DIABETES AND CANCER

By Dr. C. Bour, January 5, 2021

The link between diabetes and cancer in general and diabetes and breast cancer in particular is well known, as shown in a 2012 meta-analysis [1].

This meta-analysis revealed a significant increase in the risk of breast cancer in women with diabetes compared to non-diabetic women. However, the association between diabetes and breast cancer risk appeared to be limited to postmenopausal women. Type 1 diabetes and diabetes in premenopausal women were not associated with a significant increase in breast cancer risk.

People with type 2 diabetes have a higher risk of developing cancers of the breast, pancreas, liver, kidney, endometrium and colon. 
While patients with type 1 diabetes are more likely to develop cervical and stomach cancers.

Several studies have also shown that patients with diabetes and cancer have a poorer prognosis than those without diabetes. Diabetes and hyperglycemia are associated with higher infection rates, shorter remission periods and shorter median survival times, as well as higher mortality rates[2].

Several mechanisms might explain why type 2 diabetes could increase the risk of cancer are being implicated: hyperinsulinemia, hyperglycemia and inflammation. The increase in blood glucose levels is believed to have carcinogenic effects by causing DNA damage.

Particular case of breast cancer

The meta-analysis discussed at the beginning of this article was conducted using a random effects model to study the association between diabetes and breast cancer risk [3].

The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreases to 16% after adjusting for BMI. Obesity is an aggravating factor as shown in other studies.  

No increase in risk has been observed in women in pre-menopausal age or with type 1 diabetes.

In addition to the over-risk of cancer in the diabetic patient, what about the management of the patient with both diabetes AND cancer? [4] [5]

The management of the diabetic patient requires treatment not only by hygienic and dietetic measures but also by a finely tuned medication protocol that may include insulin and one or more oral agents.

Chemotherapy and analgesics can affect glucose homeostasis[6] and insulin sensitivity; drug interactions can interfere with the patient's tolerance to diabetes drugs; decreased appetite, nausea, vomiting and weight loss resulting from both disease and cancer treatment can cause imbalances in blood glucose levels.

Chemotherapeutic agents

Several chemotherapies are known to cause or exacerbate these adverse conditions. For example, cisplatin is known to cause kidney failure, and anthracyclines can cause cardiotoxicity. Cisplatin, paclitaxel and vincristine may be neurotoxic. Unfortunately, many of these side effects may remain permanent.

For cancer treatment to be effective, at least 85% of the chemotherapy dose must usually be administered. Patients with diabetes should be carefully monitored before the start and during chemotherapy. Treatment decisions should be based on the patient's clinical picture, but always be aware that any change in dose, or alteration in the timing of administration, or substitution of another chemotherapeutic agent may compromise results by reducing the response rate to treatment.

Corticosteroids

They represent an important part of treatment in cancer pathologies and are widely used to improve nausea and vomiting associated with chemotherapy, as well as to suppress neurological symptoms when the cancer has metastasized to the spine or brain. And they cause significant hyperglycemia within hours after administration. 

The treatment of hyperglycemia resulting from glucocorticoids then depends on the type of diabetes, the severity of the hyperglycemia levels, the dose and the duration of therapy. Administering steroids in multiple doses throughout the day instead of a single bolus dose, or administering the entire daily dose of steroids intravenously over 24 hours, can help control hyperglycemia.

Patients with pre-existing diabetes can be maintained on oral hypoglycemic agents and closely monitored. However, these medications are generally unsuitable for managing hyperglycemia in this setting and insulin is used.

Patients using insulin prior to glucocorticoid therapy will typically require both basal and preprandial insulin. These patients may require two to three times their usual insulin dose. Insulin is the preferred drug for the management of steroid-induced or steroid-exacerbated hyperglycemia in patients with known diabetes.

Patients with type 1 diabetes will need to adjust their dose. Type 2 patients who are already taking oral agents at baseline will add insulin, but only during this period when their blood glucose levels are high.

Several studies of cancers as disparate as small cell lung cancer and breast cancer have found an association between poorly controlled hyperglycemia and poor outcomes in these patients with both diabetes and cancer. Hyperglycemia also increases the risk of infection.

