Insulin therapy in type 2 diabetes: Insights into clinical efficacy, patient-reported outcomes, and adherence challenges

Insulin therapy plays a crucial role in the management of type 2 diabetes as the disease progresses.Over the past century,insulin formulations have undergone significant modifications and bioengineering,resulting in a diverse range of available insulin products.These products show distinct pharmacokinetic and pharmacodynamic profiles.Consequently,various insulin regimens have em-erged for the management of type 2 diabetes,including premixed formulations and combinations of basal and bolus insulins.The utilization of different insulin regimens yields disparate clinical outcomes,adverse events,and,notably,patient-reported outcomes(PROs).PROs provide valuable insights from the patient’s perspective,serving as a valuable mine of information for enhancing healthcare and informing clinical decisions.Adherence to insulin therapy,a critical patient-reported outcome,significantly affects clinical outcomes and is influenced by multiple factors.This review provides insights into the clinical effectiveness of various insulin preparations,PROs,and factors impacting insulin therapy adherence,with the aim of enhancing healthcare practices and informing clinical decisions for individuals with type 2 diabetes.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

Selenoprotein-p and insulin resistance in children and adolescents with obesity

BACKGROUND Insulin resistance and obesity present significant challenges in pediatric populations.Selenoprotein P1(SEPP1)serves as a biomarker for assessing selenium levels in the body.While its association with metabolic syndrome is established in adults,its relevance in children remains underexplored.AIM To ascertain SEPP1 blood levels in children and adolescents diagnosed with obesity and to assess its correlation with insulin resistance and adiposity indices.METHODS 170 children participated in this study,including 85 diagnosed with obesity and an equal number of healthy counterparts matched for age and sex.Each participant underwent a comprehensive medical evaluation,encompassing a detailed medical history,clinical examination,and anthropometric measurements like waist circumference and waist-to-height ratio.Furthermore,routine blood tests were conducted,including serum SEPP1,visceral adiposity index(VAI),and Homeostatic Model Assessment of Insulin Resistance(HOMA-IR)level.RESULTS Our findings revealed significantly lower serum SEPP1 levels in children with obesity compared to their healthy peers.Moreover,notable negative correlations were observed between serum SEPP1 levels and body mass index,VAI,and HOMA-IR.CONCLUSION The study suggests that SEPP1 could serve as a valuable predictor for insulin resistance among children and adolescents diagnosed with obesity.This highlights the potential utility of SEPP1 in pediatric metabolic health assessment and warrants further investigation.

基于ADE优化的IPMSM全速域无传感器控制

为了实现内置式永磁同步电机(IPMSM)全速域的无传感器控制和切换速域的平滑过渡,提出了一种基于自适应差分进化(ADE)算法优化的复合控制方法。分别在零低速域、中高速域采用旋转高频电压注入法和滑模观测器法来对电机转速和转子位置进行估算,并在切换速域采用基于ADE算法的权重系数优化法来实现上述两种控制方法的平滑切换,从而实现IPMSM全速域无传感器控制。仿真结果表明:提出的复合控制方法能够实现电机全速域的无感控制和切换速域的平滑过渡,且具有良好的稳定性。

儿童维生素AD滴剂,这样吃才对

众所周知,维生素A、D对孩子的生长发育至关重要。而补充维生素A、D,最好选择专门的维生素AD制剂,比如维生素AD滴剂。但许多家长对其又不甚了解,有诸多疑问。以下,笔者将一一进行解答。

ADS-B信号在对流层大气波导中的传播性能

对流层大气环境存在特殊大气结构“大气波导”,可形成电波超视距传播或产生雷达盲区等。目前,通过雷达、GNSS信号等可以对大气波导进行一定程度的反演探测,但均存在一定的不足。ADS-B信号具有应用范围广、信号密度大、实时性高等特点,为此提出利用ADS-B信号受到不同大气环境影响后能量损耗不同的特点对ADS-B信号与对流层大气环境关联性进行分析研究。以武汉地区ADS-B信号数据为例,基于抛物方程传播理论对路径损耗进行仿真分析,并进行了实验验证。结果表明:ADS-B接收信号与仿真结果存在线性相关性并给出线性表述,为后续利用ADS-B信号反演大气波导提供参考依据。

星基ADS-B系统空天链路的建模与仿真

星基广播式自动相关监视(ADS-B,automatic dependent surveillance-broadcast)系统是一种新型的航空器监视技术,在未来空中交通管理系统中具有广阔的应用前景。为了深入研究星基ADS-B系统中航空器到卫星的空天链路通信性能,将专业软件Matlab和STK(system tool kit)有效联合,构建符合国际标准的星基ADS-B空天链路完整模型;通过离散事件动态交互模拟ADS-B消息的发送与接收全过程,最后统计得出体现星基ADS-B空天链路通信性能的消息识别概率(POI,possibility of identify)、消息检测概率(POD,possibility of detective)、信号接收功率、信号冲突概率、卫星覆盖范围等指标。仿真结果表明,随着区域内航空器数量上升,POI、POD下降,消息冲突概率上升。

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

Icariin ameliorates memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice

Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.

