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Caturano A, Erul E, Nilo R, Nilo D, Russo V, Rinaldi L, Acierno C, Gemelli M, Ricotta R, Sasso FC, Giordano A, Conte C, Ürün Y. Insulin resistance and cancer: molecular links and clinical perspectives. Mol Cell Biochem 2025:10.1007/s11010-025-05245-8. [PMID: 40089612 DOI: 10.1007/s11010-025-05245-8] [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: 12/18/2024] [Accepted: 02/23/2025] [Indexed: 03/17/2025]
Abstract
The association between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cancer is increasingly recognized and poses an escalating global health challenge, as the incidence of these conditions continues to rise. Studies indicate that individuals with T2DM have a 10-20% increased risk of developing various solid tumors, including colorectal, breast, pancreatic, and liver cancers. The relative risk (RR) varies depending on cancer type, with pancreatic and liver cancers showing a particularly strong association (RR 2.0-2.5), while colorectal and breast cancers demonstrate a moderate increase (RR 1.2-1.5). Understanding these epidemiological trends is crucial for developing integrated management strategies. Given the global rise in T2DM and cancer cases, exploring the complex relationship between these conditions is critical. IR contributes to hyperglycemia, chronic inflammation, and altered lipid metabolism. Together, these factors create a pro-tumorigenic environment conducive to cancer development and progression. In individuals with IR, hyperinsulinemia triggers the insulin-insulin-like growth factor (IGF1R) signaling pathway, activating cancer-associated pathways such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PIK3CA), which promote cell proliferation and survival, thereby supporting tumor growth. Both IR and T2DM are linked to increased morbidity and mortality in patients with cancer. By providing an in-depth analysis of the molecular links between insulin resistance and cancer, this review offers valuable insights into the role of metabolic dysfunction in tumor progression. Addressing insulin resistance as a co-morbidity may open new avenues for risk assessment, early intervention, and the development of integrated treatment strategies to improve patient outcomes.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166, Rome, Italy
| | - Enes Erul
- Department of Medical Oncology, Faculty of Medicine, Ankara University, Ankara, 06620, Turkey
| | - Roberto Nilo
- Data Collection G-STeP Research Core Facility, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy
| | - Davide Nilo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Vincenzo Russo
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, 19122, USA
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Luca Rinaldi
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, 86100, Campobasso, Italy
| | - Carlo Acierno
- Azienda Ospedaliera Regionale San Carlo, 85100, Potenza, Italy
| | - Maria Gemelli
- Medical Oncology Unit, IRCCS MultiMedica, Milan, Italy
| | | | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Antonio Giordano
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, 19122, USA
| | - Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166, Rome, Italy
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20099, Milan, Italy
| | - Yüksel Ürün
- Department of Medical Oncology, Faculty of Medicine, Ankara University, Ankara, 06620, Turkey.
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Salgado TM, Birari PB, Alshahawey M, Hickey Zacholski E, Mackler E, Buffington TM, Musselman KT, Irvin WJ, Perkins JM, Le TN, Dixon DL, Farris KB, Sheppard VB, Jones RM. Optimal hyperglycemia thresholds in patients undergoing chemotherapy: a cross sectional study of oncologists' practices. Support Care Cancer 2024; 32:563. [PMID: 39088060 PMCID: PMC11294379 DOI: 10.1007/s00520-024-08756-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 07/21/2024] [Indexed: 08/02/2024]
Abstract
PURPOSE Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. METHODS This national, cross sectional study utilized a questionnaire to collect oncologists' perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists' approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. RESULTS Respondents (n = 229) were on average 52.1 years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121 mg/dL and 105-135 mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130 mg/dL and 128-150 mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists' approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. CONCLUSION Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.
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Affiliation(s)
- Teresa M Salgado
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy and Massey Cancer Center, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA.
| | - Poorva B Birari
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
| | - Mona Alshahawey
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Organization of African Unity St, El-Qobba Bridge, El Weili, Cairo Governorate, 4393005, Egypt
| | - Erin Hickey Zacholski
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
| | - Emily Mackler
- Michigan Oncology Quality Consortium (MOQC) and Michigan Institute for Care Management and Transformation (MICMT), 4251 Plymouth Road Arbor Lakes, Building 3, Floor 3, Ann Arbor, MI, 48105, USA
| | - Tonya M Buffington
- Bon Secours Mercy Health, 611 Watkins Centre Parkway, Suite 250, Midlothian, VA, 23114, USA
| | - Kerri T Musselman
- Emcara Health and PopHealthCare, 113 Seaboard Lane, Suite B200, Franklin, TN, 37067, USA
| | - William J Irvin
- Bon Secours St Francis, 14051 St Francis Blvd Suite 2210, Midlothian, VA, 23114, USA
| | - Jennifer M Perkins
- Division of Endocrinology, University of California San Francisco Medical Center, 400 Parnassus Ave., Suite A-550, San Francisco, CA, 94143, USA
| | - Trang N Le
- Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, 1101 E. Marshall St. Sanger Hall Suite 1-030, Richmond, VA, 23298, USA
| | - Dave L Dixon
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N. 12Th Street PO Box 98053, Richmond, VA, 23298, USA
| | - Karen B Farris
- Department of Clinical Pharmacy Translational Sciences, College of Pharmacy and Michigan Institute for Care Management and Transformation (MICMT), University of Michigan, 428 Church St, Ann Arbor, MI, 48109, USA
| | - Vanessa B Sheppard
- Department of Social and Behavioral Sciences, School of Public Health, and Massey Cancer Center, Virginia Commonwealth University, 830 East Main Street, Richmond, VA, 23219, USA
| | - Resa M Jones
- Department of Epidemiology and Biostatistics, College of Public Health, and Fox Chase Cancer Center, Temple University, 1301 Cecil B. Moore Avenue Ritter Annex, 9Th Floor, Suite 917, Philadelphia, PA, 19122, USA
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Pourhassan H, Murphy L, Aldoss I. Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection. Curr Hematol Malig Rep 2024; 19:175-185. [PMID: 38867099 DOI: 10.1007/s11899-024-00735-w] [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] [Accepted: 05/16/2024] [Indexed: 06/14/2024]
Abstract
PURPOSE OF REVIEW Glucocorticoids are a mainstay in acute lymphoblastic leukemia treatment and lack of early response is predictive for overall disease prognosis. Given the vital position of glucocorticoids and well known long and short-term side effects associated with differing glucocorticoids, we aim to highlight the wide breadth of historical and more contemporary data to describe the current landscape of glucocorticoid use in this arena. RECENT FINDINGS Emerging studies aim to overcome issues such as steroid resistance and to optimize the antileukemic effects of glucocorticoids while aiming to mitigate the risks and side effects associated with their exposure. Glucocorticoids have and likely always will be a fundamental component of acute lymphoblastic leukemia treatment and understanding how to navigate short- and long-term effects and how to optimize regimens is at the heart of continued treatment success.
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Affiliation(s)
- Hoda Pourhassan
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, USA
| | - Lindsey Murphy
- Department of Pediatrics, City of Hope National Medical Center, Duarte, California, USA
| | - Ibrahim Aldoss
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, USA.
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Moore-Vasram S, Sawhney M, Houlden RL, Groome PA, Goldie C, Li W, Hay AE, Tranmer J. Determining the Associations Between Glucocorticoid Use During Hematologic Chemotherapy Treatment and New-onset Diabetes and Hyperglycemia and Mortality: A Population-based Cohort Study. Can J Diabetes 2024; 48:195-203.e1. [PMID: 38211830 DOI: 10.1016/j.jcjd.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 08/09/2023] [Accepted: 01/04/2024] [Indexed: 01/13/2024]
Abstract
OBJECTIVES The aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described. METHODS We conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities. RESULTS Our cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts. CONCLUSIONS Hyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration.
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Affiliation(s)
| | - Monakshi Sawhney
- School of Nursing, Queen's University, Kingston, Ontario, Canada
| | - Robyn L Houlden
- Division of Endocrinology and Metabolism, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada
| | - Patti A Groome
- Division of Cancer Care and Epidemiology, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada; ICES, formerly the Institute for Clinical Evaluative Sciences, Queen's University Site, Kingston, Ontario, Canada
| | - Catherine Goldie
- School of Nursing, Queen's University, Kingston, Ontario, Canada
| | - Wenbin Li
- ICES, formerly the Institute for Clinical Evaluative Sciences, Queen's University Site, Kingston, Ontario, Canada
| | - Annette E Hay
- Division of Hematology, Queen's University, Kingston, Ontario, Canada
| | - Joan Tranmer
- School of Nursing, Queen's University, Kingston, Ontario, Canada; ICES, formerly the Institute for Clinical Evaluative Sciences, Queen's University Site, Kingston, Ontario, Canada
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Cho JH, Suh S. Glucocorticoid-Induced Hyperglycemia: A Neglected Problem. Endocrinol Metab (Seoul) 2024; 39:222-238. [PMID: 38532282 PMCID: PMC11066448 DOI: 10.3803/enm.2024.1951] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 02/19/2024] [Accepted: 02/20/2024] [Indexed: 03/28/2024] Open
Abstract
Glucocorticoids provide a potent therapeutic response and are widely used to treat a variety of diseases, including coronavirus disease 2019 (COVID-19) infection. However, the issue of glucocorticoid-induced hyperglycemia (GIH), which is observed in over one-third of patients treated with glucocorticoids, is often neglected. To improve the clinical course and prognosis of diseases that necessitate glucocorticoid therapy, proper management of GIH is essential. The key pathophysiology of GIH includes systemic insulin resistance, which exacerbates hepatic steatosis and visceral obesity, as well as proteolysis and lipolysis of muscle and adipose tissue, coupled with β-cell dysfunction. For patients on glucocorticoid therapy, risk stratification should be conducted through a detailed baseline evaluation, and frequent glucose monitoring is recommended to detect the onset of GIH, particularly in high-risk individuals. Patients with confirmed GIH who require treatment should follow an insulin-centered regimen that varies depending on whether they are inpatients or outpatients, as well as the type and dosage of glucocorticoid used. The ideal strategy to maintain normoglycemia while preventing hypoglycemia is to combine basal-bolus insulin and correction doses with a continuous glucose monitoring system. This review focuses on the current understanding and latest evidence concerning GIH, incorporating insights gained from the COVID-19 pandemic.
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Affiliation(s)
- Jung-Hwan Cho
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Sunghwan Suh
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
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Tsilingiris D, Vallianou NG, Spyrou N, Kounatidis D, Christodoulatos GS, Karampela I, Dalamaga M. Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges. Curr Obes Rep 2024; 13:1-34. [PMID: 38159164 PMCID: PMC10933194 DOI: 10.1007/s13679-023-00542-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/06/2023] [Indexed: 01/03/2024]
Abstract
PURPOSE OF REVIEW To examine the epidemiological data on obesity and leukemia; evaluate the effect of obesity on leukemia outcomes in childhood acute lymphoblastic leukemia (ALL) survivors; assess the potential mechanisms through which obesity may increase the risk of leukemia; and provide the effects of obesity management on leukemia. Preventive (diet, physical exercise, obesity pharmacotherapy, bariatric surgery) measures, repurposing drugs, candidate therapeutic agents targeting oncogenic pathways of obesity and insulin resistance in leukemia as well as challenges of the COVID-19 pandemic are also discussed. RECENT FINDINGS Obesity has been implicated in the development of 13 cancers, such as breast, endometrial, colon, renal, esophageal cancers, and multiple myeloma. Leukemia is estimated to account for approximately 2.5% and 3.1% of all new cancer incidence and mortality, respectively, while it represents the most frequent cancer in children younger than 5 years. Current evidence indicates that obesity may have an impact on the risk of leukemia. Increased birthweight may be associated with the development of childhood leukemia. Obesity is also associated with worse outcomes and increased mortality in leukemic patients. However, there are several limitations and challenges in meta-analyses and epidemiological studies. In addition, weight gain may occur in a substantial number of childhood ALL survivors while the majority of studies have documented an increased risk of relapse and mortality among patients with childhood ALL and obesity. The main pathophysiological pathways linking obesity to leukemia include bone marrow adipose tissue; hormones such as insulin and the insulin-like growth factor system as well as sex hormones; pro-inflammatory cytokines, such as IL-6 and TNF-α; adipocytokines, such as adiponectin, leptin, resistin, and visfatin; dyslipidemia and lipid signaling; chronic low-grade inflammation and oxidative stress; and other emerging mechanisms. Obesity represents a risk factor for leukemia, being among the only known risk factors that could be prevented or modified through weight loss, healthy diet, and physical exercise. Pharmacological interventions, repurposing drugs used for cardiometabolic comorbidities, and bariatric surgery may be recommended for leukemia and obesity-related cancer prevention.
