August 23, 2021

Metabolic disease

#173 – AMA #26: Continuous glucose monitors, zone 2 training, and a framework for interventions

Zone two is a metabolic state. It's not determined by speed. It's determined by which energy system you're requiring and what the equilibrium is.” —Peter Attia

Read Time 27 minutes

In this “Ask Me Anything” (AMA) episode, Peter and Bob answer numerous follow-up questions to recently discussed deep-dive topics such as the use of continuous glucose monitors and getting the most from zone 2 exercise. They also discuss the incredible feats of cyclists in the Tour de France through the lens of the amazing performance physiology required from these athletes. Additionally, Peter ties the conversation together by sharing his foundational framework when considering different interventions, even in the absence of data from a randomized controlled trial.

If you’re not a subscriber and listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or on our website at the AMA #26 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

AMA #26 Sneak Peek

We discuss:

  • Peter’s foundational framework when considering different interventions [1:30];
  • Applying Peter’s framework to the idea of using a CGM [8:00];
  • Why certain fruits have a bigger impact on glucose, and the limitations of a CGM can tell you [16:00];
  • Importance of paying attention to insulin, and the prospects of a continuous monitor for insulin levels [20:00];
  • How exercise impacts glucose and peak glucose numbers to stay under [24:15];
  • Impact of anxiety on stress on glucose, and why it’s important to calibrate your CGM [26:30];
  • The five main tools for managing blood glucose numbers [33:45];
  • Benefits of moving or exercising after a meal, and where ingested carbohydrates get can be stored [37:15];
  • How to make decisions about an action or intervention in the absence of data from a rigorous, randomized controlled trial [40:30];
  • The incredible athletic feats of Tour de France cyclists [48:30];
  • Different modalities for doing zone 2 exercise: running, rowing, cycling, and more [1:00:15];
  • Proxies for knowing your in zone 2 short of using a lactate monitor [1:07:30];
  • Monitoring lactate for zone 2 exercise [1:10:00]; and
  • More.


Peter’s foundational framework when considering different interventions [1:30]

Intro to the AMA discussion:

Peter’s framework for different interventions as foundation for how you think about CGM and their use in different populations

  • Peter’s framework for interventions helps in laying the foundation for how one should think about CGM and their use in different populations
  • The framework really pertains to anything that comes across Peter’s plate

⇒ Example, when looking critically at the data around meditation (which asks a series of questions)

-First question is what is the risk of harm from doing this thing? 

  • If you do X, how high is the probability of harm? 

-Second question is obviously the contrapositive of that. If you do X, what is the probability of benefit?

  • Mirrored in the way the FDA organizes drug trials
    • After you get through the preclinical data, the animal work, after the IND has been filed, your first trial in humans, which is called the phase one trial, is looking at harm
    • a small trial with dose escalation that is only trying to understand if as you escalate the dose, do you see an increase in side effects?
      • Very occasionally, you see some benefits in a phase one trial. And if you do, that’s interesting, but you generally can’t take it to the bank because the study is so small and generally it’s quite homogeneous
    • That’s when you move on to phase two studies, which are geared towards efficacy, i.e., is this thing doing good? 
      • if the phase two trial is positive, you move to a much larger trial called the phase three trial, which really doubles down on efficacy
      • But the real point here is you’re raising the bar, so to speak, for what you’re demanding of this.
      • Again, what’s the risk of harm, what’s the probability of benefit are two obvious questions

-Third question, what’s the opportunity cost of this intervention? 

  • Let’s use an example, Peter came across a device that would put you in a trance 
    • there was this device that you would listen to and it would supposedly put you in a trance and the company that was proposing this thing had all sorts of theoretical benefits from using it (you are less likely to get breast cancer, all of these other things)
    • Was there any harm in this device? As far as I could tell, no
    • Was there any benefit of this device? Certainly not to the extent that they made claims
      • That said, I had tried the device because a friend of mine bought it for me. I have to admit, it was the most relaxing thing I’d ever done (virtually every time I tried it, I fell asleep)
    • But there were opportunity costs
      • First, it was pretty expensive
      • More importantly, there was a time cost
        • It was two 20-minute sessions a day, much along the lines of like transcendental meditation, which is similar, but has much better data
        • Well, there’s a problem because for most people who are super busy, 40 minutes a day for very questionable benefit didn’t make a lot of sense if it came at the expense of other things that undoubtedly had benefits such as could that be 40 minutes a day of actual meditation
        • 40 additional minutes a day of sleep
        • 40 minutes a day of exercise? All things that I would point to as having far greater evidence in favor of.
        • any time you’re thinking about doing something, you want to go through that
        • especially important questions to be asking when the answer is not readily apparent from RCTs that have generally already answered one and two

*Remember, The easiest RCTs to do are the ones that are based on pharmacology

  • They’re generally addressing questions one and two, but they’re not really addressing question three
  • And that’s because there really isn’t much of an opportunity cost to taking a pill outside of the economic cost (the time cost of it is relatively low)
  • When it comes to RCTs that are more intervention based such as exercise, yes, you want to be able to think about the time cost


Applying Peter’s framework to the idea of using a CGM [8:00]

The framework applied to CGM in non-diabetics

  • As you look to something like CGM in the case of non-diabetics, this framework is very helpful 
  • At this time, we don’t have great RCTs to point to that say in people who are not yet diabetic, there is a benefit to using CGM

-First ask the question, What is the risk of harm?

