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.

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。

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。

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.

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.

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.

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。

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。

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。

Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance

Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.

基于动态离散模型的机场ADS-B攻击威胁影响研究

随着航空业信息技术的发展,空中交通管制系统面临着多种网络攻击的威胁。广播式自动相关监视(ADS-B)系统因其明文广播的数据传输方式,存在着被网络攻击的安全问题。依据“等待降落-降落-停泊-排队起飞-起飞”的航班运行全流程,建立了WLPQD动态离散模型,研究机场流量和航班延误。模型引入了系统冗余能力、处理速率等参数,模拟了攻击场景;通过受影响飞机数量和延误时间等指标研究了机场航班延误的传播影响。模型展示了ADS-B消息注入攻击对降落、起飞航班造成的延误,提出了两种攻击缓解方法。结果表明,延误规模的大小与攻击强度呈现正相关,且攻击对起飞航班的延误影响更大;提升对“幽灵飞机”和合法飞机的处理速率都可提升机场系统的抗毁性,但前者对提升机场系统冗余能力的效果更加显著。所做研究为机场系统抵御网络攻击、增强抗毁性提供了决策分析的参考依据。

采用AD654芯片的直流电压传感器及其温度漂移补偿

提出一种基于电压-频率变换的光电式电压传感器及电压传感信号温度漂移的补偿方法。电压传感系统主要包括电阻分压器、电压-频率变换芯片、发光二极管、光纤、光电探测与信号处理单元等。利用两块AD654型芯片分别作为被测电压和温度传感单元,通过对两路光传感信号进行非线性数据拟合等方式实现了对电压传感信号温度漂移的实时补偿。实验测量了0.6 kV~5.0 kV范围内的直流电压,并实现了电压传感信号的温度漂移补偿,在-40℃~+60℃的温度范围内,电压传感信号温度漂移的平均相对误差约为±0.7%。

Exogenous insulin autoimmune syndrome:A case report and review of literature

BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.

面向Ad-Hoc协作的局部观测重建方法

在多智能体强化学习的研究中,如何进行Ad-Hoc协作,也就是说如何适应种类和数量变化的队友,是一个关键问题。现有方法或者有很强的先验知识假设,或者使用硬编码的规则进行合作,缺乏通用性,无法泛化到更一般的Ad-Hoc协作场景。为解决该问题,提出一种面向Ad-Hoc协作的局部观测重建算法,利用注意力机制和采样网络对局部观测进行重建,使得算法认识到并充分利用不同局面中的高维状态表征,实现了在Ad-Hoc协作场景下的零样本泛化。在星际争霸微操环境和Ad-Hoc协作场景上与代表性算法的性能进行对比与分析,验证了算法的有效性。

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Dynamics in the Prevalence of Insulin Resistance between 2005 and 2023 in Type 2 Diabetics in South Kivu in the East of the Democratic Republic of Congo: Cross-Sectional Studies

Aim: Sub-Saharan Africa is undergoing an epidemiological transition responsible for a change in the metabolic profile in favour of insulin resistance. The aim of this study was to assess the dynamics of the prevalence of insulin resistance and associated risk factors in diabetic patients in the Democratic Republic of Congo between 2005 and 2023. Method: We measured fasting blood glucose and insulin levels and looked for metabolic syndrome parameters (2009 criteria) in type 2 diabetes patients in 2005-2008 (n = 176) and in 2018-2023 (n = 303). The HOMA model was used to measure insulin sensitivity and islet β-cell secretory function. Results: Between 2005 and 2013, the trend was towards an increase in the prevalence of insulin resistance (from 13.1% to 50.8%;p Conclusion: This present study shows an increase in insulin resistance in Congolese urban areas and a persistence of atypical diabetes mellitus in Congolese rural areas, confirming the particularity of the pathophysiology of the disease in African areas currently influenced by the epidemiological transition. Further studies using an appropriate methodology are required.

情境目标和Ad hoc关联影响言语产生的语义效应

干扰词与目标词之间的语义关联性是影响言语产生中语义效应性质的关键因素。相比其他语义关联类型,Ad hoc关联是一种较为特殊的概念联系类型。考察情境目标和Ad hoc关联对语义效应的影响,结果表明:与其他语义关联性相比,Ad hoc关联对语义效应的影响既有共性,又有差异。共性表现在:Ad hoc关联抑制图片命名,产生语义干扰效应,这种效应发生在图片命名早期(SOA从-200ms至0ms)。差异表现在:Ad hoc关联的语义干扰效应的产生要以情境目标提示为前提,有情境目标提示时,Ad hoc关联效应非常显著;无情境目标提示时,Ad hoc关联效应消失。不同语义关联类型产生不同语义效应的根源在于类别概念结点是否得到激活。

Vitamin D, Parathyroid Hormone, Insulin Sensitivity and Islet β-Cell Secretory Function in Diabetic Patients from South Kivu in the Democratic Republic of Congo: Cross-Sectional Study

Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.