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Affiliation(s)
- Dimitrios Tsilingiris
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, 68100, Alexandroupolis, Greece
| | - Natalia G Vallianou
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, 10676, Athens, Greece
| | - Nikolaos Spyrou
- Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, 1190 One Gustave L. Levy Place, New York, NY, 10029, USA
| | - Dimitris Kounatidis
- Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, 10676, Athens, Greece
| | | | - Irene Karampela
- 2nd Department of Critical Care, Medical School, University of Athens, Attikon General University Hospital, 1 Rimini Str, 12462, Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str, 11527, Athens, Greece.
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Ross K, Kulkarni K, MacDonald T, Pinto T. Assessing Risk Classification in Medication-Induced Diabetes during Induction Therapy in Pediatric Acute Lymphoblastic Leukemia. Pediatr Diabetes 2023; 2023:1057639. [PMID: 40303251 PMCID: PMC12016910 DOI: 10.1155/2023/1057639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 11/05/2023] [Accepted: 11/30/2023] [Indexed: 05/02/2025] Open
Abstract
Medication-induced diabetes (MID) is common during induction therapy for pediatric acute lymphoblastic leukemia (ALL) and has potentially significant negative consequences. Reported risk factors for MID are variable with limited data comparing patients treated with standard-risk (SR) vs. high-risk (HR) regimens. This study aims to evaluate the incidence and risk factors for MID during induction in patients with ALL from the Maritimes over a 20-year period. We performed a retrospective single-center study of 262 patients (142 males, 120 females) diagnosed with ALL at IWK Health in Halifax, Nova Scotia, Canada, from 2000 to 2019. Older age, higher body mass index, greater central nervous system status, Trisomy 21, and prednisone steroid type were risk factors associated with MID in our cohort. HR patients developed significantly more complications than SR patients including MID and infection. Screening for MID should be routine during ALL induction treatment, particularly in those with HR disease.
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Affiliation(s)
- Katie Ross
- Faculty of Medicine, Dalhousie University, Halifax B3H 4R2, Canada
| | - Ketan Kulkarni
- Division of Hematology/Oncology, Department of Pediatrics, IWK Health, Halifax B3K 6R8, Canada
| | - Tamara MacDonald
- Department of Pharmacy, IWK Health, Halifax B3K 6R8, Canada
- Faculty of Health Professions, Dalhousie University, Halifax B3H 4R2, Canada
| | - Teresa Pinto
- Division of Endocrinology, Department of Pediatrics, IWK Health, Halifax B3K 6R8, Canada
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Kristjanson M, Lambert P, Decker KM, Bruin S, Tingey E, Skrabek P. Steroid-Induced Hyperglycemia and Its Effect on Outcomes of R-CHOP Chemotherapy for Diffuse Large B-Cell Lymphoma. Curr Oncol 2023; 30:10142-10151. [PMID: 38132372 PMCID: PMC10742719 DOI: 10.3390/curroncol30120738] [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: 10/12/2023] [Revised: 11/10/2023] [Accepted: 11/21/2023] [Indexed: 12/23/2023] Open
Abstract
Large doses of steroids are integral to R-CHOP, a first-line systemic therapy for diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin Lymphoma (NHL). Patients on R-CHOP often develop clinically significant hyperglycemia from steroids. There is evidence of harms from steroid-induced hyperglycemia in the context of chemotherapy which are associated with a reduction in overall survival. The objective of our study was to characterize the effect of steroid-induced hyperglycemia on the outcomes of R-CHOP chemotherapy for DLBCL. METHODS We performed a retrospective chart review of 188 patients with DLBCL treated with R-CHOP through CancerCare Manitoba (CCMB) from 1 January 2010 to 31 December 2014. Patients diagnosed with DLBCL were identified using the Manitoba Cancer Registry. The CCMB electronic medical record was reviewed to examine the association between steroid-induced hyperglycemia and subsequent infection, including febrile neutropenic events and overall survival (OS). RESULTS Patients who developed hyperglycemia with steroid exposure became hyperglycemic during their first R-CHOP cycle. No significant differences in OS or rates of infection were found between euglycemic and hyperglycemic subjects. CONCLUSIONS Patients destined to develop steroid-induced hyperglycemia declare themselves early in the course of steroid exposure. No statistically significant reduction in overall survival attributable to steroid-induced hyperglycemia was found.
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Affiliation(s)
- Mark Kristjanson
- Department of Family Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
- Urgent Cancer Care, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
| | - Pascal Lambert
- Paul Albrechtsen Research Institute CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada; (P.L.); (K.M.D.)
- Department of Epidemiology and Cancer Registry, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
| | - Kathleen M. Decker
- Paul Albrechtsen Research Institute CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada; (P.L.); (K.M.D.)
- Department of Epidemiology and Cancer Registry, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
- Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 750 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada
| | - Sonja Bruin
- Ongomiizwin Health Services Institute of Indigenous Health and Healing, 745 Bannatyne Avenue, Winnipeg, MB R3E 3N4, Canada;
| | - Elizabeth Tingey
- Max Rady College of Medicine, Rady Faculty of Health Sciences 750 Bannatyne Avenue, Winnipeg, MB R3E 0W2, Canada;
| | - Pamela Skrabek
- Department of Medical Oncology & Hematology, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada;
- Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada
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Shimony S, Flamand Y, Valtis YK, Place AE, Silverman LB, Vrooman LM, Brunner AM, Sallan SE, Stone RM, Wadleigh M, Neuberg DS, DeAngelo DJ, Luskin MR. Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials. Blood Adv 2023; 7:5234-5245. [PMID: 37432068 PMCID: PMC10500474 DOI: 10.1182/bloodadvances.2023009976] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/24/2023] [Accepted: 05/16/2023] [Indexed: 07/12/2023] Open
Abstract
Adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) treated with asparaginase-containing pediatric regimens are commonly overweight or obese. We studied the association of body mass index (BMI) on outcomes of 388 AYAs aged 15 to 50 years treated on Dana-Farber Cancer Institute (DFCI) consortium regimens (2008-2021). BMI was normal in 207 (53.3%) and overweight/obese in 181 (46.7%). Patients who were overweight or obese experienced higher nonrelapse mortality (NRM; 4-year, 11.7% vs 2.8%, P = .006), worse event-free survival (4-year, 63% vs 77%, P = .003), and worse overall survival (OS; 4-year, 64% vs 83%, P = .0001). Because younger (aged 15-29 years) AYAs more frequently had a normal BMI (79% vs 20%, P < .0001), we conducted separate analyses in each BMI group. We found excellent OS among younger and older (30-50 years) AYAs with normal BMI (4-year OS, 83% vs 85%, P = .89). Conversely, in AYAs who were overweight/obese, worse outcomes were seen in older AYAs (4-year OS, 55% vs 73%, P = .023). Regarding toxicity, AYAs who were overweight/obese experienced higher rates of grade 3/4 hepatotoxicity and hyperglycemia (60.7% vs 42.2%, P = .0005, and 36.4% vs 24.4%, P = .014, respectively) but had comparable rates of hypertriglyceridemia (29.5% vs 24.4%, P = .29). In a multivariable analysis, higher BMI was associated with worse OS, hypertriglyceridemia was associated with improved OS, and age was not associated with OS. In conclusion, among AYAs treated on DFCI Consortium ALL regimens, elevated BMI was associated with increased toxicity, increased NRM, and decreased OS. The deleterious effect of elevated BMI was more pronounced in older AYAs.
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Affiliation(s)
- Shai Shimony
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Hematology Department, Rabin Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Flamand
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
| | - Yannis K. Valtis
- Department of Medicine, Memorial Sloan Kettering Cancer Institute, New York, NY
| | - Andrew E. Place
- Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital, Boston, MA
| | - Lewis B. Silverman
- Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital, Boston, MA
| | - Lynda M. Vrooman
- Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital, Boston, MA
| | - Andrew M. Brunner
- Leukemia Department, Hematology/Oncology, Massachusetts General Hospital, Boston, MA
| | - Stephen E. Sallan
- Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital, Boston, MA
| | - Richard M. Stone
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Martha Wadleigh
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Donna S. Neuberg
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
| | - Daniel J. DeAngelo
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Marlise R. Luskin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
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10
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Salgado TM, Radwan RM, Hickey Zacholski E, Mackler E, Buffington TM, Musselman KT, Irvin WJ, Perkins JM, Le TN, Dixon DL, Farris KB, Sheppard VB, Jones RM. Oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients with cancer undergoing chemotherapy: a cross sectional study. Support Care Cancer 2023; 31:450. [PMID: 37421495 DOI: 10.1007/s00520-023-07927-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 07/02/2023] [Indexed: 07/10/2023]
Abstract
PURPOSE To assess oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients undergoing chemotherapy. METHODS In this cross-sectional study, a questionnaire collected oncologists' perceptions about professionals responsible for managing hyperglycemia during chemotherapy; comfort (score range 12-120); and knowledge (score range 0-16). Descriptive statistics were calculated including Student t-tests and one-way ANOVA for mean score differences. Multivariable linear regression identified predictors of comfort and knowledge scores. RESULTS Respondents (N = 229) were 67.7% men, 91.3% White and mean age 52.1 years. Oncologists perceived endocrinologists/diabetologists and primary care physicians as those responsible for managing hyperglycemia during chemotherapy, and most frequently referred to these clinicians. Reasons for referral included lack of time to manage hyperglycemia (62.4%), belief that patients would benefit from referral to an alternative provider clinician (54.1%), and not perceiving hyperglycemia management in their scope of practice (52.4%). The top-3 barriers to patient referral were long wait times for primary care (69.9%) and endocrinology (68.1%) visits, and patient's provider outside of the oncologist's institution (52.8%). The top-3 barriers to treating hyperglycemia were lack of knowledge about when to start insulin, how to adjust insulin, and what insulin type works best. Women (ß = 1.67, 95% CI: 0.16, 3.18) and oncologists in suburban areas (ß = 6.98, 95% CI: 2.53, 11.44) had higher comfort scores than their respective counterparts; oncologists working in practices with > 10 oncologists had lower comfort scores (ß = -2.75, 95% CI: -4.96, -0.53) than those in practices with ≤ 10. No significant predictors were identified for knowledge. CONCLUSION Oncologists expected endocrinology or primary care clinicians to manage hyperglycemia during chemotherapy, but long wait times were among the top barriers cited when referring patients. New models that provide prompt and coordinated care are needed.
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Affiliation(s)
- Teresa M Salgado
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, and Massey Cancer Center, Virginia Commonwealth University, PO Box 98053, 410 N. 12th Street, Richmond, VA, 23298, USA.
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, PO Box 980533, 410 N. 12th Street, Richmond, VA, 23298, USA.
| | - Rotana M Radwan
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, PO Box 980533, 410 N. 12th Street, Richmond, VA, 23298, USA
| | - Erin Hickey Zacholski
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, PO Box 980533, 410 N. 12th Street, Richmond, VA, 23298, USA
| | - Emily Mackler
- Michigan Oncology Quality Consortium (MOQC) and Michigan Institute for Care Management and Transformation (MICMT), 4251 Plymouth Road Arbor Lakes, Building 3, Floor 3, Ann Arbor, MI, 48105, USA
| | - Tonya M Buffington
- Bon Secours Mercy Health, 611 Watkins Centre Parkway, Suite 250, Midlothian, Richmond, VA, 23114, USA
| | - Kerri T Musselman
- Emcara Health and PopHealthCare, 113 Seaboard Lane, Suite B200, Franklin, TN, 37067, USA
| | - William J Irvin
- Bon Secours Cancer Institute, Bon Secours Mercy Health, 14051 St Francis Blvd Suite 2210, Midlothian, VA, 23114, United States
| | - Jennifer M Perkins
- Division of Endocrinology, University of California San Francisco Medical Center, Endocrinology Clinic at Parnassus 400 Parnassus Ave., Suite A-550, San Francisco, CA, 94143, USA
| | - Trang N Le
- Division of Endocrinology, Diabetes & Metabolism, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, 1101 E. Marshall St. Sanger Hall Suite 1-030, Richmond, VA, 23298, USA
| | - Dave L Dixon
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, PO Box 980533, 410 N. 12th Street, Richmond, VA, 23298, USA
| | - Karen B Farris
- Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, 428 Church St, Ann Arbor, MI, 48109, USA
| | - Vanessa B Sheppard
- Department of Health Behavior and Policy, School of Population Health, and Massey Comprehensive Cancer Center, Virginia Commonwealth University, 830 East Main Street, Richmond, VA, 23219, USA
| | - Resa M Jones
- Department of Epidemiology & Biostatistics, College of Public Health, and Fox Chase Cancer Center, Temple University, 1301 Cecil B. Moore Avenue Ritter Annex, 9th Floor, Suite 917, Philadelphia, PA, 19122, USA
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11
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The association of hyperglycemia with the development of infectious complications in adult Filipino patients with acute lymphoblastic leukemia. Hematol Transfus Cell Ther 2023; 45:66-71. [PMID: 34593366 PMCID: PMC9938473 DOI: 10.1016/j.htct.2021.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 05/03/2021] [Accepted: 06/13/2021] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Hyperglycemia occurs in Acute Lymphoblastic Leukemia (ALL) due to chemotherapeutic agents and may be stress-induced. Given the potential impact of hyperglycemia on the clinical outcomes of ALL patients, we sought to determine the association of hyperglycemia with the development of infectious complications. METHODS This is a retrospective cohort involving adult Filipino ALL patients admitted at a tertiary referral center. Patients were stratified according to blood glucose levels and infections were classified into microbiologically and clinically defined infections. Logistic regression was performed to determine whether hyperglycemia was associated with the development of infectious complications. RESULTS Of the 174 patients admitted for ALL, only 76 patients (44%) underwent blood glucose monitoring and were thus included in this study. Hyperglycemia was observed in 64 patients (84.21%). Infectious complications were seen in 56 patients (73.68%), of whom 37 patients (48.68%) had microbiologically defined infections and 19 (25%) had clinically defined infections. The respiratory tract was the most common site of infection and gram-negative bacteria were the predominant isolates. Hyperglycemia significantly increased the likelihood of infectious complications, particularly at blood glucose levels ≥ 200 mg/dL. CONCLUSION Hyperglycemia is associated with an increased likelihood of infectious complications in Filipino ALL patients. With sepsis being one of the main causes of mortality in this population, our study provides compelling evidence for us to consider routine blood glucose monitoring in order to manage and potentially decrease the occurrence of infections in these patients.
