Seong Su Lee

Malignant gastrointestinal stromal tumor of the gallbladder.

Gastrointestinal stromal tumors (GISTs) of the gallbladder are representative of an extremely rare group of tumors. We have encountered a patient with a malignant GIST of the gallbladder and presented it with a review of some articles. A 72-yr-old woman initially presented with right upper quadrant abdominal pain, fever and chills. Emergency cholecystectomy was performed under the impression of gallbladder empyema. Liver metastasis was found at 7 months postoperatively and the patient expired 9 months after the surgery. At the time of cholecystectomy, the gallbladder showed a necrotic serosal surface with an irregular thickened wall. A mass, 6 cm in length and 3 cm in width, encircled the whole wall of the neck and upper body of the gallbladder. Microscopic findings revealed frequent mitotic figures (more than 20/50 HPF) and tumor necrosis. Hyperchromatic, pleomorphic and spindle shaped neoplastic cells that were arranged in a pattern of short fascicles infiltrated the entire layer of the gallbladder. The tumor cells were immunoreactive for CD117 antigen (c-kit protein) and vimentin. They were negative for desmin, smooth muscle actin and S-100 protein. Mutations of the c-kit proto-oncogene were not found in this case. These findings were sufficient to provide enough clinical, histopathological and immunohistochemicalevidence in diagnosing our case as a malignant GIST.

The relationship between the regional abdominal adipose tissue distribution and the serum uric acid levels in people with type 2 diabetes mellitus

BackgroundHyperuricemia is associated with obesity. The visceral adiposity and subcutaneous adiposity may be associated with the differential metabolic risk, and the distribution of abdominal adipose tissue was significantly altered in people with type 2 diabetes mellitus (DM) compared to healthy people. Our study was performed to determine to the association between the regional abdominal adipose tissue distribution and serum uric acid levels in people with type 2 DM.MethodsA total of 699 people with type 2 DM and who had undergone abdominal computed tomography assessment of the visceral fat area and subcutaneous fat area were included. The serum uric acid levels were measured by the uricase method. Hyperuricemia was defined by cut-off value of > 7 mg/dl for men and > 6 mg/dl for women.ResultsThe visceral fat area was positively associated with the serum uric acid levels after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, serum creatinine, hemoglobin, serum albumin, serum high-density lipoprotein, serum triglyceride and hemoglobin A1c (β-coefficient = 0.117, p < 0.001). The logistic regression analysis showed that the visceral fat area was the significant independent predictor of hyperuricemia (OR 2.33, 95% CI, 1.21-4.50, p = 0.012). But there was no significant association between the subcutaneous fat area and the serum uric acid levels (β-coefficient = 0.061, p = 0.255).Conclusionsour data shows that the visceral fat area was positively associated with the serum uric acid levels, but the subcutaneous fat area was not in people with type 2 DM.

Prevalence, awareness, treatment and control of hypertension in adults with diagnosed diabetes: the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

We evaluated the prevalence, awareness, treatment and control of hypertension in Korean adults with diagnosed diabetes using nationally representative data. Among subjects aged ⩾30 years who participated in the Fourth Korea National Health and Nutrition Examination Survey in 2007 and 2008, a total of 745 subjects (336 men and 409 women) with a previous diagnosis of diabetes mellitus were analyzed. The prevalence of hypertension in adults with diagnosed diabetes was 55.5%. The rates of awareness, treatment and control were 88.0, 94.2, and 30.8%, respectively. Compared with the general population, the prevalence of hypertension in adults with diagnosed diabetes was higher in all age groups in both genders. Factors independently associated with a high prevalence of hypertension included being male, increasing age, single, <9 years of education, the presence of chronic kidney disease risk, hypercholesterolemia (⩾240 mg dl−1) and high body mass index (⩾25 kg m−2). Regular medical screening was positively associated with hypertension control, whereas a high triglyceride level (⩾150 mg dl−1) was inversely associated. A high prevalence and a low control rate of hypertension in adults with diagnosed diabetes suggest that stringent efforts are needed to control blood pressure in diabetic patients.

