Efficacy and Safety of 6-Month High Dietary Protein Intake in Hospitalized Adults Aged 75 or Older at Nutritional Risk: An Exploratory, Randomized, Controlled Study.

The aim of this study was to investigate the effects of increased dietary protein in daily-life settings in Japan for 6 months on the activities of daily living (ADL) in adults aged 75 or older at nutritional risk. The study was an open-label, exploratory, randomized controlled trial conducted at seven hospitals in Japan. The study participants were adults aged 75 or older who were hospitalized for treatable cancer, pneumonia, fractures, and/or urinary-tract infection at nutritional risk. The primary outcome was change in grip strength, skeletal muscle, and ADL indices (Barthel index, Lawton score). One hundred sixty-nine patients were randomly assigned to the intensive care (IC) or standard care (SC) group; the protein intake goals (g/kgw/day) were 1.5 for IC and 1.0 for SC. There was a significant improvement in grip strength only in the IC group (1.1 kg: 95% CI 0.1 to 2.1) (p = 0.02). While the skeletal muscle index and ADL indices were not significantly improved in either group, the improvement ratio tended to be greater in the IC group. There was no decrease in renal function in either group. Thus, intervention of increased dietary protein in daily-life settings for 6 months in adults aged 75 or older with treatable cancer, pneumonia, fractures, and/or urinary-tract infection and at nutritional risk may be effective in ameliorating loss of muscle strength.

Associations between dietary consumption and sleep quality in young Japanese males.

PURPOSE: Poor sleep quality has been reported to be a risk factor for cardiovascular disease, diabetes, and metabolic syndrome, as well as mental disorders including depression and anxiety. However, few studies have investigated the association between sleep quality and diet in young males. We aimed to assess this association, adjusting for psychological factors. METHODS: In this study, a total of 124 male Japanese students were analyzed. Sleep quality, diet, and psychological symptoms were assessed using self-reported questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), brief-type self-administered diet history questionnaire (BDHQ), 12-item General Health Questionnaire (GHQ12), and State-Trait Anxiety Inventory (STAI) A-Trait scale. RESULTS: Among participants, 40% exhibited a PSQI total score ≥ 6, indicating poor sleep quality. Poor sleep quality was associated with poor mental health status and higher levels of anxiety. After adjusting for covariates including these psychological factors, poor sleep quality was significantly associated with low intakes of fat, beta-carotene, retinol, alpha-tocopherol, vitamin K, vitamin B1, daidzein, genistein, and iron. Poor sleep quality was also associated with low intake of pulses, fat and oil, as well as high intakes of sugar-sweetened beverages. CONCLUSIONS: Our findings demonstrated that sleep quality among young Japanese males was associated with specific dietary features, independently of psychological status, which may help to elucidate the mechanisms underlying the link between sleep and sleep-related diseases.

Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus: a 52-week, multicenter, parallel-group randomized controlled trial.

BACKGROUND: The 52-week monotherapy with the dipeptidyl peptidase-4 inhibitor sitagliptin and the sulphonylurea glimepiride on early-phase insulin secretion in Japanese patients with type 2 diabetes mellitus (T2DM) is not known. METHODS: A randomized, parallel-group, open-label trial was conducted at 18 centers between February, 2011 and March, 2013. 171 outpatients with T2DM were recruited and randomly assigned to glimepiride or sitagliptin by minimization. Doses of glimepiride (0.25-1.0 mg/day) and sitagliptin (25-100 mg/day) were adjusted for hemoglobin A1c (HbA1c) > 6.9 %. Analyses were performed on full analysis set (FAS) of randomized subjects taking medications as allocated, and underwent 75 g oral glucose tolerance test (OGTTs) before and after treatment. The primary outcome was insulinogenic index to quantify early-phase insulin secretion after treatment, which was evaluated by analysis of covariance (ANCOVA). RESULTS: Of 171 enrolled subjects, 68 in the sitagliptin group and 65 in the glimepiride group were included in the FAS (mean age, 64 years; baseline (HbA1c), 7.4 %). The primary outcome revealed a significantly higher insulinogenic index in the sitagliptin group than that in the glimepiride group (p = 0.036). Sitagliptin also reduced plasma glucose levels at 60 and 120 min during OGTT compared with glimepiride, while achieving a similar improvement in HbA1c during treatment. Body weight did not change in either of the two groups, and one case of hypoglycemia was observed in the glimepiride group. CONCLUSIONS: Sitagliptin shows better effects on insulinogenic index after 52-week treatment compared with glimepiride in Japanese patients with T2DM. Trial registration University hospital Medical Information Network (UMIN) Clinical Trials Registry, No.00004791.