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Franklin A, Wurster S, Axell-House DB, Jiang Y, Kontoyiannis DP. Impact of Hyperglycemia and Diabetes Mellitus on Breakthrough Mucormycosis Outcomes in Patients with Hematologic Malignancies-Complex and Intriguing Associations. J Fungi (Basel) 2022; 9:jof9010045. [PMID: 36675866 PMCID: PMC9860539 DOI: 10.3390/jof9010045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/23/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022] Open
Abstract
Mucormycosis (MCR) is frequently associated with diabetic ketoacidosis and hyperglycemia, as well as hematologic malignancies (HMs) and hematopoietic stem cell transplantation (HSCT). However, little is known about the effect of hyperglycemia on MCR outcomes in patients with HMs. We therefore conducted a retrospective cohort study of adult patients hospitalized with MCR and HM or HSCT (n = 103) at MD Anderson Cancer Center from April 2000 through to April 2020. Twenty-three patients (22%) had documented episodes of severe hyperglycemia. Sixty patients had >5 serum glucose measurements within 28 days prior to MCR symptom onset; of those, 14 (23%) met the criteria for persistent hyperglycemia. Sixteen patients (16%) received insulin prior to admission. The crude mortality 42 days from the onset of MCR symptoms in our cohort was 31%. Neither severe nor persistent hyperglycemia were associated with excess mortality. Insulin use prior to index admission was associated with decreased 42-day mortality on univariate analysis (p = 0.031). In conclusion, in a setting of high crude mortality, severe and/or persistent hyperglycemia do not appear to be associated with excess mortality in patients with HM or HSCT developing MCR. Insulin use prior to MCR diagnosis may be associated with decreased mortality, although further research is needed to validate this effect and to study its mechanistic underpinnings.
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Affiliation(s)
- Alexander Franklin
- Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
| | - Sebastian Wurster
- Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Dierdre B. Axell-House
- Division of Infectious Diseases, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, TX 77030, USA
| | - Ying Jiang
- Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Dimitrios P. Kontoyiannis
- Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Correspondence:
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Dhawan A, Pifer PM, Sandulache VC, Skinner HD. Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer: Where do we go from here? Front Oncol 2022; 12:1016217. [PMID: 36591457 PMCID: PMC9794617 DOI: 10.3389/fonc.2022.1016217] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/24/2022] [Indexed: 12/15/2022] Open
Abstract
In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with potentially curable locoregional disease, instead of distant disease. Exciting developments in molecular targeted therapy and immunotherapy have resulted in dramatic improvement in patients' survival, in combination with new surgical, pathological, radiographical, and radiation techniques. Concurrent platinum-based doublet chemoradiation therapy followed by immunotherapy has set the benchmark for survival in these patients. However, despite these advances, ~50% of patients diagnosed with locally advanced NSCLC (LA-NSCLC) survive long-term. In patients with local and/or locoregional disease, chemoradiation is a critical component of curative therapy. However, there remains a significant clinical gap in improving the efficacy of this combined therapy, and the development of non-overlapping treatment approaches to improve treatment outcomes is needed. One potential promising avenue of research is targeting cancer metabolism. In this review, we will initially provide a brief general overview of tumor metabolism as it relates to therapeutic targeting. We will then focus on the intersection of metabolism on both oxidative stress and anti-tumor immunity. This will be followed by discussion of both tumor- and patient-specific opportunities for metabolic targeting in NSCLC. We will then conclude with a discussion of additional agents currently in development that may be advantageous to combine with chemo-immuno-radiation in NSCLC.
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Affiliation(s)
- Annika Dhawan
- Department of Radiation Oncology, UPMC Hillman Cancer Center and University of Pittsburgh, Pittsburgh, PA, United States
| | - Phillip M. Pifer
- Department of Radiation Oncology, UPMC Hillman Cancer Center and University of Pittsburgh, Pittsburgh, PA, United States
| | - Vlad C. Sandulache
- Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, United States
| | - Heath D. Skinner
- Department of Radiation Oncology, UPMC Hillman Cancer Center and University of Pittsburgh, Pittsburgh, PA, United States,*Correspondence: Heath D. Skinner,
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Toyoshima MTK, Cukier P, Souza ABCD, Pereira J, Hoff AO, Nery M. Effects of glucocorticoids on interstitial glucose concentrations in individuals with hematologic cancer and without known diagnosis of diabetes: a pilot study. EINSTEIN-SAO PAULO 2022; 20:eAO8031. [PMID: 35830152 PMCID: PMC9262279 DOI: 10.31744/einstein_journal/2022ao8031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 12/02/2021] [Indexed: 01/08/2023] Open
Abstract
Objective To analyze interstitial glucose behavior during glucocorticoid use in non-diabetic patients receiving chemotherapy for hematologic malignancies. Methods Prospective pilot study carried out to assess interstitial glucose levels in 15 non-diabetic individuals with hematologic malignancies who received glucocorticoids in combination with chemotherapy. The FreeStyle Libre flash monitoring system (Abbott Diabetes Care) was used for up to 14 days to measure interstitial glucose. Results Median age and body mass index were 53 (42-61) years and 25 (23-28) kg/m2 respectively. Interstitial glucose levels >180mg/dL lasting at least one hour were detected in 60% of participants. Interstitial glucose profile parameters (median and peak interstitial glucose levels and percentage of time during which interstitial glucose levels were >180mg/dL) were significantly (p<0.01) higher during glucocorticoid use (115mg/dL, 218mg/dL and 10% respectively) than after glucocorticoid discontinuation (97mg/dL, 137mg/dL and 0% respectively). Mean interstitial glucose levels increased in the afternoon and at night during glucocorticoid use. Conclusion This pilot study was the first to evaluate interstitial glucose levels in non-diabetic individuals using glucocorticoids in treatment of hematologic cancer. Glucocorticoid use during chemotherapy significantly increases interstitial glucose levels in these patients.
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15
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Rotbain EC, Rostgaard K, Andersen MA, Da Cunha-Bang C, Niemann CU, Frederiksen H, Hjalgrim H. Healthcare Utilization and Comorbidity in Chronic Lymphocytic Leukemia. Clin Epidemiol 2021; 13:1155-1165. [PMID: 35002328 PMCID: PMC8722577 DOI: 10.2147/clep.s337495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/04/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Age-related comorbidity is highly prevalent in chronic lymphocytic leukemia (CLL). The purpose of this study was to provide information on current patterns of healthcare utilization in CLL. PATIENTS AND METHODS We used data from Danish nation-wide registers to study healthcare utilization the year before and the year after CLL diagnosis and in relation to first-line treatment. Patients diagnosed with CLL between 1997 and 2018 were included and stratified on number of comorbidities, presence of specific comorbidities, and fitness status, respectively. Healthcare utilization was studied in terms of hospital admissions, in-hospital bed days, out-patient visits, emergency room visits, and prescription drugs. Odds ratios with 95% confidence intervals were calculated using multivariable logistic regression analyses adjusting for age, sex, and calendar year. RESULTS The study comprised 9170 patients with CLL with a median age of 71 years, of whom 35% had ≥1 comorbidity. Healthcare utilization increased markedly upon CLL diagnosis both in patients with and without comorbidities. During the year after CLL diagnosis, 39% were hospitalized, 16% visited an emergency room, 88% visited an out-patient clinic, and 93% received prescription drugs. Both individual comorbidities and the total number of comorbidities were associated with increased healthcare utilization of all types, except for contacts to hematological departments. CONCLUSION Our results suggest that CLL diagnosis may unveil incipient diseases and aggravate comorbidities and thereby have considerably wider health implications than those directly related to CLL. These findings may be used by clinicians and decisions makers to guide planning of multidisciplinary care for cancer patients.
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Affiliation(s)
- Emelie C Rotbain
- Department of Hematology, Odense University Hospital, Odense, Denmark
- Department of Hematology, Rigshospitalet, Denmark
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Danish Cancer Society Research Center, Hematology Research Group, Copenhagen, Denmark
| | - Klaus Rostgaard
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
- Danish Cancer Society Research Center, Hematology Research Group, Copenhagen, Denmark
| | - Michael A Andersen
- Department of Hematology, Rigshospitalet, Denmark
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | | | | | - Henrik Frederiksen
- Department of Hematology, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
- Academy of Geriatric Cancer Research (AGECARE), Odense University Hospital, Odense, Denmark
| | - Henrik Hjalgrim
- Department of Hematology, Rigshospitalet, Denmark
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
- Danish Cancer Society Research Center, Hematology Research Group, Copenhagen, Denmark
- Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark
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Suo SS, Li CY, Zhang Y, Wang JH, Lou YJ, Yu WJ, Jin J. Characteristics of chemotherapy-induced diabetes mellitus in acute lymphoblastic leukemia patients. J Zhejiang Univ Sci B 2021; 21:740-744. [PMID: 32893530 DOI: 10.1631/jzus.b1900719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).
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Affiliation(s)
- Shan-Shan Suo
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
| | - Chen-Ying Li
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
| | - Yi Zhang
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
| | - Jing-Han Wang
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
| | - Yin-Jun Lou
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
| | - Wen-Juan Yu
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
| | - Jie Jin
- Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Institute of Hematology, Zhejiang University, Hangzhou 310003, China.,Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, China
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PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis. Proc Natl Acad Sci U S A 2021; 118:2016553118. [PMID: 33531346 DOI: 10.1073/pnas.2016553118] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Unlike other cell types, developing B cells undergo multiple rounds of somatic recombination and hypermutation to evolve high-affinity antibodies. Reflecting the high frequency of DNA double-strand breaks, adaptive immune protection by B cells comes with an increased risk of malignant transformation. B lymphoid transcription factors (e.g., IKZF1 and PAX5) serve as metabolic gatekeepers by limiting glucose to levels insufficient to fuel transformation. We here identified aberrant expression of the lactonase PON2 in B cell acute lymphoblastic leukemia (B-ALL) as a mechanism to bypass metabolic gatekeeper functions. Compared to normal pre-B cells, PON2 expression was elevated in patient-derived B-ALL samples and correlated with poor clinical outcomes in pediatric and adult cohorts. Genetic deletion of Pon2 had no measurable impact on normal B cell development. However, in mouse models for BCR-ABL1 and NRASG12D-driven B-ALL, deletion of Pon2 compromised proliferation, colony formation, and leukemia initiation in transplant recipient mice. Compromised leukemogenesis resulted from defective glucose uptake and adenosine triphosphate (ATP) production in PON2-deficient murine and human B-ALL cells. Mechanistically, PON2 enabled glucose uptake by releasing the glucose-transporter GLUT1 from its inhibitor stomatin (STOM) and genetic deletion of STOM largely rescued PON2 deficiency. While not required for glucose transport, the PON2 lactonase moiety hydrolyzes the lactone-prodrug 3OC12 to form a cytotoxic intermediate. Mirroring PON2 expression levels in B-ALL, 3OC12 selectively killed patient-derived B-ALL cells but was well tolerated in transplant recipient mice. Hence, while B-ALL cells critically depend on aberrant PON2 expression to evade metabolic gatekeeper functions, PON2 lactonase activity can be leveraged as synthetic lethality to overcome drug resistance in refractory B-ALL.
