Macrophage modulation with dipeptidyl peptidase-4 inhibitors:A new frontier for treating diabetic cardiomyopathy?

This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients.

Review on the Effect of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors:A meta-analysis of cardiovascular outcome trials

BACKGROUND Dipeptidyl peptidase-4(DPP-4)inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus(T2DM).Recently,a series of large,randomized controlled trials(RCTs)addressing cardiovascular outcomes with DPP-4 inhibitors have been published.AIM To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias.METHODS We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020.We extracted data concerning the following“hard”efficacy outcomes:fatal and non-fatal myocardial infarction,fatal and non-fatal stroke,hospitalization for heart failure,hospitalization for unstable angina,hospitalization for coronary revascularization and cardiovascular death.We also extracted data regarding the risk for major cardiac arrhythmias,such as atrial fibrillation,atrial flutter,ventricular fibrillation and ventricular tachycardia.RESULTS We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo.DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction[risk ratio(RR)=1.02,95%CI:0.94-1.11,I2=0%],hospitalization for heart failure(RR=1.09,95%CI:0.92-1.29,I2=65%)and cardiovascular death(RR=1.02,95%CI:0.93-1.11,I2=0%).DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke(RR=0.96,95%CI:0.85-1.08,I2=0%)and coronary revascularization(RR=0.99,95%CI:0.90-1.09,I2=0%),Finally,DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina(RR=1.00,95%CI:0.85-1.18,I2=0%).As far as cardiac arrhythmias are concerned,DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation(RR=0.95,95%CI:0.78-1.17,I2=0%),while they were associated with a significant increase in the risk for atrial flutter,equal to 52%(RR=1.52,95%CI:1.03-2.24,I2=0%).DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias.CONCLUSION DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM,while they do not seem to be associated with a significant risk for any major cardiac arrhythmias,except for atrial flutter.Therefore,this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors,except for those cases when newer antidiabetics(glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors)are not tolerated,contraindicated or not affordable for the patient.

Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases:Current evidence

Dipeptidyl peptidase-4 inhibitors(DPP-4i)have an important place in the management of type 2 diabetes.The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological functions.DPP-4 regulates several immune functions,including T-cell activation,macrophage function,and secretion of cytokines.Studies have reported an increase in autoimmune diseases like bullous pemphigoid,inflammatory bowel disease,and arthritis with DPP-4i use.The relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more clearly.Whether a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious issue.Nevertheless,a heightened awareness from the clinicians is required to identify and treat any such diseases.Through this review,we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.

Association between plasma dipeptidyl peptidase-4 levels and cognitive function in perinatal pregnant women with gestational diabetes mellitus

BACKGROUND Dipeptidyl peptidase-4(DPP4)is associated with cognitive dysfunction in patients with type 2 diabetes.AIM To assess a possible relationship between serum DPP4 and cognitive function in perinatal pregnant women with gestational diabetes mellitus(GDM).METHODS The study subjects were divided into three groups:GDM group(n=81),healthy pregnant(HP)group(n=85),and control group(n=51).The Montreal Cognitive Assessment(MoCA)was used to assess the cognitive status of each group.Venous blood samples were collected to measure blood lipids,glycated hemoglobin,and glucose levels.For each participant,a 3-mL blood sample was collected and centrifuged,and the serum was collected.Blood samples were stored at-80℃,and DPP4,interleukin-6(IL-6),and 8-iso-prostaglandin F2α(8-iso-PGF2α),and brain-derived neurotrophic factor(BDNF)were detected using ELISA.RESULTS The MoCA scores in the GDM and HP groups were significantly different from those in the control group in terms of visuospatial/executive function and attention(P<0.05);however,the scores were not significantly different between the GDM and HP groups(P>0.05).In terms of language,the GDM group had significantly different scores from those in the other two groups(P<0.05).In terms of memory,a significant difference was found between the HP and control groups(P<0.05),as well as between the GDM and HP groups.The levels of DPP4,IL-6,and 8-iso-PGF2αin the GDM group were significantly higher than those in the HP and control groups(P<0.05);however,the differences between these levels in the HP and control groups were not significant(P>0.05).The level of BDNF in the GDM group was significantly lower than that in the HP and control groups(P<0.05),although the difference in this level between the HP and control groups was not significant(P>0.05).CONCLUSION Cognitive dysfunction in perinatal pregnant women with GDM mainly manifested as memory loss,which might be associated with elevated DPP4 levels.

