SH3YL1 protein as a novel biomarker for diabetic nephropathy in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Oxidative stress contributes to development of diabetic nephropathy. We implicated SH3YL1 in oxidative stress-induced inflammation and examined whether SH3YL1 could be used as a new biomarker of diabetic nephropathy. METHODS AND RESULTS: In this study, we investigated the relationship between plasma level of SH3YL1 and diabetic nephropathy in patients with type 2 diabetes. In addition, we examined the physiological role of SH3YL1 in db/db mice and cultured podocytes. Plasma SH3YL1 concentration was significantly higher in patients with diabetes than in controls, even in normoalbuminuric patients, and was markedly increased in the macroalbuminuria group. Plasma SH3YL1 level was positively correlated with systolic blood pressure, HOMA-IR, postprandial blood glucose, plasma level of retinol binding protein 4 (RBP 4), and urinary albumin excretion (UAE) and was inversely correlated with BMI. Regression analysis showed that plasma level of RBP 4, UAE, and BMI were the only independent determinants of plasma SH3YL1 concentration. In db/db mice, plasma and renal SH3YL1 levels were significantly increased in mice with diabetes compared with control mice. In cultured podocytes, high glucose and angiotensin II stimuli markedly increased SH3YL1 synthesis. CONCLUSION: These findings suggest that plasma level of SH3YL1 offers a promising new biomarker for diabetic nephropathy.

Efficacy, safety and albuminuria-reducing effect of gemigliptin in Korean type 2 diabetes patients with moderate to severe renal impairment: A 12-week, double-blind randomized study (the GUARD Study).

AIMS: This multicentre, randomized, double-blind study investigated the efficacy and safety of gemigliptin in Korean type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment (RI). METHODS: The study comprised a 12-week main part and a 40-week extension. We report here the results from the main part. In total, 132 patients were randomized to receive gemigliptin (n = 66) or placebo (n = 66). Changes in glycated haemoglobin (HbA1c; primary endpoint), other glycaemic control parameters (fasting plasma glucose, glycated albumin and fructosamine), lipid profiles, renal function parameters and safety profiles were evaluated. RESULTS: Baseline characteristics were comparable between the groups (mean HbA1c, 8.4% [68 mmol/mol]; age, 62.0 years; duration of type 2 diabetes, 16.3 years; estimated glomerular filtration rate, 33.3 mL/min/1.73 m2 ). At Week 12, the adjusted mean change ± standard error in HbA1c with gemigliptin was -0.82% ± 0.14% (-8.9 ± 1.5 mmol/mol), whereas it was 0.38% ± 0.14% (4.2 ± 1.5 mmol/mol) with placebo (significant between-group difference, P < .001). Other glycaemic control parameters showed beneficial changes as well. Body weight change (gemigliptin, -0.3 kg; placebo, -0.2 kg) was not significant. In the gemigliptin group, the mean decrease in urinary albumin creatinine ratio (UACR) was significant, both in patients with microalbuminuria (-41.9 mg/g creatinine, P = .03) and macroalbuminuria (-528.9 mg/g creatinine, P < .001). Drug-related adverse events were similar with gemigliptin and placebo (15% and 12%, respectively). CONCLUSIONS: A 12-week treatment with gemigliptin improved glycaemic control and provided UACR reduction in T2DM patients with moderate to severe RI. Gemigliptin was well tolerated, with no additional risk of hypoglycaemia and change in body weight.

Aggressive Treatment Including Endonasal Surgical Sequestrectomy with Vascularized Nasoseptal Flap Can Improve Outcomes of Skull Base Osteoradionecrosis.

Objective Skull base osteoradionecrosis (SB-ORN) is a serious, potentially lethal complication of radiation therapy. We aimed to review the clinical characteristics and outcomes of SB-ORN according to the extent of treatment. Design Retrospective analysis design was used for this study. Setting The study was conducted in two tertiary care hospitals. Participants Patients included who had been clinically diagnosed with SB-ORN from January 2006 to 2017. Main Outcome Measures Clinical characteristics, including demographics, predisposing factors, presenting symptoms, radiological findings, treatment modalities, and treatment outcomes, were reviewed. Treatment was classified into conservative and aggressive types. Aggressive treatment included radical surgical removal of soft tissue and bony sequestrum with the placement of vascularized tissue. Treatment outcome was analyzed in terms of clinical control, survival, and carotid artery blow out. Results Fifteen patients (11 males and 4 females) were identified during the study period. Eight patients were managed conservatively, whereas seven patients were managed with aggressive treatment. The 2-year survival was 75% in the aggressive treatment group and 15% in the conservative group (log-rank, p = 0.049). The estimated 2-year blow out free rate was 46.7% for the conservative group and 100% for the aggressive group (log-rank, p = 0.100). Conclusion In patients with SB-ORN, aggressive management, including surgical removal of sequestrum and coverage with a pedicled flap, is associated with increased survival.

