The Association of Serum Cystatin C with Glycosylated Hemoglobin in Korean Adults

BACKGROUND: Cystatin C has been known to be associated not only with early renal impairment but also with the incidence of diabetic conditions (prediabetes plus diabetes). However, it is not clear whether cystatin C levels are associated with the prevalence of diabetic conditions in Asian populations. We evaluated this association using glycosylated hemoglobin (HbA1c) levels as the definition of diabetes in Korean adults. METHODS: We analyzed data from 1,559 Korean adults (937 men and 622 women) with available serum cystatin C and HbA1c values. RESULTS: The serum cystatin C levels in subjects with prediabetes and diabetes were significantly increased (0.91+/-0.14 mg/L in prediabetes and 0.91+/-0.17 mg/L in diabetes vs. 0.88+/-0.13 mg/L in patients with normal glucose levels, P=0.001). At increasing cystatin C levels, the prevalence of subjects with prediabetes (30.2% vs. 14.6%, P<0.001) and those with diabetes (10.6% vs. 8.0%, P<0.001) significantly increased in the group with the highest cystatin C levels. The group with the highest cystatin C levels had a significantly increased odds ratio (OR) for the presence of diabetic conditions compared to the group with the lowest values in total subjects (OR, 2.35; 95% confidence interval [CI], 1.54 to 3.58; P<0.001) and in women (OR, 4.13; 95% CI, 1.97 to 8.65; P<0.001), though there was no significant increase after adjusting for multiple variables. CONCLUSIONS: Higher levels of serum cystatin C are associated with an increased prevalence of diabetic conditions in Korean adults. Our findings may extend the positive association of cystatin C with diabetes incidence to an Asian population.

Prevalence of Reduced Kidney Function by Estimated Glomerular Filtration Rate Using an Equation Based on Creatinine and Cystatin C in Metabolic Syndrome and Its Components in Korean Adults

BACKGROUND: It is known that metabolic syndrome (MetS) is associated with chronic kidney disease. We evaluated and compared the prevalence of reduced kidney function in MetS and its components by estimated glomerular filtration rate (eGFR) using an equation based on creatinine (eGFRcr), cystatin C (eGFRcys), and combined creatinine-cystatin C (eGFRcr-cys) in Korean adults. METHODS: We analyzed data from 3,649 adults who participated in a comprehensive health examination. RESULTS: Mean values of eGFRcys were higher compared with mean values of eGFRcr (96.1±18.2 mL/min/1.73 m² vs. 91.2±13.6 mL/min/1.73 m²) in total subjects. The prevalence of reduced kidney function increased with age (9.6% for eGFRcys vs. 5.8% for eGFRcr-cys vs. 4.9% for eGFRcr, in subjects aged ≥60 years), and significantly increased with MetS, abdominal obesity, hypertension, high triglyceride, low high density lipoprotein (HDL), and high insulin resistance. The prevalence of MetS, abdominal obesity, hypertension, high insulin resistance, low HDL, and hepatic steatosis was significantly increased in subjects with reduced kidney function. This increased prevalence and the odds ratio of reduced kidney function for prevalence of MetS was highest for eGFRcys, followed by those of eGFRcr-cys, and eGFRcr. CONCLUSION: The prevalence of reduced kidney function by eGFR was significantly increased in subjects with MetS and its related components. eGFRcys and eGFRcr-cys were superior to eGFRcr in detecting reduced kidney function.

Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes

BACKGROUND: Nonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD) event in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: Laboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events. RESULTS: Nonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR) and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m², and albuminuria. CONCLUSION: The results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.

Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells

Osteoprotegerin (OPG), receptor activator of NF-kappaB ligand (RANKL)/receptor activator of NF-kappaB (RANK) axis, and TNF-related apoptosis-inducing ligand (TRAIL) participate in vascular calcification process including atherosclerosis, but their contributions under high glucose (HG) and phosphate (HP) condition for a long-term period (more than 2 weeks) have not been fully determined. In this study, we evaluated the effects of HG and HP levels over 2 or 4 weeks on the progression of vascular calcification in rat vascular smooth muscle cells (VSMCs). Calcium deposition in VSMCs was increased in medium containing HG (30 mmol/L D-glucose) with beta-glycerophosphate (beta-GP, 12 mmol/L) after 2 weeks and increased further after 4 weeks. OPG mRNA and protein expressions were unchanged in HG group with or without beta-GP after 2 weeks. However, after 4 weeks, OPG mRNA and protein expressions were significantly lower in HG group with beta-GP. No significant expression changes were observed in RANKL, RANK, or TRAIL during the experiment. After 4 weeks of treatment in HG group containing beta-GP and rhBMP-7, an inhibitor of vascular calcification, OPG expressions were maintained. Furthermore, mRNA expression of alkaline phosphatase (ALP), a marker of vascular mineralization, was lower in the presence of rhBMP-7. These results suggest that low OPG levels after long term HG and phosphate stimulation might reduce the binding of OPG to RANKL and TRAIL, and these changes could increase osteo-inductive VSMC differentiation, especially vascular mineralization reflected by increased ALP activity during vascular calcification.

