化疗对恶性肿瘤患者血糖代谢的影响

大部分肿瘤患者起病隐匿,多数不能早期发现,早期治疗,全身化疗逐渐发挥着不可替代的作用。但化疗引起的副作用也须引起足够的重视。国内外多项研究报道,临床有相当部分病人化疗后出现血糖升高,甚或继发糖尿病,严重影响化疗的效果及患者生活质量。本文就血糖升高的机制,恶性肿瘤化疗与血糖异常的相关性及化疗影响血糖代谢的可能机制做一综述。     

肺癌与高血糖

<正>肺癌的发病率逐年上升,已成为我国发病率及死亡率第一位的恶性肿瘤。糖尿病的发病率也逐年攀升,直接影响了人们的生活质量及寿命。肺癌与糖尿病可通过多种机制相互促进,相互影响,加重患者病情,因而受到了人们的重视。一、肺癌引起血糖升高的机制有研究显示,肺癌患者中糖尿病发病率较一般人群高,且在化疗期间常出现血糖的进一步升高,如化疗后病情缓解,血糖水平又可下降。提示在肺癌患者中,血糖水平与化疗及病情的进展或缓解相关[1]。肺癌患者血糖水平升高的     

多西他赛对乳腺癌患者糖代谢的影响

目的 探讨多西他赛对乳腺癌患者糖代谢的影响.方法 124例经术后病理证实的女性乳腺癌患者术后均接受含多西他赛方案化疗,化疗前均已排除血糖异常及糖尿病,观察每周期化疗前后血糖及糖化血红蛋白变化.结果 全部124例患者均按计划完成6周期化疗.化疗后有11例(8.87％)空腹血糖升高,24例(19.35％)糖耐量减低;其中诊断为2型糖尿病者8例(6.45％),一过性血糖增高5例(4.03％).结论 乳腺癌接受含多西他赛方案化疗后可能引起血糖增高、糖耐量减低,甚至2型糖尿病,化疗期间应密切监测血糖及糖化血红蛋白水平,及时干预治疗.     

顺铂为基础的联合化疗对非小细胞肺癌患者血糖影响的临床观察

目的:探讨顺铂(DDP)为基础的联合化疗在非小细胞性肺癌(NSCLC)治疗中对血糖变化的影响.方法:以顺铂为基础的联合化疗患者150例,回顾性分析化疗前后的血糖变化情况及相关临床资料.结果:150例患者中,化疗期间6例(4.00%)确诊为糖尿病(DM),6例(4.00%)出现糖耐量减低(IGT),10例(6.67%)出现空腹血糖受损(IFG),8例(5.33%)一过性血糖升高,继发DM患者化疗前后的平均血糖值分别为(5.08±0.18)和(10.79±2.80)mmol/L,化疗前后空腹血糖水平差异有统计学意义,t=5.200,P=0.003.继发DM多发生在化疗的第3.5个周期,DDP的累积量约280 mg/m2.结论:常规剂量顺铂化疗能引起DM、IGT、IFG及一过性血糖升高,化疗期间应密切监测血糖.     

化疗对恶性肿瘤合并糖尿病患者血糖的影响

目的:探讨恶性肿瘤合并糖尿病患者接受化疗后血糖的变化及临床意义,并分析血糖变化的影响因素.方法:对2005年3月～2006年9月收住本院的23例恶性肿瘤合并糖尿病患者化疗前后按时检测血糖的变化,收集相关临床资料,分析化疗后血糖变化规律及影响因素.结果:化疗后即刻测血糖较化疗前显著升高(P＜0.01),化疗后第1、2、3、4天血糖随时间推移逐渐下降,约至第5、6天左右降至化疗前水平.化疗后即刻血糖30.4%(7/23)高于16.7mmol/L,最高达23.1mmol/L.化疗前血糖升高的患者化疗后血糖更高(P＞0.05).单个药化疗方案或多药联合方案,含抗代谢药、铂类、蒽环类、紫杉类的化疗方案分别较不含该类药的方案相比对化疗后血糖影响无差异.结论:化疗可导致恶性肿瘤合并糖尿病患者血糖进一步升高,尤其发生在化疗前血糖升高的患者,有可能发生酮症酸中毒.随时间推移血糖逐渐下降,约至第5、6天降至化疗前水平.     