Insulin Secretory Defect and Insulin Resistance in Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance.

OBJECTIVE: To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels. METHODS: We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity. RESULTS: In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.; p < 0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.; p < 0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r = -0.245, p < 0.0001) and had the strongest correlation with 2 h PG (ß = -0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r = -0.162, p < 0.0001) and had the strongest correlation with FPG (ß = -0.214). CONCLUSIONS: We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects.

Contrasting Effects of the Cytotoxic Anticancer Drug Gemcitabine and the EGFR Tyrosine Kinase Inhibitor Gefitinib on NK Cell-Mediated Cytotoxicity via Regulation of NKG2D Ligand in Non-Small-Cell Lung Cancer Cells.

INTRODUCTION: Several cytotoxic anticancer drugs inhibit DNA replication and/or mitosis, while EGFR tyrosine kinase inhibitors inactivate EGFR signalling in cancer cell. Both types of anticancer drugs improve the overall survival of the patients with non-small-cell lung cancer (NSCLC), although tumors often become refractory to this treatment. Despite several mechanisms by which the tumors become resistant having been described the effect of these compounds on anti-tumor immunity remains largely unknown. METHODS: This study examines the effect of the cytotoxic drug Gemcitabine and the EGFR tyrosine kinase inhibitor Gefitinib on the expression of NK group 2 member D (NKG2D) ligands as well as the sensitivity of NSCLC cells to the NK-mediated lysis. RESULTS: We demonstrate that Gemcitabine treatment leads to an enhanced expression, while Gefitinib downregulated the expression of molecules that act as key ligands for the activating receptor NKG2D and promote NK cell-mediated recognition and cytolysis. Gemcitabine activated ATM and ATM- and Rad-3-related protein kinase (ATR) pathways. The Gemcitabine-induced phosphorylation of ATM as well as the upregulation of the NKG2D ligand expression could be blocked by an ATM-ATR inhibitor. In contrast, Gefitinib attenuated NKG2D ligand expression. Silencing EGFR using siRNA or addition of the PI3K inhibitor resulted in downregulation of NKG2D ligands. The observations suggest that the EGFR/PI3K pathway also regulates the expression of NKG2D ligands. Additionally, we showed that both ATM-ATR and EGFR regulate MICA/B via miR20a. CONCLUSION: In keeping with the effect on NKG2D expression, Gemcitabine enhanced NK cell-mediated cytotoxicity while Gefitinib attenuated NK cell killing in NSCLC cells.

Solitary pleural metastasis from renal cell carcinoma: a case of successful resection.

While renal cell carcinoma frequently metastasizes to the lung, solitary pleural metastasis without lung involvement is extremely rare. A 69-year-old man was admitted to our hospital with a solitary pleural metastasis 6 years after surgery for renal cell carcinoma. Needle biopsy was performed, and the tumor was diagnosed as a metastasis of renal cell carcinoma. The pleural tumor was surgically resected. The patient received interferon-α as postoperative therapy. He has been alive for 9 years without recurrence. Only 11 cases of solitary pleural metastasis have been reported thus far, and of these, 7 involved a large amount of pleural effusion resulting in a poor prognosis. This is the first reported case of solitary pleural metastasis from renal cell carcinoma, which was curatively resected, as indicated by long-term survival.

Cyclooxygenase-2 genetic variants influence intratumoral infiltration of Foxp3-positive regulatory T cells in non-small cell lung cancer.

The immune microenvironment of primary tumors has been reported to be a prognostic factor. We previously reported that the tumor-infiltrating regulatory T cell (Treg) count was positively correlated with the intratumoral cyclooxygenase-2 (COX-2) expression level and was associated with a poor survival among patients with non-small cell lung cancer (NSCLC). Recently, numerous single nucleotide polymorphisms (SNPs) in the COX-2 gene have been identified, and these SNPs may contribute to differential gene expression and enzyme activity levels. However, whether COX-2 genetic variants influence the functions of COX-2 in NSCLC remains unclear. Eighty NSCLC patients who underwent a complete resection at our institute were enrolled. We extracted DNA from the peripheral blood and identified five different COX-2 SNPs. The correlations between the COX-2 SNPs and the expression levels of COX-2, Tregs and Ki-67 were studied. The prognostic significance of the COX-2 SNPs was also evaluated. COX-2 SNPs were not correlated with the expression of COX-2. However, for the COX-2 -1195G/A polymorphism, the AA genotype group had a significantly higher Treg score. Furthermore, the AA group had a significantly higher Treg score regardless of the COX-2 expression level. The COX-2 -1195AA genotype group tended to have a shorter disease-free survival period than the GA/GG group. In conclusion, the COX-2 -1195G/A polymorphism influences the infiltration of Tregs into NSCLC, and the COX-2 SNP factor may be a prognostic factor reflecting Treg infiltration in NSCLC.

