pioglitazone and bladder cancer
As a practicing clinician in primary care, I was pleased to hear Dr. DeFronzo discuss the utility of pioglitazone in the insulin resistant patient. This treatment no question has been falling out of favor with the addition of SGLT2-inhibitors and glp1-agonists on the market. In considering reaching back into the toolbox and re-utilizing pioglitazone as a low cost and effective option, I was reminded of the concern for possible increased risk of bladder cancer. I would love to hear Peter's take on this after him and his team review the literature. Of course if has already been discussed and I missed it, let me know! Thank you for your expertise. From a long time listener, Bryan Lavoie PA-C, Dip ACLM
Injection for things like BPC-157, and GLP1
I'm considering using BPC157 and possibly a GLP1. I'm concerned that injection's daily will damage my skin, similar to what happens to someone that injects thing like heroin into their body, aka track marks on a junkie. Do I have anything to worry about long term, not as much with the BPC-157, but more with the GLP1, and the longevity of taking this to loose and maintain weight loss.
TRT, resting HR, endurance training
40 year-old, male here. I am a trained endurance athlete, with a history of competing in multiple Ironmans and half-Ironmans, and I twice qualified as an age group athlete for the IM world championships. After retiring from competition last year, I started focusing more on holistic health. As part of that process, I got my bloodwork done twice over a two-week period; both times, my total testosterone was about 250 ng/dL. I made the decision to begin TRT 12 weeks ago, injecting 2x 75 mg/wk coupled with 1,500 IU 2x/wk to preserve testicular function. Despite retiring from competition (and now banned from competition on account of my using TRT), I still enjoy training and participate in my local triathlon club. My training volume is roughly what it was during the off-season from my competitive years (~10 hrs/wk, 80%z2 20% threshold/vo2). Historically, my resting HR during my off-season would be 40-42 bpm (and it stayed this way for essentially my entire 30s). Since starting TRT, however, I’ve noticed my resting HR has ticked up to 47-50 bpm. I’ve never noticed it this high since I started regularly tracking my HR nearly a decade ago. While I understand much could be contributing to this, I believe I’ve controlled for a lot of variables: my weight is the same, my body comp is the same, my off-season training is the same, my diet is the same, my sleep is the same, etc. The only thing I’ve changed is introducing testosterone and HCG. My doctor first thought this may be because of blood thickening on account of increased red blood cell production, but my hematocrit has barely budged at all compared against my pre-TRT blood work. My blood pressure is also testing the same. My doctor suggested that TRT can sometimes affect the balance in the sympathetic/parasympathetic nervous system, but my HRV is also pretty much the same as before (and I would think changes in nervous system function would be detectable in one’s HRV). I’m interested in learning more about the general science here from you. Can you talk in general about any studies concerning TRT administered to trained endurance athletes, what endurance athletes can expect from TRT, if anything, and why TRT/HCG may be affecting my resting HR?
Fiber and is Peter Protein biased?
Hi Peter, First of all, I am a huge fan and learned the most from you and I really follow your advice. Thank you for all that you do! If it wasn’t for you I would have never found out I have a very high Lp(a) and my wife would not resistance train or eat 90g protein per day! I do have a genuine question about nutrition that is really puzzling me. In your book you say something like that all we know about nutrition is we need adequate protein. And in your AMA’s you always stress protein. Two questions: How come you don’t mention importance of fiber? Do you not see it as an important pillar for good nutrition? Also, it seems to me that you have a bias (that you don’t realize you have just like we all don’t realize our biases) towards protein and so you are as guilty as the ‘low carb’ or ‘low fat’ or ‘fill in the blank’ diet followers, you are just a ‘high protein’ camp. Are you 😀? I say that and I eat 2.2g/Kg protein and I love that way of eating! I am protein biased for sure! But many epidemiology studies show that plant protein is amazing, and plant protein is associated with highest fiber content of any food (think beans). You seem to ignore the strong signal of plant protein and associated fibers impact on health? Btw: 80% l of my protein is animal source! But I am trying to see if I should maximize fiber intake to 38g per RDA, which I find really difficult to achieve without switching a lot of protein to come from plants. Example this study shows a strong signal for plant protein and healthy aging. It doesn’t show the same for animal protein. Even if there is an argument of confounders for animal, the plant protein signal is strong? https://ajcn.nutrition.org/article/S0002-9165%2823%2966282-3/pdf Kind regards
High APOB 109 last check , CAC zero
61 year old woman.Mother died 40 years ago at 41 massive heart attack. I am Probably in top 3 % physically.Can not eat any cleaner. No alcohol. Have had every test for disease prevention imaginable (Tri 51,HDL 70,LDL150)All other numbers so good that cardiologist says do nothing. But adds “ eventually you’ll be on something” to which I respond, but why wouldn’t you just address this now? I’m exhausted searching for options.Plant sterols,Red yeast rice? Pcsk 1 inhibitors , ezetimide with or without bamboic acid ? I am avoiding traditional statins but realise may have no choice . Your opinion, what should I throw at this now ? Seems like a lot of folks have no idea where to turn as traditional Cardiologist are absolutely useless. I should mention that my APOB has increased every year since I started testing three years ago from 103 to 106 to 109 and my diet and exercise routine has only gotten better in the last three years.