化疗对肿瘤患者血糖的影响及其防治措施

肿瘤与糖尿病关系密切,如胰腺癌、结直肠癌、乳腺癌等.肿瘤患者合并糖尿病往往更容易死亡和复发.化疗能够挽救和延长肿瘤患者的生命,而化疗药物、化疗辅助药物、化疗副反应等却可能引起肿瘤患者血糖的波动,诱发或加重糖尿病,甚至出现酮症酸中毒、昏迷、死亡.因而,化疗应在血糖有效控制下进行.化疗引起血糖异常主要与化疗药物的毒性作用、化疗辅助药物引起的糖代谢紊乱等有关.依据美国2003年新版的化疗毒副作用评价体系CTCAE V3.0.严格监测肿瘤患者化疗期间血糖水平,并采取合适的措施控制高血糖、防护低血糖,使肿瘤患者能够安全顺利地完成肿瘤化疗.目前,血糖控制理想的肿瘤有乳腺癌、结直肠癌、恶性淋巴瘤、肺癌、食管癌等,血糖控制较差的肿瘤有原发性肝癌、胰腺癌等.本文拟就化疗引起血糖异常的有关因素、可能机制及英防治措施作一综述.     

化疗对恶性肿瘤合并糖尿病40例血糖的影响

[目的]探讨恶性肿瘤合并糖尿病患者化疗前后血糖的变化。[方法]检测40例恶性肿瘤合并糖尿病患者化疗前后血糖的变化。[结果]40例患者完成预计的化疗周期数,12例患者化疗期间出现高血糖（〉14.0mmol/L）,其中3例血糖高于27.8mmol/L,尿酮体阳性;3例患者出现低血糖反应;6例患者均对症处理后好转。化疗期间及化疗后血糖均较化疗前显著升高（P〈0.01）。[结论]化疗可导致恶性肿瘤合并糖尿病患者血糖进一步升高,尤其发生在化疗前血糖升高的患者。     

癌症合并糖尿病患者应用糖皮质激素安全性的前瞻性随机对照研究

目的从循证医学的角度探讨癌症合并糖尿病的患者使用糖皮质激素(glucorticoids,GC)是否安全。方法有糖尿病史或治疗前发现糖尿病者进入糖尿病组,无糖尿病史治疗前空腹血糖高于正常但未达到糖尿病诊断标准者进入空腹血糖损害(i m-paired fasting glucose,IFG)组,通过计算机随机筛选出最适合与实验组配对者作为对照组。GC及化疗根据需要按常规选择,定期测定全部患者的静脉血糖、糖尿病患者和IFG患者的毛细血管血糖,前瞻性评价GC治疗后的血糖变化、不良反应及其影响因素。结果糖尿病组患者29例,使用GC后恶心呕吐、腹部不适、头痛、失眠、肺炎、多汗、心慌及血压升高的比例高于对照组,但均无统计学意义。接受GC治疗期间,只有1例(3%)血糖正常,28例(97%)有1次以上血糖升高,显著高于对照组,t=6·309,P=0·000。但均在可以控制且不影响肿瘤治疗及GC治疗的范围内。对照组患者有5例(17%)血糖高于正常,其中1例血糖有4次血糖高于正常。入院前未接受降糖治疗的糖尿病患者,需要改变降糖措施的比例(2/11)高于入院前已接受降糖治疗的糖尿病患者(2/18)和IFG患者(2/24),但差异无统计学意义,F=0·73,P=0·694。IFG组24例,与糖尿病组有类似的结果。入院血糖正常的220例患者中,化疗后20例空腹血糖升高(9·09%)。未化疗仅使用GC者34例,4例空腹血糖升高(11·76%),无统计学意义。但在化疗患者中,不同的化疗方案影响血糖升高的发生率。NP方案治疗后发生空腹血糖升高的比例为34·61%,高于CAF(4·76%)、FLP(4·76%)、EP(3·70%)等治疗方案。结论癌症患者伴发糖尿病及IFG的比例远高于一般人群,但常规应用GC是安全的。血糖正常患者化疗同时使用GC,个别化疗药物、年龄、地塞米松日剂量和病期影响空腹血糖升高的发生率。     

