Effects of Walking and Physical Activity on Glucose Regulation among Type 2 Diabetics

BACKGROUND: Physical activity, especially walking is strongly recommended to control blood glucose among type 2 diabetic patients. Furthermore, physical activity is one of the most important tools to prevent secondary diabetes complications among type 2 diabetic patients such as retinopathy, nephropathy, neuropathy etc. The purpose of the study was to examine the association between the level of walking and physical activity and glucose control among Korean adults with type 2 diabetes. METHODS: A total of 250 patients with type 2 diabetes (98 males and 152 females) were recruited (mean age = 62.1 +/- 10.2 years) in the current study. The height, weight, waist and hip circumference were measured, and the level of physical activity and total walking hour were measured by physical activity scale for elderly (PASE). High density lipoprotein cholesterol (HDL-C), total cholesterol, triglyceride, fasting glucose and oral glucose tolerance test, creatinine, uric acid, total protein, albumin, hemoglobin A1c were measured. RESULTS: After adjusting for potential covariates such as age, education, occupation income, smoking, and drinking, male patients who spent least time in walking were more likely to have 2 hour serum glucose level in oral glucose tolerance above 200 mg/dL than counterparts who spent most time in walking with age adjusted (Relative Risk (RR) = 11.75, 95% Confidence Interval (CI) = 1.94-71.00). Male patients who were in the least active group were 5.92 time (95% CI = 1.39-25.28) more likely to have 2 hour serum glucose level in oral glucose tolerance over 200 mg/dL than counterparts in the most active group. However, there was no significant finding in females. CONCLUSIONS: The current study showed that physical activity and walking are effective method to maintain glucose tolerance among type 2 diabetic male patients.ope

Prognostic value of elevated cardiac troponin I in ESRD patients with sepsis

BACKGROUND: Elevated cardiac troponin (cTn) levels have been reported to predict adverse cardiovascular outcomes in asymptomatic ESRD patients. However, the prognostic value of elevated cTn levels associated with sepsis in ESRD patients is unknown. Therefore, this study aimed to elucidate the clinical implications of elevated cTnI levels in ESRD patients with sepsis. METHODS: Of the 305 ESRD patients in whom cTnI was measured between January 2003 and December 2005, sepsis developed in 121 patients during follow-up. Based on cTnI levels at the onset of sepsis, patients were classified as elevated cTnI group (ET, n = 50, >0.2 ng/ml) and lower cTnI group (LT, n = 71, < or =0.2 ng/ml). Study endpoints were short- and long-term mortality. Short-term mortality was defined as death occurring within 90 days after sepsis, and patients who survived during this period were followed till death after 90 days. RESULTS: Before sepsis, the median concentration of cTnI was 0.05 (0.01-3.59) ng/ml and it was significantly increased to 0.11 (0.01-22.0) ng/ml when sepsis supervened (P < 0.01). Compared to the LT group, the short-term mortality rate was significantly higher in the ET group (P < 0.05). After adjustment for age, diabetes, serum albumin and CRP levels, presence of shock and previous cardiovascular disease history, the ET group had a greater odds ratio of short-term mortality (OR 5.13, P < 0.01). In addition, the Kaplan-Meier plot for long-term survival revealed a significantly higher mortality rate in the ET group. In a multivariate Cox regression analysis, the elevation of cTnI levels was an independent determinant for long-term mortality (HR 5.90, P < 0.01). CONCLUSION: This study showed that elevated cTnI levels were significantly associated with short- and long-term mortality in ESRD patients with sepsis. Therefore, elevated cTnI levels in these patients should not be overlooked and be followed for adverse outcomes.ope

Effects of pioglitazone on subclinical atherosclerosis and insulin resistance in nondiabetic renal allograft recipients.

BACKGROUND: The aim of this study was to evaluate the effect of pioglitazone treatment on the progression of subclinical atherosclerosis and insulin resistance in renal allograft recipients with no preoperative history of diabetes. METHODS: Eighty-three patients without diabetes were randomly assigned to either the pioglitazone group or the control group. Carotid intima-media thickness (IMT), serum adiponectin level and lipid profile were assessed before transplantation and at 12 months after transplantation. Insulin secretory function and insulin resistance were evaluated by the oral glucose tolerance test. RESULTS: The pioglitazone group showed a significant reduction in the mean and maximum carotid IMT compared with the control group after 12 months (mean carotid IMT, 0.05 +/- 0.04 vs -0.03 +/- 0.07 mm, P < 0.001; maximum carotid IMT, 0.08 +/- 0.05 vs -0.05 +/- 0.09 mm, P < 0.001). Pioglitazone increased the adiponectin level, and the change in adiponectin was negatively correlated with carotid IMT changes. Pioglitazone treatment increased the insulin sensitivity index compared with the control group (-0.8 +/- 3.1x10(-)(2) vs +1.1 +/- 3.7x10(-)(2), P = 0.036). CONCLUSIONS: These results suggest that pioglitazone treatment reduces the progression of carotid IMT and improves insulin resistance in renal allograft recipients without a history of diabetes. Trial Registration. Clinicaltrials.gov Identifier: NCT00598013ope

