Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.

Gestational Diabetes and Infertility

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications which affect the mother and offspring. In addition to adverse perinatal outcomes, it may lead to permanent health problems for the mother, such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), while increasing the risk of future obesity, CVD, T2DM and GDM in the child. Approximately 15% of women seek fertility treatment. Over the last decade, it has come to attention that patients with an infertility history are more prone to having GDM during their pregnancies, and this review examines the relationship between GDM and infertility. The elevated estrogen, progesterone, leptin, placental lactogen and growth hormone are the main reasons for increased insulin resistance during pregnancy. Despite some confounding factors in the mechanism of GDM in patients with an infertility history, infertility treatment increases the risk, according to numerous studies. The obesity epidemic and associated disorders have become a significant public health concern worldwide. Lifestyle modification for weight loss before pregnancy is encouraged, but there is no strong evidence for improvement in perinatal results. GDM, infertility and infertility treatment have a potential risk of alteration in the embryo’s environment and cause epigenetic reprogramming, which may be inherited to the next generation. The fertility treatment impacts the patient’s and offspring’s health. Patients should be informed about the risks so that they consent and get involved in the decision. Infertility treatment may be accepted as a reason for high-risk pregnancy, and patients can be screened for GDM in early pregnancy.

Radiofrequency ablation of hepatocellular carcinoma in difficult locations:Strategies and long-term outcomes

AIM:To investigate the treatment strategies and longterm outcomes of radiofrequency ablation(RFA) of hepatocellular carcinoma(HCC) in difficult locations and to compare the results with non-difficult HCC.METHODS:From 2004 to 2012,a total of 470 HCC patients underwent ultrasound-guided percutaneous RFA.Among these HCC patients,382 with tumors located ≤ 5 mm from a major vessel/bile duct(n = 87),from peripheral important structures(n = 232) or from the liver capsule(n = 63) were regarded as difficult cases.There were 331 male patients and 51 female patients,with an average age of 55.3 ± 10.1 years old.A total of 235 and 147 patients had ChildPugh class A and class B liver function,respectively.The average tumor size was 3.4 ± 1.2 cm.Individual treatment strategies were developed to treat these difficult cases.During the same period,88 HCC patients with tumors that were not in difficult locations served as the control group.In the control group,74 patients were male,and 14 patients were female,with an average age of 57.4 ± 11.8 years old.Of these,62 patients and 26 patients had Child-Pugh class A and class B liver function,respectively.Regular follow-up after RFA was performed to assess treatment efficacy.Survival results were generated from Kaplan-Meier estimates,and multivariate analysis was performed using the Cox regression model.RESULTS:Early tumor necrosis rate in the difficult group was similar to that in the control group(97.6% vs 94.3%,P = 0.080).The complication rate in the difficult group was significantly higher than that in thecontrol group(4.9% vs 0.8%,P = 0.041).The followup period ranged from 6 to 116 mo,with an average of 28 ± 22.4 mo.Local progression rate in the difficult group was significantly higher than that in the control group(12.7% vs 7.1%,P = 0.046).However,the 1-,3-,5-,and 7-year overall survival rates in the difficult group were not significantly different from those in the control group(84.3%,54.4%,41.2%,and 29.9% vs 92.5%,60.3%,43.2%,and 32.8%,respectively,P = 0.371).Additionally,a multivariate analysis revealed that tumor location was not a significant risk factor for survival.CONCLUSION:There was no significant difference in long-term overall survival between the two groups even though the local progression rate was higher in the difficult group.

The emerging role of autophagic-lysosomal dysfunction in Gaucher disease and Parkinson's disease

Gaucher disease（GD）,the commonest lysosomal storage disorder,results from the lack or functional deficiency of glucocerebrosidase（GCase） secondary to mutations in the GBA1 gene.There is an established association between GBA1 mutations and Parkinson＇s disease（PD）,and indeed GBA1 mutations are now considered to be the greatest genetic risk factor for PD.Impaired lysosomal-autophagic degradation of cellular proteins,including α-synuclein（α-syn）,is implicated in the pathogenesis of PD,and there is increasing evidence for this also in GD and GBA1-PD.Indeed we have recently shown in a Drosophila model lacking neuronal GCase,that there are clear lysosomal-autophagic defects in association with synaptic loss and neurodegeneration.In addition,we demonstrated alterations in mechanistic target of rapamycin complex 1（mTORC1） signaling and functional rescue of the lifespan,locomotor defects and hypersensitivity to oxidative stress on treatment of GCase-deficient flies with the mT OR inhibitor rapamycin.Moreover,a number of other recent studies have shown autophagy-lysosomal system（ALS） dysfunction,with specific defects in both chaperone-mediated autophagy（CMA）,as well as macroautophagy,in GD and GBA1-PD model systems.Lastly we discuss the possible therapeutic benefits of inhibiting mT OR using drugs such as rapamycin to reverse the autophagy defects in GD and PD.

Reply to “Is physical performance (in mice) increased by Veillonella atypica or decreased by Lactobacillus bulgaricus?”