血糖升高与胰腺癌的早期诊断

目的探讨血糖升高能否成为早期诊断胰腺癌的一个指标,是否有助于胰腺癌的早期治疗.方法总结1983年1月～2003年1月经病理证实的128例胰腺癌的临床资料.结果 128例中血糖升高者67例,行根治性手术8例(11.9%);血糖正常者61例,行根治性手术20例(32.8%).结论胰腺癌合并血糖升高者行根治性手术机会小,要提高其早期诊断率,应在胰腺癌高危人群中定期监测血糖及行其他相关检查.     

癌症合并糖尿病患者应用糖皮质激素安全性的前瞻性随机对照研究

目的：从循证医学的角度探讨癌症合并糖尿病的患者使用糖皮质激素（glucorticoids，GC）是否安全。方法：有糖尿病史或治疗前发现糖尿病者进入糖尿病组，无糖尿病史治疗前空腹血糖高于正常但未达到糖尿病诊断标准者进入空腹血糖损害（impaired fasting glucose，IFG）组，通过计算机随机筛选出最适合与实验组配对者作为对照组。GC及化疗根据需要按常规选择，定期测定全部患者的静脉血糖、糖尿病患者和IFG患者的毛细血管血糖，前瞻性评价GC治疗后的血糖变化、不良反应及其影响因素。结果：糖尿病组患者29例，使用GC后恶心呕吐、腹部不适、头痛、失眠、肺炎、多汗、心慌及血压升高的比例高于对照组，但均无统计学意义。接受GC治疗期间，只有1例（3％）血糖正常，28例（97％）有1次以上血糖升高，显著高于对照组，t=6．309，P=0．000。但均在可以控制且不影响肿瘤治疗及GC治疗的范围内。对照组患者有5例（17％）血糖高于正常，其中1例血糖有4次血糖高于正常。入院前未接受降糖治疗的糖尿病患者。需要改变降糖措施的比例（2／11）高于入院前已接受降糖治疗的糖尿病患者（2／18）和IFG患者（2／24），但差异无统计学意义，F=0．73，P=0．694。IFG组24例，与糖尿病组有类似的结果。入院血糖正常的220例患者中，化疗后20例空腹血糖升高（9．09％）。未化疗仅使用LH者34例，4例空腹血糖升高（11．76％），无统计学意义。但在化疗患者中，不同的化疗方案影响血糖升高的发生率。NP方案治疗后发生空腹血糖升高的比例为34．61％，高于CAF（4．76％）、FLP（4．76％）、EP（3．70％）等治疗方案。结论：癌症患者伴发糖尿病及IFG的比例远高于一般人群，但常规应用GC是安全的。血糖正常患者化疗同时使用GC，个别化疗药物、年龄、地塞米松日剂量和病期影响空腹血糖升高的发生率。     