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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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Metabolic determinants of B-cell selection. Biochem Soc Trans 2021; 49:1467-1478. [PMID: 34196360 DOI: 10.1042/bst20201316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/01/2021] [Accepted: 06/07/2021] [Indexed: 11/17/2022]
Abstract
B-cells are antibody-producing cells of the adaptive immune system. Approximately 75% of all newly generated B-cells in the bone marrow are autoreactive and express potentially harmful autoantibodies. To prevent autoimmune disease, the immune system has evolved a powerful mechanism to eliminate autoreactive B-cells, termed negative B-cell selection. While designed to remove autoreactive clones during early B-cell development, our laboratory recently discovered that transformed B-cells in leukemia and lymphoma are also subject to negative selection. Indeed, besides the risk of developing autoimmune disease, B-cells are inherently prone to malignant transformation: to produce high-affinity antibodies, B-cells undergo multiple rounds of somatic immunoglobulin gene recombination and hypermutation. Reflecting high frequencies of DNA-breaks, adaptive immune protection by B-cells comes with a dramatically increased risk of development of leukemia and lymphoma. Of note, B-cells exist under conditions of chronic restriction of energy metabolism. Here we discuss how these metabolic gatekeeper functions during B-cell development provide a common mechanism for the removal of autoreactive and premalignant B-cells to safeguard against both autoimmune diseases and B-cell malignancies.
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20
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Larouche V, Bellavance C, Tibout P, Bergeron S, Simonyan D, Gagné J. Screening for asymptomatic diabetes and metabolic comorbidities in pediatric patients during therapy for acute lymphoblastic leukemia. J Pediatr Endocrinol Metab 2021; 34:627-632. [PMID: 33838097 DOI: 10.1515/jpem-2020-0457] [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: 08/05/2020] [Accepted: 01/19/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Chronic metabolic disturbances related to cancer treatment are well reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, few studies have investigated the incidence of these complications during the phase of chemotherapy. We evaluated the incidence of acute metabolic complications occurring during therapy in our cohort of patients diagnosed with ALL. METHODS A prospective study involving 50 ALL pediatric patients diagnosed and treated between 2012 and 2016 in our oncology unit. We collected weight, blood pressure, fasting plasma glucose and hemoglobin A1C (HBA1c) levels during the two years of therapy. RESULTS Obesity and overweight occurred in 43 and 25%, respectively among patients and have been reached at 12 months of chemotherapy. About 26% of the patients developed high blood pressure and 14% experienced hyperglycemias without meeting diabetes criteria. There was a significant decrease of HBA1c levels between the beginning and the end of therapy (p<0.0001). CONCLUSIONS Increase of body mass index in our ALL pediatric patients occurred during the first months of therapy and plateaued after a year of treatment. We should target this population for early obesity prevention. HbA1c levels measured during therapy did not reveal diabetes criteria. Hence, fasting blood glucose levels are sufficient to monitor ALL pediatric patients' glycemia.
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Affiliation(s)
- Valerie Larouche
- Department of Pediatric Hematology-Oncology, CHU de Québec-Université Laval, Quebec, Canada
| | | | - Pauline Tibout
- Department of Pediatric, CHU de Québec-Université Laval, Quebec, Canada
| | | | - David Simonyan
- Clinical and Evaluative Research Platform, Research Center, CHU de Québec-Université Laval, Quebec, Canada
| | - Julie Gagné
- Department of Pediatric, CHU de Québec-Université Laval, Quebec, Canada
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Savage B, Cole PD, Lin H. Racial and Economic Differences in the Risk of Hyperglycemia in Children Hospitalized With Acute Lymphoblastic Leukemia. J Pediatr Oncol Nurs 2021; 38:277-284. [PMID: 33949234 DOI: 10.1177/10434542211011040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Background: The underlying mechanism of hyperglycemia in children with acute lymphoblastic leukemia (ALL) is insulin resistance. Although race and economic status have been linked to increased insulin resistance in children, these have not been explored as predictors of hyperglycemia in children with ALL. The objective of this study was to analyze race and income as predictors of hyperglycemia in a diverse sample of children hospitalized with ALL in the United States in the year 2016. Methods: We performed a secondary analysis of 18,077 hospitalizations of White, Black, and Hispanic children under the age of 21 years with ALL contained in a nationally representative database. Multilevel binary logistic regression models were constructed to estimate the relationships between race, median household income, age, sex, and obesity and the odds of hyperglycemia in hospitalized children with ALL. Results: Hyperglycemia occurred during 5.3% of the hospitalizations. Black children were 37% more likely to develop hyperglycemia than White children. The risk for hyperglycemia did not differ between Hispanic and White children. Residing in areas where annual median income was below $54,000 was associated with 1.4-fold increased odds of hyperglycemia, compared to the wealthiest areas. Older children, females, and those diagnosed with obesity were also at increased risk for hyperglycemia. Discussion: An association has been found between treatment-induced hyperglycemia and increased mortality. For this reason, the racial and economic differences in the risk for hyperglycemia identified in this study deserve further consideration.
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Affiliation(s)
- Beth Savage
- Division of Nursing Science, 16118Rutgers School of Nursing, Rutgers, The State University of New Jersey, Newark, NJ, USA
| | - Peter D Cole
- Division of Pediatric Hematology/Oncology, 145249Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Haiqun Lin
- Division of Nursing Science, 16118Rutgers School of Nursing, Rutgers, The State University of New Jersey, Newark, NJ, USA
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Lee EK, Koo B, Hwangbo Y, Lee YJ, Baek JY, Cha YJ, Kim SY, Sim SH, Lee KS, Park IH, Lee H, Joo J, Go S, Heo SC, Moon MK. Incidence and disease course of new-onset diabetes mellitus in breast and colorectal cancer patients undergoing chemotherapy: A prospective multicenter cohort study. Diabetes Res Clin Pract 2021; 174:108751. [PMID: 33722701 DOI: 10.1016/j.diabres.2021.108751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 02/24/2021] [Accepted: 03/05/2021] [Indexed: 10/21/2022]
Abstract
AIMS To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. METHODS This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. RESULTS Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). CONCLUSIONS DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. TRIAL REGISTRATION ClinicalTrials.gov (NCT03062072).
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Affiliation(s)
- Eun Kyung Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Bokyung Koo
- Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yul Hwangbo
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - You Jin Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Ji Yeon Baek
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Yong Jun Cha
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sun Young Kim
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Sung Hoon Sim
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Keun Seok Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - In Hae Park
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea; Center for Breast Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Hyewon Lee
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea
| | - Jungnam Joo
- Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
| | - Sujeong Go
- Center for Thyroid Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Min Kyong Moon
- Division of Endocrinology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Zaitsev VG, Zheltova AA, Martynova SA, Tibirkova EV. Can conventional clinical chemistry tests help doctors in the monitoring of oncology patients? RUSSIAN OPEN MEDICAL JOURNAL 2021. [DOI: 10.15275/rusomj.2021.0103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
The use of laboratory assays in the diagnostic care of oncology patients can markedly increase the efficacy of cancer treatments. Many cancer-specific biomarker assays have been developed. However, the use of these has some limitations due to their cost. Moreover, not every diagnostic laboratory can perform a complete set of these assays. On the other hand, the smart use of conventional clinical chemistry tests could improve the management of cancer. They could be especially valuable tools in the long-term care of patients with a verified diagnosis. In this review, we discuss the utilization of the conventional clinical chemistry assays for the diagnosis, monitoring and prognosis of various oncological diseases. The use of conventional blood tests to assess the levels of chemical elements, metabolites and proteins (including enzymatic activity measurements) in the care of oncology patients is discussed. We have shown that some clinical chemistry assays could be used in the management of distinct kinds of cancer.
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Rao S, Prasad K, Abraham S, George T, Chandran SK, Baliga MS. Incidence of Hyperglycemia/Secondary Diabetes in Women who have Undergone Curative Chemotherapy for Breast Cancer: First Study from India. South Asian J Cancer 2021; 9:130-135. [PMID: 33937134 PMCID: PMC8075627 DOI: 10.1055/s-0041-1723104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Purpose Development of cancer chemotherapy treatment-induced hyperglycemia/ diabetes (secondary diabetes) is a major problem and has never been reported from India. The present study was planned to ascertain this in women undergoing curative chemotherapy for their breast cancer. Materials and Methods This was a retrospective chart-based study and was conducted in a cancer specialty hospital. The information on women who were nondiabetic at the start of the treatment was collected from the files. Details on cancer diagnosis, domicile, body mass index (BMI), type of diet, marital status, number of children, and previous history of diabetes if any were considered. The blood glucose levels before surgery and after the completion of radiotherapy were considered. World Health Organization (WHO) guidelines for diabetes were considered. The data were subjected to frequency and percentage and analyzed using Chi-square test. Association between the demographic details and development of Hyperglycemia or secondary diabetes or prediabetes was done using the Pearson's correlation analysis. p < 0.05 was considered as statistically significant. Results A total of 474 cases were included in accordance with the inclusion criteria. The results indicated that by the end of the radiation treatment, 24.89% were prediabetic, 10.97% were diabetic after being in prediabetic stage, 8.22% became diabetic without going through a prediabetic stage, and that 55.91% did not develop either prediabetic or diabetic condition. Analysis of development of secondary diabetes and prediabetes with BMI ( p < 0.0001) and age ( p < 0.024) showed a strong correlation and was significant. Conclusion To the best of the authors' knowledge, this is the first study from India, and the results indicate that the development of secondary diabetes in women undergoing curative chemotherapy is high. Attempts are underway to ascertain the cause for the development and how it can be mitigated.
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Affiliation(s)
- Suresh Rao
- Department of Radiation Oncology, Mangalore Institute of Oncology, Mangalore, Karnataka, India
| | - Krishna Prasad
- Department of Medical Oncology, Mangalore Institute of Oncology, Mangalore, Karnataka, India
| | - Soniya Abraham
- Research Unit, Mangalore Institute of Oncology, Mangalore, Karnataka, India
| | - Thomas George
- Research Unit, Mangalore Institute of Oncology, Mangalore, Karnataka, India
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Prescribed Walking for Glycemic Control and Symptom Management in Patients Without Diabetes Undergoing Chemotherapy. Nurs Res 2021; 70:6-14. [PMID: 32852358 DOI: 10.1097/nnr.0000000000000468] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Hyperglycemia may potentiate symptom experiences. Exercise is a nonpharmacological intervention that can potentially improve glycemic control and mitigate symptom experiences in patients undergoing chemotherapy for cancer. OBJECTIVES The primary objective was to assess the feasibility of patients engaging in a walking exercise study for 6 months. We also evaluated the effects of a prescribed walking program on glycemic control and for changes over time in the severity of pain, fatigue, depression, and sleep disturbance in patients undergoing chemotherapy for breast, lung, gynecologic, or gastrointestinal cancer. METHODS A randomized pilot intervention study was conducted to evaluate differences within and between a prescribed walking program intervention group and a control group. All patients were followed for 6 months, had glycosylated hemoglobin A1c measured at enrollment and 6 months, and completed symptom questionnaires at enrollment, 3 months, and 6 months. Data were analyzed using descriptive statistics and analysis of covariance. RESULTS Most of the patients who enrolled completed the 6-month study. The few who withdrew expressed feeling overwhelmed. The sample was predominately non-Hispanic White female patients with breast cancer with a normal-to-slightly-overweight body mass index. The intervention group had a slight decrease in glycosylated hemoglobin A1c at 6 months. In addition, at 6 months, compared to the control group, the intervention group had significantly less sleep disturbance and depression. No other within- or between-group differences were found. DISCUSSION It is feasible for patients undergoing chemotherapy to participate in a prescribed walking program. Exercise, such as walking, may decrease hyperglycemia and symptom severity. Additional research with larger samples is warranted.
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Sadras T, Chan LN, Xiao G, Müschen M. Metabolic Gatekeepers of Pathological B Cell Activation. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2021; 16:323-349. [DOI: 10.1146/annurev-pathol-061020-050135] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Unlike other cell types, B cells undergo multiple rounds of V(D)J recombination and hypermutation to evolve high-affinity antibodies. Reflecting high frequencies of DNA double-strand breaks, adaptive immune protection by B cells comes with an increased risk of malignant transformation. In addition, the vast majority of newly generated B cells express an autoreactive B cell receptor (BCR). Thus, B cells are under intense selective pressure to remove autoreactive and premalignant clones. Despite stringent negative selection, B cells frequently give rise to autoimmune disease and B cell malignancies. In this review, we discuss mechanisms that we term metabolic gatekeepers to eliminate pathogenic B cell clones on the basis of energy depletion. Chronic activation signals from autoreactive BCRs or transforming oncogenes increase energy demands in autoreactive and premalignant B cells. Thus, metabolic gatekeepers limit energy supply to levels that are insufficient to fuel either a transforming oncogene or hyperactive signaling from an autoreactive BCR.