  • when we talk about CGM specifically, the risk of harm is very low (but now zero)
    • Example, the most obvious thing that comes to my mind is anxiety that it can stoke. It can create obsession in someone
    • For instance, we have some patients who have a history of eating disorders. These are patients I would not in any way, shape or form advocate the use of CGM

-Secondly, Is there any chance of it doing good? 

  • First potential benefit could be insight-based good, which is teaching you what your carbohydrate tolerance is
  • Second potential benefit is behavior modification, which is effectively a strapped on version of the Hawthorne effect
    • When you’re wearing a CGM, you’re basically utilizing a tool that is monitoring you. There is no shortage of data to support the idea that when people are asked to monitor food intake, they make changes in the right direction.
    • How you create accountability for patients. You say, “Look, we’re going to check in once a day and I just want you to tell me what you ate”
      • even if you provide no other instruction, just need you to tell me what you ate,” that level of accountability immediately changes a person’s behavior

-Third question, what is the opportunity cost?

  • The biggest opportunity cost is the economic cost
    • If you are not diabetic, you are not going to have your insurance company cover one of these devices
    • There are really three companies that make CGMs in the clinical grade
    • Then there are lots of companies that help with plugging in those CGMs into their apps to help users with their goals, be it weight loss or otherwise, such as…
    • But these devices are not cheap
      • daily cost of CGM is about $10 per day
        • That’s a huge expense assuming you need it every minute of every day. I don’t think you do. I think you can gain a lot of insight using these things periodically. I don’t think this is something you need to be tethered to every minute of every day
        • There are some people like me who enjoy that

{end of show notes preview}

Would you like access to extensive show notes and references for this podcast (and more)?

Check out this post to see an example of what the substantial show notes look like. Become a member today to get access.

Become a Member

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.


  1. After your last AMA on Glucose and CGMs, I got a Dexcom cGM as a non-diabetic. Was frustrated with my primary care doc suggesting that I might be prediabetic with a twice a year reading of 98 for fasting glucose. 30 day Dexcom was 89 eAG with 11 variability. 99.7% between 65 and 135.

    One thing I noticed was an elevation in glucose during/after a hot bath at night. Probably relates to your podcast on Saunas. I remembered that sauna acted like exercise. Assume the same thing on hot bath and it’s exercise-like impact on glucose as mentioned in this AMA.

    Really appreciate your podcasts and info. Has dramatically improved my sleep (Oura ring), and physical and mental well-being. Thanks!

    • I am also wearing a Dexcom occasionally as a non-diabetic, and do semi-regular saunas. I notice a very distinct “blip” up of blood glucose corresponding to the time in the sauna, quickly dropping after. Something like 5 mmol/L to maybe 7 then back to 5 (90 to 125 mg/dL).

      I wonder if it is due to the real release of serum glucose, or could it be a blip in the device due to temperature sensitivity … or a combo of both ?

      • Thermoregulation is a major function of our skin. Arterioles in the dermis dilate so that excess heat carried by the blood can dissipate through the skin and into the surrounding environment. Due to the fact that the dexcom gets mostly superficial samples from the skin, I’m betting that the increased blood flow creates an artificial “high”. A deeper blood draw would give you more accurate results which might not reflect the dilation factor. Just an opinion based on n=1 data 🙂

  2. Another way to consider finding the aerobic threshold (top of Zone 2) is to use a heart rate drift test. Basically you run/ride/row at a set power level (you can figure out this power level via the talk test or the nasal breathing test, or the power attained at the heart rate set by the MAF formula, whatever), and stay there for 60 minutes. Then you compare the average heart rate over the first 30 minutes vs. the average heart rate over the second 30 minutes. The difference between them is your “heart rate drift”, and if it’s 3.5-5%, that’s a good proxy for your aerobic threshold. If it’s lower, you’re probably going too easy, and if it’s higher, you’re going too hard.

    Training Peaks has a nice feature where they can calculate this heart rate drift even if your power varies over the hour by looking at the ratio between average power and average heart rate as well (you can do it by hand too).

    Some more details on the idea and a protocol is here:

    I find this method to be a very approachable way to continuously monitor my aerobic threshold heart rate and power level. I personally find the talk test and nasal breathing test to be too subject to uncertainty – am I unconsciously gaming it to get a higher value, or is my nose a bit clogged up today?

