Metabolic Syndrome [MetS] and PCa

[pca2004]

A new study [1]:

"Association of metabolic syndrome {MetS} and its components with the risk of urologic cancers: a prospective cohort study"

reports that "Compared to the non-MetS group, the risk of developing ... prostate [HR ... = 1.47 ...] cancer was significantly higher in the MetS group."

Back in 2004 there was already enough data to suggest that a man could reduce his risk for PCa by becoming diabetic. lol

My take on this was that the pre-diabetic state had to be a risk factor for PCa. Note that most prediabetics do not become diabetics.

The difference between prediabetes & diabetes is insulin production. The prediabetic over-produces insulin because he has become insulin-resistant. The diabetic has "solved" that problem via exhaustion of pancreatic beta cells and produces insufficient insulin - ultimately curing his insulin resistance.

"Prediabetes, which is a combination of excess body fat and insulin resistance, is considered an underlying etiology of metabolic syndrome. " [2]

In essence, the new study links insulin resistance to PCa risk. (A surrogate for insulin resistance is the triglycerides:HDL-cholesterol ratio. Should be <2 imo.)

From 1998 ([3], Giovannucci):

"... the Health Professionals Follow-Up Study from 1986 and 1994, in which 1,369 new cases of non-stage A1 prostate cancer were documented in 47,781 men. A prior history of a diagnosis of diabetes (mostly adult-onset) was associated with a reduced risk of prostate cancer (multivariate relative risk [RR] = 0.75 ..."

"After excluding the first year of follow-up after the diagnosis of diabetes, the RR was 0.63 ..."

"Prostate cancer was not reduced in the first five years after diagnosis (RR = 1.24 ...), but was lower in the next five years (RR = 0.66 ...) and lowest after 10 years (RR = 0.54 ...)"

"The basis of this relationship is unclear but may reflect hormonal changes related to diabetes, perhaps low testosterone levels."

Giovannucci is now author/coauthor/lead on 28 PCa/diabetes papers. (None referenced below.)

From 2004 [4]:

"History of diabetes mellitus and risk of prostate cancer in physicians"

"Odds ratio estimates were 0.63 .., 0.77 .., 0.59 .., and 0.59 ... for diabetes diagnosed 1-5, 6-10, 11-15, and > or = 16 years prior to prostate cancer diagnosis"

"Adjusted odds ratios were 1.44 ... for stage A prostate cancer and 0.48 ... for stages B-D. Results suggest that history of diabetes may be associated with a decreased risk of prostate cancer, especially late-stage tumors."

In a 1991 study from Uppsala, Sweden [5]:

"... a lower than expected number of prostatic cancers (RR = 0.7 ...) were found in this cohort of diabetic patients."

This study is of interest in that it used pre-PSA era data, and, in any case, is from a country not previously noted for PCa screening.

From a 2004 meta-analysis [6]:

"We included 14 studies, published between 1971 and 2002, in the meta-analysis (five case-control studies, nine cohort studies)."

"Our meta-analysis findings provide strong evidence that people with diabetes have a significant decrease in risk of developing prostate cancer. There is biological evidence to support this association."

In the 19 years since 2004, there have been countless such studies. (There are currently 3,302 PubMed hits for "prostate cancer diabetes".) Not every study supports the hypothesis of protection, of course.

One complication is the washout period. New diabetes cases start out with an increased risk of PCa. Some studies ignore PCa cases diagnosed within 12 months of a diabetes diagnosis, but a much longer period seems to be needed.

Then there is the problem of how diabetes is treated. In the US, it is common to try Metformin as monotherapy, along with dietary advice. This may not be successful (10-year failure is common), in which case other drugs might be used in addition to Metformin. Note that my hypothesis depends on the exclusion of cases where insulin is used.

You will note that this post suffers from bias. A recent UK study reported no protection. It's interesting, & perhaps there is something in the full text to explain why British diabetics are different, but I'm stuck in my beliefs.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/377...

[2] pubmed.ncbi.nlm.nih.gov/262....

[3] pubmed.ncbi.nlm.nih.gov/948...

[4] pubmed.ncbi.nlm.nih.gov/151...

[5] pubmed.ncbi.nlm.nih.gov/193...

[6] pubmed.ncbi.nlm.nih.gov/151...

[Bacana]

So I calculated my husband’s Triglycerides to HDL level (152/46), so 3.30. His A1C is 5.1 so not even prediabetic according to doctor. So looks like he’s insulin resistant, I suspected as much. Will ask MO for Metformin.