Association between cardiorespiratory fitness level and insulin resistance in adolescents with various obesity categories

BACKGROUND An association between cardiorespiratory fitness(CRF)and insulin resistance in obese adolescents,especially in those with various obesity categories,has not been systematically studied.There is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents,despite their continuous rise.AIM To investigate the association between CRF and insulin resistance in obese adolescents,with special emphasis on severely obese adolescents.METHODS We performed a prospective,cross-sectional study that included 200 pubertal adolescents,10 years to 18 years of age,who were referred to a tertiary care center due to obesity.According to body mass index(BMI),adolescents were classified as mildly obese(BMI 100% to 120% of the 95^(th)percentile for age and sex)or severely obese(BMI≥120% of the 95^(th)percentile for age and sex or≥35 kg/m^(2),whichever was lower).Participant body composition was assessed by bioelectrical impedance analysis.A homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.Maximal oxygen uptake(VO_(2)max)was determined from submaximal treadmill exercise test.CRF was expressed as VO_(2)max scaled by total body weight(TBW)(mL/min/kg TBW)or by fat free mass(FFM)(mL/min/kg FFM),and then categorized as poor,intermediate,or good,according to VO_(2)max terciles.Data were analyzed by statistical software package SPSS(IBM SPSS Statistics for Windows,Version 24.0).P<0.05 was considered statistically significant.RESULTS A weak negative correlation between CRF and HOMA-IR was found[Spearman’s rank correlation coefficient(rs)=-0.28,P<0.01 for CRF_(TBW);(r_(s))=-0.21,P<0.01 for CRF_(FFM)].One-way analysis of variance(ANOVA)revealed a significant main effect of CRF on HOMA-IR[F(2200)=6.840,P=0.001 for CRF_(TBW);F_((2200))=3.883,P=0.022 for CRF_(FFM)].Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF(P=0.001 for CRF_(TBW);P=0.018 for CRF_(FFM)).Two-way ANOVA with Bonferroni correction confirmed significant effect of interaction of CRF level and obesity category on HOMA-IR[F_((2200))=3.292,P=0.039 for CRF_(TBW)].Severely obese adolescents had higher HOMA-IR than those who were mildly obese,with either good or poor CRF.However,HOMA-IR did not differ between severely obese adolescents with good and mildly obese adolescents with poor CRF.CONCLUSION CRF is an important determinant of insulin resistance in obese adolescents,regardless of obesity category.Therefore,CRF assessment should be a part of diagnostic procedure,and its improvement should be a therapeutic goal.

基于迁移学习-元学习的ADS-B攻击分类研究

准确分类通航领域ADS-B攻击类型,采取预防攻击措施,对保障通航运行安全性具有重要意义。针对通航领域ADS-B攻击数据样本少,提出一种基于迁移学习-元学习的ADS-B攻击分类模型。该模型将迁移学习与深度卷积自编码器相结合,建立ADS-B攻击特征提取模型,提取数据样本的攻击有效特征表示,并运用元学习策略在特征空间中实现ADS-B攻击准确分类。实例研究表明,基于迁移学习-元学习的攻击分类模型可有效分类小样本ADS-B攻击,且正确率在95%以上。

基于多时间特征融合网络的ADS-B实采信号分离

不同于以往单天线广播式自动相关监视(Automatic Dependent Surveillance-Broadcast,ADS-B)信号分离中利用仿真的ADS-B信号制作数据集,将单天线接收的真实飞机发射的ADS-B原始信号通过调整信号起始时间以及功率并人为增加噪声来制作数据集。为了提高信号分离的时域波形精度,提出一种多分辨率多时间特征融合重采样(Multi-Temporal fusion Resampling of Multi-Resolution Features,MTRM-RF)网络,通过卷积将信号转化成不同采样率的信号并分别使用多层堆叠逐渐膨胀的一维卷积提取不同时间间隔的特征,以获得更多的时间信息。对多种基于深度学习的语音分离网络进行比较发现,MTRM-RF网络能够有效地融合ADS-B信号的不同采样率、不同时间间隔采样点的特征进行训练。并且随着训练集数据量的增加,分离信号的平均解码正确率达到88.39%,证明该网络可有效分离单天线实采的ADS-B交织信号。

