ObjectiveTo evaluate the effect of low-protein diet on kidney function in patients with diabetic nephropathy.DesignA systematic review and a meta-analysis of randomised controlled trials.Data sourcesMEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) Register and University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) from inception to 10 December 2012. Internet searches were also carried out with general search engines (Google and Google Scholar).Study selectionRandomised controlled trials that compared low-protein diet versus control diet and assessed the effects on kidney function, proteinuria, glycaemic control or nutritional status.Primary and secondary outcome measures and data synthesisThe primary outcome was a change in the glomerular filtration rate (GFR). The secondary outcomes were changes in proteinuria, post-treatment value of glycated haemoglobin A1C (HbA1c) and post-treatment value of serum albumin. The results were summarised as the mean difference for continuous outcomes and pooled by the random effects model. Subgroup analyses and sensitivity analyses were conducted regarding patient characteristics, intervention period, methodological quality and assessment of diet compliance. The assessment of diet compliance was performed based on the actual protein intake ratio (APIR) of the low-protein diet group to the control group.ResultsWe identified 13 randomised controlled trials enrolling 779 patients. A low-protein diet was associated with a significant improvement in GFR (5.82 ml/min/1.73 m2, 95% CI 2.30 to 9.33, I2=92%; n=624). This effect was consistent across the subgroups of type of diabetes, stages of nephropathy and intervention period. However, GFR was improved only when diet compliance was fair (8.92, 95% CI 2.75 to 15.09, I2=92% for APIR <0.9 and 0.03, 95% CI −1.49 to 1.56, I2=90% for APIR ≥0.9). Proteinuria and serum albumin were not differed between the groups. HbA1c was slightly but significantly decreased in the low-protein diet group (−0.26%, 95% CI −0.35 to −0.18, I2=0%; n=536).ConclusionsLow-protein diet was significantly associated with improvement of diabetic nephropathy. The adverse effects of low-protein diet were not apparent such as worsening of glycaemic control and malnutrition.

PurposeThe transcription factor NRF2 plays a pivotal role in protecting normal cells from external toxic challenges and oxidative stress, whereas it can also endow cancer cells resistance to anticancer drugs. At present little information is available about the genetic polymorphisms of the NRF2 gene and their clinical relevance. We aimed to investigate the single nucleotide polymorphisms in the NRF2 gene as a prognostic biomarker in lung cancer.Experimental DesignWe prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and detected SNP (c.–617C>A; rs6721961) in the ARE-like loci of the human NRF2 gene by the rapid genetic testing method we developed in this study. We then analyzed the association between the SNP in the NRF2 gene and patients’ overall survival.ResultsPatients harboring wild-type (WT) homozygous (c.–617C/C), SNP heterozygous (c.–617C/A), and SNP homozygous (c.–617A/A) alleles numbered 216 (55.8%), 147 (38.0%), and 24 (6.2%), respectively. Multivariate logistic regression models revealed that SNP homozygote (c.–617A/A) was significantly related to gender. Its frequency was four-fold higher in female patients than in males (10.8% female vs 2.7% male) and was associated with female non-smokers with adenocarcinoma. Interestingly, lung cancer patients carrying NRF2 SNP homozygous alleles (c.–617A/A) and the 309T (WT) allele in the MDM2 gene exhibited remarkable survival over 1,700 days after surgical operation (log-rank p = 0.021).ConclusionSNP homozygous (c.–617A/A) alleles in the NRF2 gene are associated with female non-smokers with adenocarcinoma and regarded as a prognostic biomarker for assessing overall survival of patients with lung adenocarcinoma.

No abstract

Aims/IntroductionTo define a set of criteria using indices of β‐cell function, including results from the glucagon stimulation test, for liraglutide introduction in patients with type 2 diabetes.Materials and MethodsIn the present retrospective cohort study, patients were included in our analysis if their β‐cell function had been evaluated with a glucagon stimulation test and a 24‐h urinary C‐peptide (U‐CPR) excretion test before switching from insulin therapy to liraglutide monotherapy. The efficacy of liraglutide was determined by the extent to which glycemic control was achieved or if glycated hemoglobin levels were maintained at <7.0% after liraglutide monotherapy for 24 weeks.ResultsLiraglutide was effective in 36 of 77 patients. In the liraglutide‐effective cases, the following parameters were higher: fasting C‐peptide (CPR0) levels, C‐peptide levels 6 min after glucagon stimulation (CPR6), the C‐peptide index (CPI; CPR0 × 100/fasting plasma glucose) and stimulated C‐peptide index (S‐CPI; CPR6 × 100/plasma glucose 6 min after glucagon stimulation). U‐CPR did not differ between liraglutide‐effective and liraglutide‐ineffective cases. Using receiver operating characteristic analysis adjusted for baseline characteristics, the independent cut‐off value for effective liraglutide introduction was 0.72 for CPI and 1.92 for S‐CPI.ConclusionsEvaluation of β‐cell function using the glucagon stimulation test is useful for determining the efficacy of liraglutide introduction in patients with type 2 diabetes.