BACKGROUND: Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.
Adult ; Alanine Transaminase ; Cholesterol ; Estrogens ; Female ; gamma-Glutamyltransferase ; Humans ; Menopause ; Obesity, Abdominal ; Perimenopause ; Postmenopause ; Premenopause ; Prevalence ; Waist Circumference

BACKGROUND: Telmisartan, used for the treatment of hypertension, has been shown to function as a partial agonist of peroxime proliferative activated receptor-nu (PPAR-nu). Theoretically, telmisartan which simultaneously blocks the angiotensin II receptor and activates PPAR-nu should be more effective in improving atherosclerotic surrogate markers than angiotensin II receptor blockers alone. Therefore, this pilot study was designed to evaluate and compare the efficacy of telmisartan and valsartan on plasma adiponectin levels and pulse wave velocity as a marker of arterial stiffness in patients with type 2 diabetes. METHODS: Thirty two patients with type 2 diabetes (mean duration 7.6 +/- 5.1 years) taking oral hypoglycemic agents were randomly assigned to receive telmisartan or valsartan for 12 weeks. RESULTS: Telmisartan and valsartan treatment significantly increased circulating adiponectin levels (P = 0.013 and P = 0.013, respectively) and reduced systolic (P = 0.001 and P = 0.002, respectively) and diastolic blood pressure (P = 0.001 and P < 0.001, respectively), and brachial-ankle PWV (P = 0.019 and P = 0.002, respectively), without significant differences between the two treatments. Before and after treatment, the fasting plasma glucose, interleukin-6, homeostasis model of assessment insulin resistance (HOMAIR) levels and lipid profile were unchanged in both treatment groups. CONCLUSION: Contrary to our expectation, telmisartan, even with its partial PPAR-nu activity, is not superior to valsartan in improving plasma adipocytokine levels and arterial stiffness in patients with type 2 diabetes. These data suggest that the partial PPAR-nu activity of telmisartan beyond valsartan may have less significant therapeutic implications than expected in treating patients with type 2 diabetes.
Adiponectin ; Angiotensin Receptor Antagonists ; Benzimidazoles ; Benzoates ; Biomarkers ; Blood Pressure ; Fasting ; Glucose ; Homeostasis ; Humans ; Hypertension ; Hypoglycemic Agents ; Insulin Resistance ; Interleukin-6 ; Pilot Projects ; Plasma ; Pulse Wave Analysis ; Receptors, Angiotensin ; Tetrazoles ; Valine ; Vascular Stiffness ; Valsartan

BACKGROUND: Adipocytes produce several adipokines that modulate insulin action as well as glucose and lipid metabolism. The aim of this study was to evaluate the relationship between serum adiponectin concentrations and metabolic syndrome (MS) in patients with type 2 diabetes mellitus. METHODS: This study included 127 type 2 diabetic patients (males 63, females 64). The subjects were divided into two groups as with or without metabolic syndrome (MS(+) or MS(-)). The MS was diagnosed by International Diabetes Federation. Serum adiponectin, leptin, fasting plasma insulin, glucose, glycated hemoglobin, lipid profile, white blood corpuscle (WBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid and C-reactive protein (CRP) were examined. RESULTS: Serum adiponectin concentrations were significantly lower in MS(+) than MS(-) (4.8 +/- 2.4 microgram/mL vs 7.6 +/- 5.8 microgram/mL, 7.6 +/- 3.7 microgram/mL vs 11.5 +/- 7.2 microgram/mL, P < 0.05 in males and females). After adjustment for age and body mass index (BMI), in MS (+), the serum levels of adiponectin correlated positively with high density lipoprotein - cholesterol (HDL-C) and negatively with height, body weight, ALT and CRP. In MS(-), the serum levels of adiponectin correlated positively with HDL-C and negatively with diastolic blood pressure (DBP), triglyceride and CRP. By multiple regression analysis, no parameters were independently correlated with serum adiponectin concentrations in MS(+), while DBP and HDL-C were independently related to serum adiponectin concentrations in MS(-). CONCLUSION: Serum adiponectin concentrations were lower in type 2 diabetic patients with MS than without MS. There were no significant parameters related to decrease serum adiponectin concentrations in MS. But further study is needed to confirm this result.
Adipocytes ; Adipokines ; Adiponectin ; Alanine Transaminase ; Aspartate Aminotransferases ; Blood Pressure ; Body Height ; Body Mass Index ; C-Reactive Protein ; Cholesterol ; Fasting ; Female ; Glucose ; Hemoglobins ; Humans ; Insulin ; Leptin ; Leukocytes ; Lipid Metabolism ; Lipoproteins ; Male ; Plasma ; Uric Acid

