BACKGROUND: Several epidemiologic studies have shown that increased uric acid is a risk factor of cardiovascular mortality. Elevated serum uric acid is also a feature of insulin resistance. However, increased or decreased levels of uric acid have been variably reported in diabetes and impaired glucose tolerance. The aim of the present study is to evaluate the relation between uric acid and metabolic parameters and chronic complications in type 2 diabetes. METHODS: Total 387 patients with type 2 diabetes were evaluated and divided according to their uric acid level in quartiles. Plasma glucose, lipid profiles, blood pressure, C-peptide levels and complications including nephropathy and retinopathy were compared between four groups according to plasma uric acid levels. Patients were divided as follows : Quartile 1 (<3.7 mg/dL, n=94), Quartile 2 (>or=3.7 mg/dL and < 4.5 mg/dL, n=96), Quartile 3 (>or=4.5 mg/dL and < 5.4 mg/dL, n=101), Quartile 4 (>or=5.4 mg/dL, n=96). RESULTS: Patients within the highest quartile showed significantly longer duration of diabetes, higher prevalence of retinopathy and higher blood pressure, higher level of triglyceride, creatinine and C-peptide (p<0.05). Patients within the lowest quartile showed significantly higher concentrations of fasting plasma glucose, postprandial glucose and HbA1c (p<0.05). In the multiple regression analysis after adjustment for age, sex, duration of diabetes, a positive correlation was found between uric acid levels and creatinine (beta=0.245, p<0.01), triglyceride (beta=0.127, p<0.05), diastolic blood pressure (beta=0.156, p<0.05) and percentage of proliferative diabetic retinopathy (beta=0.141, p<0.05). After readjustment for age, sex, duration of diabetes and creatinine, the strong predictor of uric acid was triglyceride levels (beta=0.161, p<0.05) and diastolic pressure (beta=0.227, p<0.05). CONCLUSION: In type 2 diabetes, elevated uric acid level was related with the components of insulin resistance syndrome and the degree of microvascular complications.
Blood Glucose ; Blood Pressure ; C-Peptide ; Creatinine ; Diabetes Complications* ; Diabetes Mellitus ; Diabetic Retinopathy ; Epidemiologic Studies ; Fasting ; Glucose ; Humans ; Hypertension ; Insulin Resistance ; Mortality ; Plasma* ; Prevalence ; Risk Factors ; Triglycerides ; Uric Acid*

In light of the anti-inflammatory properties of histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), we examined a new HDAC inhibitor KBH-A42 for its anti-inflammatory activities. KBH-A42 showed noteworthy anti-inflammatory properties in vitro via suppression of the production of TNF-alpha, a proinflammatory cytokine, and nitric oxide (NO), a proinflammatory effector molecule, in LPS-stimulated RAW264.7 cells and peritoneal macrophages. It also inhibited TNF-alpha production in vivo as demonstrated in a LPS-induced mouse endotoxemia model. The levels of TNF-alpha, IL-1beta, IL-6 and iNOS mRNAs determined by RT-PCR propose that the inhibition of these pro-inflammatory mediators by KBH-A42 resulted from inhibiting expression of these genes. However, the EMSA study to see the effect of KBH-A42 on the binding of NF-kappaB, a transcription factor, to a specific DNA sequence showed that the binding of NF-kappaB to DNA was not changed regardless of increasing the concentration of KBH-A42 in the presence and absence of LPS stimulation. Interestingly, DNA binding of another transcription factor AP-1 dose-dependently increased by KBH-A42. KBH-A42 differentially regulated the phosphorylation of MAP kinases. While the phosphprylation of ERK1/2 and SAPK/JNK was not affected by KBH-A42, the phosphorylation of p38 decreased by KBH-A42. These results showed that KBH-A42 inhibits production of proinflammatory cytokines in macrophages by decreasing their mRNA levels, and p38 kinase is involved in the KBH-A42-mediated inhibition.
Animals ; Blotting, Western ; Cell Line ; Cell Survival/drug effects ; Cytokines/blood/genetics/*metabolism ; Electrophoretic Mobility Shift Assay ; Endotoxemia/blood/metabolism/pathology ; Enzyme Inhibitors/chemistry/*pharmacology ; Histone Deacetylases/*antagonists & inhibitors ; Hydroxamic Acids/chemistry/*pharmacology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Macrophages/cytology/*drug effects/metabolism ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Molecular Structure ; NF-kappa B/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics/metabolism ; Phosphorylation/drug effects ; Piperidones/chemistry/*pharmacology ; Protein Binding/drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factor AP-1/metabolism ; Tumor Necrosis Factor-alpha/blood/genetics/metabolism

