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Popevic S, Maric N, Ilic B, Belic S, Sekulovic Radovanovic I, Dimic-Janjic S, Stjepanovic M. Hyperglycemia and Lung Cancer-A Possible Relationship. Diagnostics (Basel) 2025; 15:651. [PMID: 40149994 PMCID: PMC11941620 DOI: 10.3390/diagnostics15060651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 01/31/2025] [Accepted: 03/04/2025] [Indexed: 03/29/2025] Open
Abstract
Glucose is the main source of energy in human cells. Elevated levels of glucose are one of the most common metabolic disorders, and it has been shown to have a significant, mostly negative, effect on multiple chronic and acute diseases. Lung cancer remains one of the biggest challenges for treatment in modern medicine, with a high prevalence, incidence and mortality. Hyperglycemia is not uncommon in patients with lung cancer; however, it is usually overlooked. Patients with unregulated glycemia and lung cancer have been shown to have worse outcomes, reduced therapeutic effect and more complications during treatment. Studies have identified multiple molecular pathways common in both hyperglycemia and lung cancer; however, no clear correlation has been identified. By understanding these signaling pathways, we can influence the outcome therapeutically and thereby improve the survival of patients with lung cancer.
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Affiliation(s)
- Spasoje Popevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.I.); (S.B.); (S.D.-J.); (M.S.)
- Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.M.); (I.S.R.)
| | - Nikola Maric
- Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.M.); (I.S.R.)
| | - Branislav Ilic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.I.); (S.B.); (S.D.-J.); (M.S.)
- Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.M.); (I.S.R.)
| | - Slobodan Belic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.I.); (S.B.); (S.D.-J.); (M.S.)
- Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.M.); (I.S.R.)
| | | | - Sanja Dimic-Janjic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.I.); (S.B.); (S.D.-J.); (M.S.)
- Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.M.); (I.S.R.)
| | - Mihailo Stjepanovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.I.); (S.B.); (S.D.-J.); (M.S.)
- Clinic of Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.M.); (I.S.R.)
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Mandal A, Sappati S, Karmakar A, Pradhan S, Gabriel I, Varanasi S. Smartphone-Assisted and Optical Quantification of Copper and Glucose Using Palm Wine-Tailored Carbon Dots and Their Multiple Logic Gate Application. ACS Biomater Sci Eng 2024; 10:5362-5380. [PMID: 39078112 DOI: 10.1021/acsbiomaterials.4c00640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2024]
Abstract
In this work, potassium, sulfur, nitrogen, and chlorine self-doped carbon dots (CDs) were hydrothermally synthesized using palm wine as a carbon source. The palm wine-derived CDs (PW-CDs) are amorphous in nature and displayed an average particle size of 4.19 ± 0.89 nm. The as-synthesized CDs are used to fabricate a photoluminescent sensing probe to simultaneously detect Cu2+ and glucose via the "Turn ON-OFF-ON" mechanism. The PL quenching mechanism of PW-CDs enables the selective and sensitive detection of Cu2+ ions with a detection limit (LOD) of 0.8 ppb (4.7 nM). The sensing probe quantified Cu2+ in tap water, drinking water, and e-waste samples to prove its viability. Using CDs to quantify copper in e-waste leachate samples is a novel approach as no prior instances of such application have been reported. The system's performance is considered to be highly reproducible due to the relative standard deviation being <6.64%, along with excellent recoveries within the range of 93.24-109.86%. The quenched PL can be recovered by introducing glucose into the PW-CD + Cu2+ system; this strategy is employed to quantify glucose with a LOD of 0.11 ppm (0.61 μM). The feasibility of this sensor was confirmed by the determination of glucose in actual human plasma specimens of diabetic patients. It is to be noted that these samples were neither diluted nor spiked with glucose. The developed PW-CD + Cu2+ sensing system yields satisfactory recoveries of 93.45-107.37%. This probe was also incorporated into a smartphone-based sensing platform to detect Cu2+ and glucose with desirable recoveries. The proposed smartphone-based sensing platform is flexible, reliable, and accurate, making it suitable for resource-constrained areas. Furthermore, based on the effect of Cu2+ ions and glucose on the PL response and absorbance spectra of PW-CDs, four logic gates (YES, IMPLICATION, NOT, and OR) were designed, and PW-CDs were also used for cell imaging applications.