In patients with active cancer, the management of hyperglycemia focuses on the prevention of long-term complications to avoid acute and sub-acute outcomes, such as dehydration due to polyuria, infection, catabolic weight loss, hyperosmolar non-ketotic states and diabetic ketoacidosis [7].

Analgesics

Analgesics can cause constipation that affects patients in two ways. It can make them want to not eat, but also, by slowing down intestinal motility, narcotics may delay the absorption of nutrients. This can lead to a mismatch between the administration of insulin and the absorption of glucose. The patient faces the risk of hypoglycemia.

Statins and chemotherapy [8]

Statins and chemotherapeutic agents are metabolized by the same enzymes in the liver. 

If the liver enzymes are all captured by statin therapy, this may result in less elimination of chemotherapy. Some research suggests that it also works the other way around. If you give a statin to a patient on chemo and then stop the statin, he or she will eliminate the chemotherapy drug much more quickly. 

In general, therefore, there is a reluctance to start statin therapy in someone just starting chemotherapy because of possible hepatotoxicity," says Lavis [9] . If patients are already on statins, it is important to be aware of their effects and monitor them carefully. 

It is appropriate to target therapeutic interventions according to the patient's prognosis. If the prognosis is poor, we should be less demanding about the goals and not overburden the patient's treatment based on excessive expectations.

Prognosis and comfort

Prognosis, longevity and quality of life are important considerations in setting blood glucose targets. A pragmatic approach to the management of hyperglycemia in these patients is necessary.

The interest of a very strict glycemic control is to try to prevent complications in 10, 15, 20 years. 

But in a person with a poor prognosis or a life expectancy of only a few years, one must be more concerned about comfort and quality of life in the remaining years.

The goal would then be to avoid the effects of acute hyperglycemia, such as dehydration and ketoacidosis.

Conclusion

There is strong epidemiological evidence that diabetic diseases are associated with an accumulated risk of several cancers. There is also growing evidence that the degree of hyperglycemia and the treatment modalities for hyperglycemia influence cancer risk. 

The risk of breast cancer in women with type 2 diabetes is increased and obesity is an aggravating factor. On the other hand, there is no over-risk observed in women in pre-menopausal age or with type 1 diabetes.

The management of blood glucose levels in patients with diabetes and cancer can pose a significant clinical challenge. As there is no clear evidence that tight glucose control improves cancer outcomes, hyperglycemia must be managed pragmatically to ensure that the patient remains asymptomatic and at low risk of acute decompensation. 

Proactive management of glucocorticoid-induced hyperglycemia can help reduce large fluctuations in glucose levels. 

Read also :

https://www.healthline.com/diabetesmine/living-with-cancer-and-diabetes#1

References

[1] Diabetes and breast cancer risk: a meta-analysis  British Journal of Cancer (2012) 107, 1608–1617 https://pubmed.ncbi.nlm.nih.gov/22996614/

P Boyle M Boniol A Koechlin .....and P Autier1/Prevention Research Institute, 95 cours Lafayette, 69006 Lyon, France

[2] Clinical Challenges in Caring for Patients With Diabetes and Cancer
Helen M. Psarakis, RN, APRN-Diabetes Spectrum Volume 19, Number 3, 2006

https://spectrum.diabetesjournals.org/content/19/3/157

[3] https://pubmed.ncbi.nlm.nih.gov/22996614/

[4] https://endocrinenews.endocrine.org/july-2014-double-jeopardy/

[5] Clinical Challenges in Caring for Patients With Diabetes and Cancer-Helen M. Psarakis, RN, APRN-Diabetes Spectrum Volume 19, Number 3, 2006

https://spectrum.diabetesjournals.org/content/19/3/157

[6]  Phenomenon by which a key factor is regulated to persist around a beneficial value for the body.

[7] https://www.cancernetwork.com/view/diabetes-management-cancer-patients

[8] https://endocrinenews.endocrine.org/july-2014-double-jeopardy/

[9] Victor Lavis, MD, professeur au Département de néoplasie endocrinienne et des troubles hormonaux à l'Université du Texas MD Anderson Cancer Center à Houston.( https://endocrinenews.endocrine.org/july-2014-double-jeopardy/)