OGGT
I insisted my husband have an OGGT after listening to the metabolism masterclass. In the episode at the very end you discussed the test and results for different patient profiles. When my husband went for the oggt today they only drew a before baseline draw and a 2hr post draw. This leaves me without the 30, 60 and 90 to see if he fit any of those profiles. How can we request more specific draws in the future? Frustrated with this standard medical model of care and trying to get the tests/answers needed. Thanks
Hand Osteoarthritis Ouch!
Hi Peter I am a big fan of yours and so I want to thank you first for all I have learned from you! To be honest you have turned my life around in many ways. So I am a psychotherapist by day and a sculpture, guitar player, hands on person the rest of the time. My way of balancing things I guess. I am sure over the years I have over done working with my hands. When I was in a band I built a dining room table in the shape of a guitar. Lots of using tools in my studio. But I have recently been diagnosed with Osteoarthritis in my right thumb, base of thumb towards wrist. Im told it is severe loss of cartilage and that it will only get worse as I age. I have been very active but now can't do weight training without worrying I am making this worse. I got a shot which didn't work. I am seeing a hand OT but keep getting the news there isn't much we can do with this. I read that both Metformin and Berberine help but only if you are willing to chance losing muscle growth as a side effect. I don't want to do surgery because it can lower range of motion and maybe something better will come down the pike. Radiation? Where should I go. Would you do recommend this? Seems like everything else can be replaced but not your hands. I do hand exercises but it doesn't help much. I have been told to stop yoga because downward dog/ push ups are bad for the place that is where my thumb meets my wrist. I am really looking for some hope so when I do exercise and use my hands I don't have to worry that while I am making my arm muscles stronger I am making use of my hands worse in the future. I have been carrying 10 -15 lb kettlebells when I walk the dog for about 20 mins every other day. I also walk with a ruck pack which doesn't hurt my hands. I am a very motivated person but not sure what to do next. I am working on improving my metabolic health as my sugar is at prediabetic level which is why I thought Metformin might help. Is it worth he trade off of possibly losing other muscle growth. I am following my sugar on a GCM. I get mixed messages but not sure if I get my sugar down will my arthritis go away or change at all. My hand hurts often and I try not to take Ibuprofen very often. I guess I am fearful this will only get worse. Everything else I study seems to have clear outlines on what to do to help. Like knee arthritis. But this one seems to not get addressed much and the news doesn't seem very promising. I mostly want to know what you would do if you were me? Thank you again
Processing and interaction of Supplements (especially Magnesium)
My initial question is how fat is processed, where in the body it ends up and interacts with other substances – in the stomach, the bloodstream or in cells – and how long it stays in each place and is available for such interactions. I´m talking about normal daily processing, not superfluous fat resulting in weight gain. I´m trying to find out how fat helps in the absorbtion of various elements and compounds, particularly vitamin D, which is fat soluble rather than water soluble. How soon after eating a fatty substance may one still get the benefit from it for absorbing Vitamin D? Does vitamin D from sunlight mean we don´t have to worry about fat? How much sun exposure would be necessary? I have read that it doesn´t have to be bright sun, that even on cloudy days one can get the necessary light exposure. Lets say its a cloudy winter day and someone walks 20 minutes each way to school or work. Only their face will be exposed. Is this enough? I am concerned about absorbtion/metabolizing of vitamin D because I understand that it is required for the absorbtion of both Calcium and Magnesium (in fact the calcium pills I take at the instruction of my doctor also contain vitamin D). However, I have also read that magnesium is required for metabolizing vitamin D, and that calcium can prevent the proper absorbtion of magnesium – and vice versa. Yet there are pills which contain both magnesium and calcium. Which, if either, of these statements is accurate? In what relative order and at what times should I take these supplements to get maximum advantage from them? With or without food? Likewise, internet sources say both that L-theonine works with caffeine to increase concentration and that it 'cancels out´ the stimulant effects of caffeine. Which is correct? Does it have any experimentally supported effects? Related questions Does vitamin C and/or citric acid influence on any of the above? I tend to get vitamin C in the form of fizzy tablets which contain citric acid – but maybe that´s what vitamin C is? Would it be preferable to eat, say, a red or green pepper or some cantelope? Calcium – is said to decrease stomach acid so should not be eaten with meals as it causes problems with digestion. In fact, the bottle says to take it with food. Which is correct? I have been taking it with meals forever with no problems. 