Safety and metabolic advantages of steroid withdrawal after 6 months posttransplant in de novo kidney transplantation: A 1-year prospective cohort study.

INTRODUCTION: This prospective multicenter study aimed at investigating the safety and metabolic advantages of steroid withdrawal (SW) therapy in kidney transplant recipients with tacrolimus-mycophenolate mofetil-based immunosuppression. METHODS: We analyzed 179 recipients who received kidney transplantation from March 2016 and September 2018. In 179 recipients, 114 patients maintained an immunosuppressive regimen including steroids (steroid continuation [SC] group). The remaining 65 patients were determined to withdraw steroid therapy after 6 months posttransplant (SW group). Metabolic parameters and graft functions of the two groups were evaluated. RESULTS: The estimated glomerular filtration rates at 12 months posttransplant were 67.29 ± 20.29 ml/min/1.73 m2 in SC group and 73.72 ± 17.57 ml/min/1.73 m2 in SW group (p < .001). The acute rejection occurred to four recipients in the SC group (3.5%) and no acute rejection occurred to SW group recipients during the 6-2 months posttransplant period. Oral glucose tolerance tests revealed that recipients in the SW group were more improved in glucose metabolism than the SC group during 6-12 months posttransplant. In addition, cholesterol levels and blood pressure decreased after the withdrawal of steroids in the SW group. CONCLUSION: In conclusion, a 6-month withdrawal of steroids in recipients with low immunological risk and stable graft function can be safely conducted and result in improvement of metabolic profiles. Stable recipients without biopsy-proven acute rejection and proteinuria can safely withdraw from steroids out of a maintenance immunosuppressive regimen 6-months posttransplant. A long-term follow-up study is needed to verify our results.

Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue.

Adipose tissue is recognized as a pivotal organ in the development of insulin resistance. This study seeks to determine the effect of angiotensin receptor blockade (ARB) on insulin resistance of adipocytes in culture and in a rat model of type 2 diabetes. Treatment of Otsuka Long-Evans Tokushima Fatty rats with the ARB L158809 for six months significantly lowered fasting plasma glucose, cholesterol and triglyceride levels but led to higher plasma adiponectin levels. Insulin resistance, measured by an intraperitoneal glucose tolerance test, of the treated rats was significantly improved along with an increase in the number of small differentiated adipocytes; however, epididymal fat mass decreased. Treatment significantly lowered lipid peroxidation and MCP-1 expression while increasing adiponectin production by the adipose tissue. ARB treatment significantly improved insulin sensitivity and markedly suppressed AT2-induced oxidative stress, PAI-1 and MCP-1 levels and NF-kappaB activation of adipocytes in culture. Treatment increased adiponectin and PPARgamma expression along with intracellular triglyceride levels reflecting differentiation of the cultured adipocytes. Our study suggests that ARB treatment improves insulin resistance by modification of adipose tissue thereby blunting the development of diabetes.

Fabrication and characterization of plasma-polymerized poly(ethylene glycol) film with superior biocompatibility.

A newly fabricated plasma-polymerized poly(ethylene glycol) (PP-PEG) film shows extremely low toxicity, low fouling, good durability, and chemical similarity to typical PEG polymers, enabling live cell patterning as well as various bioapplications using bioincompatible materials. The PP-PEG film can be overlaid on any materials via the capacitively coupled plasma chemical vapor deposition (CCP-CVD) method using nontoxic PEG200 as a precursor. The biocompatibility of the PP-PEG-coated surface is confirmed by whole blood flow experiments where no thrombi and less serum protein adsorption are observed when compared with bare glass, polyethylene (PE), and polyethylene terephthalate (PET) surfaces. Furthermore, unlike bare PE films, less fibrosis and inflammation are observed when the PP-PEG-coated PE film is implanted into subcutaneous pockets of mice groin areas. The cell-repellent property of PP-PEG is also verified via patterning of mammalian cells, such as fibroblasts and hippocampal neurons. These results show that our PP-PEG film, generated by the CCP-CVD method, is a biocompatible material that can be considered for broad applications in biomedical and functional materials fields.