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Affiliation(s)
- Teresa Sadras
- Center of Molecular and Cellular Oncology, Yale Cancer Center, and Department of Immunobiology, Yale University, New Haven, Connecticut 06520, USA
| | - Lai N. Chan
- Center of Molecular and Cellular Oncology, Yale Cancer Center, and Department of Immunobiology, Yale University, New Haven, Connecticut 06520, USA
| | - Gang Xiao
- Current affiliation: Department of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Markus Müschen
- Center of Molecular and Cellular Oncology, Yale Cancer Center, and Department of Immunobiology, Yale University, New Haven, Connecticut 06520, USA
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Marsà A, Ascanio M, Diaz-García J, Darbà J. Epidemiology, management, and economic impact of acute myeloid leukemia and myelodysplastic syndrome in Spain at the hospital level: a claims database analysis. J Med Econ 2020; 23:1477-1484. [PMID: 33084440 DOI: 10.1080/13696998.2020.1840180] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES This study reviewed patient characteristics, management, and medical costs of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs) in Spanish hospitals. METHODS Data were extracted from the Spanish Ministry of Health records via a claims database containing patient records from 192 private and 313 public hospitals between 1997 and 2015 for AML, and 2008 and 2015 for MDS. Direct medical costs at the hospital level were calculated based on mean medical procedure costs determined per the Spanish Ministry of Health. RESULTS Records for 39,568 patients with AML and 33,091 with MDS were analyzed. The median age of AML patients was 65 years (interquartile range (IQR) = 27) and of MDS patients was 81 years (IQR = 12). In terms of disease management, 58% and 83% of admissions were due to emergencies for patients with AML and MDS, respectively; median length of hospital stay was 14 days (IQR = 25) for AML and seven days (IQR = 9) for MDS. There was an increase in allogeneic hematopoietic stem cell transplantations over time for patients with AML or MDS. Mean annual direct medical costs of AML and MDS, respectively, were €66,422,245 and €42,635,313 for total costs, and €30,775 and €10,312 per patient. Of the total costs, transplantations contributed total annual costs of €15,843,982 and €2,705,791 for patients with AML and MDS, respectively. CONCLUSIONS This study provides novel data to assist decision makers in allocating resources. AML and MDS represent a significant burden for the National Spanish Healthcare System, with substantial costs incurred in secondary care, principally associated with the increasing number of transplantations.
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Affiliation(s)
- Alicia Marsà
- Department of Health Economics, BCN Health Economics & Outcomes Research SL, Barcelona, Spain
| | - Meritxell Ascanio
- Department of Health Economics, BCN Health Economics & Outcomes Research SL, Barcelona, Spain
| | | | - Josep Darbà
- Department of Economics, Universitat de Barcelona, Barcelona, Spain
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Milluzzo A, Vigneri P, Martorana F, Vigneri R, Sciacca L. Type 2 diabetes and cancer: problems and suggestions for best patient management. EXPLORATION OF MEDICINE 2020. [DOI: 10.37349/emed.2020.00013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Diabetes and cancer are widespread worldwide and the number of subjects presenting both diseases increased over the years. The management of cancer patients having diabetes represents a challenge not only because of the complexity and heterogeneity of these pathologies but also for the lack of standardised clinical guidelines. The diagnosis of cancer is traumatizing and monopolizes the attention of both patients and caregivers. Thus, pre-existent or new-onset diabetes can be overshadowed thus increasing the risk for short- and long-term adverse events. Moreover, drugs used for each disease can interfere with the clinical course of the concomitant disease, making challenging the management of these patients. Over the years, this issue has become more relevant because of the increased patients’ life expectancy due to the improved efficacy of diabetes and cancer therapies.
The purpose of this review is to highlight what is known and what should be taken into consideration to optimise the clinical management of patients with diabetes and cancer. Due to the complexity of these diseases, a multidisciplinary, shared approach, including all the protagonists involved, is necessary to improve patients’ quality of life and lifespan.
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Affiliation(s)
- Agostino Milluzzo
- Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania Medical School, 95122 Catania, Italy
| | - Paolo Vigneri
- Center of Experimental Oncology and Hematology, Department of Clinical and Experimental Medicine, University of Catania, A.O.U. Policlinico-Vittorio Emanuele, 95124 Catania, Italy
| | - Federica Martorana
- Center of Experimental Oncology and Hematology, Department of Clinical and Experimental Medicine, University of Catania, A.O.U. Policlinico-Vittorio Emanuele, 95124 Catania, Italy
| | - Riccardo Vigneri
- Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania Medical School, 95122 Catania, Italy; Institute of Crystallography, Catania Section, National Research Council, CNR, 95126 Catania, Italy
| | - Laura Sciacca
- Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania Medical School, 95122 Catania, Italy
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Orgel E, Sea JL, Mittelman SD. Mechanisms by Which Obesity Impacts Survival from Acute Lymphoblastic Leukemia. J Natl Cancer Inst Monogr 2020; 2019:152-156. [PMID: 31532535 DOI: 10.1093/jncimonographs/lgz020] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/22/2019] [Accepted: 07/01/2019] [Indexed: 01/29/2023] Open
Abstract
The prevalence of obesity has steadily risen over the past decades, even doubling in more than 70 countries. High levels of body fat (adiposity) and obesity are associated with endocrine and hormonal dysregulation, cardiovascular compromise, hepatic dysfunction, pancreatitis, changes in drug metabolism and clearance, inflammation, and metabolic stress. It is thus unsurprising that obesity can affect the development of and survival from a wide variety of malignancies. This review focuses on acute lymphoblastic leukemia, the most common malignancy in children, to explore the multiple mechanisms connecting acute lymphoblastic leukemia, obesity, and adipocytes, and the implications for leukemia therapy.
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Affiliation(s)
- Etan Orgel
- Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA Department of Pediatrics, Keck School of Medicine, University of Southern California
| | - Jessica L Sea
- Division of Pediatric Endocrinology, UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA
| | - Steven D Mittelman
- Division of Pediatric Endocrinology, UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA
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Shelby RA, Dorfman CS, Arthur SS, Bosworth HB, Corsino L, Sutton L, Owen L, Erkanli A, Keefe F, Corbett C, Kimmick G. Improving health engagement and lifestyle management for breast cancer survivors with diabetes. Contemp Clin Trials 2020; 92:105998. [PMID: 32289471 PMCID: PMC7590108 DOI: 10.1016/j.cct.2020.105998] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 04/03/2020] [Accepted: 04/09/2020] [Indexed: 01/19/2023]
Abstract
Breast cancer survivors with type 2 diabetes are at high risk for cancer recurrence, serious health complications, more severe symptoms, psychological distress, and premature death relative to breast cancer survivors without diabetes. Maintaining glycemic control is critical for decreasing symptoms and preventing serious health problems. Many breast cancer survivors with type 2 diabetes have difficulty maintaining diabetes self-management behaviors and achieving glycemic control. Both cancer and diabetes-related symptoms (e.g., physical symptoms and psychological distress) are often barriers to engaging in diabetes self-management strategies. This study evaluates a novel diabetes coping skills training (DCST) intervention for improving breast cancer survivors' abilities to manage symptoms and adhere to recommended diabetes self-management behaviors. The telephone-based DCST protocol integrates three key theory-based strategies: coping skills training for managing symptoms, adherence skills training, and healthy lifestyle skills training. A randomized clinical trial will test the DCST intervention plus diabetes education by comparing it to diabetes education alone. Symptoms, distress, diabetes self-management behaviors, and self-efficacy will be assessed at baseline and 3, 6, and 12 months. Glycosylated hemoglobin (HbA1c) will be assessed at baseline, 6, and 12 months. This study addresses a critical gap in the care of breast cancer survivors by evaluating a novel behavioral intervention to improve the management of symptoms, adherence, and glycemic control in breast cancer survivors with type 2 diabetes. Special considerations for this medically underserved population are also provided. The findings of this study could lead to significant improvements in clinical care and beneficial outcomes for breast cancer survivors. Trials registration: ClinicalTrials.gov, NCT02970344, registered 11/22/2016.
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Affiliation(s)
- Rebecca A Shelby
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States of America.
| | - Caroline S Dorfman
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States of America
| | - Sarah S Arthur
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States of America
| | - Hayden B Bosworth
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States of America; Division of General Internal Medicine, Duke University, Durham, NC, United States of America; Department of Population Health Sciences, Duke University, Durham, NC, United States of America
| | - Leonor Corsino
- Division of Endocrinology, Metabolism and Nutrition, Duke University, Durham, NC, United States of America
| | - Linda Sutton
- Duke Cancer Network, Duke University, Durham, NC, United States of America
| | - Lynda Owen
- Duke Cancer Network, Duke University, Durham, NC, United States of America
| | - Alaattin Erkanli
- Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, United States of America
| | - Francis Keefe
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States of America
| | - Cheyenne Corbett
- Supportive Care and Survivorship Center, Duke Cancer Institute, Durham, NC, United States of America
| | - Gretchen Kimmick
- Division of Medical Oncology, Duke University Medical Center, Durham, NC, United States of America
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Gregoriou K, Craigie I, Gibson B, Mason A, Shaikh MG. Risk factors and management of corticosteroid-induced hyperglycaemia in paediatric acute lymphoblastic leukaemia. Pediatr Blood Cancer 2020; 67:e28085. [PMID: 31736211 DOI: 10.1002/pbc.28085] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 09/23/2019] [Accepted: 10/30/2019] [Indexed: 02/02/2023]
Abstract
Corticosteroids are incorporated into protocols for the treatment of acute lymphoblastic leukaemia, and hyperglycaemia is a recognised side effect. Corticosteroids exert their hyperglycaemic effect with a multifactorial mechanism. Complications of hyperglycaemia include an increased risk of infection - bacterial, viral and fungal. Approximately half of the children who develop corticosteroid-associated hyperglycaemia are predicted to require insulin treatment, with age and obesity having found to be predictive factors. Fasting and random glucose values can be used to define hyperglycaemia. This review focuses on the published evidence for significant predictive factors for the development of corticosteroid-induced hyperglycaemia and provides guidance on management.
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Affiliation(s)
- Kyriacos Gregoriou
- Departments of Endocrinology, Royal Hospital for Children, Glasgow, UK.,Department of Diabetes, Royal Hospital for Children, Glasgow, UK
| | - Ian Craigie
- Department of Diabetes, Royal Hospital for Children, Glasgow, UK
| | - Brenda Gibson
- Department of Haematology, Royal Hospital for Children, Glasgow, UK
| | - Avril Mason
- Departments of Endocrinology, Royal Hospital for Children, Glasgow, UK.,Department of Diabetes, Royal Hospital for Children, Glasgow, UK
| | - Mohamad Guftar Shaikh
- Departments of Endocrinology, Royal Hospital for Children, Glasgow, UK.,Department of Diabetes, Royal Hospital for Children, Glasgow, UK
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Ochola LA, Nyamu DG, Guantai EM, Weru IW. Metformin's effectiveness in preventing prednisone-induced hyperglycemia in hematological cancers. J Oncol Pharm Pract 2019; 26:823-834. [PMID: 31495292 DOI: 10.1177/1078155219873048] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Research has established the development of steroid-induced hyperglycemia as a glucometabolic side effect of high-dose prednisone therapy. Few studies, however, have demonstrated preventative measures that could effectively curtail this side effect in susceptible patients undergoing high-dose prednisone treatment. OBJECTIVE To assess metformin's prophylactic effectiveness of prednisone-induced hyperglycemia among hematological cancer patients. SETTING Prospective randomized controlled trial conducted at the Kenyatta National Hospital Oncology Clinic and Wards, Nairobi, Kenya. METHOD Non-hyperglycemic hematological cancer patients on current or newly initiated high-dose prednisone-based chemotherapy were randomized to receive metformin 850 mg once then 850 mg twice daily for two successive weeks each or to the control group receiving the standard care. Patients were subjected to once weekly fasting and 2-h postprandial glucose measurements for four weeks. MAIN OUTCOME MEASURE The primary outcome of measure was the development of hyperglycemia defined by fasting capillary blood glucose values >5.6 mmol/L or 2-h postprandial capillary blood glucose values >7.8 mmol/L. RESULTS Eighteen of 24 randomized patients completed the study (11 control and 7 treatment). The proportion of the control subjects that developed prediabetes was 72.7% (95% confidence interval 45.5-90.9%) using fasting glucose and 54.5% (95% confidence interval 27.3-81.8%) using 2-h postprandial glucose. One treatment group participant developed prediabetes using fasting glucose, representing 14.3% (95% confidence interval 0-42.9%). No prediabetes was detected using the 2-h postprandial glucose. Analysis of mean fasting glucose between the two arms found no significant difference. However, significant differences in mean 2-h postprandial glucose were noted in week 2 (p = 0.0144), week 3 (p = 0.0095), and week 4 (p = 0.0074) of the study. Double dose (1700 mg) metformin was more effective in lowering blood glucose than single dose (850 mg) (p = 1.0000 (fasting), p = 0.4531(2-h postprandial). CONCLUSION Metformin's prophylactic effectiveness was demonstrated in this randomized study on new and previously exposed non-diabetic cancer patients on high-dose prednisone-based chemotherapy.