Comparison of Serum Ferritin and Vitamin D in Association with the Severity of Nonalcoholic Fatty Liver Disease in Korean Adults

BACKGROUND: Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D3 levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults. METHODS: A cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OH)D3, from men (n=295) and women (n=263) who underwent a routine health check-up in 2012. RESULTS: In men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and FLI > or =60 (P=0.010) were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012). Regarding 25(OH)D3, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001); however, no significant differences in 25(OH)D3 level were observed in men. No significant differences in either serum ferritin or 25(OH)D3 level were observed among women with different levels of severity of US-NAFLD. CONCLUSION: Increased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.

Effect of Short-Term Hypothyroid State on Lipid Profile and Cardiovascular Risk Markers in Subjects Preparing Radioactive Iodine Therapy / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: The relationship between short-term hypothyroidism due to levothyroxine (LT4) withdrawal for radioactive iodine (RI) therapy in patients with differentiated thyroid cancer (DTC) and risk of cardiovascular disease is not clear. In this study, we evaluated the impact of short-term overt hypothyroidism on lipid profiles and cardiovascular parameters in patients with DTC. MATERIALS AND METHODS: We recruited 195 patients with DTC who were preparing RI therapy from March 2008 to February 2012. We analyzed the effect of thyroid stimulating hormone (TSH) level on the clinical, biochemical, and cardiovascular risk markers at the end of LT4 withdrawal protocol (P2). RESULTS: After LT4 withdrawal (P2), TSH and total cholesterol (TC) levels were significantly increased (p121 microIU/mL), all values did not have a statistical significant meaning except Apo A1. CONCLUSION: Short-term hypothyroidism induced worsening of lipid metabolic parameters, but not enough to induce the cardiovascular risk in patients with thyroid cancer.

Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with abnormal cortisol secretion mediated by catecholamines

No abstract available.

Letter: Diabetic Retinopathy and Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2013;37:262-9)

No abstract available.

Letter: Diabetic Retinopathy and Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2013;37:262-9)

No abstract available.

C-Peptide and Vascular Complications in Type 2 Diabetic Subjects

No abstract available.

The Association between Apolipoprotein A-II and Metabolic Syndrome in Korean Adults: A Comparison Study of Apolipoprotein A-I and Apolipoprotein B

BACKGROUND: Apolipoprotein A-II (apoA-II) is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) in Korean adults. METHODS: We analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations. RESULTS: The mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5+/-4.6 mg/dL vs. 31.2+/-4.6 mg/dL, P=0.261). ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956). CONCLUSION: Compared with apoA-I (negative association with MetS) and apoB (positive association with MetS) levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties.

Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes

Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in subjects with diabetes. Disorders of the physiological signaling functions of reactive oxygen species (superoxide and hydrogen peroxide) and reactive nitrogen species (nitric oxide and peroxynitrite) are important features of diabetes. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the vascular complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great benefit to these subjects. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigation of therapeutic interventions to prevent or delay the progression of diabetic vascular complications is needed.

A Case of Subacute Thyroiditis Associated with Papillary Thyroid Carcinoma and Takayasu's Arteritis

Subacute thyroiditis is a self-limiting inflammation of the thyroid, presenting with painful thyroid swelling, thyrotoxicosis and low radioactive iodine uptake. The characteristic US findings for this disease are focal ill-defined hypoechoic areas in one lobe or diffuse hypoechoic areas in both lobes. Thyroid carcinomas should be included in the differential diagnosis for a lesion with focal hypoechoic areas and have been rarely reported to coexist with subacute thyroiditis. Takayasu's arteritis is an autoimmune disease that affects the aorta and its branches as well as pulmonary arteries. Subacute thyroiditis associated with Takayasu's arteritis is extremely rare, with only three cases being reported. We report here on the first case with the simultaneous diagnosis of subacute thyroiditis, papillary thyroid carcinoma and Takayasu's arteritis.