Eosinophilic peritonitis is defined as when there are more than 100 eosinophils present per milliliter of peritoneal effluent, of which eosinophils constitute more than 10% of its total WBC count. Most cases occur within the first 4 weeks of peritoneal catheter insertion and they usually have a benign and self-limited course. We report a patient of eosinophilic peritonitis that was successfully resolved without special treatment. An 84-year-old man with end stage renal disease secondary to diabetic nephropathy was admitted for dyspnea and poor oral intake. Allergic history was negative. and physical examination was unremarkable. Complete blood count showed a hemoglobin level of 11.1 g/dL, WBC count was 24, 500/mm3 (neutrophil, 93%; lymphocyte, 5%; monocyte, 2%), platelet count was 216, 000/mm3, serum BUN was 143 mg/dL, Cr was 5.7 mg/dL and albumin was 3.5 g/dL. Creatinine clearance was 5.4 mL/min. Three weeks after peritoneal catheter insertion, he was started on peritoneal dialysis with a 6-hour exchange of 2L 1.5% peritoneal dialysate. After nine days, he developed turbid peritoneal effluents with fever (38.4degrees C), abdominal pain and tenderness. Dialysate WBC count was 180/mm3 (neutrophil, 20%; lymphocyte, 4%; eosinophil, 76% [eosinophil count: 136/mm3]). Cultures of peritoneal fluid showed no growth of aerobic or anaerobic bacteria, or of fungus. Continuous ambulatory peritoneal dialysis (CAPD) was commenced, and he was started on intraperitoneal ceftazidime (1.0 g/day) and cefazolin (1.0 g/day). After two weeksr, the dialysate had cleared up and clinical symptoms were improved. Dialysate WBC count decreased to 8/mm3 and eosinophils were not detected in peritoneal fluid. There was no recurrence of eosinophilic peritonitis on follow-up evaluation, but he died of sepsis and pneumonia fifteen weeks after admission.
Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Cefazolin/therapeutic use ; Ceftazidime/therapeutic use ; Diabetic Nephropathies/complications ; Eosinophilia/drug therapy/*etiology ; Humans ; Kidney Failure, Chronic/etiology/therapy ; Male ; Peritoneal Dialysis, Continuous Ambulatory/*adverse effects ; Peritonitis/drug therapy/*etiology

BACKGROUND: Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastogenesis through binding to receptor activator of nuclear factor-kappaB ligand (RANKL). OPG-knockout mice develop early-onset osteoporosis and arterial calcification. Recent studies report that serum OPG levels are elevated in diabetic patients with cardiovascular disease and are associated with the presence and severity of coronary artery disease. We examined the relationships between serum OPG levels and insulin resistance, bone metabolism and cardiovascular risk factors in diabetic patients. METHODS: In 84 diabetic patients (33 men, 51 women, mean age 56.7 years old) were studied. Blood pressure, body mass index (BMI), fasting blood glucose, postprandial 2-hour blood glucose, fasting insulin and lipid profiles were measured. Serum OPG levels were measured with sandwich ELISA method. Bone mineral density (BMD)s were checked and serum osteocalcin and urine deoxypyridinoline levels were checked as bone turnover markers. 24-hour urine microalbumin were checked and left ventricular mass index (LVMI) were evaluated with echocardiography. From simple chest X-ray, the presence of aortic calcification were confirmed by a trained radiologist. Homeostatic model assessment (HOMA)-insulin resistance (IR), quantitative insulin sensitivity check index (QUICKI) were calculated as insulin resistance indices. RESULTS: Serum OPG levels were positively correlated with age, LVMI, HOMA and negatively correlated with lumbar spine BMD and QUICKI. After adjustment for age, only LVMI showed persistent correlation with serum OPG levels and when multiple regression analysis was performed with LVMI as the dependent variable, BMI and OPG were the significant predictors of LVMI (R2=0.054, p=0.012). Dividing the subjects into 3 groups according to 24-hour urine microalbumin levels, mean values for serum OPG levels increased as 24-hours urine microalbumin levels increased, but without statistical significance. Mean serum OPG levels were higher in patients with aortic calcification, without statistical significance. CONCLUSION: Serum OPG levels were positively correlated with insulin resistance indices and negatively correlated with lumbar spine BMD in diabetic patients, suggesting a compensatory mechanism to counteract bone loss progression. Serum OPG levels were independent predictor for LVMI in diabetic patients, warranting further research on OPG as the marker for future cardiovascular mortality in diabetic patients.
Animals ; Blood Glucose ; Blood Pressure ; Body Mass Index ; Bone Density ; Cardiovascular Diseases ; Coronary Artery Disease ; Diabetes Mellitus ; Echocardiography ; Enzyme-Linked Immunosorbent Assay ; Fasting ; Female ; Glycoproteins ; Humans ; Hypertrophy, Left Ventricular ; Insulin Resistance* ; Insulin* ; Male ; Metabolism* ; Mice ; Mortality ; Osteocalcin ; Osteoporosis ; Osteoprotegerin* ; RANK Ligand ; Risk Factors* ; Spine ; Thorax

