Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma.

PURPOSE Hyperglycemia has been associated with poor outcomes in many disease states. This retrospective study assessed the association between hyperglycemia and survival in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS; Between 1999 and 2004, before the standard use of temozolomide, 191 patients were accrued onto New Approaches to Brain Tumor Therapy CNS Consortium trials with similar eligibility criteria. Time-weighted mean glucose and mean glucocorticoid dose were calculated for each patient using all values collected regularly in follow-up. The primary outcome was survival. RESULTS Mean glucose levels ranged between 65 and 459 mg/dL. These were divided into quartiles: quartile one (< 94 mg/dL), quartile two (94 to 109 mg/dL), quartile three (110 to 137 mg/dL), and quartile four (> 137 mg/dL). Median survival times for patients in quartiles one, two, three, and four were 14.5, 11.6, 11.6, and 9.1 months, respectively. The association between higher mean glucose and shorter survival persisted after adjustment for mean daily glucocorticoid dose, age, and baseline Karnofsky performance score (KPS). Compared with patients in the lowest mean glucose quartile, those in quartile two (adjusted hazard ratio [HR], 1.29; 95% CI, 0.85 to 1.96), quartile three (adjusted HR, 1.35; 95% CI, 0.89 to 2.06), and quartile four (adjusted HR, 1.57; 95% CI, 1.02 to 2.40) were at progressively higher risk of dying (P = .041 for trend). CONCLUSION In these patients with newly diagnosed GBM and good baseline KPS, hyperglycemia was associated with shorter survival, after controlling for glucocorticoid dose and other confounders. The effect of intensive management of glucocorticoid-related hyperglycemia on survival deserves additional study in patients with GBM.

[1]  A. Brandes,et al.  MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  C Arús,et al.  Perturbation of mouse glioma MRS pattern by induced acute hyperglycemia , 2008, NMR in biomedicine.

[3]  J. Olson,et al.  Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma. , 2008, Neuro-oncology.

[4]  E. Shaw,et al.  Phase I study of gadolinium texaphyrin in newly diagnosed glioblastoma , 2007 .

[5]  T. Mikkelsen,et al.  Phase II clinical and pharmacologic study of radiation therapy and carboxyamido-triazole (CAI) in adults with newly diagnosed glioblastoma multiforme , 2007, Investigational New Drugs.

[6]  J. Coebergh,et al.  Less aggressive treatment and worse overall survival in cancer patients with diabetes: A large population based analysis , 2007, International journal of cancer.

[7]  R. Delfini,et al.  Prognostic Implication of Clinical and Pathologic Features in Patients with Glioblastoma Multiforme Treated with Concomitant Radiation plus Temozolomide , 2007, Tumori.

[8]  N. Burnet,et al.  Interpretation of Early Imaging after Concurrent Radiotherapy and Temozolomide for Glioblastoma , 2007 .

[9]  B. Nordestgaard,et al.  Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome , 2007, Diabetologia.

[10]  M. Saul,et al.  Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients. , 2006, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[11]  W. R. Bruce,et al.  Hyperinsulinemia, but not other factors associated with insulin resistance, acutely enhances colorectal epithelial proliferation in vivo. , 2006, Endocrinology.

[12]  C. Franceschi,et al.  Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice , 2005, Experimental Gerontology.

[13]  F. Schellevis,et al.  Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  T. Mikkelsen,et al.  Phase 2 trial of copper depletion and penicillamine as antiangiogenesis therapy of glioblastoma. , 2005, Neuro-oncology.

[15]  D. Fry,et al.  Acute hyperglycemia and the innate immune system: Clinical, cellular, and molecular aspects , 2005, Critical care medicine.

[16]  A. Ahlbom,et al.  Prior Hospitalization for Epilepsy, Diabetes, and Stroke and Subsequent Glioma and Meningioma Risk , 2005, Cancer Epidemiology Biomarkers & Prevention.

[17]  K. Makino,et al.  The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme. , 2004, Journal of neurosurgery.

[18]  M. Thun,et al.  Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. , 2004, American journal of epidemiology.

[19]  M. Konopleva,et al.  Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate–cytarabine regimen , 2004, Cancer.

[20]  C. Loria,et al.  Abnormal glucose tolerance and the risk of cancer death in the United States. , 2003, American journal of epidemiology.

[21]  J. Meyerhardt,et al.  Impact of diabetes mellitus on outcomes in patients with colon cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  H. Fine,et al.  History of allergies and autoimmune diseases and risk of brain tumors in adults , 2002, International journal of cancer.

[23]  A. Peiris,et al.  Insulin: a novel factor in carcinogenesis. , 2002, The American journal of the medical sciences.

[24]  R. Clatterbuck,et al.  The Prognostic Value of Tumor Markers in Patients with Glioblastoma Multiforme: Analysis of 32 Patients and Review of the Literature , 2001, Journal of Neuro-Oncology.

[25]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[26]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[27]  M. Décorps,et al.  High glycolytic activity in rat glioma demonstrated in vivo by correlation peak 1H magnetic resonance imaging. , 2001, Cancer research.

[28]  R Yancik,et al.  Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. , 2001, JAMA.

[29]  F. Brancati,et al.  Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. , 1999, Diabetes care.

[30]  G. Giles,et al.  Role of medical history in brain tumour development. Results from the international adult brain tumour study , 1999, International journal of cancer.

[31]  H Wedel,et al.  Infarction : Long-Term Results From the Diabetes and Insulin-Glucose Infusion Conventionally Treated Patients With Diabetes Mellitus and Acute Myocardial Glycometabolic State at Admission : Important Risk Marker of Mortality in , 1999 .

[32]  M Linet,et al.  Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. , 1997, Journal of the National Cancer Institute.

[33]  J. McNeil,et al.  Association of adult glioma with medical conditions, family and reproductive history , 1997, International journal of cancer.

[34]  A. Stuck,et al.  Risk of infectious complications in patients taking glucocorticosteroids. , 1989, Reviews of infectious diseases.

[35]  G. Grunberger,et al.  Insulin receptor of human cerebral gliomas. Structure and function. , 1986, The Journal of clinical investigation.

[36]  T Jones,et al.  In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas , 1983, Annals of neurology.

[37]  M. Cassader,et al.  An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects. , 1983, The Journal of clinical investigation.

[38]  R A Brooks,et al.  Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography , 1982, Neurology.

[39]  J. Olefsky Effect of dexamethasone on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes. , 1975, The Journal of clinical investigation.

[40]  A. Polednak Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study. , 2006, Cancer detection and prevention.

[41]  K. Sugimachi,et al.  Hyperinsulinemia in patients with colorectal cancer. , 2005, Hepato-gastroenterology.

[42]  M. Gilbert,et al.  Suramin and radiotherapy in newly diagnosed glioblastoma: phase 2 NABTT CNS Consortium study. , 2004, Neuro-oncology.

[43]  F. Frasca,et al.  Insulin and hybrid insulin/IGF receptors are major regulators of breast cancer cells. , 2003, Breast disease.

[44]  B. Hoffman,et al.  Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study , 2002 .

[45]  D. Cox Regression Models and Life-Tables , 1972 .