Clinically Related Factors and Features of Central Compartment Neck Lymph Nodes in Thyroid Micropapillary Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Despite the overall excellent prognosis for patients with thyroid papillary microcarcinoma (PMC), PMC is associated with central compartment lymph node metastasis. The aim of this study is to evaluate the effect of clinical and pathological factors affecting the central compartment lymph node metastasis in thyroid PMC. SUBJECTS AND METHOD: We undertook a retrospective study of 161 patients treated between January, 2003 and June, 2007 for papillary thyroid microcarcinoma by total thyroidectomy and central compartment neck dissection (n=161) with or without comprehensive lateral neck dissection. Following factors were included to analyze the relationship of tumor size and central compartment lymph node metastasis; sex, age, extracapsular extension, lymphovascular tumor emboli, multifocality, bilaterality, AMES risk group, lateral cervical lymph node involvement. RESULTS: In 109 of 161 patients (67.7%), tumor size between 5-10 mm was significantly related with extracapsular extension (p=0.027) and also with the AMES high risk group (p=0.007). In 75 of 161 patients (46.6%), central compartment lymph node metastasis were found. By univariate analysis, tumor multifocality, bilaterality, and lateral lymph node involvement were related with central compartment lymph node metastasis. But on multivariate analysis, tumor bilaterality (p=0.008) and lateral lymph node involvement (p=0.018) were significantly related with central compartment lymph node metastasis. CONCLUSION: Prophylactic neck dissection of central compartment lymph nodes in PMC should be recommended as a routine procedure particularly for patients with tumor bilaterality and metastatic lymph nodes in the lateral neck.

High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils / 당뇨병

BACKGROUND: Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty acids on the production of superoxide from neutrophils and their role in endothelial cell damage. METHODS: Human neutrophils were incubated in the media containing 5.5 mM D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 microM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured with neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. RESULTS: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial cells was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91(phox)). Endothelial cells co-cultured with neutrophils exposed to high glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. CONCLUSION: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils.

Clinical Characteristics of Multifocal Papillary Thyroid Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Papillary thyroid cancers (PTCs) often present as multifocal tumors. Whether multifocal tumors are associated with increased risk of recurrence and mortality is still the subject of controversy. The aim of current study was to individualize factors associated with multifocality of papillary thyroid cancer and determine the clinical significance of multifocal thyroid cancer. SUBJECTS AND METHOD: We undertook a retrospective study of 403 patients treated between January, 2003 and June, 2007 for papillary thyroid carcinoma by total thyroidectomy and central compartment neck dissection (n=403) with or without comprehensive lateral neck dissection. There were 342 women and 61 men whose mean age was 47.3 years old. Following criteria were used to study the pattern of and factors related with multifocality : sex, age, extracapsular extension, central compartment lymph node metastasis, the involvement of lateral neck lymph node, AMES risk group, distant metastasis. RESULTS: Of those factors, sex (p=0.0481), central compartment lymph node metastasis (p=0.0007), the involvement of lateral neck lymph node (p=0.0001) were significantly related factors for multifocality of papillary thyroid cancer. Age, primary tumor size, AMES risk group were not significantly related with multifocality. Bilateral or contralateral central compartment lymph node metastasis occurred more frequently in multifocal PTCs (64.0%) than solitary PTCs (46.9)(p=0.012). CONCLUSION: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma are associated with increased risk of bilateral central compartment and lateral cervical lymph node metastasis. Therefore, total thyroidectomy and bilateral central compartment lymph node dissection should be recommended as a routine procedure in multifocal papillary carcinoma

Oxidative Stress and Cell Dysfunction in Diabetes: Role of ROS Produced by Mitochondria and NAD(P)H Oxidase / 당뇨병

Oxidative stress has been considered to be a major contributor to the pathogenesis of the diabetic macrovascular and microvascular complications. In the absence of an appropriate antioxidant defense mechanism, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause damage and contribute to the late complications ofdiabetes. The source of reactive oxygen species (ROS) in the pancreatic beta cells and insulin sensitive cells has postulated to be the mitochondrial electron transport chain. NAD(P)H oxidase-dependent ROS production is also important as the source both in pancreatic beta cells and other cells. NAD(P)H oxidase mediated ROS can alter parameters of signal transduction, insulin secretion, insulin action, cell proliferation and cell death. Additionally, oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both pancreatic beta cells and endothelial cells, eventually leads to diabetes and its complications. Further investigation of the mechanisms and its therapeutic interventions based on focusing NAD(P)H oxidase associated ROS production in the islet cells and other islet cells are needed

Association of Serum Cystatin C with Metabolic Syndrome and Its Related Components in Korean Adults / 당뇨병

