Objectives Dietary Approaches to Stop Hypertension (DASH) pattern has been found to aid in the reduction of obesity, oxidative stress, and chronic inflammation, which are all strongly linked to the development of head and neck cancer (HNC). Nevertheless, no epidemiological studies have investigated the association between this dietary pattern and HNC risk. This study was conducted with the purpose of bridging this gap in knowledge. Design A prospective cohort study involving 98,459 American adults aged 55 years and older. Setting and Participants Data were drawn from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. In the present study, participants with dependable energy intake data who furnished baseline and dietary history information were identified as the study population. Methods Diet was assessed by food frequency questionnaires and the DASH score was calculated to assess each participant’s adherence to DASH eating pattern. Cox proportional hazards models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the occurrence of HNC. To visualize the variation in cancer risk for HNC and its subtypes across the entire spectrum of DASH scores, restricted cubic spline plots were utilized. Additionally, a series of predefined subgroup analyses were performed to identify potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. Results During a follow-up period of 871,879.6 person-years, 268 cases of HNC were identified, comprising 161 cases pertaining to oral cavity and pharynx cancers, as well as 96 cases of larynx cancer. In the fully adjusted model, adherence to the DASH diet was associated with a remarkable 57% reduction in the risk of HNC when comparing extreme quartiles (HR quartile 4 vs 1: 0.43; 95% CI: 0.28, 0.66; P for trend < 0.001). The restricted cubic spline plots demonstrated a linear dose-response relationship between the DASH score and the risk of HNC as well as its subtypes. Subgroup analysis revealed that the protective effect of the DASH diet against HNC was particularly pronounced in individuals with lower daily energy intake. The primary association remained robust in the sensitivity analysis. Conclusions In American middle-aged and older population, adherence to the DASH diet may help prevent HNC, particularly for individuals with lower daily energy intake.

OBJECTIVE:To investigate the effects of vaspin signaling conveyed by the brain on liver glucose fluxes in rats.METHODS:To determine the effects and underlying mechanisms of central vaspin signaling, normal-chow-diet- and high-fat-diet (HFD)-fed rats with or without hepatic branch vagotomy (HBV) received acute infusion of vaspin to the third cerebral ventricle or MK801, a dorsal vagal complex (DVC) N-methyl-D-aspartate (NMDA) receptor inhibitor, to the DVC during the pancreatic euglycemic clamp.RESULTS:Central administration of vaspin in HFD-fed rats significantly increased glucose infusion required to maintain euglycemia owing to an inhibition of glucose production during the clamps. These changes were accompanied by decreased hepatic phosphoenolpyruatecarboxykinase and G6Pase expression levels and increased hepatic insulin receptor, insulin receptor substrate-1, Akt kinase and the forkhead box-containing protein of the O subfamily-1 phosphorylation, suggesting improving hepatic insulin sensitivity in these animals. Conversely, selective HBV or DVC MK-801 infusion in HFD-fed rats blocked the effect of central vaspin on glucose production and hepatic insulin sensitivity.CONCLUSIONS:Our findings suggest that brain vaspin inhibited hepatic glucose production and improved insulin sensitivity via DVC to the hepatic branch of the vagus nerve in insulin resistance rats induced by HFD.

