Aims: Rosiglitazone and fenofibrate, specific agonists of the peroxisome proliferator activated receptors-gamma (PPAR gamma) and -alpha (PPAR alpha), respectively, improve insulin sensitivity in diabetic animals and in patients with type 2 diabetes. Here we investigated how pre-diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed with normal and high-fat diets respond to these PPAR agonists.Main methods: Pre-diabetic OLETF rats were subjected to high-fat or standard diets with or without rosiglitazone or fenofibrate for 2 weeks. The metabolism of the rats and the levels of malonyl-CoA and activities of malonyl-CoA decarboxylase (MCD), acetyl-CoA carboxylase (ACC), and AMP-activated protein kinase (AMPK) in metabolic tissues were assessed.Key findings: Rosiglitazone and fenofibrate significantly improved insulin sensitivity and reduced the levels of plasma triglycerides and free fatty acids in OLETF rats fed with a high-fat diet. Fenofibrate particularly reduced the body weight, fat, and total cholesterol in high fat diet OLETF rats. The highly elevated malonyl-CoA levels in the skeletal muscle and liver of OLETF rat were significantly reduced by rosiglitazone or fenofibrate due to, in part, the increased MCD activities and expression. On the other hand, ACC activities were unchanged in skeletal muscle and decreased in liver in high fat diet group. AMPK activities were dramatically decreased in OLETF rats and not affected by these agonists.Significance: These results demonstrate that treatment of pre-diabetic OLETF rats-particularly those fed a high-fat diet-with rosiglitazone and fenofibrate significantly improves insulin sensitivity and fatty acid metabolism by increasing the activity of MCD and reducing malonyl-CoA levels in the liver and skeletal muscle. (c) 2009 Elsevier Inc. All rights reserved.

Rosiglitazone (RSG) is known to be an agonist for the peroxisome proliferator-activated receptor-γ (PPARγ) and promotes differentiation of pre-adipocytes into adipocytes. Leptin is highly correlated with adiposity, while the activation of PPARγ is known to inhibit Lep gene expression and leptin release. This study was performed to evaluate the relationship between changes in circulating leptin levels, insulin sensitivity and regional adiposity after RSG treatment. Two hundred fifty-one type 2 diabetic patients (176 men and 75 women) who had been treated with sulfonylurea and/or metformin received 4 mg of RSG daily, in addition to the previous medications. Before and after RSG treatment (average duration 5.6 ± 0.9 months), indices of insulin resistance, metabolic parameters, and serum leptin and adiponectin levels were measured. Abdominal subcutaneous fat thickness (SFTmax) and visceral fat thickness were measured by sonography. After RSG treatment, HOMA-IR index decreased significantly (2.82 ± 1.94 vs. 2.01 ± 1.58), while BMI and SFTmax increased, and leptin (4.72 ± 3.77 vs. 5.69 ± 4.30 ng/ml) and adiponectin levels (7.54 ± 10.20 vs. 12.89 ± 10.13 μg/ml) increased. The increase in serum leptin correlated with an increase in SFTmax (r = 0.511, p < 0.001) and with a reduction in HOMA-IR (r = −0.368, p < 0.001). The correlation of Δleptin with ΔHOMA-IR and with ΔSFTmax was higher in females and among insulin-resistant subjects. In conclusion, RSG improves the insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus, which is related to an increase in subcutaneous adiposity.

Purpose: The aim of this study was to evaluate the effect of lowering the fasting plasma glucose (FPG) criteria for impaired fasting glucose (IFG) on the prevalence of IFG and the risk for the development of diabetes associated with IFG in Koreans. Materials and Methods: A total of 7,211 subjects who had normal glucose tolerance (NGT) or IFG were recruited. Subjects were evaluated at baseline and after two years follow up. Clinical data including total cholesterol, FPG and blood pressure were examined. Results: Lowering the criteria for IFG from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL) increased the prevalence of IFG from 6.6% (494 subjects) to 24.4% (1829 subjects). After the 2 years follow up period, 91 subjects (1.3%) developed diabetes. Twenty one (0.3%) subjects developed diabetes among 5,382 NGT subjects and 70 (3.8%) subjects developed diabetes among 1,829 IFG (5.6 - 7.0 mmol/L) subjects. Lowering the IFG threshold from 6.1 mmol/L to 5.6 mmol/L resulted in a 18.4% decrease in specificity and 23.9% increase in sensitivity for predicting diabetes. The baseline FPG for predicting the development of diabetes after 2 years at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 5.7 mmol/L (103 mg/dL). Conclusion: Lowering the FPG criterion of IFG should have benefits in predicting new onset type 2 diabetes mellitus in Koreans. The economic and health benefits of applying the new IFG criteria should be evaluated in future studies.