Activation of local aldosterone system within podocytes is involved in apoptosis under diabetic conditions

Previous studies have shown that mineralocorticoid receptor (MCR) blocker reduces proteinuria in diabetic nephropathy (DN), but the role of aldosterone in podocyte injury has never been explored in DN. This study was undertaken to elucidate whether a local aldosterone system existed in podocytes and to examine its role in podocyte apoptosis under diabetic conditions. In vitro, immortalized podocytes were exposed to 5.6 mM glucose (NG), NG + 24.4 mM mannitol, and 30 mM glucose (HG) with or without 10(-7) M spironolactone (SPR). In vivo, 32 Sprague-Dawley rats were injected with diluent (C, n = 16) or streptozotocin intraperitoneally [diabetes mellitus (DM), n = 16], and 8 rats from each group were treated with SPR for 3 mo. Aldosterone synthase (CYP11B2) and MCR mRNA and protein expression were determined by real-time PCR and Western blot, respectively, and aldosterone levels by radioimmunoassay. Western blot for apoptosis-related molecules, Hoechst 33342 staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to determine apoptosis. CYP11B2 and MCR expression were significantly higher in HG-stimulated podocytes and DM glomeruli compared with NG cells and C glomeruli, respectively, along with increased aldosterone levels. Western blot analysis revealed that cleaved caspase-3 and Bax expression was significantly increased, whereas Bcl-2 expression was significantly decreased in HG-stimulated podocytes and in DM glomeruli. Apoptosis determined by Hoechst 33342 staining and TUNEL assay were also significantly increased in podocytes under diabetic conditions. These changes in the expression of apoptosis-related proteins and the increase in apoptotic cells were inhibited by SPR treatment. These findings suggest that a local aldosterone system is activated and is involved in podocyte apoptosis under diabetic conditions.ope

Non-functional Pituitary Adenoma Detected on 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) in a Patient with Mucosa-associated Lymphoid Tissue Lymphoma

Magnetic resonance imaging (MRI) is the modality of choice for the detection and characterization of a pituitary adenoma. Uptake of 18F-fluorodeoxyglucose (FDG) by intrasellar tumors, including pituitary adenomas, has been reported in several previous studies. We report a case where a pituitary adenoma was detected on FDG-positron emission tomography(PET), but the tumor was not detected with the use of sellar MRI. A 31-year-old woman was referred to the clinic due to a focal increase of FDG uptake at the pituitary fossa seen on whole body FDG-PET. The patient was receiving chemotherapy due to a recurred B-cell lymphoma of the mucosa-associated lymphoid tissue type. Subsequently, sellar MRI was performed, and images showed a small non-enhancing heterogenous cystic lesion in the midline of the pituitary gland, radiologically suggestive of a Rathke`s cleft cyst. However, sellar MRI failed to identify a lesion consistent with a pituitary tumor that corresponded to the site of increased FDG uptake detected by the use of PET, despite the inclusion of a dynamic contrast enhanced sequence. Despite the negative findings of the MRI examination, basal and stimulated levels of the GnRH free α-subunit were profoundly increased. Therefore, we suspected the presence of a non-functional pituitary tumor in addition to a Rathke`s cleft cyst, rather than pituitary involvement of a lymphoma, based on the hormone levels and PET scan findings.ope

A Case of Multiple Endocrine Neoplasia Type 1 with Mutation of MENIN Gene

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominantly inherited syndrome, characterized by the combined occurrence of tumors of the parathyroid glands, endocrine pancreas, and anterior pituitary gland. The MENIN gene, which is a kind of tumor suppressor gene, is located at the chromosomal locus 11q13. It consists of one untranslated exon and nine exons encoding the menin protein. We report a case of a 22-yearss-old woman with MEN type 1, who was proven to have a mutation in the MENIN gene. The patient was admitted because of repeated hypoglycemia. The fasting plasma glucose level was 32 mg/dL. Seventy two hours fasting test showed an the insulin/glucose ratio as 0.33. Endoscopic ultrasonography detected multiple masses on the pancreas. The arterial-stimulated venous sampling (ASVS) with calcium showed sudden step up of insulin at the head and tail portions of the pancreas. The sellar MRI showed a pituitary mass that produced prolactin. Instead of a pathologic diagnosis from operational specimen, the genetic analysis revealed a mutation in the MENIN 1 gene (exon 2, 200~201insAGCCC).ope

A polymorphism in the zinc transporter gene SLC30A8 confers resistance against posttransplantation diabetes mellitus in renal allograft recipients.