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Affiliation(s)
- Anisha Mandal
- Department of Chemical Engineering, Indian Institute of Technology, Kharagpur, West Bengal 721302, India
| | - Subrahmanyam Sappati
- Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., Gdansk 80-233, Poland
| | - Ankita Karmakar
- Department of Physics, Indian Institute of Technology, Kharagpur, West Bengal 721302, India
| | - Supratim Pradhan
- School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal 721302, India
| | - Iwona Gabriel
- Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry and BioTechMed Center, Gdansk University of Technology, 11/12 Narutowicza Str., Gdansk 80-233, Poland
| | - Swambabu Varanasi
- Department of Chemical Engineering, Indian Institute of Technology, Kharagpur, West Bengal 721302, India
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Fang TZ, Wu XQ, Zhao TQ, Wang SS, Fu GMZ, Wu QL, Zhou CW. Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma. World J Diabetes 2024; 15:645-653. [PMID: 38680689 PMCID: PMC11045413 DOI: 10.4239/wjd.v15.i4.645] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/15/2023] [Accepted: 02/21/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). METHODS The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.
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Affiliation(s)
- Tian-Zheng Fang
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Xian-Qiao Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Ting-Qi Zhao
- Department of Endocrine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Shan-Shan Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Guo-Mei-Zhi Fu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Qing-Long Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Cheng-Wei Zhou
- Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
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Yuan Q, Li L, Wang LS, Xing SG. Epidemiological and transcriptome data identify shared gene signatures and immune cell infiltration in type 2 diabetes and non-small cell lung cancer. Diabetol Metab Syndr 2024; 16:64. [PMID: 38468345 DOI: 10.1186/s13098-024-01278-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 01/25/2024] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Numerous previous studies have reported an association between type 2 diabetes mellitus (T2DM) and lung cancer risk, but the underlying mechanism of the interaction remains unclear. This study aimed to investigate the shared genetic features and immune infiltration processes between lung cancer and T2DM. METHODS Epidemiological data from the National Health and Nutrition Examination Survey (NHANES) 2000-2018 was used to explore the relationship between lung cancer and diabetes systematically. In addition, we also used bioinformatics methods to analyze the transcriptome data from the Gene Expression Omnibus (GEO) to explore the potential functional mechanisms from the perspective of genes and immune infiltration. RESULTS Logistic regression analysis showed that prediabetes (OR = 3.289,95%CI 1.231, 8.788, p = 0.01760, model 3)and type 2 diabetes (OR = 3.032 95%CI,1.015, 9.054, p = 0.04689) were significantly associated with an increased risk of lung cancer after adjusting for multiple covariates. Data from NHANES showed an inverted U-shaped relationship between fasting blood glucose and glycosylated haemoglobin and the risk of lung cancer (P for non-linear < 0.001). Transcriptome data showed that we screened 57 co-DEGs, of which 25 were up-regulated co-DEGs and 32 were down-regulated. Ten core DEGs were identified by bioinformatics analysis, which were SMC6, CDC27, CDC7, RACGAP1, SMC4, NCF4, NCF1, NCF2, SELPLG and CFP. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells. CONCLUSION The identified core genes of NSCLC and T2DM are associated with dysregulated immune cells, which provides a potential research avenue for diagnosing and treating lung cancer combined with diabetes.