Efficacy of omarigliptin,once-weekly dipeptidyl peptidase-4 inhibitor,in patients with type 2 diabetes

BACKGROUND Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors(DPP-4is).Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice,data regarding its efficacy in patients with type 2 diabetes(T2D)after switching are limited.AIM To analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents.METHODS Forty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is:switched from linagliptin,switched from sitagliptin,and switched from vildagliptin.During a 3-mo follow-up,the clinical parameters among these groups were assessed and compared,with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups.RESULTS Hemoglobin A1c levels saw a significant decrease of-0.32%±0.41%in the add-on group(P=0.002).However,the other groups’variables depended on the preswitch daily DPP-4i:switched from linagliptin,-0.05%±0.22%;switched from sitagliptin,-0.17%±0.33%;and switched from vildagliptin,0.45%±0.42%,which saw significant worsening(P=0.0007).Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control(P=0.0013).The mean and standard deviation of sensor glucose value,the mean amplitude of glycemic excursions,and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin.However,in patients switched from vildagliptin,not only did the glucose variability indices see no improvements,the mean of daily difference even underwent significant worsening.CONCLUSION Administering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin,but not vildagliptin,improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients.

Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes

The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.

Risk of pancreatic adverse events associated with the use of glucagon-like peptide-1 receptor agonist and dipeptidyl peptidase-4 inhibitor drugs: A systematic review and metaanalysis of randomized trials

AIM: To systematically assess risk of pancreatic adverse events with glucagon-like peptide-1(GLP-1) receptor agonist and dipeptidyl peptidase-4(DPP-4) inhibitor drugs.METHODS: We searched Pub Med, Embase, CINAHL, Cochrane review of clinical trials, pharmaceutical company clinical trials register, United States Food and Drug Administration website, European Medicines Agency website and Clinical Trials.gov for randomized controlled trials from inception to October 2013. Randomized control trial studies were selected for inclusion if they reported on pancreatic complication events and/or changes in pancreatic enzyme levels(serum amylase and serum lipase) as adverse events or as serious adverse events for patients who were on GLP-1 receptor agonist and DPP-4 inhibitor drugs. Two independent reviewers extracted data directly. We performed Peto odds ratio(OR) fixed effect meta-analysis of pancreatic adverse events a, and assessed heterogeneity with the I^2 statistic.RESULTS: Sixty-eight randomized controlled trials were eligible. A total of 60720 patients were included in our analysis of the association of risk of pancreatic complication events with GLP-1 agents. A total of 89 pancreatic related adverse events occurred among the GLP-1 agents compared to 74 events among the controls. There was a statistically significant increased risk of elevation of pancreatic enzymes associated with GLP-1 agents compared with control(Peto OR = 3.15, 95%CI: 1.56-6.39, P = 0.001, I2 = 0%). There was no statistically significant difference in the risk of pancreatic adverse event associated with GLP-1 agent compared with controls(Peto OR = 1.00, 95%CI: 0.73-1.37, P = 1.00, I2 = 0%). There were a total of 71 pancreatitis events in patients on GLP-1 agents and 56 pancreatitis events occurred in the control patients. There were 36 reports of pancreatic cancer in these studies. Of these cases, 2 used linagliptin, 2 used alogliptin, 1 used vildagliptin, 7 used saxagliptin while 6 used sitagliptin. The remaining 18 cases occurred among controls.CONCLUSION: Although GLP-1 based agents are associated with pancreatic enzyme elevation, we were unable to confirm a significant risk of pancreatitis or pancreatic cancer.

Renoprotection Provided by Dipeptidyl Peptidase-4 Inhibitors in Combination with Angiotensin Receptor Blockers in Patients with Type 2 Diabetic Nephropathy

Background: Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy (DN) has not been well characterized. This study aimed to assess the renoprotection of this combined treatment in DN patients.Methods: A total of 159 type 2 DN patients from 2013 to 2015 were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases, Jinling Hospital (China). Fifty-seven patients received DPP4i and ARB treatment, and 102 patients were treated with ARBs alone. All patients were followed up for at least 12 months. Statistical analyses were performed using Stata version 12.0.Results: There were no significant differences at baseline for age, sex, body mass index, duration of diabetes, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) between the two groups. Antihypertensive and antidiabetic medication use was similar in each group except calcium channel antagonists (P = 0.032). No significant changes in FBG and HbA1c were observed in the two groups after treatment. The eGFR decreased slower in the DPP4i + ARB group than in the ARB group at 12 months (?12 months: -2.48 ± 13.86 vs. -6.81 ± 12.52 ml·min–1·1.73m–2,P = 0.044). In addition, proteinuria was decreased further in the DPP4i + ARB group than in the ARB group after 24 months of treatment (?24 months: -0.18 [-1.00, 0.17] vs. 0.32 [-0.35, 0.88],P = 0.031). There were 36 patients with an eGFR decrease of more than 30% over 24 months. After adjusting for FBG, HbA1c, and other risk factors, DPP4i + ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%.Conclusions: The combined treatment of DPP4i and ARBs is superior to ARBs alone, as evidenced by the greater proteinuria reduction and lower eGFR decline. In addition, the renoprotection of DPP4i combined with ARBs was independent of glycemic control.

Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagonlike peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease

Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD.On the other hand,diabetes mellitus(DM)is a risk factor for the cognitive dysfunction.The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate,which contains neuro-inflammation and/or neurodegeneration and dementia.Glucagon-like peptide-1(GLP1)is interesting as a possible link between metabolism and brain impairment.Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD.The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit.They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes.Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4(DPP4)inhibitors,being currently used for DM therapy,may also be effective for AD treatment.The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models.Although further studies for mTOR,GLP1,and DPP4 signaling pathways in humans would be intensively required,they seem to be a promising approach for innovative AD-treatments.We would like to review the characteristics of AD pathogenesis,the key roles of mTOR in AD and the preventive and/or therapeutic suggestions of directing the mTOR signaling pathway.

5个原研二肽基肽酶4抑制剂的综合评价

目的:对5个原研二肽基肽酶4(DPP-4)抑制剂进行可量化的客观评价,为医疗机构遴选药品提供量化参考,为临床药品选择提供依据。方法:应用《中国医疗机构药品评价与遴选快速指南(第二版)》(以下简称“指南”)的评价体系,对5个原研DPP-4抑制剂的药学特性、有效性、安全性、经济性和其他属性等5个维度进行量化打分。结果:所有纳入评价的DPP-4抑制剂的评分均>70分,依次为西格列汀79.0分、维格列汀72.8分、沙格列汀76.1分、利格列汀78.7分、阿格列汀76.9分。结论:基于指南的标准,本次评价涉及的5个原研DPP-4抑制剂的评价结论均为“保留”,强推荐。但是,本次药品评价维度较多,涉及药品在各维度均有不同的优势,各医疗机构可根据评价细则及权重,按照医疗机构特点和实际需求对评价结果进行采用。

基于医院卫生技术评估的5种二肽基肽酶4抑制剂的临床应用情况

目的通过医院卫生技术评估(HB-HTA)对5种二肽基肽酶4抑制剂(DPP-4i)(西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀)进行评估,为医疗机构药品的遴选、临床的合理安全使用提供依据。方法通过HB-HTA,依照百分制评分体系,参考药品说明书、临床指南和文献,从安全性、有效性、经济型、创新性、适宜性和可及性等方面分别对5种DPP-4i进行评估。结果西格列汀、维格列汀、沙格列汀、利格列汀和阿格列汀得分分别为85.0、75.0、77.0、80.0、78.5分。评分差异主要在安全性、经济性、适宜性和可及性方面。西格列汀综合得分最高。结论HB-HTA评估DPP-4i结果比较合理,为医院药品遴选、安全合理使用提供依据。

利用受体配体亲和技术筛选黄芩中血管紧张素转换酶2和二肽基肽酶4抑制剂

目的筛选中药黄芩中血管紧张素转换酶2(ACE2)和二肽基肽酶4(DPP-4)抑制剂。方法以ACE2和DPP-4作为靶蛋白,利用受体配体亲和超滤和液质联用技术,对黄芩中与ACE2和DPP-4亲和的化合物进行筛选和分析,以筛选具有同时抑制ACE2和DPP-4的化合物。结果从黄芩中筛选出了5,7,2′,6′-4羟基黄酮、5,7,2′,5′-4羟基-8,6′-二甲氧基黄酮、白杨素-7-O-葡萄糖醛酸苷、黄芩素-6-O-葡萄糖醛酸苷、千层纸素A-7-O-葡萄糖醛酸苷、汉黄芩苷、白杨素、千层纸素A,可以同时亲和抑制ACE2和DPP-4,具有潜在的抗新型冠状病毒的作用。结论从黄芩中筛选出与新型冠状病毒肺炎有关的靶蛋白抑制剂,具备潜在开发价值。

