[show abstract][hide abstract] ABSTRACT: The objective of this study was to assess relationships between adiponectin and the status of glucose metabolism and to investigate
whether low adiponectin levels were independently associated with the risk of impaired glucose metabolism and type 2 diabetes
in Korean population. A total of 3,508 participants (mean age 56.3±8.0 years; BMI 24.7±3.2 kg/ m2; 41.0% male) were enrolled. Participants with normal glucose metabolism (NGM), impaired glucose metabolism (IGM), and type
2 diabetes were 58.0%, 28.9%, and 13.1%. Adiponectin levels in both men and women were significantly lower in participants
with IGM and type 2 diabetes than participants with NGM. Low adiponectin levels in both men and women were strongly associated
with the risk of IGM and type 2 diabetes in large population-based cohort of rural adult Koreans.
Toxicology and Environmental Health Sciences. 08/2013; 1(1).
[show abstract][hide abstract] ABSTRACT: Although PPAR-α and PPAR-γ agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-δ has not been fully investigated. In this study, we examined the effects of the PPAR-δ agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-δ agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) and also, peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-α and MCP-1 was also examined in supernatant of Raw264.7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-α, MCP-1, and PGC-1α were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-δ agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1α gene expression, and improvement of insulin signaling.
Experimental and Molecular Medicine 07/2012; · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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%).
Our results suggest that the optimal HbA1c level for DM screening is 5.95%.
[show abstract][hide abstract] ABSTRACT: To clarify the association between serum sex hormone-binding globulin (SHBG) levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes.
Two hundred seventy nine patients with type 2 diabetes were consecutively enrolled and metabolic parameters were checked. High-grade NAFLD was defined as moderate or severe fatty liver disease, measured using liver ultrasound. SHBG, testosterone, and estradiol levels were measured.
SHBG levels were lower in patients with high-grade NAFLD than in those with normal ultrasound and decreased significantly based on the severity of fatty liver disease. SHBG levels were negatively correlated with hypertension, body mass index (BMI), waist circumference, high-grade NAFLD, triglycerides, alanine aminotransferase (ALT), γ-glutamyltransferase (γGT), homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein (CRP) and were positively correlated with testosterone and estradiol levels. The odds ratios (ORs) predicting the presence of high-grade NAFLD in men and women decreased significantly with increasing SHBG tertile. The ORs remained significant even after further adjusting for BMI, waist circumference, hypertension, triglycerides, γGT, ALT, CRP, HOMA-IR, testosterone, estradiol, and anti-diabetic medications.
Serum SHBG levels were independently associated with the high-grade NAFLD in patients with type 2 diabetes.
Diabetes research and clinical practice 08/2011; 94(1):156-62. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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).
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.
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.
[show abstract][hide abstract] ABSTRACT: The Korean Society for the Study of Obesity (KSSO) has defined the waist circumference cutoff value of central obesity as 90 cm for men and 85 cm for women. The purpose of this investigation was to determine the corresponding waist circumference values. A total of 3,508 persons in the Korean Rural Genomic Cohort Study were enrolled in this survey. Receiver operating characteristic (ROC) curve analysis was used to find appropriate waist circumference cutoff values in relation to insulin resistance determined by homeostasis model assessment for insulin resistance (HOMA-IR), body mass index (BMI), and components of metabolic syndrome. The optimal waist circumference cutoff values were 87 cm for men and 83 cm for women by ROC analysis to HOMA-IR and 86 cm for men and 83 cm for women by ROC analysis to value with more than two components of metaobolic syndrome. By using a BMI > or =25 kg/m(2), 86 cm for men and 82 cm for women were optimal waist circumference cutoff values. In this study, we suggest that the most reasonable waist circumference cutoff values are 86-87 cm for men and 82-83 cm for women.