Predictors for diabetic retinopathy in normoalbuminuric people with type 2 diabetes mellitus.

BackgroundPrevious studies have reported that microalbuminuria is an independent risk factor for the prevalence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). For this reason, the clinical significance of DR in normoalbuminuric type 2 DM patients may be overlooked. The aim of this study was to investigate the prevalence of DR and predictors for DR in normoalbuminuric patients with type 2 DM.MethodsA total 310 patients with type 2 DM and normoalbuminuria, who were referred to the Department of Ophthalmology for screening of DR were included in this study. DR was clinically graded according to the International Clinical Diabetic Retinopathy guidelines. The urinary albumin excretion rate (UAER) was assessed via 24-hour urine collection and measured by immunoturbidimetric assay. Normoalbuminuria was defined as a UAER < 20 μg/min in 2 out of 3 consecutive tests taken within 2–3 months.ResultsDR of any grade was present in 64/310 (20.7 %) patients. Mild non-proliferative diabetic retinopathy (NPDR) was most prevalent in patients with DR of any grade (36/64, 56 %). The duration of diabetes (OR 1.01, 95 % CI, 1.01 – 1.02, p < 0.001), hemoglobin levels (OR 0.73, 95 % CI, 0.59 – 0.91, p = 0.004) and a higher tertile of UAER (OR 4.04, 95 % CI, 1.71 – 9.57, p = 0.001) had independently significant association with DR. NPDR as well as PDR was more prevalent in patients with higher tertile of UAER compared with those with lower tertile of UAER (NPDR, p = 0.002 and PDR, p = 0.027, respectively).ConclusionsOur findings suggest that patients with normoalbuminuric type 2 DM also require close monitoring for the early detection of DR, especially if they have a higher UAER, longer duration of diabetes, or lower hemoglobin levels.

Relationship of visceral and subcutaneous adiposity with renal function in people with type 2 diabetes mellitus

BACKGROUND Obesity and diabetes mellitus (DM) are established risk factors for the development of chronic kidney disease. Visceral adiposity (VAT) and subcutaneous adiposity (SAT) may be associated with the differential metabolic risk. Our study was performed to determine whether VAT or SAT was associated with the decrease of renal function in people with type 2 DM. METHODS Nine hundred and twenty-nine people with type 2 DM and who had undergone abdominal computed tomography assessment of the SAT and VAT areas were included. The estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease (MDRD) four-variable equation at the time of the assessment of the SAT and VAT areas. RESULTS VAT was negatively associated with eGFR using the MDRD equation after adjustment for the clinical variables (β-coefficient = - 0.075, P = 0.034), while SAT was not significantly associated with eGFR. There was no significant association between the abdominal adiposity measurements and the eGFR using the Cockcroft-Gault formula. When stratifying the individuals by the body mass index groups, VAT was negatively associated with eGFR by the MDRD equation and the Cockcroft-Gault formula in the overweight and obese subjects after adjustment for the clinical variables, while there was no significant association between the VAT and the eGFR in the normal weight subjects. SAT was not significantly associated with eGFR in the normal weight, overweight and obese subjects. CONCLUSIONS Our data suggest that VAT may be an additional prognostic factor for the decrease of renal function especially in the overweight or obese subjects with type 2 DM.

Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA). In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

The Changes of Blood Glucose Control and Lipid Profiles after Short-Term Smoking Cessation in Healthy Males

Objective Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males. Methods Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the β-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). Results The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA β-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively). Conclusion During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.

