Association of point in range withβ-cell function and insulin sensitivity of type 2 diabetes mellitus in cold areas

Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

What can we learn from β-cell failure biomarker application in diabetes in childhood?A systematic review

BACKGROUND The prevalence of diabetes as a catastrophic disease in childhood is growing in the world.The search for novel biomarkers ofβ-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic syndrome.AIM To determine which biomarkers are currently used to identifyβ-cell failure among children and adolescents with high risk factors for diabetes mellitus.METHODS This systematic review was carried out using a modified version of the PICO protocol(Participants/Intervention/Comparison/Outcome).Once our research question was established,terms were individually researched on three different databases(PubMed,BIREME and Web of Science).The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further analysis.They were assessed individually according to quality criteria.RESULTS First,we made the classification of theβ-cell-failure biomarkers by the target tissue and the evolution of the disease,separating the biomarkers in relation to the types of diabetes.Second,we demonstrated that most biomarkers currently used as early signs ofβ-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes.Third,we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid oligomers.Finally,we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in childhood.CONCLUSION This review makes widely evident that most biomarkers currently used as early signs ofβ-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes.Landing in the clinical practice we propose that real human islet amyloid polypeptide amyloid oligomers is good for identifying patients withβ-cell damage and potentially could substitute many biomarkers.

Pancreatic β-cell failure,clinical implications,and therapeutic strategies in type 2 diabetes

Pancreaticβ-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes(T2D).Reserving insulin-producingβ-cells and hence restoring insulin production are gaining attention in translational diabetes research,andβ-cell replenishment has been the main focus for diabetes treatment.Significant findings inβ-cell proliferation,transdifferentiation,pluripotent stem cell differentiation,and associated small molecules have served as promising strategies to regenerateβ-cells.In this review,we summarize current knowledge on the mechanisms implicated inβ-cell dynamic processes under physiological and diabetic conditions,in which genetic factors,age-related alterations,metabolic stresses,and compromised identity are critical factors contributing toβ-cell failure in T2D.The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promotingβ-cell proliferation,inducing non-β-cell transdifferentiation,and reprograming stem cell differentiation.Although a significant challenge remains for each of these strategies,the recognition of the mechanisms responsible forβ-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenousβ-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

The relationship between insulin resistance/β-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus： the Desheng Diabetic Eye Study

AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

The Influence of the Pro12Ala Mutation of PPARγ2 Receptor Gene on β-cells Restoration and Insulin Resistance in Type 2 Diabetes with Hypertension

The aim of this investigation was to determine whether a PPAR72 Prol2Ala polymorphism was associated with insulin resistance, β-cellfunction and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes （HbAC1〈6.0） were investigated, including 132 hypertensive diabetic （HTD） subjects, 157 normotensive diabetic （NTD） subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test （OGTT）. Biochemical measurements （high-density lipoprotein （HDL） and low-density lipoprotein-cholesterol （LDL）, triglycerides） and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group （3. 03 %） than in the non-hypertension group （5.7 %） （P〈0.05） after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level （P=0. 0127）, and better glucose tolerance 60 min after oral glucose （P=0. 0361）. Moreover, plasma insulin concentrations at 60 min was lower than those without A variant （P = 0. 0275）, and both hypertensive Ala/Pro in HOMA-β （P ： 0. 0455） and AUC for insulin （P=0. 0473） were higher, and HOMA-IR was lower （P=0. 0375） as compared with hypertensive Pro/Pro subjects. No association was observed between Prol2Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPARγ2 on glucose homeostasis and insulin resistance.

Association of β-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children

BACKGROUND In addition to insulin resistance,impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Scarce clinical data exist for pediatric T2DM.AIM To investigate the association ofβ-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.METHODS This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019.Children with normal glycemic levels(n=1935)were included as healthy control subjects.The homeostasis models(HOMAs)were used to assess theβ-cell function(HOMA2-%B)and insulin resistance(HOMA2-IR)levels.The HOMA index was standardized by sex and age.We performed logistic regression analysis to obtain odds ratios(ORs)for T2DM risk using the standardized HOMA index,adjusted for confounding factors including sex,Tanner stage,T2DM family history,body mass index z-score,and lipid profile.RESULTS The male-female ratio of newly diagnosed T2DM patients was 1.37:1(OR=2.20,P=0.011),and the mean ages of onset for boys and girls were 12.5±1.9 years and 12.3±1.7 years,respectively.The prevalence of related comorbidities including obesity,elevated blood pressure,and dyslipidemia was 58.2%,53.2%,and 80.0%,respectively.The T2DM group had lower HOMA2-%B levels(P<0.001)and higher HOMA2-IR levels(P<0.001)than the control group.Both the decrease in HOMA2-%B z-score(OR=8.40,95%CI:6.40-11.02,P<0.001)and the increase in HOMA2-IR z-score(OR=1.79,95%CI:1.60-2.02,P<0.001)were associated with a higher risk of T2DM,and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.CONCLUSION Besides insulin resistance,β-cell function impairment is also strongly associated with Chinese pediatric T2DM.Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