基于AD与TRIZ的加工中心主轴松拉刀机构优化设计

数控加工中心在加工过程中常出现主轴松刀力不足或无法松刀的现象。针对此问题,通过TRIZ系统组件分析明确现有松拉刀机构各组件间作用关系,利用因果链分析得出影响松刀的根本原因,最终应用TRIZ理论中的物场模型分析方法和AD独立性原理提出优化设计方案。根据新方案计算出实际工况下的主轴松刀力和螺杆强度,并对松刀杆进行建模和仿真。结果表明:最大位移量为6.995μm,最大应力为45.24 MPa,符合结构设计要求。最后,经过现场实物测试,当液压力为5 MPa时,松刀行程、松刀力以及打刀量均符合生产要求,验证了优化设计方案的合理性。

白菜型冬油菜BrADS2基因的克隆、表达分析与亚细胞定位

【目的】探究白菜型冬油菜(Brassica rapa L.)脂肪酸去饱和酶ADS2(Δ9 fatty acid desaturase)基因与抗寒性的关系。【方法】基于前期转录组结果,采用一步定向克隆法得到BrADS2基因;构建GFP融合表达载体,通过注射法在烟草下表皮细胞进行瞬时转化,同时采用农杆菌侵染法侵染‘中双11号’;利用qRT-PCR技术,检测抗寒性不同的白菜型冬油菜品种叶片中ADS2基因的表达模式,并对低温下冬油菜的形态变化和抗氧化酶活性、电导率含量进行分析。【结果】白菜型冬油菜BrADS2基因可编码307个氨基酸,该基因编码的蛋白具有亲水性特性;qRT-PCR结果显示,BrADS2基因的表达量呈先升后降的单峰型变化,且在-4℃时表达量达到峰值;亚细胞定位结果显示BrADS2蛋白在细胞质和细胞膜上表达;低温处理下3个品种叶片的相对电导率、抗氧化物酶活性均显著上升,强抗寒品种抗氧化酶活性高于弱抗寒品种,电导率却相反;农杆菌介导侵染‘中双11号’下胚轴后获得15株转基因阳性苗,且转基因油菜阳性植株叶中的BrADS2基因表达量均显著高于野生型。【结论】推测BrADS2基因在白菜型冬油菜膜脂不饱和调节中起重要作用,揭示了ADS2基因与冬油菜抗低温胁迫的关系。

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

基于改进型多斜Ⅲ技术的7位半AD转换器设计

高精度测试仪器在环境试验中扮演着重要角色,而积分型AD转换器被广泛的应用在高精度测试仪器中。针对传统型积分型AD转换器转换速率较低的问题,提出了一种提高转换速率的改进型多斜ⅢAD转换器,详细的介绍了其原理和设计思路。该转换器以单片机与CPLD一同控制积分型ADC,在积分末尾利用单片机片内ADC测量积分器的残留电压,以达到提高转换速率的目的。经理论分析该AD转换器比传统型转换速率快836倍,分辨率可达到31位,在±10V直流电压测量中可实现7位半分辨率。

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.

Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and neurodegeneration.Aging is considered the major risk factor for Parkinson’s and Alzheimer’s disease develops.Likewise,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders.Currently,no treatment can effectively reverse these neurodegenerative pathologies.However,some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes.In the previous framework,Vanadium species have demonstrated a notable antidiabetic effect.Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome.The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms.This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

基于FPGA与AD9786的调制解调电路的设计

谐振式光学陀螺因其高理论精度、小型化以及高稳定性受到了国内外的强烈关注。针对于谐振式光学陀螺检测信号微弱的特点,需要对该信号进行调制解调,以实现陀螺的稳定输出,设计了一种基于FPGA和AD9786的高精度模拟信号源,该信号以FPGA作为核心控制单元,AD9786作为数模转换器,实现16位的高精度DA转换,通过上位机实现指令的通信过程,可实现不同频率的交流信号。该实验结果表明,该系统符合陀螺测试系统调制解调要求,通过上位机对不同输出信号进行测试,且测试结果无纹波时输出噪声Vrms269μV,交流信号精度达到0.01%,最高频率可达到2M,稳定性高。

基于AD7616的16通道数据采集系统设计

针对传统数据采集系统因通道不足或数据量过大,无法满足多通道同步采集的问题,设计了一种基于AD7616的16通道数据采集系统。系统以Xilinx系列FPGA作为主控芯片,ADI公司的AD7616作为模数转换芯片,DDR3 SDRAM作为缓存单元。介绍了各个模块硬件的设计思路,重点介绍了FPGA控制AD7616模数转换模块、DDR3 SDRAM缓存模块的软件程序设计,并对系统的多通道采样功能、同步性能以及实际水下超声信号的采集能力进行了实验验证,结果表明,系统可以完成水下超声信号的多通道同步采集。