奥利司他对肥胖IGT人群糖尿病预防效果

目的 探讨奥利司他(Orlistat,赛尼可)对肥胖糖耐量低减(IGT)患者的干预效果。方法 患者随机分两组奥利司他治疗组(50例)和对照组(51例),治疗为期1年,于治疗前后测量血脂、口服糖耐量试验(OGTT)、体重、身高等指标。结果1年后,治疗组上述指标明显改善(P<0.01),其恶化为糖尿病的发病率明显低于对照组(P<0.01)。结论 在肥胖IGT干预治疗中,奥利司他加饮食和运动治疗后可使体重减轻,改善糖耐量,明显减少糖尿病的发生。     

Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters

PurposeWe have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.MethodsIntracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.ResultsBCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.ConclusionsBCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.     

The clinical significance of thyroid hormone-responsive in thyroid carcinoma and its potential regulatory pathway

The study aimed to evaluate the clinical significance of thyroid hormone-responsive (THRSP) and explore its relevant pathways in thyroid carcinoma (THCA).The gene expression data of THRSP were obtained and the prognostic significance of THRSP in THCA was analyzed through various bioinformatics databases. Then, the factors influencing THRSP mRNA expression were explored, and the function of THRSP in predicting the lymph node metastasis (LNM) stage was determined. We further performed the enrichment analysis and constructed a protein–protein interaction (PPI) network to examine potential regulatory pathways associated with THRSP.THRSP gene expression was significantly increased in THCA compared with the normal tissues. High THRSP mRNA expression had a favorable overall survival (OS) in THCA patients (P < .05). Additionally, the mRNA expression of THRSP was related to stage, histological subtype, and methylation among THCA patients (all P < .05). Besides, THRSP served as a potent predictor in discriminating the LNM stage of thyroid cancer patients. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) on THRSP-associated genes, THRSP was positively related to metabolic pathways.The upregulation of THRSP predicted a good OS in THCA patients. Furthermore, THRSP might inhibit THCA progression through positive regulation of metabolism-associated pathways.     

Glucose Stimulates Gut Motility in Fasted and Fed Conditions: Potential Involvement of a Nitric Oxide Pathway

(1) Background: Type 2 diabetes (T2D) is associated with a duodenal hypermotility in postprandial conditions that favors hyperglycemia and insulin resistance via the gut-brain axis. Enterosynes, molecules produced within the gut with effects on the enteric nervous system, have been recently discovered and pointed to as potential key modulators of the glycemia. Indeed, targeting the enteric nervous system that controls gut motility is now considered as an innovative therapeutic way in T2D to limit intestinal glucose absorption and restore the gut-brain axis to improve insulin sensitivity. So far, little is known about the role of glucose on duodenal contraction in fasted and fed states in normal and diabetic conditions. The aim of the present study was thus to investigate these effects in adult mice. (2) Methods: Gene-expression level of glucose transporters (SGLT-1 and GLUT2) were quantified in the duodenum and jejunum of normal and diabetic mice fed with an HFD. The effect of glucose at different concentrations on duodenal and jejunal motility was studied ex vivo using an isotonic sensor in fasted and fed conditions in both normal chow and HFD mice. (3) Results: Both SGLT1 and GLUT2 expressions were increased in the duodenum (47 and 300%, respectively) and jejunum (75% for GLUT2) of T2D mice. We observed that glucose stimulates intestinal motility in fasted (200%) and fed (400%) control mice via GLUT2 by decreasing enteric nitric oxide release (by 600%), a neurotransmitter that inhibits gut contractions. This effect was not observed in diabetic mice, suggesting that glucose sensing and mechanosensing are altered during T2D. (4) Conclusions: Glucose acts as an enterosyne to control intestinal motility and glucose absorption through the enteric nervous system. Our data demonstrate that GLUT2 and a reduction of NO production could both be involved in this stimulatory contracting effect.     

Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer

Many types of cancer have metabolic alterations with increased glycolysis. Identification of alternative sweeteners that do not fuel cancer is a novel approach to cancer control. The present study aimed to investigate the effects of xylitol on tumor growth and survival of mice bearing orthotopic xenograft of tongue cancers. The results showed that partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume, and significantly prolonged the median survival time from 19 days in the control to 30.5 days in the xylitol group. Immunohistochemical data of the tongue tissue shows significantly lower intense-to-mild staining ratios of the proliferation marker Ki-67 in the xylitol than those of the control group (p = 0.04). Furthermore, the xylitol substitution significantly reduced the expression of the rate-limiting glycolytic enzyme, phosphofructokinase-1 (PFK-1) (p = 0.03), and showed a non-significant inhibition of PFK activity. In summary, partial substitution of glucose with xylitol at the equivalent dose to human household use of 10 g/day slows down tumor proliferation and prolongs survival of mice bearing an orthotopic oral cancer xenograft, possibly through glycolytic inhibition, with minimal adverse events. The insight warrants clinical studies to confirm xylitol as a candidate sweetener in food products for cancer survivors.     