Journal of Korean medical science 05/2010; 25(5):734-7. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Moderate alcohol consumption is known to be associated with a reduced risk of cardiovascular disease and mortality. However, few studies reported that long-term alcohol drinking may increase the prevalence of central obesity, and cardiovascular disease. We examined the association between metabolic syndrome, nutritional factors and alcohol intake amount in Korean male rural population. We performed a cross-sectional analysis on data from Korean Rural Genomic Cohort (KRGC) study. We used multiple logistic regression analysis to estimate the adjusted odds ratio of metabolic syndrome according to alcohol intake amount categories (never, 0-16 g/day, 16-40 g/day, and >40 g/day). The age adjusted odds ratio for the prevalence of metabolic syndrome was significantly increased in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group (1.33; C.I., 1.11-1.59). These results were similar in the high energy intake group, but not in the low energy intake group. Waist circumference, blood pressure, and serum triglyceride levels were significantly higher in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group. These results suggest that large alcohol consumption is associated with metabolic syndrome and may be a modifiable risk factor of metabolic syndrome especially in subjects with high calorie intake.
Diabetes research and clinical practice 02/2010; 88(2):196-202. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated the associations of gamma-glutamyltransferase (GGT) with visceral obesity, adiponectin and retinol binding protein 4 (RBP4), and insulin resistance (IR) and compared these associations with other liver enzymes in non-diabetes. We enrolled 94 healthy subjects 30-69 years old. Clinical and biochemical metabolic parameters were measured. Adiponectin and RBP4 were determined by ELISA. IR was examined by HOMA-IR. Visceral fat was determined by computed tomography scan. GGT and alanine aminotransferase (ALT) were positively correlated with waist circumference (WC), waist-to-hip ratio (WHR), visceral fat area (VFA), visceral-to-subcutaneous fat area ratio (VSR), HOMA-IR, and RBP4, but was negatively correlated with adiponectin (p<0.05). In multivariate regression, GGT was associated with male sex, HOMA-IR, and RBP4 (R(2)=0.48, p<0.05) and ALT was associated with HOMA-IR (R(2)=0.22, p<0.05). By logistic regression after adjusted for age and sex, the odds ratio (OR) for IR in the highest tertile of sex-specific GGT and ALT were significantly increased compared to those in the lowest [OR (95% CI); 6.90 (2.08-22.82), 3.38 (1.08-10.57), respectively]. However, these relationships after further adjustments for RBP4, adiponectin, VFA, VSR, WHR, WC, TG, and HDL remained significant in only GGT. In conclusions, GGT may be a useful marker of IR in non-diabetes.
Diabetes research and clinical practice 03/2009; 84(2):152-7. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n=9), control OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.
Diabetes research and clinical practice 01/2009; 83(2):176-82. · 2.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The short insulin tolerance test is a simple and reliable method of estimating insulin sensitivity. This study was designed to compare the insulin sensitizing effects of thiazolidinediones (TZDs) on the degree of insulin resistance, determined by a short insulin tolerance test (Kitt) in type 2 diabetic patients. Patients and
Eighty-three subjects (mean age = 57.87 +/- 10.78) with type 2 diabetes mellitus were enrolled and received daily one dose of rosiglitazone (4 mg) or pioglitazone (15 mg). The mean follow-up duration was 25.39 +/- 9.66 months. We assessed insulin sensitivity using HOMA-IR and the short insulin tolerance test before and after TZDs treatment.
When we compared patients' characteristics before and after TZDs treatment, the mean fasting glucose level was significantly decreased (183.27 +/- 55.04 to 137.35 +/- 36.42 mg/dL, p < 0.001) and the mean HbA1C level was significantly decreased (9.24 +/- 1.96 to 8.11 +/- 1.39%, p < 0.001). Also, Kitt values were significantly increased (2.03 +/- 1.14 to 2.67 +/- 0.97%/min, p = 0.003), whereas HOMA-IR was significantly decreased (2.98 +/- 0.68 to 1.04 +/- 0.24, p < 0.05). When classifying insulin resistance by Kitt values, insulin resistant subjects' values were increased (< 2.5%/min; 1.51 +/- 0.53%/min to 2.63 +/- 0.88, p < 0.001), whereas the values decreased in insulin sensitive subjects (>or= 2.5%/min; 3.50 +/- 0.75%/min to 2.75 +/- 1.12%/min, p = 0.002).
