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Obesity, insulin and cancer: the hidden mechanisms of the link
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Obesity, insulin and cancer: the hidden mechanisms of the link

Obesity, defined as a chronic disease characterised by excessive fat accumulation, affects one in eight people worldwide in 2022, according to the World Health Organisation. It is associated with an increased risk of developing various diseases, including type 2 diabetes and certain cancers. Type 2 diabetes, which usually results in tissue resistance to insulin, further increases the risk of cancer and worsens the outcome of cancer treatment. The mechanisms behind this link are still not fully understood and remain the subject of research. One possible explanation puts the spotlight on the hormone insulin, which is normally involved in blood sugar regulation in the body. However, in overweight individuals with insulin resistance, it is hypothesised to be a key factor in the growth and development of tumours.

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Obesity and the link with cancer

According to the CDC, obesity is linked to 13 types of cancer, including the most commonly diagnosed cancers in Slovenia (breast, colorectal and colon cancer). In addition, weight gain alone can increase the risk of certain cancers by 20-50%.

Type 2 diabetes, which is often caused by excess fat build-up in the liver and muscles, makes it harder for glucose to enter muscle cells. As a result, the body’s metabolism is altered and there is an increased production of glucose in the liver, leading to high levels of sugar and insulin in the blood, both fasting and after eating.

Obesity is linked to 13 types of cancer, including the most commonly diagnosed cancers in Slovenia.

Weight gain at the expense of fat gain increases blood levels of IGF-1 (insulin-like growth factor), lipids, other hormones and inflammatory cytokines, in addition to glucose and insulin, and lowers levels of IGF-1-binding proteins, which can contribute to cancer.

Research shows that plasma concentrations of insulin and IGF-1 independently predict the risk of certain types of tumours in humans. The effect of these two hormones is likely to be direct, due to the expression of insulin receptors on malignant cells, and manifest as tumour growth promotion and altered tumour cell metabolism.

Exercise has been shown to improve cancer treatment outcomes.

Insulin lowering as a possible therapeutic approach

As a result of the above findings, scientists are trying to find out what impact lowering insulin would have in cancer patients. Current research is examining the safety and potential benefits of metformin (the first-line treatment for type 2 diabetes), which could potentially help prevent or slow tumour growth. Some early findings suggest a potential beneficial effect, but since metformin works mainly by reducing glucose synthesis in the liver, it is most effective when blood sugar levels are low, i.e. fasting.

On the other hand, exercise is an important non-pharmacological measure that has been shown to improve cancer treatment outcomes, whether before, during or after treatment, and to help lower post-meal blood sugar and insulin.

A combination of the above measures could prove most effective in slowing the progression of obesity-related cancers, as individuals could achieve control of their blood insulin levels throughout the day.

Potential approaches to treatment

  • In addition to the effects of metformin and exercise, studies are also focusing on other measures that could improve tissue insulin sensitivity. These include the use of SGLT2 inhibitors, a reduced carbohydrate diet and weight loss, which should be controlled in cancer patients as the disease itself often leads to involuntary weight loss. Various laboratory tests, such as blood glucose, fasting insulin, glycated haemoglobin (HbA1c) and oral glucose tolerance test (OGTT), could be used to determine which additional measures would be most beneficial for patients. This would increase the effectiveness of cancer treatment with existing therapies and move towards personalised medicine.

Measuring blood glucose levels.

Literature and resources:

  1. Perry, R. J., & Shulman, G. I. (2020). Mechanistic Links between Obesity, Insulin, and Cancer. Trends in cancer, 6(2), 75-78. https://doi.org/10.1016/j.trecan.2019.12.003
  2. Ljubljana Oncology Institute. (2021). Annual Report 2021. Ljubljana Oncology Institute. https://www.onko-i.si/fileadmin/onko/datoteke/rrs/lp/LetnoPorocilo2021.pdf
  3. World Health Organization. (2024). Obesity and overweight. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
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