Dear editor,In a recent longitudinal metagenomic study of the gut microbiome in elite athletes,1 we conducted multiple, repeated sampling from runners in the 2015 Boston Marathon as well as sedentary controls approximately 1 week prior to and 1 week after marathon day. We also analyzed an independent cohort of endurance athletes, including Olympic-caliber rowers。

糖尿病患者肾小球基底膜硫酸类肝素的特异性结构改变

影响肾小球基底膜和邻近系膜(GBM)大分子的改变相信在糖尿病肾小球功能异常中起着重要的作用.肾小球滤过屏障的胶原与非胶原成分在糖尿病时发生了生物化学改变,从而导致肾脏的病理生理变化. 硫酸类肝素作为肾脏滤过屏障的一种阴离子成分起着重要的作用.采用生物化学和免疫化学方法测量发现,在糖尿病患者肾脏中硫酸肝素蛋白多糖和其氨基葡聚糖链的含量下降,在糖尿病大鼠中也有N-去乙酰/N-硫酸化下降. 切开氨基葡聚糖的方法使识别和定量分析各种硫酸化二糖单位成为可能.这种方法在研究牛肾小球GBM的硫酸肝素的完整结构方面提供了有价值的信息.在此研究中,我们应用了联氨/ 亚硝酸/NaB[3H4]技术处理人糖尿病肾小球基底膜以及非糖尿病标本,以了解硫酸肝素序列或硫酸化模式或两者在疾病状态下的改变.分析结果显示,糖尿病GBM一种特异性的结构单位,即IdUA(2S)α1→4GlcN(3S)数量明显下降.有趣的是,这种曾经在牛GBM中找到的特殊的二糖仅限于出现在GBM硫酸肝素蛋白多糖,硫酸肝素链的少有成分3-氧-硫酸葡糖胺是抗凝血酶结合区的组成成分.而且,最近有人报道了一种特异性葡糖胺3-氧-硫酸转移酶,它参与了IdUA(2S)α1→4GlcN(3S)的产生,提示GBM中的这个序列可能有明显的生物功能.

Diabetic and Prediabetic Profile of Patients in a Family Health Care Unit of Salvador, Northeastern Brazil

Diabetes Mellitus is one of the most prevalent diseases in the world. In Brazil, 8.7% of the population between 20 and 79 years of age has diabetes, estimating 11.6 million diabetics. It is commonly associated with other co-morbidities such as hypertension, dyslipidemia and obesity, which put these patients into a high cardiovascular risk profile. This study was performed using the medical records of enrolled population attending a Family Health Unit of Alto do Coqueirinho, Salvador, Northeastern Brazil, consisting of one doctor, one nurse, one dentist, one nursing technician and six community health workers. Medical records and data provided by the system of the Primary Care Information (SIAB), showed total of 2495 patients. Considering the prevalence morbidities in this population, hypertension was present in 9.8% of patients and Type 2 Diabetes in only 3.6%. Since the prevalence of morbidities is the key indicator to the development of public health policies, it seems important a better knowledge on the prevalence rates of diabetes, prediabetes and its co-morbidities of this population. Future plans and projects for health professionals will be based on a consistent medical record.

Linking circular intronic RNA degradation and function in transcription by RNase H1

Circular intronic RNAs(ci RNAs) escaping from DBR1 debranching of intron lariats are co-transcriptionally produced from prem RNA splicing, but their turnover and mechanism of action have remained elusive. We report that RNase H1 degrades a subgroup of ci RNAs in human cells. Many ci RNAs contain high GC% and tend to form DNA:RNA hybrids(R-loops) for RNase H1 cleavage, a process that appears to promote Pol II transcriptional elongation at ci RNA-producing loci. One ci RNA, ciankrd52, shows a stronger ability of R-loop formation than that of its cognate pre-m RNA by maintaining a locally open RNA structure in vitro. This allows the release of pre-m RNA from R-loops by ci-ankrd52 replacement and subsequent ci RNA removal via RNase H1 for efficient transcriptional elongation. We propose that such an R-loop dependent ci RNA degradation likely represents a mechanism that on one hand limits ci RNA accumulation by recruiting RNase H1 and on the other hand resolves Rloops for transcriptional elongation at some GC-rich ci RNA-producing loci.

The thermogenic circuit: Regulators of thermogenic competency and differentiation

In mammals,a thermogenic mechanism exists that increases heat production and consumes energy.Recent work has shed light on the cellular and physiological mechanisms that control this thermogenic circuit.Thermogenically active adipocytes,namely brown and closely related beige adipocytes,differentiate from progenitor cells that commit to the thermogenic lineage but can arise from different cellular origins.Thermogenic differentiation shares some features with general adipogenesis,highlighting the critical role that common transcription factors may play in progenitors with divergent fates.However,thermogenic differentiation is also discrete from the common adipogenic program and,excitingly,cells with distinct origins possess thermogenic competency that allows them to differentiate into thermogenically active mature adipocytes.An understanding of this thermogenic differentiation program and the factors that can activate it has led to the development of assays that are able to measure thermogenic activity both indirectly and directly.By combining these assays with appropriate cell models,novel therapeutic approaches to combat obesity and its related metabolic disorders by enhancing the thermogenic circuit can be developed.