Relationship and factors responsible for regulating fasting and post-challenge plasma glucose levels in the early stage development of type 2 diabetes mellitus.

AIMS/INTRODUCTION: Elevation of 2-h plasma glucose (2-h PG) levels keeps step with fasting plasma glucose (FPG) levels elevation, but some individuals show dominant elevation of 2-h PG and others FPG. We analyzed dependent and independent relationships between 2-h PG and FPG, and investigated the factors regulating 2-h PG and FPG. MATERIALS AND METHODS: In 1,657 Japanese participants who underwent a 75-g oral glucose tolerance test at the initial examination for a medical check-up, we carried out simple linear regression analysis between 2-h PG and FPG levels on the three patterns of independent variables. We divided the participants into two subgroups: the 2-h PG-side group and the FPG-side from the regression line, and examined the relationships between 2-h PG-FPG and factors responsible for elevation of plasma glucose levels. RESULTS: There was a significant positive correlation between 2-h PG and FPG levels. The regression line of both 2-h PG and FPG as independent variables was in accordance with the regression line of 2-h PG as an independent variable and FPG as a dependent variable. In 2-h PG-side group, age was the independent factor affecting 2-h PG in addition to insulinogenic index and insulin sensitivity index (ISI composite). In the FPG-side group, triglyceride was the independent factor affecting FPG in addition to insulinogenic index and ISI composite. CONCLUSIONS: Two-hour PG was an independent predictor of FPG. In addition to the importance of decreased insulin secretion and insulin sensitivity, age was the strong factor to elevate 2-h PG levels in the 2-h PG-side group and triglyceride was the strong factor to elevate FPG levels in the FPG-side group in the early stage of development of type 2 diabetes.

Hyperoxia reverses glucotoxicity-induced inhibition of insulin secretion in rat INS-1 ß cells.

Chronic hyperglycemia has deleterious effects on pancreatic ß-cell function, a process known as glucotoxicity. This study examined whether chronic high glucose (CHG) induces cellular hypoxia in rat INS-1 ß cells, and whether hyperoxia (35% O2) can reverse glucotoxicity-induced inhibition of insulin secretion. CHG (33.3 mm, 96 h) reduced insulin secretion, and down-regulated insulin and pancreatic duodenal homeobox factor 1 gene expression. CHG also increased intracellular pimonidazole-protein adducts, a marker for hypoxia. CHG also enhanced hypoxia-inducible factor 1α (HIF-1α) protein expression and its DNA-binding activity, which was accompanied by a decrease in mRNA expression of glucose transporter 2 (GLUT2), glucokinase and uncoupling protein-2 and an increase in mRNA expression of GLUT1 and pyruvate dehydrogenase kinase 1. Hyperoxia restored the decrease in insulin secretion and the gene expression except for GLUT2, and suppressed intracellular hypoxia and HIF-1α activation. These results suggest that glucotoxicity may cause ß-cell hypoxia. Hyperoxia might prevent glucotoxicity-induced ß-cell dysfunction and improve insulin secretion.

A case report of intrapulmonary schwannoma.

A 38-year-old man without any symptoms was admitted to our institution because of an abnormal shadow found incidentally on a chest X-ray. Chest computed tomography showed a round mass in the lingular segment of the left upper lobe. Lingular segmentectomy was performed, and the histopathological diagnosis was intrapulmonary schwannoma. Immunohistochemical staining revealed a positive result for S-100 protein and negative results for CD34 and desmin. We report this case of intrapulmonary schwannoma, which is extremely rare.

Role of 2-[18F]fluoro-2-deoxyglucose positron emission tomography in preoperative management of solid-type small-sized lung cancer.

