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Background/Aims: Inflammatory bowel disease (IBD) is a chronic disabling gastrointestinal disorder that diminishes the quality of life of the affected individuals. Limited data are available regarding the impact of IBD on the daily life of Koreans. Methods: Self-administered, computer-aided, internet-based questionnaires were distributed to members of a Korean patient organization for IBD from March to April 2013, by the Korean Association for the Study of Intestinal Diseases. Results: A total of 599 patients with IBD (387 with Crohn's disease [CD] and 212 with ulcerative colitis [UC]) were enrolled. The majority of patients (81%) expressed feelings of fatigue, weakness, and being worn out in their daily lives during times of flare; this percentage was reduced to 61% during remission. Respondents were absent from work or school for an average period of 18 days because of illness, within the first 6 months; the majority of respondents (64%) felt stressed about their absence. Forty-six percent of the respondents reported having received unfair comments at work, or having suffered discrimination. Forty-seven percent of the respondents felt that IBD had negatively affected their income and earnings. Compared with patients with UC, those with CD reported a more frequent negative impact of IBD on work, or more economic burden. More than half of the respondents (61%) reported that IBD had prevented them from making or keeping friends. Conclusions: IBD significantly impacts daily life, including work, education, and social relationships. Treatment that addresses the full spectrum of life of a patient would be more effective. [ABSTRACT FROM AUTHOR]

Aim: Vascular endothelial growth factor (VEGF) is important in the pathogenesis of diabetic microvascular complications and the genetic polymorphism of this gene may contribute to the development and progression of diabetic microvascular complications. In this study, we investigated whether a genetic polymorphism of VEGF is associated with diabetic complications. Methods: A total of 398 type 2 diabetic patients and 526 healthy controls were enrolled. The study subjects were divided based on the state of nephropathy, retinopathy and neuropathy. The VEGF 936 C/T polymorphism was evaluated using standard PCR techniques, and plasma and urinary levels of VEGF were determined by enzyme-linked immunosorbent assay. Results: There was no difference in VEGF genotype distribution between the control and diabetic patients based on the state of diabetic nephropathy and neuropathy. However, a higher frequency of the TT genotype was observed in patients with proliferative diabetic retinopathy. Additionally, plasma levels of VEGF were significantly higher in the TT genotype. However, urinary levels of VEGF did not show a significant relationship with the VEGF genotype. Urinary VEGF levels showed a significant relationship with urinary albumin excretion, proteinuria, serum creatinine level and creatinine clearance, as well as fasting blood glucose levels, postprandial 2 h glucose levels and C-reactive protein. Conclusion: Our study suggests that the 936 C/T polymorphism of the VEGF gene may be an important factor determining plasma VEGF levels and that its polymorphism is related with diabetic retinopathy. Urinary levels of VEGF are not associated with plasma VEGF levels and associated with the stage of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Aim: Inhibition of aldosterone system is beneficial in diabetic nephropathy, and aldosterone synthesis is regulated at the gene-encoding aldosterone synthase (CYP11B2). Considering the role of aldosterone in diabetic nephropathy, genetic polymorphism of this gene may contribute to the development and progression of diabetic nephropathy. In this study, we investigated whether it is associated with diabetic nephropathy in type 2 diabetic patients. Methods: 197 type 2 diabetic patients and 71 healthy controls were enrolled. The study subjects were divided into four groups: healthy controls with normoalbuminuria ( n = 71), normoalbuminuric diabetic group ( n = 71), microalbuminuric diabetic group ( n = 51) and overt proteinuria group ( n = 51). Polymorphism of aldosterone synthase gene was determined using standard PCR technique. Results: Higher frequency of TT genotype and T allele in steroidogenic factor-1 (SF-1) binding site and wild type (WT) in intronic conversion (IC) in CYP11B2 was observed in diabetic patients than controls. However, there was no significant difference in SF-1 and IC genotype among diabetic patients according to the state of diabetic nephropathy. Subgroup analysis based on SF-1 polymorphism demonstrated that TT genotype is associated with higher systolic and diastolic blood pressure and higher plasma aldosterone level. In addition, WT in IC genotype showed a significantly higher urinary albumin excretion rate. Plasma aldosterone level was significantly related with systolic blood pressure. Conclusion: Our study suggests that aldosterone synthase gene polymorphism is not associated with progression of diabetic nephropathy, but it may contribute to the development of hypertension associated with increased aldosterone secretion in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Background. Recent data suggest that aldosterone antagonists have beneficial effects on diabetic nephropathy. In this study, we investigated the dose-dependent effect of eplerenone and a combined treatment with eplerenone and enalapril compared with each drug alone on renal function in type II diabetic rats. To further explore the molecular mechanism of action of combination therapy, we also performed in vitro study. Methods. The animals were divided into six groups as follows: normal control Long-Evans Tokushima Otsuka (LETO) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, OLETF rats treated with low dose of eplerenone (50 mg/kg/day), OLETF rats treated with high dose of eplerenone (200 mg/kg/day), OLETF rats treated with enalapril (10 mg/kg/day) and OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and enalapril 10 mg/kg/day) for 6 months. Results. Treatment of OLETF rats had no significant effect on body weight, kidney weight and blood glucose levels. However, urinary albumin excretion, glomerular filtration rate and glomerulosclerosis were significantly improved in the enalapril group and improvement was observed in a dose-dependent manner in the eplerenone groups; the most dramatic decreases were observed in the combination group. In accordance with these findings, renal expressions of TGF-β1, type IV collagen and PAI-1 were also markedly decreased in the treatment groups, with the combined treatment providing the most significant level of improvement. In cultured mesangial cells, combined treatment resulted in an additive decrease in TGF-β1, PAI-1 and collagen gene expressions and protein production induced by high glucose and aldosterone stimulation. Conclusions. Aldosterone receptor antagonism provided additional benefits beyond blockade of the renin–angiotensin system in type II diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in insulin sensitivity, lipid metabolism and inflammation. However, the effects of PPARγ agonist on renal inflammation have not been fully examined in type 2 diabetic nephropathy. Methods. In the present study, we investigated the effect and molecular mechanism of the PPARγ agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats. Inflammatory markers including NF-κB, MCP-1 and pro-fibrotic cytokines were determined by RT-PCR, western blot, immunohistochemical staining and EMSA. In addition, to evaluate the direct anti-inflammatory effect of PPARγ agonist, we performed an in vitro study using mesangial cells. Results. Treatment of OLETF rats with pioglitazone improved insulin sensitivity and kidney/body weight, but had a little effect on blood pressure. Pioglitazone treatment markedly reduced urinary albumin and MCP-1 excretion, and ameliorated glomerulosclerosis. In cDNA microarray analysis using renal cortical tissues, several inflammatory and profibrotic genes were significantly down-regulated by pioglitazone including NF-κB, CCL2, TGFβ1, PAI-1 and VEGF. In renal tissues, pioglitazone treatment significantly reduced macrophage infiltration and NF-κB activation in association with a decrease in type IV collagen, PAI-1, and TGFβ1 expression. In cultured mesangial cells, pioglitazone-activated endogenous PPARγ transcriptional activity and abolished high glucose-induced collagen production. In addition, pioglitazone treatment also markedly suppressed high glucose-induced MCP-1 synthesis and NF-κB activation. Conclusions. These data suggest that pioglitazone not only improves insulin resistance, glycaemic control and lipid profile, but also ameliorates renal injury through an anti-inflammatory mechanism in type 2 diabetic rats. [ABSTRACT FROM AUTHOR]