Pancreaticβ-cell dysfunction in type 2 diabetes:Implications of inflammation and oxidative stress

Insulin resistance and pancreaticβ-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes(T2D).Beyond the detrimental effects of insulin resistance,inflammation and oxidative stress have emerged as critical features of T2D that defineβ-cell dysfunction.Predominant markers of inflammation such as C-reactive protein,tumor necrosis factor alpha,and interleukin-1βare consistently associated withβ-cell failure in preclinical models and in people with T2D.Similarly,important markers of oxidative stress,such as increased reactive oxygen species and depleted intracellular antioxidants,are consistent with pancreaticβ-cell damage in conditions of T2D.Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D.The current review explores preclinical and clinical research on the pathological implications of inflammation and oxidative stress during the development ofβ-cell dysfunction in T2D.Moreover,important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress duringβ-cell failure in T2D.Underpinning the clinical relevance of the review,a systematic analysis of evidence from randomized controlled trials is covered,on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improveβ-cell function.

The Effect of Glucose Added to the Dialysis Fluid on Blood Pressure, Vasoactive Hormones and Energy Transfer during Hemodialysis in Chronic Renal Failure

Background: Previous studies showed that blood pressure was reduced in patients with chronic renal failure during hemodialysis with glucose added to the dialysis fluid. We wanted to test the hypotheses that blood pressure is reduced in non-diabetic and diabetic dialysis patients, when glucose is added to the dialysis fluid, and that blood pressure changes are caused by changes in plasma concentrations of vasoactive hormones or to vasodilation secondary to an increase in body temperature. Methods: The effect of dialysis with glucose added to the dialysis fluid was measured in three randomized, placebo-controlled, un-blinded and cross-over studies with periods of one week duration. In non-diabetic nephropathy (Study 1, n = 19) and diabetic nephropathy (Study 2, n = 15), we measured blood pressure (BP) and pulse rate (PR), plasma concentrations of glucose (p-Glucose), renin (PRC), angiotensin II (p-AngII), endothelin (p-Endot), insulin (p-Ins), glucagon (p-Glu), and human growth hormone (p-hGH). In non-diabetic nephropathy (Study 3, n = 24), we measured the effect of dialysis with glucose added to the dialysis fluid on energy transport from form the body using body temperature control. Results: Study 1 and 2 showed that BP, PRC, p-AngII, and p-Ins were unchanged, whereas P-Endot increased and P-hGH decreased, in dialysis patients with or without glucose added to the dialysis fluid. In diabetics, a marginal increase in p-Glu was measured during dialysis with glucose, but not without glucose. Study 3 showed that SBP increased significantly using dialysis with temperature control of dialysis fluid compared with no temperature control (145 versus 138 mm Hg). In parallel with the increase in SBP, the energy flux from the patients was significantly higher with temperature control than without. Conclusion: In non-diabetics and diabetics, blood pressure was unchanged during dialysis with glucose added to the dialysis fluid in a short-term study. Vasoactive hormones in plasma were changed in the same way independently of glucose in the dialysis fluid. Systolic blood pressure increased using dialysis with temperature control of dialysis fluid, presumably due to vasoconstriction to prevent or antagonize a fall in body temperature.

Improved <i>β</i>-cell function rather than increased insulin sensitivity is associated with reduction in hemoglobin A1c in newly diagnosed Type 2 diabetic patients treated with metformin

β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.