An insulinoma is an endocrine tumor of the pancreas derived fro m the beta cells with abnormal insulin secretion. An insulinoma is rare, the incidence being estimated at only four per one million person-years. The association of diabetes mellitus and insulinoma is extraordinarily rare, but we should not overlook an insulinoma as a possible cause of hypoglycemia in patients with diabetes mellitus. A 70-year-old diabetic man who had been treated with oral hypoglycemic agents for type 2 diabetes suffered from night sweating for 10 days. Even after he stopped taking h is oral hypoglycemic agents, the night sweating continued. The patient was admitted to evaluate the cause of the recurrent hypoglycemic events. After a 72-hour fasting test and selective arterial calcium stimulation test with venous sampling, he was diagnosed with insulinoma accompanied by type 2 diabetes mellitus. In the course of the study, the patient was also incidentally diagnosed with lung cancer. (J Kor Diabetes Assoc 31:517~519, 2007)

Type 1 diabetes is characterized by insulin deficiency due to destruction of pancreatic β-cells.A novel subtype of type 1B which is rapidly developed without any evidence of autoimmunity has been recently proposed as fulminant type I diabetes.In female patients of child-bearing age, the onset of fulminant type 1 diabetes occurred frequently during pregnancy or after delivery in Japan, however, there was no report about fulminant type 1 diabetes associated with pregnancy in Korea.We report a case of fulminant type 1 diabetes associated with pregnancy.

OBJECTIVE The goal was to investigate the interrelationships between the hypoglycemic effects of rosiglitazone and the changes in the regional adiposity of type 2 diabetic patients. DESIGN AND METHODS We added rosiglitazone (4 mg/day) to 173 diabetic patients (111 males and 62 females) already taking a stable dose of conventional antidiabetic medications except for thiazolidinediones. The abdominal fat distribution was assessed by ultrasonography at baseline and 12 weeks later. Using ultrasonographic images, the s.c. and visceral fat thickness (SFT and VFT respectively) were measured. RESULTS Rosiglitazone treatment for 3 months improved the glycemic control. However, the response to rosiglitazone was no more than 36.4%; the deterioration of the glycemic control was found in 16.8% of subjects. In addition, rosiglitazone treatment significantly increased the body fat mass, especially the s.c. fat. However that did not alter the visceral fat content. The percentage changes in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) concentrations after treatment were inversely correlated with the increase in SFT (r=-0.327 and -0.353, P<0.001 respectively) and/or body weight (r=-0.316 and -0.327, P<0.001 respectively). Multiple regression analysis revealed that the improvement in the FPG after rosiglitazone treatment was correlated with the baseline FPG (P<0.001) and the change in the SFT (P=0.019), and the reduction in the HbA1c was related with the baseline FPG (P=0.003) and HbA1c (P<0.001) and the changes in the SFT (P=0.010) or VFT (P=0.013). CONCLUSIONS The increase in the s.c. fat depot after rosiglitazone treatment may be an independent factor that determines the hypoglycemic efficacy.

1-Methyl-4-phenylpyridinium ion (MPP+), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In the present study, we investigated the protective effects of rosiglitazone on MPP+ induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as underlying mechanism. Our results suggested that the protective effects of rosiglitazone on MPP+ induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase and regulating the expression of Bcl-2 and Bax. These data indicated that rosiglitazone might provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.