药物疗法对恶性肿瘤患者糖化血红蛋白和空腹血糖的影响

目的探讨药物疗法对恶性肿瘤患者糖化血红蛋白(Hb A1c)和空腹血糖(FBG)的影响。方法将2012年2月至2014年2月收治的63例恶性肿瘤行化疗患者作为研究对象,观察患者单次化疗前后、多次化疗前后的Hb A1c和FBG水平,同时分析血糖、胰岛素水平及胰岛功能与疗程的相关性。结果单次化疗后患者的FBG、空腹C-肽及胰岛素水平均明显高于化疗前(P<0.05),但单次化疗前后Hb A1c水平的差异无统计学意义(P>0.05)。多次化疗后患者的FBG、空腹C-肽、Hb A1c及空腹胰岛素水平均高于化疗前,差异有统计学意义(P<0.05)。不同疗程胰岛素抵抗指数(HOMA-IR)、Hb A1c及胰岛素水平与化疗次数呈正相关(P<0.05),而C-肽、FBG及胰岛素分泌指数(HOMA-β)与化疗次数无相关性(P>0.05)。结论化疗会影响恶性肿瘤患者的血糖代谢指标及胰岛功能,长期化疗则会降低胰岛功能并诱发糖尿病。     

Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.     

Dichloroacetate shifts the metabolism from glycolysis to glucose oxidation and exhibits synergistic growth inhibition with cisplatin in HeLa cells

The unique bioenergetic feature of cancer, aerobic glycolysis or the Warburg effect, is an attractive therapeutic target for cancer therapy. Reversing the glycolytic phenotype may trigger apoptosis in tumor cells. Recently, dichloroacetate (DCA) was proven to produce significant cytotoxic effects in certain tumor cells through this distinct mechanism. In this study, the effect of DCA on the metabolism of cervical cancer HeLa cells was explored and its synergistic growth inhibition with cisplatin was also evaluated. The intracellular changes in HeLa cells following DCA exposure were analyzed through cell viability, intracellular H2O2 and pH levels, mitochondrial membrane potential (MMP), expression of apoptotic proteins and Kv1.5 channel, and intracellular-free Ca2+ concentration ([Ca2+]i). For the evaluation of combination chemotherapy, HeLa cells were treated with a combination of DCA and cisplatin at various concentrations for 48 h. Cell viability was determined by CCK-8 assay and the synergy of the two agents was evaluated using the R index method. DCA shifted the metabolism of HeLa cells from aerobic glycolysis to glucose oxidation as shown by the increased intracellular H2O2 and pH levels. The change of the metabolism modality led to a drop in MMP and the increase of apoptotic proteins (caspase 3 and 9). The increased Kv1.5 expression and decreased [Ca2+]i established a positive feedback loop that resulted in reduced tonic inhibition of caspases. Combination chemotherapy of DCA and cisplatin exhibited a significant synergy in inhibiting the proliferation of HeLa cells. The specific apoptotic mechanism of DCA as distinguished from the cisplatin may be partly responsible for the synergy and further in vivo study on combination chemotherapy of the two agents in cervical cancer xenografts in mice is warranted.     

恶性肿瘤化疗后血糖增高与细胞因子的相关性研究

目的 探索恶性肿瘤化疗后血糖增高与细胞因子的相关性.方法 对155例恶性肿瘤患者化疗后血糖正常组、糖耐量异常组、糖尿病组细胞因子的变化情况,进行回顾性分析.结果 糖耐量异常组、糖尿病组化疗后白细胞介素-6(IL-6),肿瘤坏死因子α(TNF-α)水平较化疗前明显增高,与血糖正常组差异有统计学意义(P＜0.01),化疗后白细胞介素-10(IL-10)较化疗前增高,差异有统计学意义(P＜0.05).结论 恶性肿瘤患者化疗后血糖增高与细胞因子有密切的相关性.     

Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin

Chondrosarcomas are malignant cartilage-forming tumors which are resistant to conventional chemotherapy and radiotherapy. By searching in Oncomine which is a cancer microarray database and web-based data mining platform, we found Glut1 and LDHA were upregulated in human chondrosarcoma patient samples. In this study, we reported total epidermal growth factor receptor (EGFR) expression and phosphorylated EGFR were highly activated in human chondrosarcoma cell lines. In addition, overexpression of EGFR contributed to cisplatin resistance. EGFR promoted glucose metabolism of chondrosarcoma cells through the upregulation of glycolysis key enzymes. Interestingly, cisplatin-resistant chondrosarcoma cells showed upregulated glucose metabolism and EGFR signaling pathway. Finally, we demonstrated that the combination of either EGFR inhibitor or anaerobic glycolysis inhibitor with cisplatin showed synergistically inhibitory effects on cisplatin-resistant chondrosarcoma cells through the inducements of apoptosis and cell cycle arrest. Our project proposed a novel function of EGFR in the regulation of glucose metabolism in chondrosarcoma cells and contributed to the development of therapeutic strategies for the clinical treatment of chondrosarcoma patient.     