黄芪、丹参、山药及其复方对高糖所致雪旺细胞凋亡的保护作用

目的:观察中药对高葡萄糖条件下与内皮细胞(以下简称EC)共培养的雪旺细胞(以下简称SC)凋亡的干预作用。方法:建立大鼠SC与EC的共培养模型,根据存活率(形态学和MTT)筛选药物最有效作用浓度。将细胞分为正常共培养SC组、高糖共培养SC组、高糖黄芪组、高糖丹参组、高糖山药组、高糖复方组,通过凋亡率(流式细胞仪)和凋亡相关基因Bcl-2和Casepase-3的mRNA(Realtime PCR)和蛋白(Western Blot)的表达观察细胞凋亡。结果:与正常共培养组相比高糖共培养组SC凋亡率明显增高、Bcl-2mRNA和蛋白表达量明显减少,Casepase-3mRNA和蛋白表达量显著增加。加中药干预后SC凋亡率都明显降低,Bcl-2mRNA和蛋白表达量都明显增加,除高糖山药组Casepase-3mRNA减少和高糖丹参组Casepase-3蛋白减少无明显统计学意义,其余各组Casepase-3mRNA和蛋白表达量均显著减少。中药干预组之间比较,高糖复方组作用最显著。中药干预组与正常组相比,SC凋亡率无明显增高,Bcl-2mRNA和蛋白表达量明显减少,Casepase-3mRNA和蛋白表达量显著增加。结论:中药对高糖环境下与内皮细胞共培养的雪旺细胞的凋亡有保护作用,不同中药作用效果不同,复方效果最佳。     

Association of admission blood glucose level and clinical outcomes in elderly community‐acquired pneumonia patients with or without diabetes

IntroductionCommunity‐acquired pneumonia (CAP) is the major cause of infection‐related mortality worldwide. Patients with CAP frequently present with admission hyperglycemia.ObjectivesThe aim of this study was to evaluate the association between admission blood glucose (ABG) level and clinical outcomes in elderly CAP patients (≥80 years of age) with or without diabetes.MethodsIn this single center retrospective study, 290 elderly patients diagnosed with CAP were included. Demographic and clinical information were collected and compared. The associations between admission blood glucose level and the 30‐day mortality as well as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) in elderly CAP patients with or without diabetes were assessed.ResultsOf the 290 eligible patients with CAP, 159 (66.5%) patients were male, and 64 (22.1%) had a known history of diabetes at hospital admission. After adjusting for age and sex, the logistic regression analysis had identified several risk factors that might be associated with clinical outcomes in elderly patients with CAP. Multivariable logistic regression analysis revealed that admission glucose level > 11.1 mmol/L was significant associated with ICU admission, IMV, and 30‐day mortality both in non‐diabetic and diabetic patients. Furthermore, Kaplan–Meier analysis indicated that patients with higher admission glucose level were correlated statistically significantly with 30‐day mortality in patients with CAP (P < 0.001).ConclusionAdmission blood glucose is correlated with 30‐day hospital mortality, ICU admission, and IMV of CAP in elderly patients with and without diabetes. Specially, admission glucose > 11.1 mmol/L was a significant risk factor for 30‐day hospital mortality.     

Combining CGM and an Online Peer Support Community for Hispanic Adults with T2D: A Feasibility Study

Background:Previous research has identified that people with type 2 diabetes (T2D) within the Hispanic community would benefit from an online peer support community (OPSC) and continuous glucose monitoring (CGM) data to facilitate diabetes self-management.Methods:A mixed-methods feasibility study enrolled Hispanic, Spanish-speaking adults with T2D, not on insulin. Participants were provided with CGM and access to an OPSC for 12 weeks. Feasibility was assessed by number of eligible participants who enrolled, attrition, quantity of CGM data, validated clinical measures of self-efficacy, quality of life and adverse events. Engagement in the OPSC was measured using objective metrics on the online platform. Qualitative interviews were conducted upon conclusion of the intervention to assess feasibility, acceptability, participant satisfaction, and key recommendations for improvement.Results:Of 46 participants screened, 39 were eligible and 26 completed the study. Participants significantly improved self-efficacy scores. Posts in the OPSC related to goal setting had the highest engagement followed by mid-week and end of week check-in posts respectively. Participant interviews described challenges accessing the OPSC platform as a barrier to engagement. Despite this, all participants were satisfied with the intervention. Key recommendations for improvement included providing greater variety of and individualized education and the use of a peer support platform that is easily accessible.Conclusions:The CGM + OPSC intervention tailored to the Hispanic community with T2D was feasible, acceptable and satisfactory and improved participant self-efficacy for diabetes management which may lead to improved clinical outcomes.     

Spanish Translation and Linguistic Validation of the Glucose Monitoring Experiences Questionnaire (GME-Q) in Continuous Glucose Monitoring Users

Background and Aims:The use of continuous glucose monitoring (CGM) has become standard practice in people with type 1 diabetes. The evaluation of user satisfaction is crucial. The Glucose Monitoring Experiences questionnaire (GME-Q) includes 23 items with a 5-point Likert scale to produce a total satisfaction score and three subscale scores. The study aimed to translate the GME-Q from English into Spanish and to validate its use in Spanish-speaking CGM users with type 1 diabetes.Methods:The linguistic translation and validation process of the GME-Q was established. T1D CGM users were asked to complete the produced Spanish version of the GME-Q and interviewed about difficulties or misunderstandings. Total satisfaction, effectiveness, convenience and intrusiveness subscales and internal consistency reliability were computed.Results:Forward and backward translations and cognitive debriefing produced a final version of the GME-Q in Spanish. Ninety-eight subjects with type 1 diabetes were selected (age: 40 ± 12 years, 63% females, Hb1c: 7.2 ± 0.9% (55 ± 10 mmol/l), pump users: 78%, CGM use: 3.7 ± 2.6 years). The completion rate was 99% and the Cronbach’s alpha coefficient was 0.8. The total satisfaction score was 3.9 ± 0.4 (effectiveness: 4.1 ± 0.6, convenience: 3.8 ± 0.6, intrusiveness: 2.2 ± 0.7).Conclusion:The GME-Q was translated into Spanish and validated for Spanish-speaking CGM users with type 1 diabetes.     

Non-diabetic urine glucose in idiopathic membranous nephropathy

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-β-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.