胰岛素抵抗代谢评分与慢性心力衰竭患者不良预后的相关性研究

背景胰岛素抵抗(IR)与心血管疾病的发生、发展关系密切,目前多项研究已经证实了IR在心力衰竭(HF)患者中非常普遍,并与不良心血管结局有关,而反映IR的指标——胰岛素抵抗代谢评分(Mets-IR)与慢性心力衰竭(CHF)患者不良预后之间的关联目前尚不明确。目的分析Mets-IR与CHF患者不良预后之间的相关性。方法本研究为回顾性研究,选取2020年1月—2021年1月在郑州大学第二附属医院心血管内科确诊为CHF的患者313例为研究对象。根据是否发生全因死亡将患者分为两组:全因死亡组(61例)和对照组(252例)。将Mets-IR作为分类变量进行分析,以中位数将Mets-IR分为两类:低水平Mets-IR(Mets-IR<37.28)和高水平Mets-IR(Mets-IR≥37.28)。收集患者基线资料,其中包括Mets-IR及其年龄、血清生物标志物和超声心动图指标,随访截至2022-12-31。通过本院电子病历系统或电话随访收集患者预后情况,主要终点事件为全因死亡,次要终点事件为因HF再入院。不同水平Mets-IR患者全因死亡及因HF再入院的生存曲线采用Kaplan-Meier图和Log-rank检验进行分析。应用Cox比例风险回归模型分析Mets-IR与全因死亡及因HF再入院风险的相关性。构建受试者工作特征(ROC)曲线,分析Mets-IR对CHF患者全因死亡及因HF再入院风险的预测价值。结果中位随访时间25.0(9.0,28.5)个月,313例CHF患者中出现全因死亡61例(19.5%)、因HF再入院121例(38.7%)。全因死亡组患者年龄、BMI、空腹血糖、Mets-IR、N末端B型钠尿肽前体、血尿酸、中性粒细胞计数、红细胞分布宽度、心房颤动、高血压、利尿剂、醛固酮受体拮抗剂、美国纽约心脏病学会分级高于对照组,三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、白蛋白、血红蛋白、血钠、左心室射血分数、血管紧张素转化酶抑制剂/血管紧张素受体拮抗剂/血管紧张素受体-脑啡肽酶抑制剂低于对照组(P<0.05)。Log-rank检验结果显示,高水平Mets-IR患者的全因死亡率及因HF再入院率均高于低水平Mets-IR患者(P<0.001)。调整多个混杂因素后的Cox比例风险回归分析结果显示,与低水平Mets-IR患者相比,高水平Mets-IR患者全因死亡风险(HR=2.90,95%CI=1.51~5.54,P=0.001)、因HF再入院风险(HR=1.55,95%CI=1.04~2.30,P=0.030)均升高。Mets-IR预测全因死亡风险、因HF再入院风险的ROC曲线下面积分别为0.68(95%CI=0.62~0.75)、0.62(95%CI=0.55~0.68)。结论Mets-IR水平升高可能会增加CHF患者的全因死亡及因HF再入院风险,可用于CHF患者的危险分层。

极化液联合小剂量多巴胺治疗射血分数降低心力衰竭疗效观察

目的:探讨极化液联合小剂量多巴胺对射血分数减低型心力衰竭(HFrEF)的临床疗效。方法:选择2022年1月至6月我院收治的HFrEF患者124例,随机分为对照组(60例,抗心力衰竭基础治疗)和治疗组(64例,在常规治疗基础上加用极化液联合小剂量多巴胺静脉滴注),疗程5d。对比两组治疗前后血N末端脑钠肽前体(NT-proBNP)、血肌酐(SCr)、左心室射血分数(LVEF)、左心室舒张末期内径(LVEDd)的变化,并记录观察两组治疗期间不良反应情况。结果:与对照组治疗后比较,治疗组NT-proBNP[(3690.68±1091.98)pg/ml比(2798.38±1112.07)pg/ml]、SCr[(93.23±7.02)μmol/L比(77.90±6.75)μmol/L]、LVEDd[(54.57±2.06)mm比(53.83±1.80)mm]均显著降低,LVEF[(40.50±3.41)%比(41.89±3.39)%]显著升高(P<0.05或<0.01)。治疗组总不良反应发生率显著低于对照组(28.1%比55.0%,P=0.002)。结论:常规治疗基础上加用极化液联合小剂量多巴胺,可以显著提高射血分数减低型心力衰竭患者的左室射血分数,缩小左室舒张末内径,保护肾脏功能,且不良反应发生率较低。