BACKGROUND: Cardiovascular disease (CVD) is the major cause of death in type 2 diabetic patients. The purpose of this study was to investigate the characteristics of Korean type 2 diabetes mellitus (DM) patients according to plasma high density lipoprotein (HDL) cholesterol level and to document the effect of diet on HDL-cholesterol. METHODS: The subjects were 252 (male: 134, female: 118) Korean type 2 DM patients recruited from a general hospital's DM clinic and divided into low HDL-cholesterol group (male < 40 mg/dL, female < 50 mg/dL) and control group (male > or = 40 mg/dL, female > or = 50 mg/dL). Anthropometric and hematological variables and dietary intake were assessed by the groups. RESULTS: The subject's mean age was 60.2 +/- 1.1 years and duration of diabetes was 9.5 +/- 1.0 years. Anthropometric measurements (body fat mass, % body fat, WHR, fat free mass, and muscle mass) and BMI were not significantly different between two groups. The male subjects with low HDL-cholesterolemia showed higher Atherogenic Index (AI, P < 0.001) and higher % carbohydrate from energy than control group (P < 0.01). The female subjects with low HDL-cholesterolemia showed higher AI (P < 0.001) and a tendency of higher triglyceride level and lower intake of energy, protein, lipid, vitamin B1 and vitamin E (P < 0.05) than control group. CONCLUSION: The subject with low HDL-cholesterolemia showed significantly higher AI. Male subject with low HDL-cholesterolemia consumed higher carbohydrate and female subject with low HDL-cholesterolemia showed lower intakes of many nutrients. This result suggests the importance of an adequate and balanced diet to manage type 2 DM patients to prevent CVD complications.
Adipose Tissue ; Cardiovascular Diseases ; Cause of Death ; Cholesterol ; Diabetes Mellitus, Type 2 ; Diet ; Female ; Humans ; Lipoproteins ; Male ; Muscles ; Plasma ; Thiamine ; Vitamin E ; Vitamins