OBJECTIVE:Type-2 diabetes is a progressive disease. However, little is known about whether decreased fasting or postprandial pancreatic beta-cell responsiveness is more prominent with increased duration of diabetes. The aim of this study was to evaluate the relationship between insulin secretion both during fasting and 2 h postprandial, and the duration of diabetes in type-2 diabetic patients.DESIGN:Cross-sectional clinical investigation.METHODS:We conducted a meal tolerance test in 1466 type-2 diabetic patients and calculated fasting (M0) and postprandial (M1) beta-cell responsiveness.RESULTS:The fasting C-peptide, postprandial C-peptide, M0, and M1 values were lower, but HbA1c values were higher, in patients with diabetes duration > 10 years than those in other groups. There was no difference in the HbA1c levels according to the tertiles of their fasting C-peptide level. However, in a group of patients with highest postprandial C-peptide tertile, the HbA1c values were significantly lower than those in other groups. After adjustment of age, sex, and body mass index (BMI), the duration of diabetes was found to be negatively correlated with fasting C-peptide (gamma = -0.102), postprandial C-peptide (gamma = -0.356), M0 (gamma = -0.263), and M1 (gamma = -0.315; P < 0.01 respectively). After adjustment of age, sex, and BMI, HbA1c was found to be negatively correlated with postprandial C-peptide (gamma = -0.264), M(0) (gamma = -0.379), and M1 (gamma = -0.522), however, positively correlated with fasting C-peptide (gamma = 0.105; P < 0.01 respectively). In stepwise multiple regression analysis, M0, M1, and homeostasis model assessment for insulin resistance (HOMA-IR) emerged as predictors of HbAlc after adjustment for age, sex, and BMI (R2 = 0.272, 0.080, and 0.056 respectively).CONCLUSIONS:With increasing duration of diabetes, the decrease of postprandial insulin secretion is becoming more prominent, and postprandial beta-cell responsiveness may be a more important determinant for glycemic control than fasting beta-cell responsiveness.

Aims: To assess the efficacy of rosiglitazone in blocking ethanol-induced hangover in rats. Methods: Rats injected with ethanol (4 g/kg body weight) were subjected to social interaction tests. Levels of aldehyde dehydrogenase 2 (ALD2), involved in an anti-hangover mechanism, were measured by semi-quantitative RT-PCR and western blot analysis. Results: Rosiglitazone caused an upregulation of mitochondrial ALD2, thus significantly detoxifying acetaldehyde. Conclusions: Rosiglitazone alleviated the symptoms of ethanol-induced hangover by inducing ALD2 expression; this result was reconfirmed by eliminating the effect of rosiglitazone by injecting cyanamide, an ALD2 inhibitor.

Background: Knowledge evaluation about diabetes mellitus is necessary to self-manage diabetes effectively.We developed two parallel diabetes knowledge tests to meet a need for reliable knowledge assessment in diabetic patients. Materials and methods:The 75-items (59 items for general knowledge test, 16 items for insulin use subscale) were administered to 102 diabetic patients who visited Inha University Hospital.The items which had the appropriate difficulty (0.25~0.80) and good discrimination index (above 0.25) were selected.However, the items which are thought to be an important item for education were also selected even though they did not meet the criteria of reliability and discrimination index.Two parallel diabetes knowledge tests were developed after matching the selected appropriate items for similar contents.Results: 102 patients fulfilled the tests and their mean age was 54.1 ± 11.5 years.Mean percentage of correct questionnaires was 60.9 ± 12.5% for general test and 45.9 ± 19.5% for insulin use subscale.There were significant differences of scores between patients with high and low education level, between patients with high income per household and low income level per household, between patients with the history of diabetes education and without history of diabetes education, and between the old (≥ 50 yrs) and the young (< 50 yrs) age group.However, there was no significant difference of scores according to diabetes duration and complication or not.The selected two tests had a similar score.And their Cronbach alpha was appropriate (> 0.70) in both tests.Conclusions: We developed two parallel diabetes knowledge tests.These tests can be used as an important means in evaluating the diabetes knowledge and effect of education in diabetic patients.(

