study
Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Park, Jeong Taek Woo, Ho Young Son
Diabetes Metab J. 2011;35(1):26-33.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.26
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  • 31 Crossref
AbstractAbstract PDFPubReader   
Background

Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.

Methods

We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.

Results

HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.

Conclusion

The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

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Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats
Jin Woo Lee, Il Seong Nam-Goong, Jae Geun Kim, Chang Ho Yun, Se Jin Kim, Jung Il Choi, Young IL Kim, Eun Sook Kim
Korean Diabetes J. 2010;34(3):191-199.   Published online June 30, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.3.191
  • 4,592 View
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  • 7 Crossref
AbstractAbstract PDFPubReader   
Background

Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes.

Methods

We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-α, interleukin [IL]-1β and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age).

Results

Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-κB expression in the skeletal muscle of OLETF rats.

Conclusion

These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

Citations

Citations to this article as recorded by  
  • Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats
    Jia Li, Yao-Ming Xue, Bo Zhu, Yong-Hua Pan, Yan Zhang, Chunxia Wang, Yuhao Li
    Journal of Diabetes Research.2018; 2018: 1.     CrossRef
  • Sirt1 and Sirt6 Mediate Beneficial Effects of Rosiglitazone on Hepatic Lipid Accumulation
    Soo Jin Yang, Jung Mook Choi, Eugene Chang, Sung Woo Park, Cheol-Young Park, Aimin Xu
    PLoS ONE.2014; 9(8): e105456.     CrossRef
  • Beneficial effects of co-enzyme Q10 and rosiglitazone in fructose-induced metabolic syndrome in rats
    Suzan M. Mansour, Hala F. Zaki, Ezz-El-Din S. El-Denshary
    Bulletin of Faculty of Pharmacy, Cairo University.2013; 51(1): 13.     CrossRef
  • Chromium Picolinate and Rosiglitazone Improve Biochemical Derangement in a Rat Model of Insulin Resistance: Role of TNF-a and Leptin
    Suzan M. Mansour, Hala F. Zaki, Ezz-El-Din El-Denshar
    Pharmacologia.2013; 4(3): 186.     CrossRef
  • Angiotensin Receptor Blockade Increases Pancreatic Insulin Secretion and Decreases Glucose Intolerance during Glucose Supplementation in a Model of Metabolic Syndrome
    Ruben Rodriguez, Jose A. Viscarra, Jacqueline N. Minas, Daisuke Nakano, Akira Nishiyama, Rudy M. Ortiz
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  • Rodent Models for Metabolic Syndrome Research
    Sunil K. Panchal, Lindsay Brown
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  • Letter: Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats (Korean Diabetes J 2010;34:191-9)
    Soo Jin Yang, Cheol-Young Park
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The Efficacy of Fixed Dose Rosiglitazone and Metformin Combination Therapy in Poorly Controlled Subjects with Type 2 Diabetes Mellitus.
Tae Seo Sohn, Jee in Lee, In Ju Kim, Kyung Wan Min, Hyun Shik Son
Korean Diabetes J. 2008;32(6):506-512.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.506
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AbstractAbstract PDF
BACKGROUND