基于心功能及IGFBP7、sST2、CGRP、ET分析沙库巴曲缬沙坦在治疗冠心病合并慢性心力衰竭中的应用效果

目的 分析冠心病(CHD)合并慢性心力衰竭(CHF)患者应用沙库巴曲缬沙坦治疗的效果。方法 选择2020年1月至2023年1月邯郸市第四医院收治的86例CHD合并CHF患者,以随机数字表法将其分为对照组和试验组各43例。两组CHD治疗均应用硝酸酯类、他汀类及抗血小板药物,对照组CHF治疗应用坎地沙坦酯片、醛固酮受体拮抗剂及β受体阻滞剂,试验组治疗则将对照组中的坎地沙坦酯片替换为沙库巴曲缬沙坦钠片。比较两组疗效、不良反应、心功能指标[左室短轴缩短率(LVFS)、左室射血分数(LVEF)、6min步行距离(6 MWD)]、心室重构指标[Ⅲ型胶原前肽(PⅢP)、层粘蛋白(LN)、基质金属蛋白酶-9(MMP-9)]、心肌损伤和血管内皮功能相关指标[胰岛素样生长因子结合蛋白7(IGFBP7)、可溶性生长刺激表达基因2(sST2)、降钙素基因相关肽(CGRP)、内皮素(ET)]。结果与对照组比,试验组治疗3个月后的总有效率更高,差异有统计学意义(P<0.05)。两组治疗3个月后的LVFS、LVEF、6 MWD、IGFBP7、CGRP与治疗前比升高,且试验组与对照组比更高,差异有统计学意义(P<0.05);PⅢP、LN、MMP-9、sST2、ET降低,试验组与对照组比更低,差异有统计学意义(P<0.05)。两组不良反应总发生率对比差异无统计学意义(P>0.05)。结论 沙库巴曲缬沙坦可有效调节CHD合并CHF患者IGFBP7、sST2、CGRP、ET,改善血管内皮功能、心肌损伤、心室重构及心功能,进而可提高疗效,且具有良好的安全性。

黑地黄丸通过调控IGF-1表达对慢性肾衰竭大鼠肾纤维化的抑制作用

目的 探讨黑地黄丸对慢性肾衰竭大鼠肾纤维化的影响及其作用机制。方法 Wistar大鼠随机分为空白组(正常饲养)和造模组,造模组大鼠采用5/6肾切除手术构建CRF大鼠模型。将造模成功的大鼠随机分为模型组、黑地黄丸组(10.43 g/kg)及黑地黄丸+IGF-1R阻断剂(JB1)组(连续7 d皮下注射18μg/kg JB1后灌胃10.43 g/kg黑地黄丸)。给药8周后,检测大鼠血清Scr、BUN水平,HE和Masson染色观察肾组织病理变化,免疫组化法检测肾组织TGF-β、HIF-1α、α-SMA蛋白表达,Western blot法检测肾组织IGF-1R、TGF-β蛋白表达,RT-qPCR法检测肾组织IGF-1R、TGF-β mRNA表达。结果 与空白组比较,模型组血清Scr、BUN水平升高(P<0.05),肾组织纤维化程度加重,纤维化面积增加(P<0.05),肾组织TGF-β、HIF-1α、α-SMA蛋白表达和TGF-β mRNA表达升高(P<0.05),IGF-1R mRNA和蛋白表达降低(P<0.05);与模型组比较,黑地黄丸组大鼠血清Scr、BUN水平降低(P<0.05),肾间质炎性细胞减少,纤维化程度减轻(P<0.05),肾组织TGF-β、HIF-1α、α-SMA蛋白表达和TGF-β mRNA表达降低(P<0.05),IGF-1R mRNA和蛋白表达升高(P<0.05);而给予JB1可减弱黑地黄丸对CRF大鼠肾纤维化的改善作用(P<0.05)。结论 黑地黄丸能够抑制CRF大鼠肾纤维化,且该抑制过程与上调IGF-1表达,促进IGF-1与IGF-1R结合有关。

