High Blood Sugar and Insulin Resistance

Repeated high blood sugar levels can create imbalances leading to insulin resistance. Chronically high levels of blood sugar and insulin can create conditions favorable to cancer growth and spread.

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This page does not replicate the other information in this handbook but provides additional details or context most relevant to professionals.

Connection to pancreatic cancer

New diabetes in adults, especially rapidly progressing diabetes, could be an indication of pancreatic cancer. Cancer evaluation is recommended in such cases.1Diabetes and Pancreatic Cancer. Pancreatic Cancer Action Network. Viewed December 7, 2022.

Modes of action

Diabetes and cancer share some common underlying pathways. For example, obesity is common in people with type 2 diabetes, and it has also been associated with several types of cancer.2American Cancer Society. Does body weight affect cancer risk? June 9, 2020. Viewed August 11, 2022. However, obesity doesn’t seem to fully explain the increased cancer risk among people with diabetes. Some researchers propose that the cancer risk among diabetics is more likely linked to metabolic factors “related to insulin resistance, hyperinsulinemia, and their influence on the insulin growth factor (IGF) system, which may stimulate cell proliferation and inhibit programmed cell death (apoptosis).”3La Vecchia C, Bosetti C. Metformin: are potential benefits on cancer risk extended to cancer survival? The Oncologist. 2013 Dec;18(12):1245-1247.

Metabolism

“A common characteristic of the tumor microenvironment is altered metabolism, or energy creation. Typically cells efficiently metabolize glucose to make ATP, the currency of energy, within the mitochondria. However, some cancer cells and other co-opted cells in the tumor microenvironment lose the ability to make ATP within the mitochondria and metabolize glucose to ATP within the cell’s cytoplasm. This method is inefficient so the demand for glucose is very high. As a result of this altered metabolism, several integrative strategies attempt to limit the availability of glucose to tumors, thereby starving them. Healthy cells can withstand the lack of glucose as they are generally more adept at using other food substrates, especially fat, and to a lesser extent, protein, to make energy.4Alschuler L. (2022). Module 3: Hallmarks of Cancer/Tumor Microenvironment/Body Terrain Online Course Lecture. In Pole L, O’Toole C, Price E, Alschuler L, Romanski B, Hepp N. Integrative Oncology Patient Navigation Training. Maryland University of Integrative Health.

Researchers have proposed that the higher cancer risk seen with diabetes is linked to metabolic factors “related to insulin resistance, hyperinsulinemia, and their influence on the insulin growth factor (IGF) system, which may stimulate cell proliferation and inhibit programmed cell death (apoptosis).”5La Vecchia C, Bosetti C. Metformin: are potential benefits on cancer risk extended to cancer survival? The Oncologist. 2013 Dec;18(12):1245-124.

Potential mechanisms of action of dietary polyphenols in the regulation of glucose homeostasis and insulin sensitivity based on in vitro and in vivo studies6Kim Y, Keogh JB, Clifton PM. Polyphenols and glycemic control. Nutrients. 2016 Jan 5;8(1). pii: E17.

  • Estrogen receptor (ER) activation under chronic hyperinsulinemic conditions increases breast cancer growth7Wairagu PM, Phan AN et al. Insulin priming effect on estradiol-induced breast cancer metabolism and growth. Cancer Biology & Therapy. 2015;16(3):484-92.
  • Discussion of the interaction between insulin and IGF signaling in cancer cells8Gallagher EJ, LeRoith D. Minireview: IGF, insulin, and cancer. Endocrinology. 2011 Jul;152(7):2546-51.
  • Summary of the nosogenesis of diabetes, giving primary focus to oxidative stress and inflammation9Meng B, Li J, Cao H. Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications. Current Pharmaceutical Design. 2013;19(11):2101-13.
  • “Breast cancer cells impair the function of pancreatic islets to make them produce less insulin than needed, leading to higher blood glucose levels in breast cancer patients compared to females without cancer.”10LaFee S. The paired perils of breast cancer and diabetes. UC San Diego News Center. May 30, 2022. Viewed July 2, 2022; Cao M, Isaac R et al. Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth. Nature Cell Biology. 2022 Jun;24(6):954-967.

Ketosis 

Some cancer cells within tumors and some tumor-associated cells in the tumor microenvironment convert to a complete dependence on glucose for energy generation. This is a key alteration. These catabolic cells do not have properly functioning mitochondria, and so normal energy production via citric acid cycling and oxidative phosphorylation is not available. Typical Western diets high in refined carbohydrates provide this glucose substrate as well as promote the insulin pathway, releasing growth factors that may be associated with promoting cancer development and progression.11Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Medical Oncology. 2017 May;34(5):72.