Obese type 2 diabetic subjects are recently increasing in Korea, indicating the importance of insulin resistance rather than insulin secretory defects in the pathophysioloy of type 2 diabetes. The purpose of this study is to evaluate the safety and efficacy of fixed dose rosiglitazone/metformin combination therapy in poorly controlled subjects with type 2 diabetes mellitus. METHODS: 12 type 2 diabetic subjects who had a HbA1c > 11% or fasting plasma glucose > 15 mmol/L were included. After a 2 week screening period, the subjected took the fixed does rosiglitazone/metformin for 24 weeks. The treatment with rosiglitazone/metformin began at week 0 with an initial dose of 4 mg/1000 mg and, unless tolerability issues arose, subjects would be increased to 6 mg/1500 mg at week 4 and at week 8 to the maximum dose of 8 mg/2000 mg. The primary object of this study was to characterize the magnitude of HbA1c reduction from baseline after 24 weeks of rosiglitazone and metformin treatment in poorly controlled type 2 diabetics. RESULTS: The mean age of the subjects was 48.9 +/- 10.6 years old, body mass index was 25.0 +/- 3.5 kg/m2, HbA1c was 12.0 +/- 1.0%, and fasting plasma glucose was 16.3 +/- 3.1 mmol/L. HbA1c was reduced to 7.54 +/- 1.45% and fasting plasma glucose reduced to 7.96 +/- 2.38 mmol/L at week 24. The proportion of HbA1c responder who showed the reduction from baseline of > or = 0.7% or HbA1c < 7% was 11 among 12 subjects (91.7%). 41% of the subjects (5 among 12 subjects) achieved HbA1c level < 7.0% and 75% (9 among 12 subjects) achieved HbA1c level < 8.0%. CONCLUSIONS: In this study, rosiglitazone and metformin combination therapy was effective in glycemic control in poorly controlled subjects with type 2 diabetes mellitus.
Randomized Controlled Trial
The Effect of Rosiglitazone and Metformin Therapy, as an Initial Therapy, in Patients with Type 2 Diabetes Mellitus.
Tae Seo Sohn, Jee In Lee, In Ju Kim, Kyung Wan Min, Hyun Shik Son
Korean Diabetes J. 2008;32(5):445-452.   Published online October 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.5.445
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  • 2 Crossref
AbstractAbstract PDF
BACKGROUND
Type 2 diabetes is usually preceded by a long and clinically silent period of increasing insulin resistance. The purpose of this study is to demonstrate that rosiglitazone and metformin fixed-dose combination therapy (RSG/MET) will safely and effectively control glycemia as a first line of oral therapy, better than rosiglitazone (RSG) or metformin (MET) monotherapy in Korean type 2 diabetes patients. METHODS: This study was a 32-week, multicenter, randomized, double-blind study. Twenty-seven type 2 diabetes patients (males 14; females 13) were included and randomly divided into the rosiglitazone, metformin group, or rosiglitazone /metformin combination groups. The primary objective of this study was to determine the change in HbA1c from baseline (week 0) to week 32. The secondary end-points were to determine changes in fasting plasma glucose (FPG) and homeostasis model assessment insulin resistance (HOMA-IR), from baseline to week 32. Other cardiovascular risk markers were also assessed. RESULTS: At week 32, there were significant reductions in HbA1c and FPG, in all three treatment groups. There was no statistical difference in HbA1c among the three groups, but the decrease in FPG in the RSG/MET group was statistically significant compared to the MET group (P < 0.05). RSG/MET significantly reduced HOMA-IR at week 32 compared to baseline, but there was no difference among the three groups. RSG/MET significantly decreased high-sensitive C-reactive protein (hs-CRP) value at week 32, compared to baseline. There were increases in adiponectin from baseline to week 32 in the RSG and RSG/MET groups, and the increase in the RSG/MET group was statistically significant compared to that of the MET group (P < 0.05). At week 32, there was a significant decrease in plasminogen activator inhibitor-1 (PAI-1) in all three treatment groups, but no statistically significant difference among them. The RSG/MET group significantly decreased in terms of urinary albumin-creatinine ratio at week 32, compared to baseline. CONCLUSIONS: In this study, rosiglitazone and metformin combination therapy was effective in glycemic control as an initial therapy, and it improved cardiovascular risk markers in Korean type 2 diabetes patients.