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Affiliation(s)
- Lucy A Ochola
- Division of Pharmaceutics and Pharmacy Practice, School of Pharmacy, University of Nairobi, Nairobi, Kenya
| | - David G Nyamu
- Division of Pharmaceutics and Pharmacy Practice, School of Pharmacy, University of Nairobi, Nairobi, Kenya
| | - Eric M Guantai
- Division of Pharmacology, School of Pharmacy, University of Nairobi, Nairobi, Kenya
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Madsen ML, Due H, Ejskjær N, Jensen P, Madsen J, Dybkær K. Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review. Cancer Chemother Pharmacol 2019; 84:471-485. [PMID: 31214762 PMCID: PMC6682573 DOI: 10.1007/s00280-019-03884-5] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 06/04/2019] [Indexed: 01/09/2023]
Abstract
PURPOSE Vincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy, possibly including both peripheral sensory and motor nerves, autonomic nervous functions, and the central nervous system. This dose-limiting side-effect can diminish quality of life and, furthermore, cause discontinuation of vincristine treatment. The present review elucidates the current knowledge regarding vincristine-induced neuropathy in hematologic malignancies, focusing on neuropathy assessment, clinical and molecular predictive markers, drug-drug interference, prevention, and treatment. METHODS This review is conducted by a systematic search strategy for the identification of relevant literature in the PubMed and Embase databases. RESULTS No clinical parameters displayed convincing potential as predictors of vincristine-induced neuropathy; however, preexisting neuropathy was consistently reported to be associated with an increased risk of neurotoxicity. In contrast, molecular markers, including polymorphisms in genes involved in the pharmacodynamics and pharmacokinetics of vincristine, displayed great potential as predictive markers of neuropathy incidence and severity. Furthermore, antifungal drugs, such as itraconazole and voriconazole, decrease the metabolism of vincristine and consequently lead to severe neuropathy when co-administered with vincristine, underscoring why fluconazole should be the antifungal drug of choice. CONCLUSION Reports from the 71 included studies clearly emphasize the lack of consistency in neuropathy assessment, grading systems, and reporting, making it difficult to interpret results between studies. Thus, truer clinical and molecular markers could emerge if the consistency of neuropathy detection and reporting increases by the use of conventional standardized neuropathy assessment tools and grading scales.
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Affiliation(s)
- Marie Lindhard Madsen
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Hanne Due
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Niels Ejskjær
- Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg University Hospital, 9000, Aalborg, Denmark
| | - Paw Jensen
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark.,Clinical Cancer Research Center, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Jakob Madsen
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark
| | - Karen Dybkær
- Department of Hematology, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark. .,Department of Clinical Medicine, Aalborg University, Sdr. Skovvej 15, 9000, Aalborg, Denmark. .,Clinical Cancer Research Center, Aalborg University Hospital, Sdr. Skovvej 15, 9000, Aalborg, Denmark.
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Liu W, Qdaisat A, Lee E, Yeung J, Vu K, Lin JZ, Canada T, Zhou S, Cohen L, Bruera E, Yeung SCJ. The association between weight stability and parenteral nutrition characteristics and survival in patients with colorectal cancer. Gastroenterol Rep (Oxf) 2019; 7:419-425. [PMID: 31857903 PMCID: PMC6911996 DOI: 10.1093/gastro/goz021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 03/17/2019] [Accepted: 04/29/2019] [Indexed: 01/06/2023] Open
Abstract
Objective Knowledge about the impact of metabolic disturbances and parenteral nutrition (PN) characteristics on the survival of cancer patients receiving PN is limited. We aimed to assess the association between clinical and PN characteristics and survival in colorectal-cancer patients receiving PN support. Methods Our study included 572 consecutive colorectal-cancer patients who had received PN support between 2008 and 2013. Patient characteristics, body mass index, weight, medical/surgical history, indication for PN, PN data and survival were recorded. Associations between clinical and PN characteristics and survival were analysed with important confounding factors. Results The final cohort included 437 evaluable patients, with a mean age of 57 years. Eighty-one percent of the study population had advanced stage of colorectal cancer. Unstable weight (weight change ≥2.5%) prior to PN initiation [hazard ratio (HR) = 1.41, P = 0.023] was adversely associated with survival after adjusting for multiple factors including cancer stage. Bowel obstruction (HR = 1.75, P = 0.017) as a PN indication was associated with worse survival when compared with without bowel obstruction. Higher PN amino acid by ideal body weight (g•kg-1) (HR = 0.59, P = 0.029) was associated with longer survival, whereas a higher percentage of non-PN intravenous calories (HR = 1.04, P = 0.011) was associated with shorter survival independently of confounding factors. Conclusions Body mass index and weight stability can be useful nutritional indices for survival prediction in cancer patients receiving PN. PN planning should take into account of non-PN calories to achieve optimal energy support and balance. Future research is needed to define optimal PN amino-acid requirement and energy balance.
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Affiliation(s)
- Wenli Liu
- Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aiham Qdaisat
- Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eric Lee
- McGovern Medical School, Houston, TX, USA
| | - Jason Yeung
- Biomedical Science, Texas A&M University, College Station, TX, USA
| | - Khanh Vu
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jun-Zhong Lin
- Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China
| | - Todd Canada
- Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shouhao Zhou
- Department of Public Health Sciences, Pennsylvania State University School of Medicine, Hershey, PA, USA
| | - Lorenzo Cohen
- Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eduardo Bruera
- Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sai-Ching J Yeung
- Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Chiu WL, Churilov L, Lim CH, Tan A, Nedumannil R, Lau LH, Lew J, Hachem M, Kong A, Robbins R, Sutcliffe H, Lam Q, Lee A, Djukiadmodjo F, Nanayakkara N, Zajac JD, Ekinci EI. Routine HbA1c among hematology and oncology inpatients: Diabetes-status and hospital-outcomes. Diabetes Res Clin Pract 2019; 152:71-78. [PMID: 31082446 DOI: 10.1016/j.diabres.2019.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 04/25/2019] [Accepted: 05/03/2019] [Indexed: 01/08/2023]
Abstract
AIMS Using routine HbA1c measurement to determine the prevalence of diabetes mellitus (known and previously unrecognized) and their hospital outcomes among hematology and oncology inpatients. METHODS This was a prospective, observational study. Routine automated HbA1c testing was performed in all hematology and oncology inpatients aged ≥54 years at a tertiary hospital, July 2013-January 2015. The outcome measures were: (i) prevalence of known and previously unrecognized diabetes, and (ii) hospital outcomes: length-of-stay (LOS), intensive-care-unit (ICU) admission, 30-day/18-month readmission, and 18-month mortality. RESULTS Over the 18-month study period, 1076 inpatients aged ≥54 years were admitted to hematology (n = 298) and oncology (n = 778) units: 21% had known diabetes and 7% had previously unrecognized diabetes. Patients with known diabetes had a longer LOS (IRR: 1.18, 95%CI: 1.02-1.37, p = 0.03), compared to those without diabetes, adjusting for age, hemoglobin level, estimated-glomerular-filtration-rate, admission specialty unit, Charlson's comorbidity index score, and glucocorticoid exposure. No significant differences were observed in ICU admission, 30-day/18-month readmission, and 18-month mortality among patients with known, previously unrecognized and no diabetes (p ≥ 0.05). CONCLUSIONS Approximately one in five hematology or oncology inpatients aged ≥54 years had known diabetes, and one in fourteen had previously unrecognized diabetes. Those with known diabetes had a longer hospital stay. Routine HbA1c measurement is can be useful for identifying previously unrecognized diabetes, particularly among patients with high glucocorticoid exposure. Further study is required to determine cost-effectiveness in screening for unrecognized diabetes and optimal management of these patients.
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Affiliation(s)
- Wei-Ling Chiu
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia.
| | - Leonid Churilov
- The Florey Institute of Neuroscience & Mental Health, Heidelberg, Victoria 3084, Australia; University of Melbourne - Austin Health, Department of Medicine, Heidelberg, Victoria 3084, Australia.
| | - Chee-Hau Lim
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Alanna Tan
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia.
| | - Rithin Nedumannil
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Lik-Hui Lau
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Jeremy Lew
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia
| | - Mariam Hachem
- University of Melbourne - Austin Health, Department of Medicine, Heidelberg, Victoria 3084, Australia.
| | - Alvin Kong
- University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia
| | - Raymond Robbins
- Department of Strategy, Quality & Service Redesign, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia.
| | - Harvey Sutcliffe
- Pathology IT Service, Austin Pathology, Heidelberg, Victoria 3084, Australia.
| | - Que Lam
- Pathology IT Service, Austin Pathology, Heidelberg, Victoria 3084, Australia.
| | - Andrew Lee
- Clinical Informatics Unit, Austin Health, Heidelberg, Victoria 3084, Australia.
| | - Frida Djukiadmodjo
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia
| | - Natalie Nanayakkara
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia.
| | - Jeffrey D Zajac
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia; University of Melbourne - Austin Health, Department of Medicine, Heidelberg, Victoria 3084, Australia.
| | - Elif I Ekinci
- Department of Endocrinology, Austin Health, 145 Studley Road, Heidelberg, Victoria 3084, Australia; University of Melbourne - Austin Health, Department of Medicine, Heidelberg, Victoria 3084, Australia.
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Zylla D, Gilmore G, Eklund J, Richter S, Carlson A. Impact of diabetes and hyperglycemia on health care utilization, infection risk, and survival in patients with cancer receiving glucocorticoids with chemotherapy. J Diabetes Complications 2019; 33:335-339. [PMID: 30717892 DOI: 10.1016/j.jdiacomp.2018.12.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 12/13/2018] [Accepted: 12/22/2018] [Indexed: 01/11/2023]
Abstract
BACKGROUND Glucocorticoids are commonly used in chemotherapy regimens and may lead to hyperglycemia and increased infection rates. METHODS We performed a retrospective analysis on 1781 patients who received intravenous chemotherapy with glucocorticoids between 2010 and 2015. Data was obtained using electronic medical record, billing modules, and tumor registry. We compared new infections and survival between patients with and without diabetes, after adjusting for demographic and cancer-related variables. RESULTS In the first 12 months following chemotherapy, patients with diabetes (n = 330) had higher rates of hospital admissions (70.9% vs 57.4%), more infection-related admissions (37.0% vs 29.2%), and increased rates of new infections (61.2% vs 49.2%) when compared to patients without diabetes (n = 1451). One-year survival was worse among patients with diabetes (67.3% vs 78.3%), and in patients with at least one elevated glucose following chemotherapy (60.8% vs 78.5). After adjusting for cancer stage, age, and gender, diabetes history increased the odds of dying within one year after diagnosis by 86% (OR 1.86, 95% CI (1.37-2.52)) and of new infections by 68% (OR 1.68, 95% CI (1.26-2.24)). CONCLUSIONS Among patients with cancer receiving intravenous chemotherapy with glucocorticoids we demonstrate those with diabetes have more hospital admissions, increased rates of infections, and worse survival.