BACKGROUND: Inflammation has been demonstrated to be an important risk factor for the development of cardiovascular disease (CVD). The relationship of the peripheral leukocyte count to the severity of stable angina remains to be clarified. The present study analyzed the relationship of the peripheral leukocyte count to the severity of stable angina determined by coronary angiography. METHODS: The data from 108 patients with stable angina, and 92 subjects with normal coronary angiograms were reviewed, and the role of the peripheral leukocyte count as a risk factor for stable angina evaluated. In addition, the correlation of the peripheral leukocyte count and the severity of stable angina, as assessed by the Gensini's score in the stable angina group, were analyzed. RESULTS: Age, the prevalence of hypertension and diabetes, and the fasting blood sugar were significantly higher, and the HDL was lower in the stable angina than the control group. A multivariate analysis showed that a peripheral leukocyte count over 6, 800/mm3 was an independent variable, but with no statistical significance (p=0.067), and diabetes (OR=3.02, 95% CI: 1.29~7.02) and old age (OR=3.62, 95% CI: 1.33~9.87) were independent risk factors for stable angina. A positive correlation between peripheral leukocyte count and Gensini's score was noted in the stable angina group even after adjusting for age, fasting blood sugar, blood pressure and lipid profiles (R2=0.198, p=0.015). CONCLUSION: An increased peripheral leukocyte count is considered not so much an indicator of the pathogenesis of stable angina, but as a predictor for disease progression. Furthermore, it is considered that the above correlation will be helpful in screening high-risk groups that require relatively active interventional therapy.
Adult ; Aged ; Angina Pectoris/*blood/epidemiology/*radiography ; *Coronary Angiography ; Cross-Sectional Studies ; Female ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Risk Factors ; Severity of Illness Index

BACKGROUND: Insulin resistance is a strong contributor to cardiovascular diseases. The increasing prevalence of diabetes and the subsequent complications confers a great importance to the early detection and intervention of diabetes. However, the exact roles of blood glucose and blood pressure in nondiabetic and normotensive range to vascular complications are not precisely defined. High-sensitivity C-reactive protein (hsCRP) levels have consistently been associated with various cardiovascular endpoints in a number of studies. The aim of this study was to find out whether the insulin resistance and hsCRP, a non-traditional cardiovascular risk factor, increase according to the fasting glucose and blood pressure levels in nondiabetic and normotensive individuals. METHODS: In 7,979 participants (4,847 males, 3,132 females, mean age 46 yrs) undergoing medical checkup program in Kangbuk Samsung Hospital, blood pressures, body mass index (BMI), fasting blood glucose, fasting insulin, lipid batteries and hsCRP levels were checked. All participants were subdivided into 5 groups according to fasting glucose level and into 4 groups according to the blood pressures. Homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: HOMA-IR and QUICKI increased according to the increment in fasting glucose and blood pressure in nondiabetic and normotensive range (p<0.01). Log (hsCRP) level significantly increased in proportion to the increment in fasting glucose and blood pressure in nondiabetic and normotensive range (p<0.01). CONCLUSION: Insulin resistance correlated with increment in the fasting glucose and blood pressure even in nondiabetic and normotensive range. Cardiovascular risk might be increased in proportion to the increment of fasting glucose and blood pressure even in the normal range. There may not be the glycemic and hypertensive threshold for the cardiovascular risk.
Blood Glucose* ; Blood Pressure* ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Fasting* ; Female ; Glucose ; Humans ; Insulin Resistance* ; Insulin* ; Male ; Prevalence ; Reference Values ; Risk Factors