OBJECTIVE: 2-[18F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is routinely used for the diagnosis of primary lung cancer. However, the role of FDG-PET in the diagnosis and staging of small-sized lung cancer has not been sufficiently evaluated. The purpose of this study was to determine the utility of FDG-PET for preoperative staging of solid-type small-sized lung cancer manifesting as solid-component predominant nodules. METHODS: One-hundred and eighteen patients with solid-type small-sized (≤2 cm) lung cancer diagnosed as clinical stage IA based on thin-slice computed tomography (TS-CT) were included in this study. Before surgery, FDG-PET was performed in 78 patients (CT/PET group), and TS-CT alone was performed in 40 patients (CT group). Clinical and pathological stage and prognosis were retrospectively reviewed according to whether FDG-PET had been performed. RESULTS: No significant differences in clinical factors were observed when comparing the CT/PET group and the CT group. Of the 78 patients in the CT/PET group, 12 (15.4 %) were diagnosed with clinical stage IIA or IIIA disease based on FDG-PET findings, but no advanced cases with contraindications for curative surgery were seen. In the CT/PET group, the pathological stage was IA in 66 patients, IB in eight patients, IIA in one patient, and IIIA in three patients; 16 patients had incorrectly staged disease. The accurate staging rate was 79.5 % for the CT-PET group and 70.0 % for the CT group (P = 0.262). Among patients diagnosed with clinical stage IA disease, the 3-year overall survival rate was 85.5 % for the 66 patients in the CT/PET group and 76.8 % for the 40 patients in the CT group (P = 0.554). No significant difference was observed in accuracy of preoperative staging and prognosis between the two groups. CONCLUSIONS: FDG-PET produced no clear benefit for the preoperative management of patients with solid-type clinical T1aN0M0 lung cancer, in terms of postoperative survival and the concordance rate of clinical and pathological stage.

Exome sequencing identifies a new candidate mutation for susceptibility to diabetes in a family with highly aggregated type 2 diabetes.

The aim of this study was to investigate the genetic background of familial clustering of diabetes using genome-wide linkage analysis combined with exome sequencing. We recruited a Japanese family with a 3-generation history of diabetes. The family comprised 16 members, 13 having been diagnosed with diabetes. Nine members had been diagnosed before the age of 40. Linkage analysis was performed assuming an autosomal dominant model. Linkage regions were observed on chromosomes 4q34, 5q11-q13, and 12p11-q22 and the logarithm of odds (LOD) scores were 1.80. To identify the susceptibility variants, we performed exome sequencing of an affected family member. We predicted that the familial clustering of diabetes is caused by a rare non-synonymous variant, and focused our analysis on non-synonymous variants absent in dbSNP131. Exome sequencing identified 10 such variants in the linkage regions, 7 of which were concordant with the affection status in the family. One hundred five normal subjects and 67 lean diabetes subjects were genotyped for the 7 variants; the only variant found to be significantly more frequent in the diabetes subjects than in the normal subjects was the N1072K variant of the early endosome antigen 1 (EEA1) gene (0 in normal subjects and 4 in diabetes subjects, p=0.022). We therefore propose that the N1072K variant of the EEA1 gene is a candidate mutation for susceptibility to diabetes in the Japanese population.

Influence of vascular endothelial growth factor single nucleotide polymorphisms on non-small cell lung cancer tumor angiogenesis.

Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. Several studies have reported that genomic VEGF polymorphisms may influence VEGF synthesis. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs), we examined the expression of several angiogenesis-related proteins [VEGF, hypoxia-inducible factor-1α (HIF-1α) and delta-like ligand 4 (Dll4)] and the spread of microvessels in resected non-small cell lung cancer (NSCLC). Blood and tumor tissue from 83 patients with NSCLC were examined for VEGF -460T/C (rs833061) and VEGF +405G/C (rs2010963) SNPs using the SNaPshot method. Immunohistochemical staining was performed to measure protein expression and microvessel density (MVD). VEGF -460T/C and +405G/C SNPs showed no association with VEGF or HIF-1α expression and MVD. Patients with VEGF -460TT and the TC genotype had significantly higher MVD compared to those with the CC genotypes. Furthermore, patients with the VEGF -460TT genotype had significantly higher Dll4 expression compared to those with the TC or CC genotypes, while the VEGF +405G/C SNP displayed no association with Dll4 expression and MVD. These findings indicate that the VEGF -460T/C SNP may have a functional influence on tumor angiogenesis in NSCLC. We hypothesize that VEGF SNPs may influence angiogenesis through Dll4.