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Affiliation(s)
- Dylan Zylla
- Park Nicollet Oncology Research, Frauenshuh Cancer Center, HealthPartners, Minneapolis, MN, USA; HealthPartners Institute, HealthPartners, Minneapolis, MN, USA.
| | - Grace Gilmore
- Park Nicollet Oncology Research, Frauenshuh Cancer Center, HealthPartners, Minneapolis, MN, USA
| | - Justin Eklund
- Park Nicollet Oncology Research, Frauenshuh Cancer Center, HealthPartners, Minneapolis, MN, USA; HealthPartners Institute, HealthPartners, Minneapolis, MN, USA
| | - Sara Richter
- Professional Data Analysts, Inc., Minneapolis, MN, USA
| | - Anders Carlson
- International Diabetes Center, Park Nicollet, Minneapolis, MN, USA
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Müschen M. Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation. Nat Rev Immunol 2019; 19:337-348. [DOI: 10.1038/s41577-019-0154-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Cardoso HJ, Vaz CV, Carvalho TM, Figueira MI, Socorro S. Tyrosine kinase inhibitor imatinib modulates the viability and apoptosis of castrate-resistant prostate cancer cells dependently on the glycolytic environment. Life Sci 2019; 218:274-283. [PMID: 30605651 DOI: 10.1016/j.lfs.2018.12.055] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 12/21/2018] [Accepted: 12/29/2018] [Indexed: 11/16/2022]
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Clemente G, Giorgini M, Mancini M, Gallo M. Diabetologists and Oncologists attitudes towards treating diabetes in the oncologic patient: Insights from an exploratory survey. Diabetes Res Clin Pract 2018; 143:420-427. [PMID: 29596952 DOI: 10.1016/j.diabres.2018.02.044] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 02/28/2018] [Indexed: 10/17/2022]
Abstract
AIMS Diabetes and cancer frequently coexist in the same subject, often having relevant effects on the management and prognosis of the oncologic patient. However, existing guidelines do not deal with many clinical issues in this setting appropriately. In evaluating the opinions of Diabetologists and Oncologists dealing with diabetes care in people with cancer, the Italian Association of Diabetologists (AMD) promoted a dedicated exploratory survey. METHODS The survey was carried out through the web or handily delivered printed copies between October 2014 and April 2015, in Italy. It was composed of 27 questions intended to gather information on the characteristics of participants and to examine their clinical habits in this context, and participation was totally free and anonymous. RESULTS A total of 252 physicians participated in the survey. Diabetologists accounted for 51.1% of respondents. According to survey results, in spite of the presence of diabetes (or diabetic complications) worsening the outcome of cancer treatments, the counseling or intervention of a Diabetologist was only required for less than two-thirds of hospitalized patients. For subjects with a life expectancy of months, 80% of specialists considered a glycemic target of 120-250 mg/dL optimal whereas Oncologists were more likely to consider a range of 180-360 mg/dL for patients with a shorter life expectancy. Furthermore, 1 participant out of 3 indicated 1-4 measurements/day as the most appropriate frequency for blood glucose monitoring including in the palliative setting. Insulin was the therapy of choice for the majority of respondents albeit with different routes of administration. CONCLUSIONS This survey provides interesting preliminary data that could help facilitate and optimize the management of patients with cancer and diabetes, promoting the delivery of an organic answer to fragmented assistance, to potentially inappropriate behaviors, and to a tailored therapy in a context of particular clinical fragility.
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Affiliation(s)
- Gennaro Clemente
- IRPPS-Institute for Research on Population and Social Policies of the Italian National Research Council, Fisciano, Salerno, Italy.
| | - Marisa Giorgini
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Marcello Mancini
- IBB-Institute of Biostructure and Bioimaging, of the Italian National Research Council, Naples, Italy
| | - Marco Gallo
- Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Turin, Italy
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Alabbood M, Ling M, Ho K. Effect of high-dose dexamethasone on patients without diabetes during elective neurosurgery: a prospective study. Diabetol Int 2018; 10:109-116. [PMID: 31139529 DOI: 10.1007/s13340-018-0370-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Accepted: 08/20/2018] [Indexed: 01/26/2023]
Abstract
Introduction The peri-operative use of high-dose dexamethasone to reduce cerebral oedema may result in worsening glycaemic control in people with diabetes and glucocorticoid-induced diabetes in susceptible individuals. This study aims to examine the incidence of glucocorticoid-induced diabetes in a cohort of neurosurgical patients receiving high-dose dexamethasone peri-operatively. Materials and methods Adult non-diabetic neurosurgical patients receiving high-dose dexamethasone were prospectively studied. Exclusion criteria included pregnancy, HbA1c > 6.0%, and use of anti-diabetes therapies. The following data were collected: Family history of diabetes, body mass index, fasting glucose, insulin, C-peptide, and HbA1c (prior to surgery and 6 weeks after last dose of dexamethasone). Homeostatic model assessment values were calculated. Peri-operative glucose readings were recorded and 75 g oral glucose tolerance tests performed at the end of 6 weeks. Paired student t tests and multiple linear regressions were used. Results Data from 21 participants (11 women) were available. The mean total dose of dexamethasone was 96 ± 34 mg, and treatment duration was 17 ± 7 days. A total of 105 random blood glucose levels were documented peri-operatively (mean 7.0 ± 1.0 mmol/L). Six weeks following cessation of dexamethasone course, none of the participants developed diabetes, defined either by fasting glucose or by 75 g OGTT. There was a statistically significant increase in the mean HOMA-β from 81.5 to 102.1% (p = 0.01) and a significant decrease in the mean fasting glucose from 5.7 to 4.8 mmol/L (p = 0.001). Conclusions The use of high-dose dexamethasone in this cohort of neurosurgical patients did not result in glucocorticoid-induced diabetes. Hyperglycaemia was transient and had resolved by 6 weeks.
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Affiliation(s)
- Majid Alabbood
- Faculty of Medicine and Health Sciences, Macquarie University, Ground Floor, 75 Talevera Road, Macquarie Park, NSW 2109 Australia
| | - Min Ling
- Faculty of Medicine and Health Sciences, Macquarie University, Ground Floor, 75 Talevera Road, Macquarie Park, NSW 2109 Australia
| | - Kenneth Ho
- Faculty of Medicine and Health Sciences, Macquarie University, Ground Floor, 75 Talevera Road, Macquarie Park, NSW 2109 Australia
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Khowaja A, Alkhaddo JB, Rana Z, Fish L. Glycemic Control in Hospitalized Patients with Diabetes Receiving Corticosteroids Using a Neutral Protamine Hagedorn Insulin Protocol: A Randomized Clinical Trial. Diabetes Ther 2018; 9:1647-1655. [PMID: 29961246 PMCID: PMC6064602 DOI: 10.1007/s13300-018-0468-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Indexed: 01/14/2023] Open
Abstract
INTRODUCTION Hospitalized patients with diabetes receiving corticosteroids are at risk of developing hyperglycemia and related complications. This study evaluated a neutral protamine Hagedorn (NPH) insulin-based protocol in improving glycemic control in hospitalized patients receiving corticosteroids. METHODS This was a randomized, prospective, non-blinded study in an inpatient setting involving patients with diabetes who were hospitalized and receiving prednisone ≥ 10 mg per day or equivalent. High dose corticosteroids group (prednisone > 40 mg/day or equivalent) received NPH insulin 0.3 U/kg between 0600 and 2000 hours if eating or 0.2 U/kg between 2000 and 0600 hours if not eating. Low dose corticosteroids group (prednisone 10-40 mg/day or equivalent) received 0.15 U/kg between 0600 and 2000 hours if eating or 0.1 U/kg between 2000 and 0600 hours if not eating. Primary outcome measure was mean blood glucose level measured pre-meal and at bedtime for days 1-5. RESULTS Mean blood glucose level was lower in the intervention (n = 29) than in the usual care (n = 31) group [226.12 vs. 268.57 mg/dL, respectively, (95% CI for difference - 63.195 to - 21.695), p < 0.0001]. Significant differences in mean glucose level were noted at fasting [170.96 vs. 221.13 mg/dL, respectively, (95% CI for difference - 72.70 to - 27.63), p < 0.0001] and pre-lunch [208 vs. 266.48 mg/dL, respectively, (95% CI for difference - 86.61 to - 30.36), p < 0.0001]. CONCLUSION In hospitalized patients with diabetes receiving corticosteroids, an NPH insulin-based protocol improves glycemic control. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01970241. FUNDING Eli Lilly and Company.
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Affiliation(s)
- Ameer Khowaja
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA.
- Center for Diabetes and Endocrinology, Hennepin Healthcare System, Minneapolis, MN, USA.
| | - Jamil B Alkhaddo
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
- The Center for Diabetes and Endocrine Health, Allegheny Health Network, Pittsburgh, PA, USA
| | - Zaighum Rana
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
| | - Lisa Fish
- Division of Diabetes, Endocrinology and Metabolism, University of Minnesota, Minneapolis, MN, USA
- Center for Diabetes and Endocrinology, Hennepin Healthcare System, Minneapolis, MN, USA
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Trussardi Fayh AP, de Carvalho Gomes C, Schroeder HT, Henrique de Lemos Muller C, Maria de Araújo Moura Lemos T, Krause M. Induction chemotherapy reduces extracellular heat shock protein 72 levels, inflammation, lipoperoxidation and changes insulin sensitivity in children and adolescents newly diagnosed with acute lymphoblastic leukemia. Oncotarget 2018; 9:28784-28795. [PMID: 29983896 PMCID: PMC6033368 DOI: 10.18632/oncotarget.25609] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 05/19/2018] [Indexed: 02/03/2023] Open
Abstract
Background Acute lymphoblastic leukemia (ALL) is associated with higher levels of pro-inflammatory cytokines and oxidative stress. Recently, the levels of extracellular heat shock protein 72 (eHSP72) were found to be elevated in ALL, and its elevation associated with poor prognosis. Therefore, considering the possible role of eHSP72 as a modulator of the immunological system and metabolism, the aim of this study was to describe the response of eHSP72 to the induction phase of chemotherapy, along with metabolic, inflammatory and oxidative stress markers, in children and adolescents newly diagnosed with ALL. Methods Nineteen patients were recruited and analysed before and after the induction phase of chemotherapy (with 28 days of duration). Blood samples were taken for the analysis of C-reactive protein (CRP), levels of lipoperoxidation, insulin (and HOMA-IR), cortisol, glucose, lipid profile and eHSP72. Results We found that induction phase of chemotherapy leads to a drop in glucose levels (from 101.79±19 to 75.8±9.7 mg/dL), improvements on inflammation (CRP levels, p<0.01) and oxidative stress (TBARS levels, p<0.01), reduction on eHSP72 (p=0.03) and improved insulin sensitivity (HOMA-IR, p=0.02). Conclusion Our results indicate that eHSP72 may have an immune and metabolic role and could be used as a marker of the treatment success and metabolic changes in children with ALL.
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Affiliation(s)
- Ana Paula Trussardi Fayh
- Departamento de Nutrição, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
| | - Camila de Carvalho Gomes
- Departamento de Nutrição, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
| | - Helena Trevisan Schroeder
- Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Carlos Henrique de Lemos Muller
- Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Telma Maria de Araújo Moura Lemos
- Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil
| | - Mauricio Krause
- Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Schultz H, Pedersen-Bjergaard U, Jensen AK, Engelholm SA, Kristensen PL. The influence on survival of glucocorticoid induced diabetes in cancer patients with metastatic spinal cord compression. Clin Transl Radiat Oncol 2018; 11:19-25. [PMID: 30014043 PMCID: PMC6019865 DOI: 10.1016/j.ctro.2018.04.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND PURPOSE The influence of glucocorticoid induced hyperglycemia on survival in patients with metastatic spinal cord compression (MSCC) is unknown. MATERIALS AND METHODS In a prospective, observational cohort study 131 patients with MSCC referred to radiotherapy, 30 Gray (Gy) in 10 fractions, and treated with ≥100 mg prednisolone a day were followed with daily blood glucose measurements during radiotherapy. RESULTS During follow-up a total of 56 patients 43% (95% CI = 35-52%) presented plasma glucose values diagnostic of diabetes. Sixteen patients who developed diabetes were treated with insulin, 12% (95% CI = [6%; 18%]) of the total population. The patients developing diabetes with need for insulin therapy during glucocorticoid therapy had a significantly increased mortality compared to those with normal glucose metabolism and with diabetes without need for therapy, hazard ratio = 2.1 (95% CI = 1.08-4.09, p = 0.0285). DISCUSSION To our knowledge this is the first prospective study to describe the influence of glucocorticoid induced diabetes on survival in patients with MSCC from different primary tumors. CONCLUSIONS The results indicate that development of diabetes during high-dose glucocorticoid therapy needing insulin treatment in patients with MSCC from different primary tumors is associated with reduced survival.