Objective Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight.Design Open labelled clinical study.Patients and measurements We prospectively evaluated fasting serum glucose, haemoglobin A(1c) (HbA(1c)), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients.Results TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained.Conclusions HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels.

concentration. Methods: 264 type 2 diabetic patients underwent ultrasonography to estimate visceral & subcutaneous fat accumulation and sd LDL-C concentrations were measured. Results: BMI, total cholesterol, sd LDL-C concentration and percentage of sd LDL-C were higher in highest tertile of visceral fat length in male than those in lowest tertile. BMI, total cholesterol, triglyceride, LDL-C, sd LDL-C concentration and percentage of sd LDL-C were higher in highest tertile of visceral fat length in female than those in lowest tertile. But sd LDL-C concentration and percentage of sd LDL-C were not different among three groups based on the tertile of subcutaneous fat length in male and female. Visceral fat length was correlated with sd LDL-C concentration and percentage of sd LDL-C, total cholesterol, triglyceride, LDL-C, but negatively with percentage of large buoyant LDL-C and HDL-C after adjustment of age, sex and BMI. Subcutaneous fat length w as not correlated with sd LDL-C and percentage of sd LDL-C, total cholesterol, triglyceride, HDL-C and LDL-C. Conclusion: The association between visceral fat length and sd LDL-C could be a factor that explains the association between visceral obesity and CVD. (J Kor Diabetes Assoc 30:207~216, 2006) ━━━━━━━━━━━━━━━━ ━━

vs 7.0 ± 1.1%, P < 0.01). Hypoglycemic effect of pioglitazone was prominent in women than in men (FPG change after 12 months, -1.80 ± 2.54 vs -0.09 ± 1.72 mmol/L, P < 0.001; HbA1c change after 12 months, -0.9 ± 1.3 vs -0.4 ± 1.1%, P < 0.05). Serum high-density lipoprotein cholesterol was increased after 3 months of pioglitazone treatment (1.16 ± 0.24 vs 1.31 ± 0.28 mmol/L, P < 0.01) without return until the end of this study. Serum triglycerides level decreased at 3 months (basal vs 3 months, 2.29 ± 1.86 vs 1.88 ± 1.21 mmol/L, P < 0.01) and 6 months (basal vs 6 months, 2.29 ± 1.86 vs 1.97 ± 1.40 mmol/L, P < 0.05) of pioglitazone treatment, but returned to basal level at 12 months. Liver enzyme, especially serum alanine transferase level decreased after 3 months of pioglitazone treatment (30.8 ± 23.7 vs 24.5 ± 18.5 IU/L, P < 0.01) without return until the end of this study. Hypoglycemic effect of pioglitazone was associated with basal BMI, fat contents and serum leptin level. Conclusion: Korean type 2 diabetes patients with pioglitazone use showed favorable metabolic effect for glycemic control, lipid metabolism and liverfunction, but pioglitazone induced body weight increase may be limited. (J Kor Diabetes Assoc 30:264~276, 2006)

Background: Leptin has been suggested as a possible cause of atherosclerotic disease. The small dense low-density lipoprotein cholesterol (LDL-C) has also been regarded as a new surrogate marker in atherosclerotic disease. The aim of this study was to evaluate the relationship between the leptin concentration and the small dense LDL-C concentration in Korean type 2 diabetic patients. Methods: One hundred-ninety one type 2 diabetic patients, who did not use any medication that could affect the concentration of lipid such as statin, fibrate, thiazolidinediones and corticosteroid, were enrolled in this study. We analyzed the relationship between leptin, the small dense LDL-C and the other metabolic parameters. Results: The small dense LDL-C concentrations were higher in the group with the highest tertile of the leptin value, both in males and females than those patients in the group with the lowest tertile of the leptin value. The small dense LDL-C concentrations were also higher in the group with the highest tertile of leptin divided by the BMI value both in males and females than those patients in the group with the lowest tertile of the leptin value. The leptin concentration was positively correlated with the small dense LDL-C, total cholesterol, triglyceride, LDL-C, insulin and HOMAIR values after adjusting for age, gender and BMI. Conclusion: The association between leptin and small dense LDL-C could be a factor that explains the association between leptin and cardiovascular disease. (J Kor Soc Endocrinol 21:319~327, 2006)

