High Blood Sugar and Insulin Resistance

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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 March 9, 2024; 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

Chemotherapy may be more toxic in people with diabetes and/or elevated blood glucose.¹⁴Gennari 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

Regulating Blood Glucose via the Gut Microbiome ›

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.

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.

Cancer Strategies Journal

• Clinical Pearls, Spring 2013: see Cancer and high HbA1c & Lumbrokinase for high fibrinogen in cancer
• Clinical Pearls Fall 2013: see Insulin-regulating herbs, nutrients, and foods for squamous cell cancers

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