老年心力衰竭并发肺炎患者血清FOXM1和IGF2表达水平及与预后价值研究

目的探究血清叉头盒蛋白M1(forkhead box protein M1,FOXM1)和胰岛素样生长因子2(insulin-like growth factor 2,IGF2)表达对老年心力衰竭合并肺炎患者预后的预测价值。方法将邯郸市中心医院2021年3月~2022年6月收治的126例老年心力衰竭并发肺炎患者设为病例组,并根据随访情况将122例患者分为预后不良组(n=33)和预后良好组(n=89),另选取该院同期126例健康体检者为对照组。检测两组(病例组和对照组)血清FOXM1和IGF2水平,检测病例组用力肺活量(forced vital capacity,FVC)和第一秒用力呼容积(forced expiratory volume in one second,FEV1)。采用Spearman分析法分析老年心力衰竭并发肺炎患者血清FOXM1和IGF2水平与心功能分级的相关性;受试者工作特征(receiver operating characteristic,ROC)曲线分析血清FOXM1和IGF2水平对老年心力衰竭并发肺炎患者预后的预测价值。结果与对照组比较,病例组血清FOXM1(2.39±0.55 vs 1.06±0.21)和IGF2(71.33±7.96pg/ml vs 47.82±5.14pg/ml)水平明显较高,差异有统计学意义(t=25.358,27.581,均P<0.05);与预后良好组比较,预后不良组血清FOXM1(3.87±1.06 vs 1.95±0.51)和IGF2水平(85.88±9.54pg/ml vs 69.14±8.73pg/ml)明显较高,差异具有统计学意义(t=13.453,9.174,均P<0.05);预后良好组和预后不良组心功能分级比较差异有统计学意义(χ^(2)=7.120,P<0.05),且与预后不良组比较,预后良好组FEV1(1.24±0.32L vs 1.08±0.25L)和FEV1/FVC(55.46%±5.77%vs 52.30%±5.38%)明显较高,差异有统计学意义(t=2.592,2.735,均P<0.05);老年心力衰竭并发肺炎患者血清FOXM1水平和IGF2水平与心功能分级呈显著正相关(r=0.496,0.517,均P<0.05)。ROC曲线结果显示,血清FOXM1单独预测老年心力衰竭并发肺炎患者预后的曲线下面积(area under the curve,AUC)为0.854(95CI%:0.779~0.912),其敏感度、特异度分别为75.76%,86.52%,最佳截断值为2.75;IGF2单独预测老年心力衰竭并发肺炎患者预后的AUC为0.874(95CI%:0.802~0.927),其敏感度、特异度分别为72.73%,85.39%,最佳截断值为78.30 pg/ml;二者联合预测老年心力衰竭并发肺炎患者预后的AUC显著大于血清FOXM1和IGF2单独诊断的AUC(Z=2.413,2.737,P=0.006,0.016)。结论血清FOXM1和IGF2水平在老年心力衰竭并发肺炎患者中升高,且二者联合检测对患者预后具有较高的预测价值。

心力衰竭与胰岛素抵抗相关性的研究进展

近年来,高血压、冠心病等心血管疾病的治疗有了显著进展。但心力衰竭(heart failure,HF)的发生率仍然很高,并且已经成为心血管领域中一个重要的挑战。目前亟需解决的问题是如何有效地延缓HF的发生和发展,降低其致死率。最新研究表明,胰岛素抵抗(insulin resistance,IR)与HF密切相关。该文对心力衰竭和胰岛素抵抗之间相关性的研究现状进行总结,为心力衰竭的治疗提供新思路和策略,现将综述报道如下。

Challenges and pitfalls of youth-onset type 2 diabetes

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are increasing.The rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications.Indeed,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell function.Therefore,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in mid-life.Due to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment options.In this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

甘油三酯-葡萄糖指数对行介入治疗的缺血性心力衰竭合并2型糖尿病患者的预后价值

目的:在以往的研究中,甘油三酯-葡萄糖(triglyceride-glucose,TyG)指数已被证明与心血管疾病的预后密切相关。然而,TyG指数对接受PCI治疗的缺血性心力衰竭(heart failure,HF)合并2型糖尿病(type 2 diabetes mellitus,T2DM)患者预后的影响仍不明确。方法:回顾性纳入792例缺血性HF合并T2DM患者,并根据TyG指数的四分位数将其分为四组。主要终点是主要不良心血管事件(major adverse cardiovascular events,MACE),包括全因死亡、非致死性心肌梗死(myocardial infarction,MI)和任意血运重建。通过Kaplan-Meier生存分析评估四组间终点的发生率。使用多因素Cox回归模型分析TyG指数与终点的独立相关性。此外,进行了限制性立方样条(restricted cubic spline,RCS)分析,以检验TyG指数与MACE之间的非线性关系。结果:随着基线TyG水平增加,MACE的发生率显著增加(P<0.001)。Kaplan-Meier曲线同样表明:随着基线TyG水平增加,MACE的发生率显著增加(Log-rank P <0.001)。多因素Cox回归分析模型表明,随着基线TyG水平的增加,患者MACE(组1作为参考;组2 HR=1.24,95%CI:0.84~1.83,P=0.279;组3 HR=2.13,95%CI:0.1.47~3.08,P <0.001;组4 HR=2.55,95%CI:1.76~3.68,P <0.001)的发生风险显著增加。RCS曲线表明,TyG指数与MACE结局之间呈线性关系,MACE发生风险随着TyG水平的升高而升高(非线性P>0.05)。结论:在缺血性HF合并T2DM行PCI术的患者中,随着TyG水平升高,MACE发生率显著升高,二者呈线性关系。TyG指数同时也是该人群MACE的独立预测因素。本研究结果仍需在前瞻性研究中得到进一步证实。

Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.