Angiotensin II Inhibits Insulin Binding to Endothelial Cells

BACKGROUND: Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance. METHODS: After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol. RESULTS: After treatment of 10(-7)M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 microM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol. CONCLUSION: ATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

Non-invasive Methods for Cardiovascular Risk Assessment in Asymptomatic Type 2 Diabetes Mellitus / 당뇨병

Cardiovascular disease (CVD) is the major cause of mortality in type 2 diabetes mellitus. CVD is a clinical manifestation of atherosclerosis, a chronic and progressive inflammatory disease characterized by a long asymptomatic phase. Progression of atherosclerosis can lead to the occurrence of acute cardiovascular events. Atherosclerosis can be identified during the subclinical phase by several methods, including using biomarkers, pulse wave velocity, augmentation index, flow-mediated dilation, carotid ultrasound, and calcium score. The appropriate criteria for identifying asymptomatic patients with type 2 diabetes who should undergo CVD screening and therapeutic intervention remain controversial. Non-invasive methods, such as markers of subclinical atherosclerosis, may aid in risk stratification and the design of tailored therapies for patients with type 2 diabetes mellitus.

Association of Spot Urine Albumin-to-Creatinine Ratio and 24 Hour-Collected Urine Albumin Excretion Rate in Patients with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Measuring urine albumin in diabetic patients is an important screening test to identify those individuals at high risk for cardiovascular disease and the progression of kidney disease. Recently, spot urine albumin-to-creatinine ratio (ACR) has replaced 24 hour-collected urine albumin excretion rate (AER) as a screening test for microalbuminuria given its comparative simplicity. The purpose of the current study was to evaluate the degree of correlation between AER and ACR in the normal, microalbuminuric and macroalbuminuric ranges, and to identify the lower limits of ACR for both genders. METHODS: A total of 310 type 2 diabetics admitted to one center were enrolled in the present study. Following the collection of a spot urine sample, urine was collected for 24 hours and albumin content was measured in both specimens. RESULTS: Mean patient age was 60.2 years. A total of 25.4% had microalbuminuria and 15.8% had macroalbuminuria. The data revealed a strongly positive correlation between AER and ACR across all ranges of albuminuria (R = 0.8). The cut-off value of ACR for 30 mg/day of AER by the regression equation was 24 microgram/mg for men, 42 microgram/mg for women and 31.2 microgram/mg for all patients. The diagnostic performance expressed as the area under the curve (AUC) was 0.938 (95% CI, 0.911-0.965) for ACR. ACR revealed a sensitivity of 84% and specificity of 84%, when a cut-off value of 31.2 microgram/mg was employed. CONCLUSION: ACR was highly correlated with AER, particularly in the range of microalbuminuria. The gender combined cut-off value of ACR in type 2 diabetic patients was determined to be 31.2 microg/mg However, additional studies of large outpatient populations, as opposed to the inpatient population used in the present study, are required to confirm the utility of this value.

The Efficacy of Fixed Dose Rosiglitazone and Metformin Combination Therapy in Poorly Controlled Subjects with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Obese type 2 diabetic subjects are recently increasing in Korea, indicating the importance of insulin resistance rather than insulin secretory defects in the pathophysioloy of type 2 diabetes. The purpose of this study is to evaluate the safety and efficacy of fixed dose rosiglitazone/metformin combination therapy in poorly controlled subjects with type 2 diabetes mellitus. METHODS: 12 type 2 diabetic subjects who had a HbA1c > 11% or fasting plasma glucose > 15 mmol/L were included. After a 2 week screening period, the subjected took the fixed does rosiglitazone/metformin for 24 weeks. The treatment with rosiglitazone/metformin began at week 0 with an initial dose of 4 mg/1000 mg and, unless tolerability issues arose, subjects would be increased to 6 mg/1500 mg at week 4 and at week 8 to the maximum dose of 8 mg/2000 mg. The primary object of this study was to characterize the magnitude of HbA1c reduction from baseline after 24 weeks of rosiglitazone and metformin treatment in poorly controlled type 2 diabetics. RESULTS: The mean age of the subjects was 48.9 +/- 10.6 years old, body mass index was 25.0 +/- 3.5 kg/m2, HbA1c was 12.0 +/- 1.0%, and fasting plasma glucose was 16.3 +/- 3.1 mmol/L. HbA1c was reduced to 7.54 +/- 1.45% and fasting plasma glucose reduced to 7.96 +/- 2.38 mmol/L at week 24. The proportion of HbA1c responder who showed the reduction from baseline of > or = 0.7% or HbA1c < 7% was 11 among 12 subjects (91.7%). 41% of the subjects (5 among 12 subjects) achieved HbA1c level < 7.0% and 75% (9 among 12 subjects) achieved HbA1c level < 8.0%. CONCLUSIONS: In this study, rosiglitazone and metformin combination therapy was effective in glycemic control in poorly controlled subjects with type 2 diabetes mellitus.