BACKGROUND/OBJECTIVES:Juxtaposed with another zinc-finger gene 1 (TIP27 or JAZF1) is a 27-kDa transcription factor, and genome-wide association studies have recently revealed TIP27 to be associated with type 2 diabetes. However, little is known about its role in the regulation of metabolism. In this study, we investigated the effects of TIP27 overexpression on glucose homeostasis and insulin signaling in high-fat diet (HFD)-fed TIP27 transgenic (TIP27-Tg) mice and db/db mice.METHODS:We assessed the effects of TIP27 overexpression in both TIP27-Tg mice and db/db mice on glucose metabolism and changes in insulin sensitivity during glucose (GTT) and insulin (ITT) tolerance tests. A hyperinsulinemic-euglycemic clamp was performed on TIP27-Tg mice. Real-time quantitative PCR and western blotting were used to assess mRNA and protein expressions.RESULTS:TIP27 overexpression in TIP27-Tg mice and in db/db mice led to reduced total cholesterol and fasting plasma insulin levels, and enhanced glucose tolerance and insulin sensitivity during GTT and ITT. Hyperinsulinemic-euglycemic clamp experiments demonstrated that HFD-fed TIP27-Tg mice had lower hepatic glucose production and higher insulin sensitivity compared with nontransgenic littermates. In addition, the hepatic expressions of phosphoenolpyruate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase) mRNAs and proteins were significantly decreased, whereas the phosphorylation of insulin receptor, insulin receptor substrate-1, adenosine monophosphate-activated protein kinase and Akt kinase (Akt) in the liver was significantly increased in HFD-fed TIP27-Tg mice compared with nontransgenic littermates. Adenovirus-mediated TIP27 overexpression in db/db mice also decreased the expression of gluconeogenic genes and increased the phosphorylation of insulin signaling molecules in the liver compared with controls. Finally, LY294002, a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, abolished the suppressive effect of TIP27 overexpression on PEPCK and G6Pase expression.CONCLUSIONS:TIP27 has an important role in glucose homeostasis through the regulation of hepatic glucose metabolism and insulin sensitivity. Furthermore, this regulation requires activation of PI3-kinase.

ObjectivesGenome-wide association studies (GWAS) have shown that Zbed3 is associated with T2DM. To date, no report has demonstrated a relationship between Zbed3 and insulin resistance in humans, however. The purpose of this study was to determine whether the Zbed3 protein is secreted and identify any associations between Zbed3 and insulin resistance in cross-sectional and interventional studies.MethodsWe found that Zbed3 protein was secreted in an in vitro secretion study. Plasma Zbed3 levels were determined in an ELISA and were compared with various parameters related to insulin resistance in subjects with NGT, IGT and nT2DM. EHC was performed in healthy subjects. Real-time PCR and Western blotting were used to assess the mRNA and protein expression of Zbed3.ResultsZbed3 was detected in an analysis of in vitro secretion in both conditioned medium and lysates of HEK-293T cells transfected with an overexpressed vector. In a clinical study, there were significantly higher levels of circulating Zbed3 in IGT and nT2DM relative to NGT. Zbed3 levels were positively correlated with BMI, WHR, FAT%, blood pressure, FBG, TG, HbA1c, FIns and HOMA-IR and inversely correlated with HDL-C. Increasing levels of Zbed3 were independently associated with IGT and T2DM. Zbed3 mRNA and protein in muscle and fat were significantly elevated in both db/db mice and T2DM patients. Moreover, there was a concentration-dependent effect of glucose on Zbed3 release, whereas insulin exhibited an inhibitory effect on Zbed3 levels. Zbed3 suppressed insulin-induced IR and Akt phosphorylation.ConclusionsThese results suggest that the Zbed3 protein may be a cytokine associated with insulin resistance in humans that is influenced by glucose and insulin levels.

The secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, plays an important role in osteoblast formation, maturation, and survival. Here, we report the effects of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)], a bone formation-stimulating agent, and elcatonin on plasma SPARC levels in patients with osteoporosis. The rhPTH (1-34) treatment significantly increased plasma SPARC levels, and the change of plasma SPARC correlated positively with changes of lumbar bone mineral density (BMD) at L2–L4. These results unveil that SPARC may be a novel marker related to the regulation of bone formation.