Serum Osteocalcin Is Inversely Associated With Adipocyte-Specific Fatty Acid–Binding Protein in the Korean Metabolic Syndrome Research Initiatives

Recent studies (1) have reported that adipokines might act in a paracrine manner on osteoblasts and suppress osteoblast activity or differentiation—or both—in pathological conditions. Adipocyte-specific fatty acid–binding protein (A-FABP) is highly expressed in adipose tissue and may act systemically to regulate lipid and glucose metabolism (2). However, the association between serum osteocalcin with adipokines and A-FABP remains unclear in humans. Therefore, the aim of this study was to clarify the relationship between serum osteocalcin and the parameters of the metabolic syndrome and the association of serum osteocalcin with adipokines and A-FABP. This was a cross-sectional study carried out by the Korean Metabolic Syndrome Research Initiative. The 124 obese subjects underwent a standardized examination at four university hospitals in Korea. The control …

The Effect of Early Intensive Insulin Therapy on Body Fat Distribution and β-Cell Function in Newly Diagnosed Type 2 Diabetes

Objectives. The aim of this study was to evaluate the effects of early intensive insulin therapy on body fat distribution, lean body mass and β-cell function in patients with newly diagnosed type 2 diabetes. Methods. Thirty-eight subjects with newly diagnosed type 2 diabetes participated in a 12-week course of intensive insulin therapy. Patients were administered a 75 g oral glucose tolerance test (OGTT), underwent measurement of visceral and subcutaneous adipose tissues (VAT and SAT) using computed tomography and appendicular skeletal muscle (ASM) mass was assessed using dual-energy X-ray absorptiometry. Results. After intensive insulin therapy, fasting plasma glucose and HbA1c levels decreased. Homeostasis model assessment (HOMA)-B, the insulinogenic index, and the C-peptide-to-glucose area under the curve (AUC) ratio increased. The insulin sensitivity index and the glucose AUC decreased after 12 weeks. The body composition analysis revealed that the VAT and the ratio of VAT to SAT decreased, whereas body weight and total fat mass increased nonsignificantly. The ASM/weight and skeletal muscle mass index increased. The restoration of β-cell function, as identified by HOMA-B, the insulinogenic index, and the C-peptide-to-glucose AUC ratio, was correlated with the changes in VAT when controlled for age and gender. In multiple regression analyses, the decrease in VAT was shown to independently contribute to improved HbA1c over the study period, after adjusting for confounding factors. Conclusions. These results suggest that a shift in fat distribution from visceral to subcutaneous fat after early intensive insulin therapy is associated with improvements in glycemic control and β-cell function in patients with newly diagnosed type 2 diabetes.

Quercetin‐induced upregulation of human GCLC gene is mediated by cis‐regulatory element for early growth response protein‐1 (EGR1) in INS‐1 beta‐cells

The catalytic subunit of γ‐glutamylcysteine ligase (GCLC) catalyses the rate‐limiting step in the de novo synthesis of glutathione (GSH), which is involved in maintaining intracellular redox balance. GSH is especially important for antioxidant defense system since beta‐cells show intrinsically low expression of antioxidant enzymes. In the present study, we investigated the regulatory mechanisms by which quercetin, a flavonoid, induces the expression of the GCLC gene in rat pancreatic beta‐cell line INS‐1. Promoter study found that the proximal GC‐rich region (from −90 to −34) of the GCLC promoter contained the quercetin‐responsive cis‐element(s). The quercetin‐responsive region contains consensus DNA binding site for early growth response 1 (EGR1) at ‐67 (5′‐CGCCTCCGC‐3′) which overlaps with a putative Sp1 binding site. Electrophoretic mobility shift assay showed that an oligonucleotide containing the EGR1 site was bound to nuclear factors EGR1, Sp1, and Sp3. In the promoter analysis, mutation of EGR1 site significantly reduced the quercetin response, whereas mutation of Sp1 site decreased only the basal activity of the GCLC promoter. Additionally, the transient overexpression of EGR1 significantly increased basal activity of the GCLC promoter. Finally, we showed that quercetin potently induced both EGR1 mRNA and its protein levels without affecting the expression of Sp1 and Sp3 proteins. Therefore, we concluded that EGR1 was bound to GC‐rich region of the GCLC gene promoter, which was prerequisite for the transactivation of the GCLC gene by quercetin. J. Cell. Biochem. 108: 1346–1355, 2009.