Post-recurrence survival of patients with non-small-cell lung cancer after curative resection with or without induction/adjuvant chemotherapy.

OBJECTIVES: Recently, the prognosis of patients with non-small-cell lung cancer (NSCLC) has improved, thanks to the standardization of adjuvant chemotherapy and the introduction of molecular-targeted drugs, notably epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and other new anti-cancer agents. However, the survival characteristics and prognosis of patients with recurrent NSCLC after curative resection are not well understood. METHODS: Of the 430 consecutive patients with NSCLC who underwent complete surgical resection at our institution between January 2004 and July 2011, we included 76 patients with recurrence whose post-recurrence treatment and outcome could be confirmed. We then retrospectively evaluated the effect of prognostic factors on post-recurrence survival. RESULTS: There were 50 men and 26 women, and the median age at recurrence was 74.5 years. The median time from surgical resection to recurrence was 12.7 months. Thirty-eight of the 76 (50%) patients underwent multimodality treatment with surgery and preoperative and/or postoperative chemotherapy as their initial treatment. For recurrence, systemic chemotherapy was administered to 64 (84%) patients, and the disease control rate for first-line chemotherapy was 55%. The 1- and 2-year post-recurrence survival rates were 68.3 and 45.8%, respectively, and the median post-recurrence survival time was 17.7 months. Six independent prognostic factors were identified: wild-type EGFR, no adjuvant chemotherapy for the primary lung cancer, age ≥ 80 years at recurrence, a poor Eastern Cooperative Oncology Group performance status at recurrence, symptomatic at recurrence and no systemic chemotherapy for recurrence, which significantly decreased the post-recurrence survival. CONCLUSIONS: The prognosis of patients with NSCLC recurrence after surgery is currently improving. Our results suggested two new prognostic factors, adjuvant chemotherapy and EGFR mutations, neither of which have been previously reported. Treatment strategies for postoperative recurrence should be established based on a more detailed subdivision of factors, such as histology and molecular markers, in the future.

Heterogeneity of the EGFR mutation status between the primary tumor and metastatic lymph node and the sensitivity to EGFR tyrosine kinase inhibitor in non-small cell lung cancer.

The purpose of this study was to clarify the distribution of epidermal growth factor receptor (EGFR) mutations between primary tumors (PT) and metastatic lymph node (MLN) in patients with resected non-small cell lung cancer (NSCLC) and to identify a better predictive marker of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI). We conducted a retrospective review of the data of 70 lung cancer patients with lymph node metastasis who underwent surgical resection. Analysis to detect EGFR mutations was performed by a peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. EGFR mutations were detected in 15.7 % of both the PT and MLN and in 14.3 % of the PT only. The response rate to EGFR-TKI tended to be higher in patients with EGFR mutations in the MLN, as all patients with EGFR mutations in the MLN showed disease control to treatment with EGFR-TKI. Our results demonstrated that the EGFR mutation status of MLN is a predictive marker of the response to EGFR-TKI therapy in patients with recurrent NSCLC after surgical resection.

Case of pleural metastasis of prostate cancer.

The most frequent sites of prostate cancer metastases are the bone and lung. Pleural metastasis of prostate cancer is clinically rare. We report a case with solitary pleural thickening arising from the metastasis of prostate cancer. A 71-year-old man was referred to our hospital for further examination of pleural thickening detected during a chest computed tomography (CT) examination. A video-assisted pleural biopsy was performed. The pathological findings showed that the tumor cells had spread from the parietal pleura to adipose tissue around the costal muscles. The tumor cells were positive for prostate-specific antigen (PSA) and negative for calretinin, cytokeratin (Ck5/6) and D2-40. These findings suggested that the pleural lesion was a metastasis of the prostate cancer.

Lung cancer with sarcoid reaction in the lymph nodes following chemoradiotherapy.

This report describes a case of lung cancer with sarcoid reaction following chemoradiotherapy, showing false-positive accumulation of (18)F-fluorodeoxyglucose on positron-emission tomography in a 55-year-old man. Treatment-related sarcoid reaction should be considered when the accumulation of (18)F-fluorodeoxyglucose shows rapid extension in the course of treatment.

Membrane-bound estrogen receptor-α expression and epidermal growth factor receptor mutation are associated with a poor prognosis in lung adenocarcinoma patients.