Citations

Citations to this article as recorded by  
  • Rosiglitazone metformin adduct inhibits hepatocellular carcinoma proliferation via activation of AMPK/p21 pathway
    Yuyang Liu, Xiangnan Hu, Xuefeng Shan, Ke Chen, Hua Tang
    Cancer Cell International.2019;[Epub]     CrossRef
  • Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study
    Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Par
    Diabetes & Metabolism Journal.2011; 35(1): 26.     CrossRef
Original Articles
Rosiglitazone Activates AMPK and Improves Non-Alcoholic Fatty Liver Disease in OLETF Rats.
Eun Hee Cho, Ki Up Lee
Korean Diabetes J. 2008;32(2):141-148.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.141
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Insulin resistance is very common in patients with nonalcoholic fatty liver disease (NAFLD). Glitazones improve insulin sensitivity by acting as a selective agonist of the peroxisome proliferators -activated receptor gamma (PPAR gamma), and were shown to activate AMP-activated protein kinase (AMPK) in skeletal muscle and the liver. Glitazones were also shown to reduce hepatic lipogenesis. The aim of this study was to investigate whether the protective mechanism of rosiglitazone on NAFLD is associated with AMPK activation. METHODS: Twelve OLETF rats were divided into 2 groups (control, treatment, n = 6 each). LETO rats served as controls. At 35 weeks of age, treatment group received rosiglitazone 4 mg/kg daily for 3 days. Fasting plasma glucose, insulin, free fatty acid, lactate and triglycerides were measured. Liver tissues from each group were processed for histological and hepatic triglyceride content analysis and western blotting. RESULTS: Fasting plasma glucose, insulin and triglycerides levels were significantly lower in treatment group than in control group. Histologic examination disclosed decreased hepatic steatosis in treatment group. Hepatic triglyceride content was also decreased in treatment group. Sterol regulatory binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) expression were increased and AMPK phosphorylation was reduced in OLETF rats compared with LETO rats, and these changes were reversed by rosiglitazone treatment. CONCLUSION: Rosiglitazone reduced hepatic steatosis in OLETF rats, and activated AMPK in the liver. These results suggest the role of AMPK activation in the protective action of rosiglitazone on NAFLD.

Citations

Citations to this article as recorded by  
  • Small Rice Bowl-Based Meal Plan for Energy and Marcronutrient Intake in Korean Men with Type 2 Diabetes: A Pilot Study
    Hee Jung Ahn, Kyung Ah Han, Jin Young Jang, Jae Hyuk Lee, Kang Seo Park, Kyung Wan Min
    Diabetes & Metabolism Journal.2011; 35(3): 273.     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
  • 2,326 View
  • 21 Download
AbstractAbstract PDF
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.
Effects of PPAR-alpha and-gamma Agonists on Fatty Acid Metabolism of Muscle Cells in Hyperlipidemic and Hyperglycemic Conditions.
Yong jik Lee, Zheng Shan Zhao, Soo Kyung Kim, Hae Jin Kim, Wan Sub Shim, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha
Korean Diabetes J. 2006;30(5):324-335.   Published online September 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.5.324
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AbstractAbstract PDF
BACKGROUND
Studies for the regulation of fatty acid metabolism are deficient relatively in skeletal muscle and heart. The investigations in pathological conditions for malonyl-CoA decarboxylase (MCD) and for the relation of MCD and PPAR-alpha.-gamma agonists are insufficient in particular. METHODS: In the current study, fully differentiated H9c2 muscle cells were exposed to pathological conditions such as hyperlipidemic (0.1 mM Palmitate) and hyperglycemic (16.5 mM Glucose) condition with 5 uM PPAR-gamma agonist (rosiglitazone) and 10 uM PPAR-alpha agonist (WY14,643) and then experiments such as MCD activity assay, MCD real-time RT-PCR, MCD reporter gene assay, MCD Western blotting, PPAR-alpha Western blotting, and palmitate oxidation test were carried out. RESULTS: Only PPAR-alpha agonist increased MCD activity. In the result of real-time RT-PCR, both PPAR-alpha and PPAR-gamma agonists elevated MCD mRNA expression in hyperlipidemic condition. MCD protein expression was decreased in hyperlipidemic condition, however, increased in rosiglitazone, or WY14,643 treated conditions. Rosiglitazone, and WY14,643 treated groups showed incresed MCD protein expression in hyperglycemic condition. Hyperlipidemic control group and PPAR-alpha.-gamma agonists treated groups presented about 3.8 times more increased palmitate oxidation level than normolipidemic control group in hyperlipidemic condition. PPAR-alpha agonist treated group showed 49% more increased palmitate oxidation rate than hyperlipidemic control group in primary cultured rat skeletal muscle cells. The amount of palmitate oxidation from differentiated H9c2 muscle cells that had overexpressed PPAR-alpha structural genes was more increased than control group. CONCLUSION: This study suggests that PPAR-alpha agonist ameliorates the defects induced by hyperlipidemic condition through the regulation of MCD. In summary, a closely reciprocal relation among PPAR-alpha agonist, MCD, and fatty acid oxidation existed distinctly in hyperlipidemic condition, but not in hyperglycemic condition.

