The Seemingly Causal Connection Between Insulin Resistance and Cancer

Insulin is a hormone produced by the pancreas which, among many functions, plays a central role in blood sugar management by supporting the entry of glucose intro the cell from the blood stream. The responsiveness of a cell to the actions of the hormone insulin is referred to as insulin sensitivity. With greater insulin sensitivity less insulin is needed to allow for transport of glucose into the cells. With lesser insulin sensitivity the cells are said to be more insulin “resistant”. With more insulin resistance, more insulin must be secreted from the pancreas to allow for glucose entry into the cells.

Diabetes mellitus, or just diabetes, is a disease characterized by high blood glucose levels. Diabetes is differentiated into 2 types; type 1 and type 2. Type 1 occurs due to a defect in insulin production from the pancreas, while type 2 is due to insulin resistance at the cells which is often too great for an increased production of insulin from the pancreas to compensate for.

With that primer, it’s reasonable that one might seek to avoid increasing insulin resistance because, if progressing far enough, the result can be type 2 diabetes. But this may not be the only disease caused by such a metabolic state. Insulin resistance has been associated with an increased risk of cancer of the pancreas (1,2,15), breast (3,4), colon (5-7,15), prostate (8), liver (9,10,15,16), kidney (15), bladder (11), uterus (12), and ovaries (15), as well as non-hodgkin’s lymphoma (13,14,16). Although such observations do not necessarily prove insulin resistance itself is responsible for such cancer rates, they lend support to the hypothesis that avoiding IR will help you avoid cancer.

Additional support for the link between insulin resistance and cancer comes from studies done on the diabetes drug Metformin. Taking Metformin, a drug clinically shown to improve insulin sensitivity (17-19), has been associated with a reduced risk of cancer in a number of studies (20-25).

Perhaps stronger evidence for the insulin resistance-cancer link comes from nutrient supplementation studies. The number of vitamins and minerals shown in randomized, controlled trials to aid in the prevention and/or treatment of cancer make up a short list. As it happens, calcium (26-28), vitamin D (26), and vitamin K (29-32) may be able to count themselves among the few nutrients on such a list. Interestingly enough calcium (33-36), vitamin D (35-41), and vitamin K (42-44) have each been shown to improve markers of insulin sensitivity in some short term clinical studies.

On the other side of the coin, preliminary evidence from human feeding trials suggests linoleic acid, a type of fat, may have adverse effects on insulin sensitivity (45-48). In conjunction with this a randomized, double blind, primary prevention study known as the LA Veterans Trial reported higher rates of cancer in men eating a diet higher in linoleic acid from vegetable oils compared to men eating a lower linoleic acid diet (49). Experiments on rodents are also strikingly in support of the promoting role of linoleic acid on cancer development.

Next, though this may seem like a stretch, we have Mediterranean diets. Mediterranean diets, particularly compared to low fat diets, seems to improve insulin sensitivity (50-53). And in the famous Lyon Diet Heart study, a Mediterranean diet similar to those cited previously was shown to significantly reduce the risk of cancer compared to a control group eating a low fat diet (54).

The topic of smoking hasn’t come up yet so let’s touch on that. Smoking cigarettes is linked to markers of insulin resistance (55-58), smoking a cigarette has been experimentally demonstrated to increase insulin resistance (59,60), and smokers who quit have seen their insulin sensitivity improve (61). Now, I’m going to make a crazy assumption and say you may have heard smoking is a risk factor for cancer. Beyond simply lung cancer, smoking has been associated with an increased risk of a number of different cancers in many studies (62-64).

Finally, a class of drugs known as salicylates, of which aspirin is an example, will provide us with our last bit of evidence connecting insulin resistance and cancer. The apparent beneficial effect of salicylates on insulin sensitivity has been observed as far back as 1876, when German physician Wilhelm Ebstein discovered that administering sodium salicylate to diabetic patients produced vast improvements in their health (65). Later, in 1901, a British physician published a paper on the effect of sodium salicylate on the glucose content of the urine in diabetic subjects (66). The drug significantly decreased the amount of urinary sugar, evidence of a decrease in blood glucose (fun fact: this paper also reported the lack of benefit accrued from giving diabetic patients heroin or uranium). In recent years, salicylates have been clinically shown to improve markers of insulin sensitivity in a few studies (67-71). With that in mind it may not be so surprising that a number of clinical trials have suggested aspirin might reduce the risk of several types of cancer, particularly of the colon (72-76).

My point in writing this is not to say the aforementioned drugs and dietary factors influence cancer risk solely due to their effect on insulin resistance. I simply wanted to lay out some of the considerable evidence supporting the idea that factors which support insulin sensitivity and thereby oppose insulin resistance are likely to be beneficial to a person’s cancer risk and this may be due in part to the effect on insulin resistance.

For those interested in learning about the possible underlying biological mechanisms linking insulin resistance to cancer development, a decent summary of some of the available evidence can be found in the 2012 review article “Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms” by Arcadiacono et al. (77). A simplified, visual synopsis of their theorizing can be seen in the following diagram:

Picture 23

Citations:

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