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Affiliation(s)
- Qian Yuan
- Department of Thoracic surgery, Nan Jing Gaochun people's Hospital (The Gaochun Affiliated Hospital of Jiang Su University), 210000, Nanjing, Jiangsu, China
| | - Long Li
- Department of Thoracic surgery, Nan Jing Gaochun people's Hospital (The Gaochun Affiliated Hospital of Jiang Su University), 210000, Nanjing, Jiangsu, China
| | - Liu-Shun Wang
- Department of Thoracic surgery, Nan Jing Gaochun people's Hospital (The Gaochun Affiliated Hospital of Jiang Su University), 210000, Nanjing, Jiangsu, China
| | - Shi-Gui Xing
- Department of Thoracic surgery, Nan Jing Gaochun people's Hospital (The Gaochun Affiliated Hospital of Jiang Su University), 210000, Nanjing, Jiangsu, China.
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Klupa T, Czupryniak L, Dzida G, Fichna P, Jarosz-Chobot P, Gumprecht J, Mysliwiec M, Szadkowska A, Bomba-Opon D, Czajkowski K, Malecki MT, Zozulinska-Ziolkiewicz DA. Expanding the Role of Continuous Glucose Monitoring in Modern Diabetes Care Beyond Type 1 Disease. Diabetes Ther 2023:10.1007/s13300-023-01431-3. [PMID: 37322319 PMCID: PMC10299981 DOI: 10.1007/s13300-023-01431-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 05/31/2023] [Indexed: 06/17/2023] Open
Abstract
Application of continuous glucose monitoring (CGM) has moved diabetes care from a reactive to a proactive process, in which a person with diabetes can prevent episodes of hypoglycemia or hyperglycemia, rather than taking action only once low and high glucose are detected. Consequently, CGM devices are now seen as the standard of care for people with type 1 diabetes mellitus (T1DM). Evidence now supports the use of CGM in people with type 2 diabetes mellitus (T2DM) on any treatment regimen, not just for those on insulin therapy. Expanding the application of CGM to include all people with T1DM or T2DM can support effective intensification of therapies to reduce glucose exposure and lower the risk of complications and hospital admissions, which are associated with high healthcare costs. All of this can be achieved while minimizing the risk of hypoglycemia and improving quality of life for people with diabetes. Wider application of CGM can also bring considerable benefits for women with diabetes during pregnancy and their children, as well as providing support for acute care of hospital inpatients who experience the adverse effects of hyperglycemia following admission and surgical procedures, as a consequence of treatment-related insulin resistance or reduced insulin secretion. By tailoring the application of CGM for daily or intermittent use, depending on the patient profile and their needs, one can ensure the cost-effectiveness of CGM in each setting. In this article we discuss the evidence-based benefits of expanding the use of CGM technology to include all people with diabetes, along with a diverse population of people with non-diabetic glycemic dysregulation.
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Affiliation(s)
- Tomasz Klupa
- Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
| | - Leszek Czupryniak
- Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Grzegorz Dzida
- Department of Internal Diseases, Medical University of Lublin, Lublin, Poland
| | - Piotr Fichna
- Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Janusz Gumprecht
- Department of Internal Medicine, Diabetology and Nephrology, Medical University of Silesia, Katowice, Poland
| | - Malgorzata Mysliwiec
- Department of Pediatrics, Diabetology and Endocrinology, Medical University of Gdansk, Gdansk, Poland
| | - Agnieszka Szadkowska
- Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland
| | - Dorota Bomba-Opon
- 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Czajkowski
- 2nd Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
| | - Maciej T Malecki
- Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland
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Yang J, Li N, Lin W, Deng M, Shi L, An Y, Yang J, Zhou C, Tong Q, Yang W. Comprehensive Analysis of Diabetes Mellitus-related Gene Expression and Associated Prognoses in Human Lung Cancer. Curr Cancer Drug Targets 2023; 23:889-899. [PMID: 37254545 DOI: 10.2174/1568009623666230529154306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 02/06/2023] [Accepted: 02/20/2023] [Indexed: 06/01/2023]
Abstract
INTRODUCTION Diabetes mellitus (DM) is a major public health problem worldwide. Cancer is the second most common cause of death in the United States and the leading cause of death in China. There is compelling evidence that individual risk for type 2 diabetes mellitus (T2DM) is strongly influenced by genetic factors. DM and cancer may interact with one another; some kinds of cancer accompany DM, and DM can also promote cancer. METHODS An analysis was conducted of diabetes mellitus-related gene (DM-gene) expression levels in tumor and normal tissues, clinical parameters, tumor stages, mutations, copy number variations (CNVs), immune cell infiltration, survival, gene enrichment, and gene ontology annotations. RESULTS This analysis revealed six genes that appear to play key roles in lung cancer survival: MTMR3 (in lung adenocarcinoma [LUAD]) and COBLL1, PPARG, PPIP5K2, RREB1, and WFS1 (in lung squamous cell carcinoma [LUSC]). CONCLUSION The results suggested that clinical practitioners and researchers should account for PPARG and RREB1 expression when selecting or testing chemotherapy drugs.