AIMS:We investigated the relation between total and differential white blood cell (WBC) count and metabolic syndrome (MS) in type 2 diabetic patients. METHODS:Eight-hundred and twenty-two patients (males 430, females 392, BMI 25.4+/-3.2 kg/m2, duration of diabetes 5.7+/-6.8 years) were enrolled in this study. We measured total WBC count and differential count, anthropometry, blood pressure, fasting glucose, insulin and lipid profiles. RESULTS:The number of components of MS and prevalence of MS were increased from 1st quartile to 4th quartile of WBC count. Total WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were increased with the increase of number of components of MS except basophil count. Total WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were higher in the patients with MS features than those without MS features. WBC count was positively correlated with waist circumference (gamma=0.134), systolic blood pressure (gamma=0.082), diastolic blood pressure (gamma=0.083), triglyceride (gamma=0.241), insulin (gamma=0.222), and HOMA-IR (gamma=0.225), and negatively with HDL cholesterol (gamma=-0.146) (p<0.05, respectively). CONCLUSIONS:Chronic inflammation, as indicated by a higher WBC count, may be related with the increased number of components of MS in type 2 diabetic patients.

OBJECTIVE:The aim of this study was to examine the effects of perilipin gene (PLIN) polymorphisms on weight gain with rosiglitazone treatment in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS:A total of 160 type 2 diabetic patients were treated with rosiglitazone (4 mg/day) for 12 weeks in addition to their previous medications, which were unchanged. Four single nucleotide polymorphisms (SNPs) at the PLIN locus were genotyped: PLIN 6209T>C, PLIN 11482G>A, PLIN 13041A>G, and PLIN 14995A>T.RESULTS:Although fasting plasma glucose and HbA(1c) levels decreased; mean body weight increased significantly after rosiglitazone treatment. Among the four SNPs tested, only the PLIN 11482G>A polymorphism was associated with weight gain from rosiglitazone treatment. In addition, there was a significant difference in the increase in the body weight among the genotypes. Patients with the 11482A/A genotype showed less increase in body weight than those with other genotypes.CONCLUSIONS:These data suggest that genetic variations in the perilipin gene can affect weight gain associated with rosiglitazone treatment in patients with type 2 diabetes.

Aim: The intracellular concentration of malonyl-CoA, a key regulator of fatty acid oxidation, is determined both from its synthesis by acetyl-CoA carboxylase and from its degradation by malonyl-CoA decarboxylase (MCD). The aim of our study was to investigate the activity and mRNA expression of MCD under insulin resistance and after treatment with insulin sensitizers in different tissues.Methods: We treated 18-week Otusuka Long-Evans Tokushima Fatty (OLETF) rats with pioglitazone (10 mg/kg/day) or metformin (300 mg/kg/day) for 8 weeks and determined the activity and mRNA expression of MCD in diabetic OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats in myocardial and skeletal muscles, and in liver.Results: The MCD activities of myocardial and skeletal muscles were remarkably reduced in OLETF rats compared with LETO rats (995 +/- 114 vs. 2012 +/- 359, 58 +/- 11 vs. 167 +/- 40 pmol/min/mg protein; p = 0.005 and p = 0.010). Surprisingly, after pioglitazone treatment, not after metformin, the MCD activities of myocardial and skeletal muscles (1906 +/- 320 and 259 +/- 44 pmol/min/mg protein) increased up to the levels in LETO rats. MCD mRNA expression in OLETF rats was also reduced in myocardial and skeletal muscles vs. LETO rats (p = 0.049 and p = 0.008) and was unchanged by pioglitazone or metformin treatment. In the liver, MCD activity and mRNA expression were similar in OLETF and LETO rats.Conclusion: Pioglitazone treatment restored MCD activity to non-diabetic level and improved the restrained fatty acid metabolism in myocardial and skeletal muscles caused by insulin-resistant diabetic status.