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  • Beneficial effect of Combination with Korean Red Ginseng and Morus alba in metabolic syndrome
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The percent change of body weight in patients with type 2 diabetes using rosiglitazone for 1 year.
Seong Bin Hong, Hwi Ra Park, Eun A Kim, Kyung wook Lee, Moonsuk Nam, Yong Seong Kim
Korean Diabetes J. 2006;30(1):47-53.   Published online January 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.1.47
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AbstractAbstract PDF
BACKGROUND
Rosiglitazone(RSG) is known as a potent agonist for the PPARgamma. It improves glycemic control by improving insulin sensitivity in peripheral tissues. And it is associated with body weight gain. The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor(PPAR)gamma2 has recently been shown to be associated with insulin sensitivity. This study was performed to evaluate the body weight change during the long term rosiglitazone treatment and the role of PPARgamma2 polymorphism, Pro12Ala as an indicator to predict the clinical response of RSG in type 2 diabetes patients. METHOD: The study subjects were 214 type 2 diabetic patients(117 male, 97 female) who were received a daily 1 year course of 4 mg RSG combined with sulfonylurea or metformin. The Pro12Ala polymorphism of the PPARgamma2 was determined by the restriction fragment length polymorphism(RFLP) method. Body weight, height, waist circumference, fasting glucose, insulin, c-peptide and lipid profile were measured. RESULTS: After RSG treatment, body weight change was 2.4 +/- 3.8%, 4.5 +/- 9.8% of baseline body weight at 12, 24 weeks respectively. Body weight gains were increased to 5.6 +/- 10.1% at the end of 1 year. The HbA1C, serum insulin level and HOMA index were decreased following the rosiglitazone therapy. The allele frequency of the Ala12Pro polymorphism of the PPARgamma2 was 0.016. The number of Ala12Pro variant of the PPARgamma2 was too low to predict clinical response of RSG. Body weight gain was correlated with basal fasting plasma glucose, post-prandial 2 hour glucose and HbA1c level(p<0.05). There was no correlation between baseline body weight and change. CONCLUSION: This results showed that Pro12Ala polymorphism was not acceptable for the predictor of RSG induced weight gain and clinical response. However, body weight gain was increased in who had high glucose level, and correlated positively with glucose decrease. 1st 3 month weight gain was best predictor of weight change during 1 year.
The long term effects of rosiglitazone on serum lipid concentration and body weight.
Wan Sub Shim, Mi Young Do, Soo Kyung Kim, Hae Jin Kim, Kyu Yeon Hur, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha
Korean Diabetes J. 2006;30(1):17-24.   Published online January 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.1.17
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AbstractAbstract PDF
BACKGROUND
Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentration and low density lipoprotein (LDL) particle size, it has adverse effects on the increment of total cholesterol (TC) and LDL cholesterol (LDL-C), and body weight in some studies. Such adverse effects of rosiglitazone on the serum lipid profiles and body weight seem to be attributed to the fact that most studies with rosiglitazone are limited to a short period of follow up. The aim of this study was to evaluate the long term effects of rosiglitazone on the serum lipid levels and body weight. MATERIALS AND METHODS: We prospectively evaluated fasting serum glucose, HbA1c, TC, LDL-C, triglyceride, HDL-C and body weight at baseline and every three months after rosiglitazone usage (4mg/d) in 202 type 2 diabetic patients. RESULTS: TC levels had increased maximally at 3 months and thereafter decreased, but were significantly higher at 18 months than those at baseline. LDL-C levels from the first 3 months to 12 months were significantly higher than those at baseline, but after 15 months, LDL-C concentration was not significantly different from the basal LDL-C concentration. HDL-C levels had increased after first 3 months and the increment of HDL-C concentration were maintained. The increment of HDL-C was more prominent in patients with low basal HDL-C concentration than in patients with high basal HDL-C concentration. Body weight from 3 months to 18 months were higher than that at baseline, but after 3 months, body weight did not increase furthermore significantly. CONCLUSIONS: The adverse effects on lipid concentration and body weight of rosiglitazone may attenuate after long term usage of rosiglitazone.