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Affiliation(s)
- Jincheng Yang
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Department of Comprehensive Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weilong Lin
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Deng
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Shi
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yu An
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Juan Yang
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chengcheng Zhou
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qin Tong
- Department of Acupuncture and Moxibustion, Wuhan Xinzhou District Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China
| | - Wenjing Yang
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Yang J, Li N, Lin W, Shi L, Deng M, Tong Q, Yang W. Machine Learning for Predicting Hyperglycemic Cases Induced by PD-1/PD-L1 Inhibitors. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:6278854. [PMID: 36032541 PMCID: PMC9417778 DOI: 10.1155/2022/6278854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 06/28/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Immune checkpoint inhibitors, such as programmed death-1/ligand-1 (PD-1/L1), exhibited autoimmune-like disorders, and hyperglycemia was on the top of grade 3 or higher immune-related adverse events. Machine learning is a model from past data for future data prediction. From post-marketing monitoring, we aimed to construct a machine learning algorithm to efficiently and rapidly predict hyperglycemic adverse reaction in patients using PD-1/L1 inhibitors. METHODS In original data downloaded from Food and Drug Administration Adverse Event Reporting System (US FAERS), a multivariate pattern classification of support vector machine (SVM) was used to construct a classifier to separate adverse hyperglycemic reaction patients. With correct core SVM function, a 10-fold 3-time cross validation optimized parameter value composition in model setup with R language software. RESULTS The SVM prediction model was set up from the number type/number optimization method, as well as the kernel and type of "rbf" and "nu-regression" composition. Two key values (nu and gamma) and case number displayed high adjusted r 2 in curve regressions (nu = 0.5649 × e (- (case/6984)), gamma = 9.005 × 10-4 × case - 4.877 × 10-8 × case2). This SVM model with computable parameters greatly improved the assessing indexes (accuracy, F1 score, and kappa) as well as coequal sensitivity and the area under the curve (AUC). CONCLUSION We constructed an effective machine learning model based on compositions of exact kernels and computable parameters; the SVM prediction model can noninvasively and precisely predict hyperglycemic adverse drug reaction (ADR) in patients treated with PD-1/L1 inhibitors, which could greatly help clinical practitioners to identify high-risk patients and perform preventive measurements in time. Besides, this model setup process provided an analytic conception for promotion to other ADR prediction, such ADR information is vital for outcome improvement by identifying high-risk patients, and this machine learning algorithm can eventually add value to clinical decision making.