Stress and other lifestyle factors

The combination of the stress hormones cortisol and adrenaline increases blood glucose levels. Chronic high blood glucose episodes can be a direct or indirect mediator of the increase in tumor cell growth.12Ryu TY, Park J, Scherer PE. Hyperglycemia as a risk factor for cancer progression. Diabetes & Metabolism Journal. 2014 Oct;38(5):330-6. Cortisol also increases insulin resistance and seems to stimulate the ability of some cancer cells to grow and metastasize.13Block KI. Life over Cancer: The Block Center Program for Integrative Cancer Treatment. New York: Bantam Dell. 2009. p. 411; Moreno-Smith M, Lutgendorf SK, Sood AK. Impact of stress on cancer metastasis. Future Oncology. 2010 Dec; 6(12):1863-1881.

Besides stress, nutrition, activity, and sleep disruption all need to be assessed and managed in people with cancer and hyperglycemia and insulin resistance. These factors are described in the section above titled Why are high blood sugar and insulin resistance important?

Interactions of hyperglycemia and insulin resistance with cancer treatments

Insulin-like growth factor may partially block tamoxifen’s effects14Singer CF, Hudelist G, Schreiber M, Kubista E. Pharmacological modulation of IGF serum concentrations as a therapeutic approach to control the growth of malignant breast tumors. Drugs of Today (Barcelona, Spain). 2003 Feb;39(2):115-25; Lee AV, Weng CN, Jackson JG, Yee D. Activation of estrogen receptor-mediated gene transcription by IGF-I in human breast cancer cells. Journal of Endocrinology. 1997 Jan;152(1):39-47. and may also enhance resistance to chemo/radiotherapy.15Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology. 2002;63(4):317-32; Lu Y, Zi X, Zhao Y, Mascarenhas D, Pollak M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). Journal of the National Cancer Institute. 2001;93(24):1852-7; Beech DJ, Parekh N, Pang Y. Insulin-like growth factor-I receptor antagonism results in increased cytotoxicity of breast cancer cells to doxorubicin and taxol. Oncology Reports. 2001 Mar-Apr;8(2):325-9.; Singer CF, Hudelist G, Schreiber M, Kubista E. Pharmacological modulation of IGF serum concentrations as a therapeutic approach to control the growth of malignant breast tumors. Drugs of Today (Barcelona, Spain). 2003 Feb;39(2):115-25. Chemotherapy may be more toxic in people with diabetes and/or elevated blood glucose.16Gennari A, Salvadori B et al. Cardiotoxicity of epirubicin/paclitaxel-containing regimens: role of cardiac risk factors. Journal of Clinical Oncology. 1999 Nov;17(11):3596-602.

Helpful links for professionals

Journal articles

Chiefari E, Mirabelli M et al. Insulin resistance and cancer: in search for a causal link. International Journal of Molecular Sciences. 2021 Oct 15;22(20):11137.

Yee LD, Mortimer JE, Natarajan R, Dietze EC, Seewaldt VL. Metabolic health, insulin, and breast cancer: why oncologists should care about insulin. Frontiers in Endocrinology (Lausanne). 2020 Feb 20;11:58.

Mirabelli M, Chiefari E et al. Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases. Nutrients. 2020 Apr 12;12(4):1066.

Shanmugalingam T, Bosco C, Ridley AJ, Van Hemelrijck M. Is there a role for IGF‐1 in the development of second primary cancers? Cancer Medicine. 2016 Nov;5(11):3353-3367.

Christopoulos PF, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Molecular Cancer. 2015 Feb 15;14:43.Christopoulos PF, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Molecular Cancer. 2015 Feb 15;14:43.

Hardy OT, Czech MP, Corvera S. What causes the insulin resistance underlying obesity? Current Opinion in Endocrinology, Diabetes, and Obesity. 2012 Apr;19(2):81-7.

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Authors

Laura Pole, RN, MSN, OCNS

Senior Clinical Consultant
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Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.

For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.

Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.

Laura Pole, RN, MSN, OCNS Senior Clinical Consultant

Nancy Hepp, MS

Lead Researcher and Program Manager
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Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher, program manager, and writer for CancerChoices. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS Lead Researcher and Program Manager

Reviewer

Dr. Fuller-Shavel is a GMC-registered integrative medicine doctor with degrees in medicine and natural sciences from the University of Cambridge. Dr. Fuller-Shavel is a fellow of the College of Medicine and the vice chair for BSIO (British Society for Integrative Oncology). Alongside her science and medical training, Dr. Fuller-Shavel holds multiple qualifications in nutrition, integrative medicine, health coaching, herbal medicine, yoga, mindfulness and other mind-body approaches.

Dr. Fuller-Shavel is the director of Synthesis Clinic, an award-winning multidisciplinary integrative medicine practice in Hampshire, UK, specializing in women’s health, gut health (microbiome and gut-brain axis) and mental health. She combines her clinical work in women’s health and supporting patients with breast and gynecological cancer with education and training for healthcare professionals and research in precision cancer medicine and precision nutrition.

Nina Fuller-Shavel, MB, BChir, MA Hons, FBANT, IFMCP, DipIM, PG Cert RYT300

Last update: May 31, 2023

Last full literature review: July 2022

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