New paper below [1] - full text.
I don't recall seeing the journal "Current Opinion in Oncology" before.
"Recent data have further solidified the association between insulin resistance and prostate cancer ...". It's good to finally read that, although data to suggest it has been around for 20 years or so.
"Data also show that peri-prostatic adipocytes promote extracapsular extension of prostate cancer through chemokines, thereby providing a mechanistic explanation for the association observed between obesity and high grade cancer."
The important thing here is not obesity, but visceral fat. And there is a connection between high carb diets & visceral fat. In the Ornish PCa trial, the men started out with elevated triglycerides and had even higher levels after 12 months. No doubt they looked trim enough, but one can be thin outside, fat inside [TOFI] (2).
{"This is difficult to establish in the general population since the necessary imaging examinations are time-consuming and expensive; however, in a 2012 research study it was estimated that 14% of the men and 12% of the women scanned with a BMI 20–25 kg/m2were classified as TOFI"}
A high-carb diet will cause glucose to spike, some of which will be converted to triglycerides & preferentially stored around internal organs - including the prostate ("peri-prostatic adipocytes").
"A number of investigators have examined the specific impact of diabetes on prostate cancer, with mixed results. In the case-control, population-based Prostate Testing for Cancer and Treatment (ProtecT) trial completed in the U.K., 1,291 men with biopsy confirmed cancer were compared to 6,479 matched controls from a group of 55,215 men enrolled in the study. Results from this analysis actually showed a reduced risk of prostate cancer with type 2 diabetes mellitus (T2DM) (OR 0.78 ...). However, a recent analysis in over 1 million men in Israel revealed an increased risk of prostate cancer incidence during the first year after a diagnosis of diabetes, with a HR of 1.65 (CI 1.55-1.76). Interestingly, the hazard ratio fell below one after two years, and stayed below one for the first 10 years after diabetes diagnosis. This suggests that treatment of diabetes may have a meaningful impact on prostate cancer development, and may also help explain the conflicting data"
Insulin resistance is a risk factor for PCa. Many men who get PCa are pre-diabetic. This is a condition that can be chronic without turning into diabetes. Men who become diabetic have begun to solve their insulin resistance problem (the hard way), but still have elevated PCa risk. The risk gradually falls. Giovannucci, in an old paper, reported that men who have been diabetic for over 12 months have reduced risk.
Interestingly, PCa is the only cancer where diabetes appears to be protective. I think it's the wrong way of viewing it, since pre-diabetes is the risk factor, i.e. before the insulin-producing beta cells have started to die off.
I am thankful that I was able to get a Metformin prescription so many years ago. It does help to control weight and, hopefully, internal adiposity. Of course, a 40% fat diet helps too.
"One of the mechanisms of castration resistance may be due to the induced hyperinsulinemia from the reciprocal crosstalk between the androgen-insulin axes. This possibility presents a unique opportunity for dietary intervention, ..." There is a section on that in the paper.
"High circulating insulin may enable or enhance de novo lipogenesis by way of upregulating the expression of multiple critical enzymes involved in lipogenesis. Since over 50% of men will develop metabolic syndrome with long term ADT, these findings suggest a potential role for dietary therapy in reducing prostate cancer associated morbidities".
-Patrick
The Warburg Effect [an increase in the rate of glucose uptake and preferential production of lactate, even in the presence of oxygen.]
Nitric Oxide -- slows prostate cancer progression and PSA doubling time.