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Affiliation(s)
- Jincheng Yang
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ning Li
- Department of Comprehensive Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weilong Lin
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Shi
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Deng
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qin Tong
- Department of Acupuncture and Moxibustion, Wuhan Xinzhou District Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China
| | - Wenjing Yang
- Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Zheng ZK, Wang JL, Li WX, Wu TQ, Chen MS, Zhou ZG. Anti-programmed Cell Death Protein-1 Therapy in Intrahepatic Cholangiocarcinoma Induced Type 1 Diabetes: A Case Report and Literature Review. Front Public Health 2022; 10:917679. [PMID: 35784237 PMCID: PMC9243496 DOI: 10.3389/fpubh.2022.917679] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/25/2022] [Indexed: 12/16/2022] Open
Abstract
Immune checkpoint inhibitors, widely used in the treatment of malignancies, can improve the prognosis of patients, while it also can induce various immune-related adverse events, and type 1 diabetes induced by anti-programmed cell death protein-1 is a rare but severe complication. Here we reported a case of type 1 diabetes induced by anti-PD-1 which was to treat intrahepatic cholangiocarcinoma. The case was a 61-year-old female who developed diabetes and ketoacidosis symptoms at the 16th week after anti-PD-1 therapy. Her blood glucose was 30.32 mmol/L, HBA1c was 8.10%, and C-peptide was <0.10 ng/ml. The patient was diagnosed as fulminant type 1 diabetes mellitus complicated with ketoacidosis induced by anti-PD-1, and was treated with massive fluid rehydration, intravenous infusion of insulin and correction of acid-base electrolyte disorder. Hepatectomy was performed after stabilization, and the patient was treated with long-term insulin. Through the case report and literature review, this study aims to improve oncologists' understanding of anti-PD-1 induced type 1 diabetes, so as to make early diagnosis and treatment of the complications and ensure medical safety.
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Affiliation(s)
- Zhi-Kai Zheng
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Jiong-Liang Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Wen-Xuan Li
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Tian-Qing Wu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Min-Shan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, China
| | - Zhong-Guo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, China
- *Correspondence: Zhong-Guo Zhou
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Yang J, Zhao B, Zhou H, Jia B, Chen L. Blood glucose related adverse drug reaction of antitumor monoclonal antibodies: a retrospective analysis using Vigibase. BRAZ J PHARM SCI 2022. [DOI: 10.1590/s2175-97902020000118893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Jincheng Yang
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Bin Zhao
- Chinese Academy of Medical Sciences & Peking Union Medical College, China
| | - Haiyan Zhou
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Bei Jia
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
| | - Lianzhen Chen
- Chinese Academy of Medical Sciences and Peking Union Medical College, China
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Joharatnam-Hogan N, Chambers P, Dhatariya K, Board R. A guideline for the outpatient management of glycaemic control in people with cancer. Diabet Med 2022; 39:e14636. [PMID: 34240470 DOI: 10.1111/dme.14636] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 12/17/2022]
Abstract
Individuals with cancer are at increased risk of developing new-onset diabetes mellitus and hyperglycaemia, and an estimated 20% of people with cancer already have an underlying diagnosis of diabetes mellitus. People with both cancer and diabetes may have an increased risk of toxicities, hospital admissions and morbidity, with hyperglycaemia potentially attenuating the efficacy of chemotherapy often secondary to dose reductions and early cessation. Numerous studies have demonstrated that hyperglycaemia is prognostic of worse overall survival and risk of cancer recurrence. These guidelines aim to provide the oncology/haemato-oncology and diabetes multidisciplinary teams with the tools to manage people with diabetes commencing anti-cancer/glucocorticoid therapy, as well as identifying individuals without a known diagnosis of diabetes who are at risk of developing hyperglycaemia and new-onset diabetes.