The glucose lowering effects of TZDs by improving insulin resistance could be determined by using Kitt. However, Kitt may be a beneficial tool to determine TZDs' effects only when patients' Kitt values are less than 2.5%/min.
Yonsei Medical Journal 12/2008; 49(6):901-8. · 1.31 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adipocyte fatty acid-binding protein (A-FABP) is a major cytoplasmic protein in adipocytes and macrophages and is closely associated with metabolic syndrome, type 2 diabetes, and atherosclerosis. Here, we investigated whether A-FABP was associated with nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes.
We enrolled 181 type 2 diabetic patients. Clinical and biochemical metabolic parameters were measured. The severity of NAFLD was measured by ultrasound. A-FABP, adiponectin, and retinol-binding protein-4 (RBP-4) were determined by enzyme-linked immunosorbent assay.
A-FABP levels, defined as more than a moderate degree of fatty liver compared with men, those without metabolic syndrome, and those without NAFLD, were higher in women, patients with metabolic syndrome, and patients with overt NAFLD, respectively. Adiponectin was decreased according to the severity of NAFLD, but RBP-4 showed no difference. Age- and sex-adjusted A-FABP showed positive correlations with BMI, waist-to-hip ratio, waist circumference, triglycerides, gamma-glutamyltransferase, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), A1C, and C-reactive protein (CRP) but showed negative correlation with HDL cholesterol. The odds ratio (OR) for the risk of overt NAFLD with increasing levels of sex-specific A-FABP was significantly increased (OR 2.90 [95% CI 1.15-7.29] vs. 7.87 [3.20-19.38]). The OR in the highest tertile of A-FABP remained significant after adjustments for BMI, waist circumference, A1C, HDL cholesterol, triglycerides, HOMA-IR, CRP, and hepatic enzymes.
Our study demonstrates that serum A-FABP is significantly associated with NAFLD in type 2 diabetes, independent of BMI, waist circumference, HOMA-IR, A1C, triglycerides, HDL cholesterol, and CRP.
Diabetes care 11/2008; 32(1):147-52. · 8.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pinitol (3-O-methyl-D-chiro-inositol) was identified in putative insulin mediator fractions that have hypoglycemic activity, and appears to mimic the act effects of insulin by acting downstream in the insulin signaling pathway. We evaluated the effect of pinitol therapy in type 2 diabetic patients who were poorly controlled with hypoglycemic drugs, such as sulfonylurea, metformin and/or insulin. Twenty type 2 diabetic patients were enrolled in our study. Fasting glucose, fasting c-peptide, total cholesterol, triglyceride, and HDL- and LDL-cholesterol were checked before and after a 12-week pinitol treatment (20 mg kg(-1)day(-1)). All subjects continued their current medications during the study. Adipocytokines, such as adiponectin, leptin, free fatty acids, and c-reactive protein (CRP) were checked before and after pinitol treatment. After pinitol treatment, fasting glucose, post-prandial glucose levels, and hemoglobin A1c were significantly decreased (P<0.05). Fasting serum adiponectin, leptin, free fatty acid, and CRP levels did not change after pinitol treatment. In the unresponsive group, serum c-peptide levels were higher than in the responsive group. Twelve weeks of pinitol treatment altered glucose metabolism, but not lipid profiles or adipocytokine levels, in type 2 diabetic patients. Additional research is needed to define the physiological and potential therapeutic effects of pinitol administration.
Diabetes Research and Clinical Practice 09/2007; 77 Suppl 1:S247-51. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF.
23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/ kg/day), and rosiglitazone treated group (3mg/kg/day).
A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats.
These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.
Yonsei Medical Journal 05/2007; 48(2):301-7. · 1.31 Impact Factor