Enhanced radiosensitivity and chemosensitivity of breast cancer cells by 2-deoxy-d-glucose in combination therapy

Breast cancer is the most common malignancy, and it is also the major cause of cancer-related deaths of women worldwide. Breast cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy, and novel strategies are needed to boost the oncologic outcome. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) which inhibits glucose synthesis and adenosine triphosphate production, is one of the important discoveries involving the disturbances that can be caused to the process of the metabolism. The glucose analogue, 2-DG, is known as a tumor sensitizer to irradiation (IR) and chemotherapy, which help improve the treatment rates. It enhances the cytotoxicity via oxidative stress, which is more redundant in tumor cells than in normal ones. This article provides a brief summary on studies related to 2-DG chemo-/radio-sensitization effects by combination therapy of 2-DG/IR or 2-DG/doxorubicin.     

Imaging of tumor glucose utilization with positron emission tomography

In recent years, imaging of tumor glucose metabolism with positron emission tomography and fluorodeoxyglucose (FDG-PET) has become a routine test for detection, staging and restaging of malignant lymphomas and many solid tumors. FDG-PET is also increasingly used to monitor the effects of chemotherapy. The success of FDG-PET in oncologic imaging has generated considerable interest in understanding the molecular mechanisms underlying the markedly accelerated glucose use of almost all human cancers. Recent studies have indicated that there may be a close relation between the activation of oncogenic signaling pathways and cellular glucose utilization. For example deregulation of Akt, ras and MYC as well as loss of p53 function have been reported to confer increased glucose metabolic rates in cancer cells. These findings suggest that imaging of tumor glucose utilization may represent a marker for the activity of oncogenic pathways and metabolic changes during therapy may be used as a readout for the effectiveness of drugs targeting these pathways. However, the mechanisms for increased glucose metabolic activity of cancers cells are multifactorial and clinical studies will be necessary to determine in which context imaging of tumor glucose metabolism may be used for treatment monitoring.     

无糖尿病病史的乳腺癌患者系统治疗后糖耐量异常状况研究

  目的  通过口服葡萄糖耐量试验(OGTT)了解无糖尿病病史的乳腺癌患者系统治疗后糖耐量异常状况。  方法  对121例系统治疗(手术治疗和/或化疗)结束后3个月以上无糖尿病病史的乳腺癌患者行OGTT检测, 检测空腹及OGTT餐后2 h血糖值以明确此类患者有无伴随糖耐量异常, 同期6例有糖尿病病史的乳腺癌患者未行OGTT检测。  结果  患者平均随访年龄为50.4岁, 系统治疗后平均随访时间为19个月。在121例无糖尿病病史的乳腺癌患者中:糖尿病(即未知晓糖尿病)和糖尿病前期发生率分别为19.8%(24/121)和45.5%(55/121), 糖耐量相对正常仅占34.7%(42/121);在所有127例系统治疗后的乳腺癌患者中已知晓糖尿病、未知晓糖尿病及糖尿病前期发生率分别为4.72%(6/127)、18.9%(24/127)和43.3%(55/127), 其中糖尿病的未知晓率高达80%。约80%的糖尿病及74.5%糖尿病前期的诊断需经OGTT餐后2 h血糖检测确诊而非空腹血糖检测。  结论  系统治疗后的乳腺癌患者存在明显的糖代谢紊乱, 伴有高比例的未知晓糖尿病和糖尿病前期, 对此类患者建议行OGTT检测, 以利于早期诊断和防治糖尿病的发生, 改善预后。