Diabetes and cancer

Dr Angela Murphy looks at the correlation between diabetes and cancer.

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A diagnosis of either diabetes or cancer causes significant stress. There is no doubt that if both conditions are present this causes true distress. Although cancer isn’t a typical complication of diabetes, there is an increase in the occurrence of cancer in people living with diabetes (PLWD).

In 2009, the American Diabetes Association and the American Cancer Society developed a consensus document to look at the following questions:

1. Is there an association between diabetes and cancer?
2. What risk factors are common to both diabetes and cancer?
3. What are the biologic links between diabetes and cancer risk?
4. Do diabetes treatments influence risk of cancer?

What is the association between diabetes and cancer?

We see an increasing incidence of both diabetes and cancer. It seems that the diagnosis of both conditions in the same person occurs more frequently than would be expected by chance.

Some cancers (liver, pancreatic, and endometrium) occur more commonly in the presence of diabetes and some cancers (prostate) are less common in the presence of diabetes. Other cancers (lung, kidney, non-Hodgkin lymphoma) haven’t been conclusively shown to have an association with diabetes. Currently the association of cancer and Type 1 diabetes is not confirmed.

In addition to seeing an increase in the incidence of cancer in PLWD, it seems that diabetes increases the risk of complications and mortality from cancer.

What biological association is there between diabetes and cancer?

1. Hyperglycaemia

In the 1920s, scientist Otto Warburg observed that cancer cells consume large amounts of glucose as they rapidly divide and proliferate. This is now called the Warburg effect.

2. Hyperinsulinemia and insulin resistance

Certain cancers possess insulin receptors and stimulation of these by high levels of circulating insulin can directly affect the metabolism of cancer cells, promoting their growth. Insulin also stimulates insulin like growth factor 1 (IGF-1) which promotes cancer cell growth and inhibits cancer cell death. Insulin increases the levels of oestrogen that the body is exposed to which in turn increases the risk of certain cancers, such as breast cancer.

3. Inflammation

Many pro-inflammatory substances (interleukin-6; tumour necrosis factor alpha, etc.) can induce malignant changes in cells and cancer progression. Both hyperglycaemia and hyperinsulinemia cause oxidative stress which in turn causes inflammation. The most common cause of chronic low-grade inflammation is obesity.

What are common risk factors between diabetes and cancer?

1. Obesity

Most people living with Type 2 diabetes are overweight or obese. As mentioned, obesity is a state of low-grade inflammation. The longer overweight or obesity is present, the greater the risk of developing cancer.

The Centre for Disease Control (CDC) in America lists 13 cancers more commonly seen in people living with obesity: oesophageal, breast in post-menopausal women, colon and rectum, uterus, liver, stomach, kidneys, gallbladder, ovaries, pancreatic, thyroid, multiple myeloma, and meningioma, a type of brain cancer.

2. Age

The incidence of most cancers increases with age with an estimated 78% of all newly diagnosed cancer occurring in people over the age of 55 years.

3. Gender

In general, men are slightly more at risk of developing cancer than women and in turn have a higher incidence of Type 2 diabetes.

4. Ethnicity

Statistics show that in the USA, African Americans develop and die from cancer more than other racial groups. This may be due to a variety of factors, such as socioeconomic status as well as genetic factors.

5. Smoking

Tobacco smoking causes over 70% of all respiratory cancers and is a strong risk factor in many other cancers. In addition, studies suggest that smoking is an independent risk factor for developing Type 2 diabetes and we know smoking will always worsen the complications of diabetes.

6. Alcohol

Even if alcohol is consumed moderately, it’s associated with an increased risk of cancers such as mouth, throat, gastrointestinal and breast. Moderate alcohol consumption may be protective against the development of diabetes, but excess alcohol is a diabetes risk.

7. Sedentary lifestyle

There is a definite link between lack of physical activity and the risk of Type 2 diabetes and cancer.

Do diabetes treatments influence the incidence of cancer and cancer prognosis?

Good glucose control lowers the risk of complications and possibly cancer too. The influence of the various drug treatments are as follows:

1. Metformin

At diagnosis all people with Type 2 diabetes are prescribed metformin and this is continued lifelong unless it can’t be tolerated, or kidney function drops below a certain threshold.

Metformin reduces circulating levels of glucose and insulin by reducing the production of glucose in the liver. Studies have shown that metformin inhibits the growth and proliferation of cancer cell lines.

Other research has demonstrated that metformin can selectively kill certain cancer stem cells, improving the effectiveness of the anticancer regimen. This has been particularly described in breast cancer.

There is significant evidence to show that PLWD who are on metformin are less likely to get cancer than PLWD that don’t take metformin. Additional observational data also suggests that PLWD taking metformin who do develop cancer are more likely to go into remission.

Metformin is sometimes used as an adjuvant treatment in a cancer regimen even in people without diabetes, particularly with breast cancer therapy.

2. Thiazolidinediones

These are medications that work in the liver to treat insulin resistance. Pioglitazone is the only one available in SA. Results of studies are conflicting whether these drugs decrease, increase or do not affect cancer risk.

3. Sulfonylureas

There is very little data to suggest any benefit or risk in this group of medications.

4. Incretins

These are the injectables liraglutide, semaglutide, and dulaglutide. They bind to the glucagon like peptide-1 (GLP1) receptor which results in lower glucose levels and weight loss.