二肽基肽酶4抑制剂对2型糖尿病患者肌酐水平影响的Meta分析

[目的]探讨二肽基肽酶4抑制剂(DPP-4i)对2型糖尿病(T2DM)患者血清肌酐(Cr)的影响。[方法]系统检索PubMed、Embase、Cochrane Library和Web of Science数据库,纳入DPP-4i治疗T2DM患者调节Cr的随机对照试验(RCT)。采用固定效应或随机效应模型进行数据拟合,采用I^(2)指数定量评价异质性,使用标准方法进行敏感性分析和发表偏倚检验。[结果]经系统检索数据库,纳入12项RCT,共计2276名受试者。由于潜在异质性的原因,故采用随机效应模型进行数据拟合,DPP-4i治疗可轻度提高T2DM患者的Cr水平(WMD:0.15 mg/L,95%CI:0.03~0.27,I^(2)=18%,P=0.02),结果具有统计学差异。根据敏感性测试,Meta分析其结果较为可靠。同时进行Begg’s与Egger’s检验,未见发表偏倚。[结论]T2DM患者应用DPP-4i进行降糖治疗,可能会出现血Cr水平轻度升高。未来还需开展更大样本量的多中心研究,以进一步探讨DPP-4i治疗引起Cr水平改变的临床意义。

GLP-1RA与DPP-4i治疗2型糖尿病的疗效及对患者并发症的影响

目的探讨胰高糖素样肽1受体激动剂(GLP-1RA)与二肽基肽酶4抑制剂(DPP-4i)治疗2型糖尿病(T2MD)的疗效及对患者并发症的影响。方法选取2020年6月至2022年6月邯郸市第一医院收治的110例T2MD随机分为GLP-1RA组和DPP-4i组,每组55例,GLP-1RA组采用利拉鲁肽或艾塞那肽治疗,DPP-4i组采用西格列汀或利格列汀治疗。对比2组临床疗效,治疗前后糖脂代谢指标[空腹血糖(FPG)、糖化血红蛋白(HbA1c)、总胆固醇、三酰甘油]、炎症指标[白介素-6(IL-6)、C反应蛋白(CRP)、中性粒细胞/淋巴细胞(NLR)]、肾功能[尿素氮、肌酐、胱抑素C];观察并统计2组并发症及不良反应。结果2组总有效率、并发症总发生率比较差异均无统计学意义(P>0.05)。治疗18周后,2组FPG、HbA1c、三酰甘油、总胆固醇水平低于治疗前,且GLP-1RA组低于DPP-4i组(P<0.05)。治疗18周后,2组IL-6、CRP、NLR水平低于治疗前(P<0.05),但2组间差异无统计学意义(P>0.05)。2组治疗前和治疗18周后尿素氮、肌酐、胱抑素C水平比较差异均无统计学意义(P>0.05)。GLP-1RA组不良反应总发生率高于DPP-4i组(P<0.05)。结论GLP-1RA与DPP-4i均能改善T2MD患者糖脂水平,减轻炎性反应,保护肾功能,预防并发症发生,但GLP-1RA在控制血糖、调脂方面优于DPP-4i,而DPP-4i耐受性更好。

DPP4抑制剂在2型糖尿病中的临床应用及研究进展

2型糖尿病(Type 2 Diabetes Mellitus,T2DM)在我国具有较高的发病率,是中老年患者常见的一种慢性代谢疾病,可累及心脑血管等多个系统发生病变,危及生命安全,需及时治疗。二肽基肽酶-4(Dipeptidyl Peptidase-4,DPP4)可促进胰岛素生成,并分泌胰高血糖素,与T2DM有着密切关联,是目前我国T2DM治疗研究中的一个新方向。DPP4抑制剂是多项研究的结果,能够提高降糖效果,对多种降糖无效的患者均有显著作用。基于此,本文主要综述了DPP4抑制剂治疗T2DM的作用机制,分析DPP4抑制剂在T2DM中的应用及研究进展,以期为T2DM治疗提供参考。

甲状腺髓样癌血浆二肽基肽酶-4水平及临床意义

目的探究血浆二肽基肽酶-4(DPP4)与甲状腺髓样癌(MTC)术后无病生存期(DFS)、总生存期(OS)、生化治愈之间的关系。方法收集2012年至2022年在邢台市人民医院就诊的144例MTC患者,采用酶联免疫吸附法测定血浆DPP4水平,分析血浆DPP4水平与MTC临床病理特征以及预后的关系。结果MTC术后存活组(n=131)血浆DPP4水平显著低于死亡组(n=12),MTC术后未复发组(n=120)血浆DPP4水平显著低于复发组(n=23),差异均有统计学意义(P<0.001)。血浆DPP4水平与性别、肿瘤数目、淋巴结清扫总数、转移性淋巴结数量、甲状腺外扩张、病理T分期、病理N分期、生存和复发均有关(P<0.05)。Kaplan-Meier结果显示,血浆DPP4≥0.12 ng/L组MTC患者术后OS、DFS更低(P<0.05)。与获得生化治愈患者比较,未获得生化治愈患者术前血浆DPP4≥0.12 ng/L比例更高(P<0.001)。结论术前血浆DPP4水平升高与MTC患者预后不良有关,具有成为低侵入性预后生物标志物的潜力。