OBJECTIVE: Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients, and insulin secretory defects play an important role in the pathogenesis of PTDM. The R325W (rs13266634) nonsynonymous polymorphism in the islet-specific zinc transporter protein gene, SLC30A8, has been reported to be associated with type 2 diabetes and possibly with a defect in insulin secretion. This study investigated the association between genetic variations in the SLC30A8 gene and PTDM in renal allograft recipients. RESEARCH DESIGN AND METHODS: A total of 624 unrelated renal allograft recipients without previously diagnosed diabetes were enrolled. Rs13266634 was genotyped in the cohort, which consisted of 174 posttransplantation diabetic patients and 450 non-posttransplantation diabetic subjects. The genotyping of the SLC30A8 polymorphism was performed using real-time PCR. RESULTS: The prevalence of PTDM was 33.8% in patients carrying the R/R genotype, 26.8% in patients with the R/W genotype, and 19.8% in patients with the W/W genotype. There was a strong association between the number of W-alleles and PTDM risk reduction (P for trend = 0.007). Patients with at least one T-allele showed a decreased risk of PTDM compared with those with the R/R genotype (R/W, risk ratio [RR] 0.78, P = 0.126; W/W, RR 0.52, P = 0.007). The effect of the SLC30A8 genotype remained significant after adjustments for age, sex, body weight gain, and type of immunosuppressant (R/W, hazard ratio [HR] 0.77, P = 0.114; W/W, HR 0.58, P = 0.026). CONCLUSIONS: These data provide evidence that the SLC30A8 rs13266634 gene variation is associated with protection from the development of PTDM in renal allograft recipients.ope

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan

BACKGROUND: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartanope

Adiponectin Gene Polymorphism and Carotid Artery Intima-Media thickness in Type 2 Diabetes

Background: The aim of this study was to examine the association between the common polymorphisms of the adiponectin gene(ACDC) and the intima-media thickness(IMT) of the common carotid arteries in type 2 diabetic patients. Methods: The B mode ultrasound examination of carotid artery was performed on 133 type 2 diabetic patients. The carotid IMT was calculated using the Intimascope computer program. The SNP45 and SNP276 of the ACDC were examined. Results: There was no significant difference in the carotid IMT among the SNP45 genotypes(0.66+/-0.18mm for TT, 0.71+/-0.12mm for TG and 0.64+/-0.15mm for GG, P=NS). Subjects carrying the SNP276 GG genotype had a markedly lower serum adiponectin concentration than those carrying the TT genotype(3.35+/-2.00microgram/mL vs. 4.98+/-2.24microgram/mL, P=0.029) The carotid IMT was significantly higher in patients with the SNP276 GG genotype than those with the TT genotype (0.70+/-0.17mm vs. 0.59+/-0.13mm, P=0.032). Patients with the +45GG/+276GG genotype combination showed significantly higher mean carotid IMT than the other genotype combinations(0.78+/-0.09mm vs. 0.71+/-0.15mm, P=0.013) Conclusions: These results suggest that the adiponectin gene, SNP276 is associated with the carotid IMT in type 2 diabetic patients. Further studies are will be needed to confirm these genotypephenotype associations.ope

Multiple Cavitary Pulmonary Metastases from Cholangiocarcinoma

Because a cavitary pulmonary metastasis is rare, it may not be readily identified. However, various types of cancers can metastasize to the lung in the form of cavities. We report a case of a multiple cavitary metastases to the lung from a cholangiocarcinoma in a 60-year-old man. He complained of generalized weakness and a poor oral intake for 2 months. The plain chest radiography and the chest computed tomography showed multiple small thick-walled cavities and nodules the both lungs. A bronchoscopic examination revealed a focal irregularly elevated surface of the mucosa at the orifice of the superior segment of the right lower lobe and the biopsy demonstrated an infiltrative metastatic adenocarcinoma. The abdomen-pelvis computed tomography showed an ill-marginated and irregularly low-dense area in the right lobe of the liver and a diffuse dilatation of the peripheral intrahepatic bile ducts. The esophagogastroscopy and colonoscopy showed no abnormal findings. It was concluded that the cholangiocarcinoma of the liver metastasized to the lung in the form of cavities. Thereafter, the patient underwent six cycles of the systemic chemotherapy with gemcitabine and cisplatin, and the follow-up imaging studies showed a partial response.ope