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Affiliation(s)
| | - Pinkie Chambers
- University College London Hospital NHS Foundation Trust, London, UK
| | - Ketan Dhatariya
- Norfolk and Norwich Hospitals NHS Foundation Trust, London, UK
| | - Ruth Board
- Lancashire Teaching Hospitals NHS Foundation Trust, London, UK
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Benedetti R, Benincasa G, Glass K, Chianese U, Vietri MT, Congi R, Altucci L, Napoli C. Effects of novel SGLT2 inhibitors on cancer incidence in hyperglycemic patients: a meta-analysis of randomized clinical trials. Pharmacol Res 2021; 175:106039. [PMID: 34929299 DOI: 10.1016/j.phrs.2021.106039] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 12/10/2021] [Accepted: 12/15/2021] [Indexed: 02/06/2023]
Abstract
Epidemiological evidence shows that diabetic patients have an increased cancer risk and a higher mortality rate. Glucose could play a central role in metabolism and growth of many tumor types, and this possible mechanism is supported by the high rate of glucose demand and uptake in cancer. Thus, growing evidence suggests that hyperglycemia contributes to cancer progression but also to its onset. Many mechanisms underlying this association have been hypothesized, such as insulin resistance, hyperinsulinemia, and increased inflammatory processes. Inflammation is a common pathophysiological feature in both diabetic and oncological patients, and inflammation linked to high glucose levels sensitizes microenvironment to tumorigenesis, promoting the development of malignant lesions by altering and sustaining a pathological condition in tissues. Glycemic control is the first goal of antidiabetic therapy, and glucose level reduction has also been associated with favorable outcomes in cancer. Here, we describe key events in carcinogenesis focusing on hyperglycemia as supporter in tumor progression and in particular, related to the role of a specific hypoglycemic drug class, sodium-glucose linked transporters (SGLTs). We also discuss the use of SGLT2 inhibitors as a novel potential cancer therapy. Our meta-analysis showed that SGLT-2 inhibitors were significantly associated with an overall reduced risk of cancer as compared to placebo (RR = 0.35, CI 0.33-0.37, P = 0. 00) with a particular effectiveness for dapaglifozin and ertuglifozin (RR = 0. 06, CI 0. 06-0. 07 and RR = 0. 22, CI 0. 18-0. 26, respectively). Network Medicine approaches may advance the possible repurposing of these drugs in patients with concomitant diabetes and cancer.
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Affiliation(s)
- Rosaria Benedetti
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy
| | - Giuditta Benincasa
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Pz. Miraglia 2, 80138 Naples, Italy.
| | - Kimberly Glass
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Ugo Chianese
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy
| | - Maria Teresa Vietri
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy
| | - Raffaella Congi
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy
| | - Lucia Altucci
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy; Biogem Institute of Molecular and Genetic Biology, 83031 Ariano Irpino, Italy.
| | - Claudio Napoli
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Pz. Miraglia 2, 80138 Naples, Italy; Clinical Department of Internal Medicine and Specialistics, Division of Clinical Immunology, Transfusion Medicine and Transplant Immunology, AOU University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy.
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12
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Yim C, Mansell K, Hussein N, Arnason T. Current cancer therapies and their influence on glucose control. World J Diabetes 2021; 12:1010-1025. [PMID: 34326951 PMCID: PMC8311484 DOI: 10.4239/wjd.v12.i7.1010] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/11/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth, proliferation and survival signaling pathways, and have been in clinical use as early as 2007. The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors (ICIs). These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors. For each drug class, the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use. The incidence of new glucose elevations in euglycemic individuals, as well as glycemic changes in those with established diabetes has been considered, as has the expected onset of hyperglycemia from their first use. This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels, whereas other classes can have lengthy delays of up to 1 year. A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs. There are distinct differences in the reversibility of glucose elevations after treatment is stopped, as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term. These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia, with clinical presentations ranging from potent yet transient insulin resistant states [type 2 diabetes mellitus (T2DM) -like] to rare permanent insulin-deficient causes of hyperglycemia. Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.