BACKGROUND: Serum cystatin C has been reported as a better marker than serum creatinine for estimation of kidney function and may be associated with cardiovascular disease. The aim of this study was to elucidate the association of serum cystatin C with metabolic syndrome (MS), a constellation of cardiovascular risk factors, and its related components and the usefulness of serum cystatin C for the cardiovascular risk assessment. METHODS: 1,468 healthy subjects (814 men and 655 women), who visited health promotion center of Pusan National University Hospital for routine medical checkup were included. MS was defined by modified, revised National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. RESULTS: Mean serum cystatin C value was 0.87 +/- 0.17 mg/L. In partial correlation analysis adjusted by age, sex and Glomerular Filtration Rate (GFR), cystatin C was associated with most of metabolic parameters and especially had significant positive correlation with waist circumference (r = 0.215), triglyceride (TG) (r = 0.141), diastolic blood pressure (BP) (r = 0.116), and correlated negatively with high density lipoprotein (HDL) cholesterol (r = -0.152) (all P < 0.001). There were increasing trends of prevalence of MS with the increase of quartiles of cystatin C and as the number of MS components increased, cystatin C values significantly increased. Serum cystatin C was also significantly increased in MS (0.90 +/- 0.19 mg/L vs. 0.86 +/- 0.16 mg/L). In stepwise multiple regression analysis including the components of MS, Waist circumference, diastolic BP, triglyceride, and HDL cholesterol were independent determinants of serum cystatin C, but with creatinine, only waist circumference was independent determinant. CONCLUSIONS: Serum cystatin C was closely associated with MS and its related cardiovascular risk factors and might be useful as a tool of cardiovascular risk assessment.

Correlation between Tumor Markers and Clinicopathologic Factors in Peripheral Blood of Papillary Thyroid Cancer Patients / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are involved in the pathogenesis and development of thyroid cancer. The purpose of this study was to find the correlation between serum VEGF, VEGF-C, MMP-9, EGF, HGF and clinicopathologic factors. SUBJECTS AND METHOD: Using enzyme linked immunosorbent assay (ELISA) kit, 64 patients with thyroid papillary cancer, 15 benign thyroid mass patients and 14 healthy normal control were analyzed to investigate the expression of human VEGF, VEGF-C, MMP-9, EGF and HGF. RESULTS: There were no significant differences in the serum levels of VEGF, VEGFC, MMP-9, TGF, EGF between papillary thyroid cancer group and the benign thyroid tumor group. Levels of VEGF and MMP-9 appeared higher in lateral cervical lymph node metastasis than N0 lymph node metastasis or only cervical component lymph node metastasis. But, the serum VEGF-C level was significantly related with tumor size, T stage, extrathyroidal extension and lateral cervical lymph node metastasis (p=0.043). CONCLUSION: VEGF, VEGF-C, MMP-9, HGF and EGF could not be used as a diagnostic tool for differentiating malignancy from benign thyroid disease. Serum VEGF, VEGF-C and MMP-9 levels were correlated with lateral cervical lymph node metastasis of papillary thyroid cancer. Consequently, this results suggests that they may serve as preoperative supplementary marker for determining the extent of papillary thyroid cancer surgery. Also, serum VEGF-C levels were correlated with some prognostic factors of papillary thyroid cancer.

Migration of Vascular Smooth Muscle Cells by High Glucose is Reactive Oxygen Dependent / 당뇨병

BACKGROUND: Oxidative stress contributes to vascular diseases in patients with diabetes. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether the oxidative stress is a major factor in hyperglycemia-induced migration of vascular smooth muscle cells (VSMCs). METHODS: We treated primary cultured rat aortic smooth muscle cells for 72 hours with medium containing 5.5 mM D-glucose (normal glucose), 30 mM D-glucose (high glucose) or 5.5 mM D-glucose plus 24.5 mM mannitol (osmotic control). We measured the migration of VSMCs and superoxide production. Immunoblotting of PKC isozymes using phoshospecific antibodies was performed, and PKC activity was also measured. RESULTS: Migration of VSMCs incubated under high glucose condition were markedly increased compared to normal glucose condition. Treatment with diphenyleneiodonium (DPI, 10 micromol/L) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed high glucose-induced migration of VSMCs. Superoxide production was significantly increased in high glucose condition and was markedly decreased after treatment with DPI and SOD. High glucose also markedly increased activity of PKC-delta isozyme. When VSMCs were treated with rottlerin or transfected with PKC-delta siRNA, nitro blue tetrazolium (NBT) staining and NAD(P)H oxidase activity were significantly attenuated in the high glucose-treated VSMCs. Furthermore, inhibition of PKC-delta markedly decreased VSMC migration by high glucose. CONCLUSION: These results suggest that high glucose-induced VSMC migration is dependent upon activation of PKC-delta, which may responsible for elevated intracellular ROS production in VSMCs, and this is mediated by NAD(P)H oxidase.