BACKGROUND: The 26S ubiquitin-proteasome system (UPS) is a principal proteolytic pathway of intracellular molecules regulating apoptosis, cell cycle, cell proliferation or differentiation, inflammation and etc. The recent study suggests that the rs1048990 (C/G) polymorphism of the proteasome subunit alpha type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of IkappaB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of IkappaB and insulin receptor substances as a substrate. We therefore investigated whether the rs1048990 (C/G) polymorphism of PSMA6 gene and the rs2230087 (G/A) polymorphism of proteasome subunit beta type 5 gene (PSMB5), that is chymotrypsin-like protease determining the rate of proteolysis, are associated with susceptibility to T2DM in Korean subjects. METHODS: We examined the polymorphisms of these genes in 309 diabetic subjects and 170 non-diabetic controls. The polymorphisms of rs1048990 (C/G) and rs2230087 (G/A) were genotyped by real-time PCR. RESULTS: The frequency of the G allele of rs1048990 (C/G) and the A allele of rs2230087 (G/A) polymorphisms was significantly higher in diabetic patients (28% and 13%) compared to that in controls (13% and 1%; P = 0.000 and P = 0.000, respectively). Logistic regression analysis of the rs1048990 (C/G) polymorphism showed that the odds ratio (OR) (adjusted for age, smoking, waist circumference, fasting plasma glucose, systolic blood pressure, HDL-C, triglyceride, and total cholesterol) was 3.93 (95% confidence interval [CI], 2.35-6.59; P = 0.000) for the G allele and 5.09 (95% CI, 2.71-9.57; P = 0.000) for CG and GG genotype when compared with the CC genotype. Logistic regression analysis of the rs2230087 (G/A) polymorphism showed that the adjusted OR was 5.70 (95% CI, 1.63-19.98; P = 0.007) for the A allele and 6.08 (95% CI, 1.66-22.29; P = 0.006) for GA and AA genotype when compared with the GG genotype. In multiple logistic regression analysis with T2DM as the independent Variable rs1048990 (C/G) and rs2230087 (G/A) polymorphisms were the predictor for T2DM. CONCLUSION: We suggest that the G allele of rs1048990 (C/G) polymorphism and the A allele of rs2230087 (G/A) polymorphism may be genetic risk factor to type 2 diabetes mellitus in Korean subjects.
Alleles ; Apoptosis ; Blood Pressure ; Cell Cycle ; Cell Proliferation ; Chymases ; Diabetes Mellitus, Type 2 ; Fasting ; Genotype ; Glucose ; Humans ; Inflammation ; Insulin Resistance ; Logistic Models ; Myocardial Infarction ; Odds Ratio ; Plasma ; Proteasome Endopeptidase Complex ; Proteolysis ; Receptor, Insulin ; Risk Factors ; Smoke ; Smoking ; Waist Circumference

BACKGROUND: The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.
3T3-L1 Cells ; Adipokines ; Animals ; Blotting, Western ; Deoxyglucose ; Gene Expression ; Glucose ; Insulin ; Insulin Resistance ; Negotiating ; Phosphorylation ; Phosphotransferases ; Resistin

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.
Acetophenones ; Animals ; Antibodies ; Benzopyrans ; Diabetic Angiopathies ; Glucose ; Humans ; Immunoblotting ; Isoenzymes ; Mannitol ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; NADPH Oxidase ; Onium Compounds ; Oxidative Stress ; Oxygen ; Protein Kinase C ; Rats ; RNA, Small Interfering ; Superoxide Dismutase ; Superoxides ; Vascular Diseases

No abstract available.
Diabetic Nephropathies ; Glomerular Filtration Rate

The adverse effects of prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations (i.e. glucose toxicity) is mediated at least in part by glucose oxidation and the subsequent generation of reactive oxygen species (ROS) that can impair insulin gene expression and beta cell function. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might cause beta cell damage. However, all these pathways have in common the formation of reactive oxygen species that, in excess and over time, cause chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. The intracellular peroxide levels of the pancreatic islets (INS-1 cells, rat islets) by flow cytometry were increased in the high glucose media compared to 5.6 mM glucose media. The insulin, MafA, PDX-1 mRNA levels and glucose stimulated insulin secretion (GSIS) were decreased in high glucose media compared to 5.6 mM glucose media. The HO-1 seems to mediate the protective response of pancreatic islets against the oxidative stress that is due to high glucose conditions. Also, we observed decreased glutathione level, gamma-GCS expression and increased oxidized LDL, malondialdehyde level at leukocytes and mesothelial cells from patients with Korean Type 2 Diabetes (esp, poorly controlled patients). In conclusion, this pathophysiologic sequence sets the scene for considering antioxidant therapy as an adjunct in the management of diabetes, especially type 2 Diabetes.
Animals ; Apoptosis ; Flow Cytometry ; Gene Expression ; Glucose ; Glutathione ; Humans ; Insulin ; Insulin-Secreting Cells ; Islets of Langerhans ; Leukocytes ; Lipoproteins, LDL ; Malondialdehyde ; Oxidative Phosphorylation ; Oxidative Stress ; Protein Kinase C ; Pyruvaldehyde ; Rats ; Reactive Oxygen Species ; RNA, Messenger ; Sorbitol

No abstract available.
Adult ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Hemoglobin, Sickle ; Humans ; Plasma