The Changes of Central Aortic Pulse Wave Analysis in Metabolic Syndrome / 당뇨병

The metabolic syndrome (MS) has been characterized as a cluster of risk factors that includes dyslipidemia, hypertension, glucose intolerance and central obesity. This syndrome increases the risk of cardiovascular disease. Augmentation index (AIx), a composite of wave reflection form medium-sized muscular arteries is related to the development of coronary artery disease. The aim of this study is to examine the change on central aortic waveforms in subjects between patients with metabolic syndrome and normal subjects. Using the non-invasive technique of pulse wave analysis by applantation tonometry, we investigated central aortic waveforms in 45 patients with MS and 45 matched controls. The MS was defined by NCEP-ATP III criteria. Age did not differ between the two groups. AIx was significantly elevated in patinets with MS compared with controls (21.91 +/- 11.41% vs 18.14 +/- 11.07%; P < 0.01). Subendocardial viability ratio (SEVR) (158.09 +/- 28.69 vs 167.09 +/- 30.06; P < 0.01) was significantly decreased in patients with MS compared with controls. Only the fasting glucose (r = 0.317, P = 0.03) among the components of MS and age (r = 0.424, P = 0.004) had a positive correlation with AIx. AIx increased as the number of MS components increased. These results show that the MS increased systemic arterial stiffness. Age and fasting blood glucose are independent risk factors of arterial stiffness in MS. The individual MS components, except for fasting blood glucose, do not affect arterial stiffness independently. But the clustering of MS components might interact to synergistically affect arterial stiffness.

The Effect of Rosiglitazone and Metformin Therapy, as an Initial Therapy, in Patients with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: Type 2 diabetes is usually preceded by a long and clinically silent period of increasing insulin resistance. The purpose of this study is to demonstrate that rosiglitazone and metformin fixed-dose combination therapy (RSG/MET) will safely and effectively control glycemia as a first line of oral therapy, better than rosiglitazone (RSG) or metformin (MET) monotherapy in Korean type 2 diabetes patients. METHODS: This study was a 32-week, multicenter, randomized, double-blind study. Twenty-seven type 2 diabetes patients (males 14; females 13) were included and randomly divided into the rosiglitazone, metformin group, or rosiglitazone /metformin combination groups. The primary objective of this study was to determine the change in HbA1c from baseline (week 0) to week 32. The secondary end-points were to determine changes in fasting plasma glucose (FPG) and homeostasis model assessment insulin resistance (HOMA-IR), from baseline to week 32. Other cardiovascular risk markers were also assessed. RESULTS: At week 32, there were significant reductions in HbA1c and FPG, in all three treatment groups. There was no statistical difference in HbA1c among the three groups, but the decrease in FPG in the RSG/MET group was statistically significant compared to the MET group (P < 0.05). RSG/MET significantly reduced HOMA-IR at week 32 compared to baseline, but there was no difference among the three groups. RSG/MET significantly decreased high-sensitive C-reactive protein (hs-CRP) value at week 32, compared to baseline. There were increases in adiponectin from baseline to week 32 in the RSG and RSG/MET groups, and the increase in the RSG/MET group was statistically significant compared to that of the MET group (P < 0.05). At week 32, there was a significant decrease in plasminogen activator inhibitor-1 (PAI-1) in all three treatment groups, but no statistically significant difference among them. The RSG/MET group significantly decreased in terms of urinary albumin-creatinine ratio at week 32, compared to baseline. CONCLUSIONS: In this study, rosiglitazone and metformin combination therapy was effective in glycemic control as an initial therapy, and it improved cardiovascular risk markers in Korean type 2 diabetes patients.

Clinical Characteristics and Outcomes of Diabetic Ketoacidosis at a Single Institution / 당뇨병

AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Hospital for past 6 years. METHODS: We reviewed the retrospective medical records of all patients admitted with a diagnosis of DKA from 2000 to 2005 in Uijeongbu St. Mary's Hospital. Clinical characteristics including precipitating factors and hospital mortality were analyzed. RESULTS: Seventy-eight patients (78 episodes) fulfilled criteria for inclusion in this study. Their mean age was 41.89 years. 66 episodes had a prior history of diabetes but DKA was the initial presentation in 12 episodes. 24.4% were on no treatment, 14.1% were using oral hypoglycemic agents and 53.8% were on insulin. Poor glycemic control were the most common precipitating factor (56.4%). There were 3 deaths. CONCLUSION: Our report is similar with past reports of DKA in Korea. but it is different that poor glycemic control is most common precipitating factor and mortality rate are lower than past reports. This observation suggests that many cases of DKA can be prevented by better access to medical care, proper education, and effective communication with a health care provider.