350 mg. caplets of magnesium glycinate seem to have caused a certain amount of stomach gas. Could I cut them in half and/or dissolve them in water, which I would then drink at two different times, say with breakfast and dinner? I want to minimize liquid intake after about 7 PM to avoid waking up to pee in the middle of the night. I have read that, in any case, it is best to get properly hydrated within the first ten hours after waking, so I tend to drink a lot of water early in the day. I note in passing that taking magnesium seems to result in a thickening of nasal mucus. It this a recognized side-effect? What about caffeine? Coffee, tea, pepsi? Which really has more caffeine, green tea or black? And alcoholic drinks - beer, wine, stronger stuff? Can one take one‘s supplements with these instead of water? (Don´t laugh, please. Relaxing with a glass of wine or beer at the end of the day might be the perfect occasion for one supplement or another. With a bit of cheese if one needs the fat for vitamin D absorbtion.) I am particularly concerned that my caffeine consumption, 3-5 cups of coffee or the equivalent in tea of pepsi, before noon, may cancel out the effects of the magnesium or calcium I would take at breakfast and/or lunch time. Also I understand that caffeine ‚cancels out‘ vitamin C consumed at the same time – so it is pointless to drink orange juice at breakfast if one is going to drink coffee at the same time. Please also comment on other factors that may be relevant. Gender or age, for example. I´m a 72 year old female. I´m not looking to extend longevity, I simply want to be able to be enjoy whatever time I have left. I´m looking for quality, not quantity! And a final post-script. I have heard that various substances in coffee, and also L-theonine in tea, are quite good for you in certain ways – but then there´s the caffeine! Decaf coffee and tea will have much less caffeine (but, I understand, not absolutely zero.) How do they get the caffeine out? Is it a chemical process that may result in even worse problems? I´m going to send these questions to Chat GBT, but am sending them to you because the best computer by far is still the (knowledgeable) human brain. Here´s the summary: I want to get the maximum advantage from magnesium (350 mg) and calcium (2 tablets, 600 mg. plus 20 mcg of vitamin D ) supplements. When, how, and how often would it be best to take these supplements, and why? Please provide bibliography.
CBTI (cognitive behavioral therapy) - Ashely Mason podcast.
The podcast with Dr. Ashley Mason was terrific, but could we have a follow-up - Part 2? As Dr. Mason noted, she has gone through the behavioral part of CBTI in detail but not so much the ‚therapy‘ part – changing one´s mindset with regard to sleep – nor how to prevent relapses. The book she recommended is also skewed in this direction. Following the behavioral guidelines she and it suggest is indeed brutal but can be done . . . but for how long? Where does one go from there if one is still (for example) waking up for two hours in the middle of the night after three weeks? How DOES one prevent relapses? (After confining my bed-time to a total of 6 hours, I did not end up sleeping for 5.5, but only 3.5-4.5, for a period of about 2 weeks. I don´t live in California but my wait for a therapist is also going to be long.)
Protein - science re impact of quantity
Can Peter discuss studies showing the impact of eating a gram of protein per pound of body weight each day, on maintaining or adding muscle? I’ve heard him say it many times, but what is the science behind it? This is important for a lot us us on Tirzepitide who have trouble maintaining muscle as we lose weight combined with decreased appetite that makes eating enough protein more difficult.
Why doctors don’t recommend Exenatide for type 2 diabetes (See Ralph Defronzo episode 337).
Similar to my question for the same episode (#337) wrt Actos/Pioglitazone Ralph did not address reports that there have been published reports linking exenatide with Pancreatic Cancer. Has the science wrt the safety of exenatide for type 2 diabetes become for settled than it was in 2020?
Doctor reluctance to prescribe Actos, aka pioglitazone, not completely addressed by Ralph Defronzo in Episode 337
In Episode 337 Ralph Defronzo claimed to be mystified about doctors’ reluctance to prescribe Actos (aka pioglitzone). Today I asked my Primary Care Physician why I was not put on a combination regimen like the one described by DeFronzo. My doctor mentioned two concerns: 1) fluid retention - which Ralph addressed and 2) cancer risk which I feel Ralph ignored. A quick google search shows that while the science may not been settled there are reports going back to 2009 of a concern that pioglitzone was connected to an increase in bladder cancer and that the relationship was both strength of dose and length of treatment dependent. More interesting is that Ralph himself is listed as an author of a 2019 article entitled: “Pioglitazone: The forgotten, cost-effective cardioprotective drug for type 2 diabetes” (Diab Vasc Dis Res. 2019 Mar;16(2):133-143. doi: 10.1177/1479164118825376. Epub 2019 Feb 1.) In that paper, the authors claim that a large study showed no relationship between the drug and bladder cancer. At the same time acknowledging, that, nevertheless, the FDA was still promulgating a warning to prescribing physcians. I am assuming that there must be liability risks for Doctors when they decide to ignore a warning from the FDA. Has the science behind the risk of Actos aka pioglitazone become more settled than it was in 2019?