Randomized Controlled Trial
The Effects of Insulin Sensitizers on the Plasma Concentrations of Adipokines in Type 2 Diabetic Patients.
Hye Seung Jung, Young Min Cho, Kyung Won Kim, Byung Soo Youn, Kang Yeol Yu, Hong Je Park, Chan Soo Shin, Seong Yeon Kim, Hong Kyu Lee, Kyong Soo Park
Korean Diabetes J. 2003;27(6):476-489.   Published online December 1, 2003
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AbstractAbstract PDF
BACKGROUND
Resistin, leptin and adiponectin are proteins secreted from adipose tissue, and have been suggested to play roles in insulin sensitivity. The effects of the circulating levels of two different types of insulin sensitizer, rosiglitazone and metformin, in type 2 diabetic patients were examined to elucidate the relationship between adipokines and insulin resistance. METHODS: Thirty type 2 diabetic patients, who showed poor glycemic control when administered 4 mg glimepiride a day, without severe diabetic complications or medical illness, were randomized to receive an additional 4mg rosiglitazone or 1000 mg metformin a day. The plasma resistin, leptin and adiponectin concentrations were measured at the baseline and after 6 months of treatment. The anthropometric parameters, fasting plasma glucose, HbA1C, total cholesterol, triglyceride, HDL-cholesterol and free fatty acids were also measured. Certain single nucleotide polymorphisms of adipokine genes were also identified. RESULTS: There were no significant differences in the reductions of the plasma glucose and HbA1C levels, after 6 months of treatment, between the two groups. The plasma resistin concentrations decreased, the adiponectin significantly increased and the leptin showed a tendency to increase in the rosiglitazone group. In the metformin group, only the resistin concentration significantly increased. However, the changes in the adipokines did not correlate with the HOMA-IR in either group. The reduction in the HbA1C due to rosiglitazone was greater if the initial leptin level was high, if there was a G allele on the -420th locus of the resistin gene, or the 45th locus of the APM1 (adiponectin gene) was the T-homozygote or there was a T allele on the 276th locus of the APM1. Those due to metfromin were greater with high initial adiponectin levels. CONCLUSION: In type 2 diabetic patients, showing poor glycemic control with sulfonylurea therapy, rosiglitazone or metformin treatment changed some of the adipokine concentrations, but these changes were not clearly related with insulin resistance. Polymorphisms of certain adipokine genes seem to have a relation to the susceptibility of rosiglitazone.
Original Articles
Efficacy of Serum Leptin Level as an Indicator to Predict the Clinical Response of Rosiglitazone in Patients with Type 2 Diabetes Mellitus.
Jae Hyuk Lee, Soo Kyung Kim, Kyu Yeon Hur, Han Seok Choi, Ji Young Jung, Wan Sub Shim, Hyun Joo Lee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha
Korean Diabetes J. 2003;27(5):420-432.   Published online October 1, 2003
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AbstractAbstract PDF
BACKGROUND
Leptin is a protein secreted by adipocytes that regulates food intake by acting on the hypothalamus and is correlated with body fat mass. Insulin resistance is also correlated with body fat mass and obesity. Rosiglitazone (RSG) is known as a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma). It improves glycemic control by improving insulin sensitivity in peripheral tissue. This study was performed to evaluate the antidiabetic and insulin sensitizing effects of RSG combination therapy and the efficacy of serum leptin level as an indicator to predict the clinical response of RSG in type 2 diabetic patients with oral agents such as metformin and/or sulfonylurea. METHODS: