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".
Lots of diverse aspects here, and mixing of different categories and qualities of evidence: mostly low with lots of speculation IMO. The most interesting considerations revolve around role of hyperinsulinemia (associated with insulin resistance, metabolic syndrome (MS) and Type II diabetes). Insulin indeed is key for uptake of glucose into adipocytes and promoting lipogenesis. Fat storage but also energy reserves. Cancer likes that for its growth requirements. So reduced carbohydrates and Metformin as well as overall caloric restriction strategies, exercise, mTOR inhibition etc. could provide benefit in regulating these. Some other T2DM drugs also reduce insulin levels and insulin resistance.
However, the strongest effects on MS, T2DM and on obesity, comes from the newer GLP-1RA drugs, now being heavily marketed and prescribed. These are "Glucagon Like Peptide-1 Receptor Agonists" and include liraglutide, semaglutide (Ozembic and Wegovy) and the strongest in class tyrzepatide (Mounjaro). These are indeed very effective for T2DM control and obesity. (Who can resist?) However, they do not actually decrease but rather increase circulating insulin levels via their very complex mechanisms of action. I just think they should be approached with some caution in case higher insulin levels are detrimental for PC patients. (Carefully monitoring cancer markers and PSA trends). We really don't know yet.
These do appear very beneficial on Health outcomes. From Wiki:
A 2021 meta-analysis found a 12% reduction in all-cause mortality when GLP-1 analogs are used in the treatment of type 2 diabetes, as well as significant improvements in cardiovascular and renal outcomes.[8] A JAMA article meta-analysis in 2018 (covering studies concerning GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors) showed GLP-1 agonists were associated with lower stroke risk than controls.[9]Preclinical research has suggested the possibility that the drugs may increase the risk of pancreatitis and pancreatic cancer.[10] Analyses of human trials have not found an increased risk of pancreatitis but are insufficiently powered to rule out an effect on pancreatic cancer.[11][12][13]
The metabolic side of things I don't think mainstream oncologist really take into consideration in the wider scheme of things. This leaves much to the patient to investigate and self discover. Certainly causation and or association is problematic to isolate...
I'm left to wonder, as I've added Lynparza to my drug regimen of Degarelix and Darolutamide, that a few months later my Blood Glucose has lowered and seemingly stabilized! Is this because the BRCA drug has stabilized and effected my PCa? Resulting in my metabolism to concur...? Interesting take I think. Diet hasn't changed much during that time, maybe a slight increase in physical exercise, but not daily. Interesting! But absent daily or weekly blood testing to try and isolate blood lipids and such, I'll not be able to know. I do use a CGM and my glucose has dropped significantly since the introduction of Lynparza. I have hit fasting normal levels (wake) in a few years, but have been hitting it lately! A happy place to be!
Interesting is how the oncologist stay in their wheelhouse! For instance my recent experience with kidney stones, lol, apparent on my scans (calculus being present in my kidney). Not once was it suggested to attend to this. I asked about the recent appearance of calcification in my arteries shown on scans and it was suggested to see my Cardiologist!?!? Lol, would be good if I had one, as I don't, never having had the need (before).
So, who then do we sit with, and consult with, for an "overall" investigation to our "complete" health picture? GP's aren't specific enough and make referrals for specialist, etc. But who would look at Blood, Diet, Metabolism, check blood levels of drugs present (Taking for PCa), and any side issues? Is like all things once diagnosed, a conundrum, lol.
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Time to impeach for prostate cancer
? Any progress in the history of \"War on Cancer\"
brca-2 advanced prostate cancer