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Affiliation(s)
- Carly Yim
- Department of Medicine, University of Saskatchewan, Saskatoon S7N 0W8, Saskatchewan, Canada
| | - Kerry Mansell
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon S7N 5E5, Saskatchewan, Canada
| | - Nassrein Hussein
- Department of Medicine, Division of Endocrinology, University of Saskatchewan, Saskatoon S7N 0W8, Saskatchewan, Canada
| | - Terra Arnason
- Departments of Anatomy and Cell Biology and Medicine, Division of Endocrinology, University of Saskatchewan, Saskatoon S7N 0W8, Saskatchewan, Canada
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13
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Cázares-Cortazar A, Uribe-Noguez LA, Mata-Marín JA, Gaytán-Martínez J, de la Luz Martínez-Rodríguez M, Villavicencio-Ferrel PE, Chapararro-Sánchez A, Mauss S, Ocaña-Mondragón A. A decrease in hepatitis C virus RNA to undetectable levels in chronic hepatitis C patients after PegIFNα + RVB or sofosbuvir + NS5A inhibitor treatment is associated with decreased insulin resistance and persistent oxidative stress. Arch Virol 2020; 165:2759-2766. [PMID: 32885325 DOI: 10.1007/s00705-020-04797-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 08/04/2020] [Indexed: 12/21/2022]
Abstract
Oxidative stress (OS) and insulin resistance (IR) induced by hepatitis C virus (HCV) infection, are involved in the development of chronic hepatitis C (CHC) complications and progression to hepatocellular carcinoma. The aim of this study was to investigate the effect of pegylated interferon alpha (IFNα) + ribavirin (PegIFNα+RVB) or sofosbuvir + NS5A inhibitor (SOF+InNS5A) on IR and the components of OS. HCV was genotyped in 20 CHC patients grouped by treatment with either PegIFNα+RVB (n = 10) or SOF+InNS5A (n = 10). The treatment's effect on OS-induced damage to lipids (HNE-HDL), proteins (advanced glycation end products [AGEs]), and DNA (8-OHdG) as well as the concentrations of proinflammatory cytokines (IL-2, TNFα, IFNγ), ALT, AST, GSH and platelets was determined. Superoxide dismutase (SOD) and catalase activity as well as IR, determined by the HOMA1-IR index, was evaluated. The HCV genotypes (GT) found were GT1b (45%), GT1a (30%), GT2b (20%), and GT2a (5%). Viral RNA became undetectable by week 12 with SOF+InNS5A in 100% of the cases and with PegIFNα+RVB in 70% of the cases. After viral RNA became undetectable, regardless of treatment and GT, a significant increase in the platelet concentration and SOD activity was observed, whereas ALT, insulin, and IR decreased (p < 0.05). However, only for the SOF+InNS5A treated group was there an increase in oxidative damage to lipids (p < 0.017) and proteins (p < 0.05). None of the other parameters demonstrated any differences. These data confirm that OS persisted after treatment with either SOF+InNS5A or PegIFNα+RVB. IR could be considered a response biomarker to treatment with direct-acting antivirals.
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Affiliation(s)
- Allison Cázares-Cortazar
- Laboratorio Central de Epidemiología, División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, IMSS, Calzada vallejo s/n Col. La Raza, Del. Azcapotzalco, CP 02990, México City, México
| | - Luis A Uribe-Noguez
- Laboratorio Central de Epidemiología, División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, IMSS, Calzada vallejo s/n Col. La Raza, Del. Azcapotzalco, CP 02990, México City, México
| | - José Antonio Mata-Marín
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social, IMSS, México City, México
| | - Jesús Gaytán-Martínez
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social, IMSS, México City, México
| | - María de la Luz Martínez-Rodríguez
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social, IMSS, México City, México
| | - Pedro Esteban Villavicencio-Ferrel
- Laboratorio de Medicina Nuclear, Unidad Médica de Alta Especialidad, Hospital de Especialidades, CMN "La Raza", Instituto Mexicano del Seguro Social, IMSS, México City, México
| | - Alberto Chapararro-Sánchez
- Departamento de Enfermedades Infecciosas, Hospital de Infectología, Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social, IMSS, México City, México
| | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Düsseldorf, Germany
| | - Alicia Ocaña-Mondragón
- Laboratorio Central de Epidemiología, División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, IMSS, Calzada vallejo s/n Col. La Raza, Del. Azcapotzalco, CP 02990, México City, México.
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