PURPOSE Intermittent administration of recombinant human PTH [rhPTH (1-34)] exerts an osteoanabolic effect characterized by direct effects on bone formation, increases bone density, and reduces fracture risk. This study was to investigate the anabolic effects of rhPTH(1-34) on postmenopausal osteoporosis in an Asian population and compare the time course and alteration in bone turnover marker (BTM) during rhPTH(1-34) and elcatonin treatment. METHODS 124 women with postmenopausal osteoporosis were enrolled in this prospective, open-label, active-controlled trial. The patients randomized to subcutaneous rhPTH(1-34) (20 ug, once daily) or elcatonin (200U, once week) injections for 12 months. Biochemical markers of bone formation (bone specific alkaline phosphatase [BSAP]), and bone resorption maker (serum C-telopeptide of type I collagen [CTX-I] were measured at baseline and at 0, 6, and 12 months. RESULTS At 12 months, rhPTH (1-34) significantly increased lumbar spine BMD significantly compared with baseline, whereas elcatonin was ineffective. BSAP levels were gradually increased in almost all rhPTH(1-34)-treated subjects and at the end of the study, the percentage of subjects with BSAP above the postmenopausal reference interval was gradually increased as high as 91.5% at month 12. Opposite trends in percentages for CTX-I was observed in rhPTH(1-34). With rhPTH(1-34), but not elcatonin, there were significant positive correlations between ratio of BSAP and CTX-I and bone mineral density (BMD) (r=0.318) at the end of month 12. Both treatments were well tolerated and there were no significant differences detected between the 2 groups in the proportion of any adverse events and any serious adverse events. CONCLUSIONS rhPTH (1-34) has more positive effects on bone formation than elcatonin for postmenopausal women with osteoporosis and was proved to be safe and well tolerated. The ratio of BSAP and CTX-I may be a useful indicator for positive bone formation.

To compare the effect and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RA) with insulin therapy on type 2 diabetes mellitus (T2DM) patients inadequately controlled with metformin and/or sulfonylurea. A systematic literature search on MEDLINE, Embase and Cochrane for randomized controlled trials (RCTs) was conducted using specific search terms 'GLP-1 insulin type 2 diabetes clinical trials' and eight eligible studies were retrieved. Data on mean change in haemoglobin A1c (HbA1C), weight loss, fasting plasma glucose (FPG), incidence of hypoglycaemia and gastrointestinal adverse events were extracted from each study and pooled in meta-analysis. Data on postprandial plasma glucose (PPG) and adverse events were also described or tabulated. Data from eight RCTs enrolling 2782 patients were pooled using a random-effects model. The mean net change [95% confidence interval (CIs)] for HbA1c, weight loss and FPG for patients treated with GLP-1 RA as compared with insulin was -0.14% (-2 mmol/mol) [95% CI; (-0.27, -0.02)%; p = 0.03]; -4.40 kg [95% CI; (-5.23, -3.56) kg; p < 0.01] and 1.18 mmol/l [95% CI; (0.43, 1.93) mmol/l; p < 0.01], respectively, with negative values favouring GLP-1 and positive values favouring insulin. The GLP-1 group was associated with a greater reduction in PPG than the insulin group. Overall, hypoglycaemia was reported less in the GLP-1 group [Mantel-Haenszel odds ratio (M-H OR) 0.45 (0.27, 0.76); p < 0.01], while there was no significant difference in occurrence of severe hypoglycaemia [M-H OR 0.65 (0.29,1.45); p = 0.29]. A significantly higher number of gastrointestinal adverse events were reported with GLP-1 group [M-H OR 15.00 (5.44,41.35) p < 0.01]. GLP-1 RA are promising new agents compared with insulin. Further prospective clinical trials are expected to fully evaluate the long-term effectiveness and safety of these therapies within the T2DM treatment paradigm.

This study was performed to examine the efficacy and safety of mitiglinide in type 2 diabetes patients (T2DM). Enrolled patients had received treatment with diet and exercise in the previous 3 months with glycosylated haemoglobin (HbA1c) 7–10%, and were randomized to receive mitiglinide (n = 111, 5–20 mg/meal) or nateglinide (n = 114,60–120 mg/meal) for 16 weeks. Primary and secondary efficacy endpoints were assessed by the changes in HbA1c, fasting blood glucose (FBG) and postprandial glucose (PBG) levels. The baseline HbA1c value was 8.2 and 8.3% in both groups. At the end of study, the reduction of HbA1c values from baseline by mitiglinide was slightly more than that by nateglinide (−1.11% vs. −0.76%), but not statically significant (p = 0.06). Final FBG and PBG were comparable for the two treatments. There were 2.8% subjects treated with nateglinide who had hypoglycaemic episodes, but none in the mitiglinide treatment group. The results indicate that mitiglinide and nateglinide had similar effects on FBG, PBG and HbA1c in T2DM patients after the 16‐week treatments.