CD26/二肽基肽酶4与甲状腺乳头状癌的相关性研究进展

随着近年来甲状腺乳头状癌(PTC)发病率的不断上升,寻找PTC诊断和预后的指标迫在眉睫。目前国内外多数CD26/二肽基肽酶4(DPP4)与PTC关系的研究均显示,CD26/DPP4在PTC组织中高表达,但是否与淋巴结转移、肿瘤直径、肿瘤分期等因素呈正相关仍不明确。既往研究存在实验方法局限、地域局限、选定病例类型粗略等的问题。因此,基于目前CD26/DPP4与PTC关系的研究现状,本研究通过检索大量文献,对国内外部分学者的相关文献进行了梳理和总结,以明确对CD26/DPP4与PTC的关系,为寻找PTC诊断和预后指标提供借鉴。

绝经后骨质疏松患者血清DPP-4、UA、P、25(OH)D_(3)水平变化及其与骨代谢指标的相关性

目的检测绝经后骨质疏松患者血清二肽基肽酶-4(DPP-4)、尿酸(UA)、孕酮(P)、25羟维生素D_(3)[25(OH)D_(3)]水平,并分析其与骨代谢指标的相关性。方法选择2022年2月至2023年2月西安医学院第一附属医院收治的320例绝经后骨质疏松患者作为观察组,并选择同期在我院接受体检的300名健康绝经女性作为对照组,比较两组受检者的血清DPP-4、UA、P、25(OH)D_(3)水平及骨代谢指标[骨钙素(OC)、I型前胶原氨基末端前肽(PINP)、β-胶联降解产物(β-CTX)及骨碱性磷酸酶(BALP)],并采用Pearson法分析血清DPP-4、UA、P、25(OH)D_(3)水平与骨代谢指标的相关性。结果观察组患者的血清DPP-4水平为(183.41±21.49)IU/L,明显高于对照组的(125.82±13.04)IU/L,UA、P、25(OH)D_(3)水平分别为(252.83±21.69)μmol/L、(1.23±0.18)nmol/L、(21.21±3.72)ng/mL,明显低于对照组的(304.34±25.77)μmol/L、(1.70±0.22)nmol/L、(32.74±3.51)ng/mL,差异均有统计学意义(P<0.05);观察组患者OC、PINP、β-CTX、BALP分别为(8.02±1.18)μg/L、(225.34±34.02)ng/mL、(0.75±0.09)ng/mL、(21.76±3.05)μg/L,明显高于对照组的(5.57±0.84)μg/L、(175.06±26.71)ng/mL、(0.45±0.06)ng/mL、(15.80±2.43)μg/L,差异均有统计学意义(P<0.05);经Pearson相关性分析结果显示,血清DPP-4与OC、PINP、β-CTX、BALP均呈正相关(P<0.05),UA、P、25(OH)D_(3)与OC、PINP、β-CTX、BALP均呈负相关(P<0.05)。结论绝经后骨质疏松患者血清DPP-4水平升高,UA、P、25(OH)D_(3)水平降低,且均与骨代谢指标具有明显相关性,临床上应予以密切关注。

DPP-4抑制剂治疗2型糖尿病合并非酒精性脂肪肝的作用研究进展

二肽基肽酶4(DPP-4)抑制剂是一种较新类型的糖尿病治疗药物,其主要的降糖机制是通过减少肠促胰素降低,来提高内源性胰高血糖素样肽1,进而促进胰岛素分泌与抑制胰高血糖素分泌,降低机体血糖水平。2型糖尿病(T2DM)与非酒精性脂肪肝(NAFLD)是临床常见的疾病类型,发病率居高不下。T2DM和NAFLD能够相互影响,相互促进,T2DM合并NAFLD不仅容易提高心血管疾病的患病风险与加重内分泌代谢紊乱,而且容易推动NAFLD病情进展,导致出现肝硬化、肝癌等恶性病变。目前大量研究显示,DPP-4抑制剂能够有效降低T2DM患者血糖水平和改善胰岛素抵抗,且对NAFLD具有较好的预防作用。本文从DPP-4抑制剂对治疗T2DM合并NAFLD的疗效与安全性方面进行综述。