BACKGROUND: The purpose of this study is to clarify the correlations between the expression of membrane-bound estrogen receptor-α (mERα) and epidermal growth factor receptor (EGFR) mutation and clinicopathological factors, especially in relation to the prognosis, in patients with lung adenocarcinoma. METHODS: We conducted a retrospective review of the data of 51 lung adenocarcinoma patients with tumors measuring less than 3 cm in diameter. Immunohistochemical staining for mERα expression and detection of the EGFR mutation status were performed. RESULTS: Among the 51 patients, the tumors in 15 showed both mERα expression and EGFR mutation. ("double positive") Significant associations between "double positive" and vascular invasion, vascular endothelial growth factor expression, and Ki-67 expression were observed. A multivariate analysis revealed that only "double positive" was an independent risk factor influencing the recurrence-free survival. CONCLUSIONS: Presence of mERα expression together with EGFR mutation was found to be an independent prognostic factor for survival in patients with lung adenocarcinoma, suggesting cross-talk between mERα and EGFR mutation.

γ-Tocotrienol attenuates TNF-α-induced changes in secretion and gene expression of MCP-1, IL-6 and adiponectin in 3T3-L1 adipocytes.

Tocotrienols, members of the vitamin E family, have been shown to possess anti-inflammatory properties and display activity against a variety of chronic diseases, such as cancer, cardiovascular and neurological diseases. However, whether tocotrienols contribute to the prevention of inflammatory responses in adipose tissue remains to be elucidated. In this study, we examined the effects of γ-tocotrienol, the most common tocotrienol isomer, on tumor necrosis factor-α (TNF-α)-induced inflammatory responses by measuring the expression of the adipokines, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and adiponectin in 3T3-L1 adipocytes. Exposure to TNF-α (10 ng/ml) for 24 h increased MCP-1 and IL-6 secretion, and decreased adiponectin secretion and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA expression. γ-tocotrienol effectively improved the TNF-α-induced adverse changes in MCP-1, IL-6 and adiponectin secretion, and in MCP-1, IL-6, adiponectin and PPARγ mRNA expression. Furthermore, TNF-α-mediated IκB-α phosphorylation and nuclear factor-κB (NF-κB) activation were significantly suppressed by the γ-tocotrienol treatment. Our results suggest that γ-tocotrienol may improve obesity-related functional abnormalities in adipocytes by attenuating NF-κB activation and the expression of inflammatory adipokines.

Insulin secretory capacity and insulin sensitivity in impaired fasting glucose in Japanese.

UNLABELLED: Aims/Introduction: Impaired fasting glucose (IFG) increases the risk of developing diabetes mellitus (DM). This study was carried out to characterize Japanese patients who have fasting glucose levels (FPG) between 100 and 109 mg/dL (IFG100-109). MATERIALS AND METHODS: A total of 1383 Japanese participants were examined by oral glucose tolerance test. We compared insulin secretory capacity (insulinogenic index) and insulin sensitivity (ISI composite) of IFG100-109/normal glucose tolerance (NGT; 100 ≤ FPG < 110 mg/dL and 2-h postchallenge glucose level (2-hPG) < 140 mg/dL) with NGT (100 mg/dL < FPG and 2-hPG < 140 mg/dL) and IFG110-125/NGT (110 ≤ FPG < 126 mg/dL and 2-hPG < 140 mg/dL). In addition, IFG100-109 patients were analyzed in three subgroups according to glucose intolerance by 2-hPG. RESULTS: Of the three categories of IFG100-109, IFG100-109/DM had the lowest insulinogenic index despite an ISI composite showing only a small decline from IFG100-109/NGT through IFG100-109/IGT (100 ≤ FPG < 110 mg/dL and 140 ≤ 2-hPG < 200 mg/dL) to IFG100-109/DM (100 ≤ FPG < 110 mg/dL and 200 mg/dL < 2-hPG). By multiple regression analysis, the insulinogenic index showed a significant relationship with 2-h PG levels. Both insulinogenic index and ISI composite were decreased significantly from NGT through IFG100-109/NGT to IFG110-125/NGT. CONCLUSIONS: Although impaired early-phase insulin secretion plays the more important role in the elevation of postchallenge glucose in IFG100-109 patients, both impaired early-phase insulin secretion and decreased insulin sensitivity are involved in the deterioration of FPG in Japanese. In addition, insulin secretory defect and decreased insulin sensitivity already have begun in patients with IFG100-109. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00201.x, 2012).