The study subjects were 140 type 2 diabetic patients (90 male, 50 female) who received a 12-week course of daily 4 mg RSG, in addition to the previous medications. The glucose level, indices of insulin resistance and metabolic parameters were measured. Serum leptin level was measured by radioimmunoassay before and after RSG treatment. Visceral fat and subcutaneous fat were measured by sonography. RESULTS: After 12 weeks of RSG treatment, FPG (12.6+/-28.1 mg/dL), HOMAIR (0.3+/-0.9), serum fasting insulin (1.9+/-4.7 microU/mL), SBP and DBP had all decreased significantly, whereas body weight, BMI, waist circumference, WHR, body fat mass, and subcutaneous fat had all increased. Serum leptin level also tended to increase after RSG treatment, but without significance. deltaFPG (delta=value after treatment- value before treatent) was inversely correlated with basal serum leptin level (r=-0.202), basal HOMAIR (r=-0.226) and basal FPG (r=-0.565). There was no correlation between deltaFPG and basal BMI or serum insulin level. RSG treatment showed significant inverse correlation between serum leptin level and deltaHOMAIR (r=-0.416), delta insulin (r=-0.365) and deltaHbA1c (r=-0.189). Serum leptin level was positively correlated with the subcutaneous fat amount (r=0.548), basal BMI (r=0.521), and basal HOMAIR (r=0.343). CONCLUSION: These results showed that RSG treatment can improve not only hyperglycemia but also insulin resistance in type 2 diabetic patients. The serum leptin level at baseline can be used as an indicator to predict the clinical response of RSG treatment in type 2 diabetes patients.
Effects of Rosiglitazone on Body Fat Mass and Distribution in Type 2 Diabetic Patients.
Hong Kyu Kim, Hyo Joong Yoon, Seung Min You, Ki Young Lee, Hye Young Park, Moon Ho Kang
Korean Diabetes J. 2003;27(3):272-279.   Published online June 1, 2003
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AbstractAbstract PDF
BACKGROUND
Rosiglitazone, an insulin-sensitizing drug of the thiazolidinediones class, has a high affinity for the ligands of the peroxisome proliferator activated receptor-gamma(PPAR-gamma), is highly expressed in adipose tissue, and plays an important role in the differentiation of adipocyte. The influence of rosiglitazone was investigated on the total fat mass and regional adiposity in type 2 diabetic patients. METHODS: Rosiglitazone (4 mg/day) was administered for 6 months to type 2 diabetic patients (n=20) whose glycemic control was unacceptable with the use of other treatments. Measurements of the total, trunk and leg region body fats (by dual energy X-ray absorptiometry) and abdominal fat distributions (by computed tomography) were compared before and after treatment. RESULTS: Nine patients received rosiglitazone monotherapy and 11 a combined therapy of sulfonylurea and/or metformin. The HbA1C, serum insulin level and homeostasis model assessment insulin resistance index were decreased following the rosiglitazone therapy, but the body weight and BMI were increased. As for the body fat changes, the total (19,382+/-4,786 vs. 22,940+/- 7,300 g, p<0.01), trunk (11,399+/- 2,678 vs. 13,960+/-4,698 g, p<0.01) and leg (4,734+/-1,319 vs. 6,203+/-2,231g, p<0.05) region fat masses were significantly increased. The percentage increase in the total, trunk and leg region fat masses were 20+/-25, 25+/-35 and 58+/-130%, respectively. As for abdominal fat distribution after the treatment, the visceral fat area (225+/-84 vs. 187+/-87 cm2, p<0.05) was significantly decreased, while the subcutaneous fat area tended to increase (178+/-83 vs. 201+/-80 cm2, NS), although these were not statistically significant. The visceral/subcutaneous fat ratio (V/S ratio) was significantly decreased (1.45+/- 0.64 vs. 0.95+/-0.25, p<0.05). CONCLUSION: Although the total body fat mass was increased following the rosiglitazone therapy, a shift in the body fat distribution, from the visceral to the subcutaneous region, was observed, which may be associated with an improvement in insulin resistance. However, a long-term assessment of the consequences of an increasing total fat mass and change in the body fat distribution will be required.

Diabetes Metab J : Diabetes & Metabolism Journal