  3. Hi Peter and team,

    you mentioned you knew of a company that could do (or was working on) a finger-stick insulin test?

    I looked thru episode 140 with Schulman but could not find any mention of that.

    Is there any public information on that? Thanks!

  4. As you have an international audience, could you have both USA and metric units when mentioning BGL, Blood Lipids and the like ? BGL divide by 18 not hard but dividing by 36 gets a bit tedious. Also remind people of the “normal range” and whats optimal.

  5. Hi Peter,

    There appears to be a dearth of information regarding how best to healthily add lbs when one’s BMI is below optimal during early adulthood (18-25). When searching about “weight gain” you’re immediately flooded with information about how to avoid it/reverse it. Wading through this barrage to find tailored information for the minority in the opposite group is tedious.

    Proponents of dietary regimes rarely pay any attention to their potential weight gain qualities for obvious reasons.

    What examples there are of “success stories” are dubiously imitable.

    The conventional wisdom is that one must simply eat far more than one is used to eating – past the point of satiation and comfort. One manifestation of this is the pizza/burger diet where the form of calorie matters far less than the quantity.

    If this conventional wisdom is infact the case, what dietary recommendations can you offer?
    Should one use a certain Protein, Fat and Carb ratios?
    Should one preferentially consume Saturated or Unsatured fats?
    Should one consume processed grain and sugar products?
    Can/should one lean on calorically concentrated foods like protein shakes/bars/etc.?

    Is there a danger in pursing any fasting protocols or keto for someone with this characteristic? Should it be avoided entirely or are certain methods safe to utilize or even beneficial?

    Is there an exercise regime that lends itself well to this context? E.g. Heavy weights to promote growth hormone

    Does HIIT or cardio have a role to play?

    I apologize if you’ve already answered these questions elsewhere. I looked but did not find anything pertaining to this subset of the population.

    Thank you for shedding whatever light you can on the subject!!

    • I would think you’d want to increase your lean mass, not fat per se. BMI is useless. depending on age, when < 25, targeting an 8-12% body fat should be healthy. So, you start eating 100-200 more calories a day split 33% each, nutritious (not empty) carbs, fats, proteins, at the same time you start pumping iron to build muscle mass, otherwise, the proteins will convert to carb calories then to fat. Do it for ~3-4 wks at a time, and up the calories if more healthy weight is needed. That time constant gives your body/habits time to adjust and also to not overshoot or do too much/little of any one nutrient source.

      Hope that helps…

  6. Stress and Glucose Levels: just reflecting on the question asked by the individual that was wearing a CGM on during a presentation at work. Isn’t this a “normal” reaction by the body in preparation to combat the perceived threat? It would have been nice to know how long the glucose levels remained high after the event had passed. Cortisol induced glucose release is kind of how its supposed to work. In my estimation, the key difference is how long the glucose levels remain elevated. I know from personal experience with GCM that high caloric density processed food creates sustained high blood glucose levels. I think this is how insulin resistance manifests over time. That said, this example reinforces the idea of how chronic stress can negatively impact the body… especially if you’re already insulin resistant. I wonder how much chronic stress contributes to obesity in those with insulin resistance? Also, it’s not too far of a leap to see the benefits of exercise as it creates a glucose sink for that cortisol induced high blood glucose.

  7. many ask how to tell if mitochondria are benefiting, re “Assuming it’s aerobic exercise but what intensity / % of LT vo2 etc?

    It is the maximum Zone 2 you can achieve.

    You’ll know by tracking your Keytone and lactate levels. If Keytones go way up and lactate goes down at the same zone 2 (and above) power output then your mitochondria (and heart) are burning more cellular fat and getting more efficient (and vice-versa). The cheap proxy for measuring lactate levels is tracking heart rate vs est. power output. Also, if your zone 2 max power level (e.g., at a certain max resistance/speed on your bike) increases (e.g., able to do higher speeds) then that is a way of knowing that you’ve mitochondria got more efficient at burning the cellular fat, which presumably should improve glucose sensitivity over time. That (along w/ HIIT) should also stimulate mitochondrial genesis, the whole grail. BTW, an easy way to gauge what is your zone 2 max for any exercise means is to do the maximum speed/power that keeps your average heart rate in the 2nd half of your workout no more than 5% higher than the average of the first half.

    the basic rule of thumb is to keep your HR bpm under 180 – your age – 5 to 10 bpm if you have a metabolic health condition like diabetes. Turns out the equation works for me, confirmed by the 5% rule. I actually notice more like a ~7% rise, but feels like zone 2 max per Attia’s talking mostly OK while breathing rule of thumb.

    hope this helps.

Facebook icon Twitter icon Instagram icon Pinterest icon Google+ icon YouTube icon LinkedIn icon Contact icon