A Case of Symmetrical Peripheral Gangrene Complicating Escherichia coli Sepsis / 감염과화학요법

We have encountered a rare case of symmetrical peripheral gangrene complicating Escherichia coli sepsis in a 47-years-old male. He was successfully treated with antibiotics, anticoagulants, and vasodilator. To our knowledge, this is the first report on symmetrical peripheral gangrene complicating E. coli sepsis in Korea.

A Case of Symmetrical Peripheral Gangrene Complicating Escherichia coli Sepsis / 감염과화학요법

We have encountered a rare case of symmetrical peripheral gangrene complicating Escherichia coli sepsis in a 47-years-old male. He was successfully treated with antibiotics, anticoagulants, and vasodilator. To our knowledge, this is the first report on symmetrical peripheral gangrene complicating E. coli sepsis in Korea.

4 Cases of Intracardiac Metastasis of Hepatocellular Carcinoma

Antemortem diagnosis of inferior vena cava (IVC) and cardiac metastasis of hepatocellular carcinoma (HCC) is difficult but important to decide on treatment strategy. There are only a few cases of cardiac metastasis of HCC which have been diagnosed antemortem by echocardiography. We experienced 3 cases of IVC and Right atrial metastasis and 1 case of Left atrial metastasis of HCC. The tumor was discovered during computed tomography scanning. The patients had exhibited no signs of cardiac involvement. In this case, transesophageal echocardiography was valuable in providing information regarding the exact location of the tumor and its relation to surrounding anatomical structures. Left atrial metastasis of HCC is unusual patterns and probably related to tumor growth from the pulmonary veins following massive metastasis to the lung.

A Case of Superior Vena Cava Syndrome Due to Catheterization of the Internal Jugular Vein for Hemodialysis / 대한신장학회잡지

Most cases of superior vena cava (SVC) syndrome are secondary to malignant disease and subacute in their presentation. However, the exponential increase in use of indwelling central venous catheters and cardiac pacemakers over the last two decades has resulted in more patients with SVC syndrome. Internal jugular vein cannulation has become the preferred approach for temporary hemodialysis catheter placement following the reports of an increased incidence of subclavian vein stenosis due to subclavian vein catheterization. We describe a patient who developed SVC syndrome after internal jugular vein catheterization. The patient had been swollen the left arm intermittently due to left central vein stenosis for 1 year and experienced balloon angioplasty and stent insertion for three times. We diagnosed the SVC syndrome through the both subclavian venography, which revealed complete obstruction of the left brachiocephalic vein with extensive collateral circulation and mild stenosis of the distal right internal jugular vein. Resolution of the clinical SVC sydrome occurred after catheter removal.

A Case of Superior Vena Cava Syndrome Due to Catheterization of the Internal Jugular Vein for Hemodialysis / 대한신장학회잡지

Most cases of superior vena cava (SVC) syndrome are secondary to malignant disease and subacute in their presentation. However, the exponential increase in use of indwelling central venous catheters and cardiac pacemakers over the last two decades has resulted in more patients with SVC syndrome. Internal jugular vein cannulation has become the preferred approach for temporary hemodialysis catheter placement following the reports of an increased incidence of subclavian vein stenosis due to subclavian vein catheterization. We describe a patient who developed SVC syndrome after internal jugular vein catheterization. The patient had been swollen the left arm intermittently due to left central vein stenosis for 1 year and experienced balloon angioplasty and stent insertion for three times. We diagnosed the SVC syndrome through the both subclavian venography, which revealed complete obstruction of the left brachiocephalic vein with extensive collateral circulation and mild stenosis of the distal right internal jugular vein. Resolution of the clinical SVC sydrome occurred after catheter removal.

Gastrosplenic Fistula Complicated in a Patient with Non- Hodgkin's Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

Reported cases of gastrosplenic fistulas are extremely rare in the literature. Malignancy is the primary cause in 50% of patients, followed by perforated peptic ulcer (40%). Fistulas can cause spleen rupture and potential bleeding that threaten the life of the patient. Lymphoma is the most common cause of malignancy complicated with gastrosplenic fistula. Most gastrosplenic fistulae caused by lymphoma eventually close following chemotherapy, although splenectomy should be performed to avoid further complications. We experienced a case of non-Hodgkin's lymphoma complicated with gastrosplenic fistula in a 21 year-old man. He was admitted to our hospital because of LUQ mass. On the abdominal CT, a splenic mass with central necrosis and gas was discovered. The biopsy specimen of the stomach and spleen displayed diffuse, large B cell type non-Hodgkin's lymphoma. After one cycle of CHOP chemotherapy, the LUQ mass was markedly regressed although the gastrosplenic fistula was still present on the follow-up CT. The fistula was treated by splenectomy and a partial resection of gastric fundus. Follow-up chemotherapy was continued after surgery.