Liraglutide showed an increased risk of medullary thyroid cancer in rats. The risk of this cancer remains a black box warning. A study published in the British Medical Journal in April 2024 calculated that there was very little increase in risk for thyroid cancer in patients using GLP1 receptor agonists. They report this would be 0.36 excess cancers per 10 000 person-years which compares favourably to a background incidence of cancer in diabetes of 1.46 per 10 000 person-years. However, if there is a history of thyroid cancer or a family history of thyroid cancer, the PLWD may still be advised not to use this therapy.

5. Insulin

As mentioned above, we know that high levels of insulin can be implicated in causing cancer. Naturally, PLWD who must inject insulin to treat their diabetes will be concerned. To date, there is no definite proof that insulin as a therapy causes cancer. However, people living with Type 2 diabetes who are using insulin will often have other risks as well: longer duration of diabetes with insulin resistance, obesity, older age.

One study also indicated a greater risk of developing cancer with higher doses of insulin. It’s critical to acknowledge that cancer cells in a person living with Type 2 diabetes may have spent years being exposed to abnormally high endogenous insulin due to insulin resistance. Thus, it’s difficult to blame the newly injected exogenous insulin to be the cause of any cancer.

How to lower cancer risk if you have diabetes

The most common cancers associated with Type 2 diabetes are breast, colon and prostate. However, as noted previously, if the PLWD also has an increased body weight there are many more cancers associated with obesity. Two main strategies are important: prevention and screening.

Prevention

There is always benefit in trying to improve the modifiable factors of lifestyle

• Weight

Keeping body weight to normal or near normal is protective. This will lower insulin resistance while improving glucose control. In addition, weight loss has been shown to decrease cancer risk.

• Diet

Having a diet that supports weight management is essential. There is also value in choosing foods that lower inflammation and have less direct carcinogens. The World Health Organization recommends avoiding processed meat as much as possible. Processed meats are prepared by smoking, curing, salting or adding chemicals (ham, bacon, pastrami, hot dogs, sandwich meat). Red meat should be restricted to 500g weekly. In fact, a plant-based diet is less inflammatory and lowers cancer risk.

• Physical activity

Recommended activity is 150 minutes weekly ideally spread out over five days. This can be aerobic and resistance exercise.

• Stop smoking

The connection between smoking and cancer has been established since 1963! Stop smoking!

• Reduce alcohol

A woman can have 1 – 2 units daily and a man 2 – 3 units daily. One unit of alcohol is 340ml beer/cider; 120ml wine; 25ml spirits.

Screening

These recommendations are for the general population but if you are at higher risk for a certain cancer (family history, radiation exposure, etc.), then please chat to your doctor about your screening schedule.

BREAST – Start age 40 years with mammograms and generally every two years thereafter unless at higher risk. Monthly self-examination is also important.

CERVICAL – Screening starts age 25 years. A Pap smear can be done every three years, but the newer human papillomavirus (HPV) screening can be done every five years.

PROSTATE – Age 40 is the recommended screening age in black men and 45 years in other races with an annual PSA blood test. Any abnormality or change in this would prompt further testing by a urologist.

COLON – Start age 50 years with a stool sample to test for occult blood. Every 10 years a colonoscopy can be done.

SKIN – Be aware of changes in your own skin. An annual check with your doctor or dermatologist is valuable.

LUNG – In smokers age 55 – 80 years (and this is even for ex-smokers), consider having a CT chest annually.

Closing remarks

There is a link between diabetes and cancer. However, scientists from Mount Sinai in the USA, who looked at diabetes and pancreatic cancer, are still not clear about what comes first – the cancer or the diabetes.

What we do know is that high blood glucose will increase cancer cell metabolism and growth so good glucose control is essential. We also know that certain medications are protective, especially metformin.

With a healthy lifestyle and avoidance of other risk factors, as well as regular cancer screenings, it should be possible for PLWD to lower the risk of a cancer diagnosis.

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References

1. Edward Giovannucci, David M. Harlan, Michael C. Archer, Richard M. Bergenstal, Susan M. Gapstur, Laurel A. Habel, Michael Pollak, Judith G. Regensteiner, Douglas Yee; Diabetes and Cancer: A consensus report. Diabetes Care 1 July 2010; 33 (7): 1674–1685.
2. Wang L, Xu R, Kaelber DC, Berger NA. Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes. JAMA Netw Open. 2024;7(7):e2421305
3. https://www.discovery.co.za/corporate/health-ovarian-cancer-screening-and-prevention
4. https://www.cedars-sinai.org/blog/link-between-pancreatic-cancer-and-diabetes.html

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Dr Angela Murphy qualified as a specialist physician in 2000 and joined the Department of Endocrinology and Metabolism at Charlotte Maxeke Johannesburg Academic Hospital. Currently she sees patients at Sunward Park Medical Centre. She retains a special interest in endocrinology and a large part of her practice is diabetes and obesity. She is a member of the Society of Endocrinology and Metabolism of South Africa and the National Osteoporosis Foundation and is actively involved in diabetes patient education. Living with diabetes in the family for 17 years has shown her that knowledge is power. Basic principles in diabetes must always be applied but people living with diabetes should also be introduced to innovations in treatment and technology which may help their diabetes journey.

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