Hyperglycemia is independently associated with post-operative function loss in patients with primary eloquent glioblastoma

Link, Thomas; Woodworth, Graeme F.; Chaichana, Kaisorn L.; Grossman, Stuart A.; Mayer, R. Samuel; Brem, Henry; Weingart, Jon; Quiñones‐Hinojosa, Alfredo

doi:10.1016/j.jocn.2011.09.031

Cited by 23 publications

(10 citation statements)

References 40 publications

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“…It is noteworthy that hyperglycemia is associated with adverse prognosis and postoperative function loss in GBM patients. Patients treated with KD tend to have lower blood sugar levels ( 12 , 13 ). Another plausible rationale focuses on β-hydroxybutyrate, the main ketone produced during ketosis, which is an endogenous and specific inhibitor of class 1 histone deacetylases capable of activation of specific genes to protect mice against oxidative stress ( 14 ).…”

Section: Rationale: Ketogenic Diet (Kd) As Anticancer Therapymentioning

confidence: 99%

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

et al. 2018

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Survival of glioblastoma multiforme (GBM) with the current recommended treatment is poor. Reported median survivals are approximately 8–15 months. Based on recent publications from animal models, combining cancer drugs, radiation, and diet-metabolic treatments may be a new route to better survivals. To investigate this possibility, we have begun a clinical trial that has enrolled 15 subjects using a ketogenic diet (KD) as an addition to current standard treatments that include surgery, radiation therapy, and chemotherapy. Of the 15 enrolled, 10 completed the protocol. This perspective describes the challenges and lessons learned during this clinical trial and discusses the critical elements that are essential for investigating treatment with a KD. We also reviewed and compared various types of KDs. We believe that the diet selected should be standardized within individual clinical trials, and more importantly, the patients’ blood should be monitored for glucose and ketones twice daily so that the supervising dietitian can work with the patient and their caregivers to make appropriate changes in the diet. Compliance with the diet is best in highly motivated patients who have excellent home support from a family member or a friend who can help to overcome administrative, physical, and cognition deficiencies associated with the disease. Treatment of GBM using a KD represents a reasonable investigative approach. This perspective summarizes the challenges and lessons learned implementing and continuing KD therapy while the patients are concurrently being treated with radiation and chemotherapy.

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Section: Rationale: Ketogenic Diet (Kd) As Anticancer Therapymentioning

confidence: 99%

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

et al. 2018

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“…After screening of the title and abstract, 1377 irrelevant studies were excluded. Then, three studies were excluded for irrelevant outcomes [26][27][28] (Fig. 1).…”

Section: Study Selectionmentioning

confidence: 99%

Prognostic Significance of Hyperglycemia in Patients with Brain Tumors: a Meta-Analysis

Liu

Jiang

et al. 2015

Mol Neurobiol

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Hyperglycemia has been associated with poor outcomes of patients with various diseases. There were several studies published to assess the association between hyperglycemia and prognosis of patients with brain tumors, but no consistent conclusion was available. We therefore performed a meta-analysis of available studies to evaluate the prognostic role of hyperglycemia in brain tumors. Several common databases were searched for eligible studies on the association between hyperglycemia and survival of patients with brain tumors. Two investigators used a set of predefined inclusion criteria to assess eligible studies independently. The pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the prognostic role of hyperglycemia. Finally, seven studies with a total of 2168 patients with brain tumors were included into the meta-analysis. Meta-analysis of total seven studies showed that hyperglycemia was significantly associated with shorter overall survival of brain tumors (HR = 2.04, 95% CI 1.51-2.76, P < 0.001). Meta-analysis of studies focusing on hyperglycemia showed that hyperglycemia was still significantly associated with shorter overall survival of brain tumors (HR = 1.82, 95% CI 1.29-2.59, P = 0.001). Meta-analysis of three studies on diabetes showed that diabetes was significantly associated with shorter overall survival of brain tumors (HR = 2.09, 95% CI 1.22-3.57, P = 0.007). Meta-regression analysis showed that there was no obvious difference in the roles of between hyperglycemia caused by glucocorticoids and hyperglycemia from diabetes (P = 0.25). Thus, hyperglycemia has an obvious prognostic significance in patients with brain tumors, and hyperglycemia is significantly associated with shorter overall survival of brain tumors.

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“…In theory, ERKD is predicted to improve survival of GBM patients simply by restricting tumors of glucose, while providing necessary metabolic fuel in the form of ketones to support vital organs including the brain. It is noteworthy that hyperglycemia is associated with adverse prognosis and post-operative function loss in patients with glioblastoma [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature

et al. 2015

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BackgroundBased on the hypothesis that cancer cells may not be able to metabolize ketones as efficiently as normal brain cells, the ketogenic diet (KD) has been proposed as a complementary or alternative therapy for treatment of malignant gliomas.Case presentationWe report here our experience in treating two glioma patients with an IRB-approved energy-restricted ketogenic diet (ERKD) protocol as monotherapy and review the literature on KD therapy for human glioma patients. An ERKD protocol was used in this pilot clinical study. In addition to the two patients who enrolled in this study, we also reviewed findings from 30 other patients, including 5 patients from case reports, 19 patients from a clinical trial reported by Rieger and 6 patients described by Champ. A total of 32 glioma patients have been treated using several different KD protocols as adjunctive/complementary therapy. The two patients who enrolled in our ERKD pilot study were monitored with twice daily measurements of blood glucose and ketones and daily weights. However, both patients showed tumor progression while on the ERKD therapy. Immunohistochemistry reactions showed that their tumors had tissue expression of at least one of the two critical mitochondrial ketolytic enzymes (succinyl CoA: 3-oxoacid CoA transferase, beta-3-hydroxybutyrate dehydrogenase 1). The other 30 glioma patients in the literature were treated with several different KD protocols with varying responses. Prolonged remissions ranging from more than 5 years to 4 months were reported in the case reports. Only one of these patients was treated using KD as monotherapy. The best responses reported in the more recent patient series were stable disease for approximately 6 weeks. No major side effects due to KD have been reported in any of these patients.ConclusionsWe conclude that 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in controlling the progression of some gliomas; and 4. further studies are needed to determine factors that influence the effectiveness of KD, whether as a monotherapy, or as adjunctive or supplemental therapy in treating glioma patients.Trial registrationClinicalTrials.gov# NCT01535911

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Hyperglycemia is independently associated with post-operative function loss in patients with primary eloquent glioblastoma

Cited by 23 publications

References 40 publications

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

Prognostic Significance of Hyperglycemia in Patients with Brain Tumors: a Meta-Analysis

Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature

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