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Affiliation(s)
- Helga Schultz
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
| | - Ulrik Pedersen-Bjergaard
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark
| | - Andreas Kryger Jensen
- Section of Biostatistics, Institute of Public Health, University of Copenhagen, Denmark
| | - Svend Aage Engelholm
- Department of Oncology, Rigshospitalet, University of Copenhagen, Belgdamsvej 9, 2100 Copenhagen N, Denmark
| | - Peter Lommer Kristensen
- Department of Endocrinology and Nephrology, Nordsjaellands Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
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Lam C, Cronin K, Ballard R, Mariotto A. Differences in cancer survival among white and black cancer patients by presence of diabetes mellitus: Estimations based on SEER-Medicare-linked data resource. Cancer Med 2018; 7:3434-3444. [PMID: 29790667 PMCID: PMC6051153 DOI: 10.1002/cam4.1554] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 02/28/2018] [Accepted: 04/23/2018] [Indexed: 02/06/2023] Open
Abstract
Diabetes prevalence and racial health disparities in the diabetic population are increasing in the US. Population‐based cancer‐specific survival estimates for cancer patients with diabetes have not been assessed. The Surveillance, Epidemiology, and End Results (SEER)‐Medicare linkage provided data on cancer‐specific deaths and diabetes prevalence among 14 separate cohorts representing 1 068 098 cancer patients ages 66 + years diagnosed between 2000 and 2011 in 17 SEER areas. Cancer‐specific survival estimates were calculated by diabetes status adjusted by age, stage, comorbidities, and cancer treatment, and stratified by cancer site and sex with whites without diabetes as the reference group. Black patients had the highest diabetes prevalence particularly among women. Risks of cancer deaths were increased across most cancer sites for patients with diabetes regardless of race. Among men the largest effect of having diabetes on cancer‐specific deaths were observed for black men diagnosed with Non‐Hodgkin lymphoma (NHL) (HR = 1.53, 95%CI = 1.33‐1.76) and prostate cancer (HR = 1.37, 95%CI = 1.32‐1.42). Diabetes prevalence was higher for black females compared to white females across all 14 cancer sites and higher for most sites when compared to white and black males. Among women the largest effect of having diabetes on cancer‐specific deaths were observed for black women diagnosed with corpus/uterus cancer (HR = 1.66, 95%CI = 1.54‐1.79), Hodgkin lymphoma (HR = 1.62, 95%CI = 1.02‐2.56) and breast ER+ (HR = 1.39, 95%CI = 1.32‐1.47). The co‐occurrence of diabetes and cancer significantly increases the risk of cancer death. Our study suggests that these risks may vary by cancer site, and indicates the need for future research to address racial and sex disparities and enhance understanding how prevalent diabetes may affect cancer deaths.
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Affiliation(s)
- Clara Lam
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
| | - Kathleen Cronin
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
| | - Rachel Ballard
- Office of Disease Prevention, Office of the Director, National Institutes of Health, Rockville, MD, USA
| | - Angela Mariotto
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA
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Schultz H, Engelholm SA, Harder E, Pedersen-Bjergaard U, Kristensen PL. Glucocorticoid-induced diabetes in patients with metastatic spinal cord compression. Endocr Connect 2018; 7:719-726. [PMID: 29669805 PMCID: PMC5952240 DOI: 10.1530/ec-18-0088] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 04/18/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND The risk of developing diabetes mellitus (DM) during treatment with high-dose glucocorticoids is unknown and monitoring of glucose is random in many settings. OBJECTIVE To determine incidence of and risk factors for induction of DM during high-dose glucocorticoid therapy of metastatic spinal cord compression (MSCC) in patients referred to radiotherapy. Furthermore, to describe the time course of development of DM. SUBJECTS AND METHODS 140 patients were recruited (131 were included in the analysis) with MSCC receiving high-dose glucocorticoid ≥100 mg prednisolone per day were included in a prospective, observational cohort study. The primary endpoint was development of DM defined by two or more plasma glucose values ≥11.1 mmol/L. Plasma glucose was monitored on a daily basis for 12 days during radiotherapy. RESULTS Fifty-six of the patients (43%; 95% CI 35-52%) were diagnosed with DM based on plasma glucose measurements during the study period. Sixteen patients, 12% (95% CI 6-18%), were treated with insulin. At multivariate analysis, only high baseline HbA1c predicted the development of insulin-treated DM. An HbA1c-value <39 mmol/mol was associated with a negative predictive value of 96% for not developing DM needing treatment with insulin. The diagnosis of diabetes with need for insulin treatment was made within 7 days in 14 of the 16 (88%; 95% CI 72-100%) patients. CONCLUSION The risk of developing DM during treatment with high-dose glucocorticoids in patients with MSCC referred to radiotherapy is high in the first treatment week. Only referral HbA1c predicts the development of DM.
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Affiliation(s)
- Helga Schultz
- Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
| | - Svend Aage Engelholm
- Department of Radiation OncologyRigshospitalet, Copenhagen, Denmark
- Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark
| | - Eva Harder
- Department of Oncology and PalliationNordsjællands Hospital, Hillerød, Denmark
| | - Ulrik Pedersen-Bjergaard
- Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
- Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark
| | - Peter Lommer Kristensen
- Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark
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Storey S, Von Ah D, Hammer MJ. Measurement of Hyperglycemia and Impact on Health Outcomes in People With Cancer: Challenges and Opportunities. Oncol Nurs Forum 2018. [PMID: 28632250 DOI: 10.1188/17.onf.e141-e151] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PROBLEM IDENTIFICATION Poor health outcomes have been associated with hyperglycemia in patients with and without diabetes. However, the impact of hyperglycemia on the health-related outcomes of patients with cancer has shown conflicting results. The purpose of this review was to explore definitions and measurement issues related to the assessment of hyperglycemia and the subsequent impact on the findings of health-related outcomes in adults with cancer.
. LITERATURE SEARCH Four electronic databases were searched. DATA EVALUATION A total of 30 articles were reviewed. Quantitative articles were synthesized using integrative review strategies.
. SYNTHESIS Three key gaps were identified in the literature. CONCLUSIONS This review highlights the inconsistencies in measuring or assessing hyperglycemia and the lack of standardized guidelines in treating hyperglycemia. Failure to have a standard approach to the measurement and management of hyperglycemia impedes the ability of healthcare providers to determine the significance of its impact on health outcomes. Further research is needed to establish appropriate measurement guidelines to address hyperglycemia in people with cancer.
. IMPLICATIONS FOR PRACTICE Evidence-based measurement and treatment guidelines are needed to inform and assist healthcare providers with clinical decision making for people with cancer who experience hyperglycemia.
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Barua R, Templeton A, Seruga B, Ocana A, Amir E, Ethier JL. Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis. Clin Oncol (R Coll Radiol) 2018; 30:215-224. [DOI: 10.1016/j.clon.2018.01.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 12/01/2017] [Accepted: 12/22/2017] [Indexed: 02/07/2023]
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Guo Y, Zeng H, Chang X, Wang C, Cui H. Additional dexamethasone in chemotherapies with carboplatin and paclitaxel could reduce the impaired glycometabolism in rat models. BMC Cancer 2018; 18:81. [PMID: 29338697 PMCID: PMC5769515 DOI: 10.1186/s12885-017-3917-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2017] [Accepted: 12/14/2017] [Indexed: 11/23/2022] Open
Abstract
Background Side-effects have been considered as the limitation of the chemotherapy agents’ administration and life quality in patients with ovarian cancers. In order to explore the influence of the chemotherapy agents commonly used in ovarian cancer patients on the blood glucose metabolism in rat models, we conducted this study which simulated the conditions of clinical protocols. Methods Eighty clean-grade female Wistar rats were randomized into 8 groups: Group 1 (Negative control), Group 1′ (Dexamethasone), Group 2 (Carboplatin), Group 2′ (Carboplatin-plus-dexamethasone), Group 3 (Paclitaxel), Group 3′ (Paclitaxel-plus-dexamethasone), Group 4 (Combined therapy), Group 4′ (Combined-therapy-plus-dexamethasone). On day 0, 4, 7 and 14, after fasted for 12 h, the rats in all groups underwent a glucose load and their blood glucose, glucagon and insulin levels were measured. Results The glucose levels in group 2, 3 and 4 at 1 h after the loading on day 4 significantly increased (P = 0.190, 0.008 and 0.025, respectively). The glucagon levels in group 3 and 4 showed a similar trend and the increase was not suppressed by the glucose loading (P < 0.001). A significant decrease of insulin levels in group 2, 3 and 4 were observed on day 14 after treatment (P = 0.043, 0.019 and 0.019, respectively). The change of HOMA2 %B, an index reflects the ability of insulin secretion was negatively corresponded to the glucose levels, and the trends of HOMA2 IR, an index shows insulin resistance, were positively correlated to the glucose levels. The application of dexamethasone could reduce the degree of increased glucose levels significantly in group 2, 3 and 4. There were no differences in overall survival between the 8 groups. Edema in the stroma of pancreases was observed in group 3, 3′, 4 and 4′ on day 4 after treatment (P = 0.002, 0.002, 0.000 and 0.000 respectively) and lasted until day 14. Conclusions Carboplatin and paclitaxel administration could cause a transient hyperglycemia in rats. This effect might occur by the combination of glucagon accumulation due to the decrease in islet cell secretion. The additional dexamethasone in the combination protocol of carboplatin and paclitaxel seemed to reduce the impaired blood glucose metabolism.
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Affiliation(s)
- Yanxiu Guo
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, 100044, China
| | - Haoxia Zeng
- Obstetrics and Gynecology Department, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China
| | - Xiaohong Chang
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, 100044, China
| | - Chaohua Wang
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, 100044, China.
| | - Heng Cui
- Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, 100044, China.
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Gallo M, Muscogiuri G, Felicetti F, Faggiano A, Trimarchi F, Arvat E, Vigneri R, Colao A. Adverse glycaemic effects of cancer therapy: indications for a rational approach to cancer patients with diabetes. Metabolism 2018; 78:141-154. [PMID: 28993227 DOI: 10.1016/j.metabol.2017.09.013] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 09/12/2017] [Accepted: 09/19/2017] [Indexed: 12/13/2022]
Abstract
Diabetes and cancer are common, chronic, and potentially fatal diseases that frequently co-exist. Observational studies have reported an increased risk of cancer in patients with diabetes. Furthermore, many patients with cancer already have diabetes, or develop hyperglycaemia as a consequence of the tumor or of cancer therapies, and coexisting diabetes confers a greater risk of mortality for many malignancies. Managing oncologic patients with diabetes is often complicated, since the co-existence of diabetes and cancer poses several complex clinical questions: what level of glycaemic control to achieve, which therapy to use, how to deal with glucocorticoid therapies and artificial nutrition, how diabetes complications can affect cancer management, which drug-drug interactions should be taken into account, or even how to manage diabetes at the end of life. In the clinical setting, both at hospital and at home, there are little agreed, evidence-based guidelines on the best management and criteria upon which clinical decisions should be based. A practical solution lies in the implementation of care networks based on communication and ongoing collaboration between Oncologists, Endocrinologists, and the nursing staff, with the patient at the centre of the care process. This manuscript aims to review the current evidence on the effect of cancer therapies on glucose metabolism and to address some of the more common challenges of diabetes treatment in patients with cancer.
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Affiliation(s)
- Marco Gallo
- Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Turin, Italy.
| | | | - Francesco Felicetti
- Transition Unit for Childhood Cancer Survivors, Department of Oncology, AOU Cittá della Salute e della Scienza di Torino, Turin, Italy
| | - Antongiulio Faggiano
- Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy
| | - Francesco Trimarchi
- Accademia Peloritana dei Pericolanti at the University of Messina, Messina, Italy
| | - Emanuela Arvat
- Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Turin, Italy
| | - Riccardo Vigneri
- Endocrinology, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and Surgery, University "Federico II", Naples, Italy
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Storey S, Von Ah D. Impact of Hyperglycemia and Age on Outcomes in Patients With Acute Myeloid Leukemia. Oncol Nurs Forum 2017; 43:595-601. [PMID: 27541552 DOI: 10.1188/16.onf.595-601] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE/OBJECTIVES To examine the prevalence and impact of hyperglycemia on health outcomes (number of neutropenic days, infection, and hospital length of stay) in patients hospitalized for acute myeloid leukemia (AML) receiving initial induction therapy.
. DESIGN Retrospective, descriptive study.
. SETTING A large urban hospital in Indianapolis, Indiana.
. SAMPLE 103 patients with AML and a subset of 41 patients aged 65 years or older.
. METHODS Demographics and medical information were extracted from electronic health records. Serum-fasting blood glucose was used to assess glycemic status. The association of hyperglycemia with the health outcomes was analyzed. A subset of patients aged 65 years or older was also analyzed.
. MAIN RESEARCH VARIABLES Hyperglycemia, age, and health outcomes in patients with AML.
. FINDINGS Forty patients experienced hyperglycemia during initial induction for AML. In the larger sample, no associations were noted between hyperglycemia and health outcomes. A significant relationship (p = 0.022) was noted between hyperglycemia and infection in patients aged 65 years or older. Patients aged 65 years or older had 5.6 times the risk of developing infection as those aged younger than 65 years. Although not statistically significant, patients aged 65 years or older with hyperglycemia had 2.5 more days of neutropenia and 1.5 days longer hospital length of stay.
. CONCLUSIONS This study provides preliminary evidence that hyperglycemia is prevalent during initial induction for AML and may have harmful consequences, particularly for patients aged 65 years or older. More research is needed to determine clinically significant levels of hyperglycemia and their impact on health outcomes.
. IMPLICATIONS FOR NURSING Oncology nurses can assess and proactively collaborate with members of the healthcare team to implement strategies to prevent or mitigate the harmful consequences of hyperglycemia.
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