The Peter Attia Drive - #69 - Ronesh Sinha, M.D.： Insights into the manifestation of metabolic disease in a patient population predisposed to metabolic syndrome, and what it teaches us more broadly

00:00:00.000 Hey everyone, welcome to the Peter Atiyah drive. I'm your host, Peter Atiyah. The drive

00:00:10.880 is a result of my hunger for optimizing performance, health, longevity, critical thinking, along

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00:00:33.000 and other topics at peteratiyahmd.com. Hey everybody, welcome to this week's episode

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00:04:11.020 monthly subscription. My guest this week is Dr. Ronesh Sinha. Ronesh, who really goes by Ron,

00:04:16.400 is an internist in the Palo Alto Medical Foundation, and he created a South Asian medical consultant

00:04:22.460 service for his medical group in Silicon Valley. I connected with Ron about five years ago, and I think

00:04:27.520 we talked about this at the very beginning of the podcast, largely because I was running up against

00:04:33.040 some brick walls and taking care of some of my South Asian patients at the time and seeing just

00:04:39.420 kind of a different pattern of metabolic illness. And when I was introduced to Ron and got familiar

00:04:45.480 with his books, we just basically began a friendship at that time. Although interestingly, this was the

00:04:50.480 first time we met in person to record this podcast. So it was sort of an interesting experience

00:04:54.400 feeling, you know, you know somebody, but then you, for the first time, get to sit down with them.

00:04:57.960 And it was great. We just had a really interesting discussion about a number of topics. Obviously,

00:05:03.220 we focus a lot on what hyperinsulinemia, insulin resistance, metabolic dysregulation,

00:05:09.200 inflammation, all these things look like in his patient population. But his patient population is

00:05:14.180 basically a model system that allows you to understand lots of patients. So if you're listening to this

00:05:19.240 as someone who takes care of patients with insulin resistance, or if you yourself have any of the

00:05:26.260 things that go along with this high blood pressure, insulin resistance, you're overweight, all these

00:05:30.940 things. In many ways, this is a really great podcast to go into the how to address these things with

00:05:38.740 respect to, you know, we talk about everything from nutrition to sleep, et cetera. I would say one of

00:05:42.960 the things about this podcast that was a totally pleasant surprise was the part of the discussion that

00:05:48.720 we ended at, which is Ron's really interesting and unique purview into what's happening in Silicon

00:05:55.800 Valley with respect to stress and with respect to how that is trickling down into kids. And in fact, you

00:06:04.100 know, something he said to me at the very end, after we would, we had stopped recording, but we were

00:06:08.260 sitting around talking, and this is often the case where you have these amazing discussions 10 minutes after

00:06:12.780 you turn the mic off. And he said something to the effect of, you know, I just can't believe at how

00:06:17.820 little happiness exists in the Silicon Valley. And he wasn't making a general statement of like,

00:06:23.320 you cross the board, but he was saying, look, I take care of patients who work for some of the

00:06:27.520 greatest companies in the world by whatever metric we would, you know, make that claim financially or

00:06:33.120 whatever. And he said, and yet it's kind of amazing how unhappy and stressed out so many of these people

00:06:38.980 are, and you can see it in their lives. Cause that's sort of something about Ron's practice.

00:06:42.680 That's pretty unique is he takes care of whole families across generations and he sort of gets

00:06:48.160 to see things that certainly I don't get to see. And that I think many patients are rather many

00:06:52.600 physicians don't. So I think this podcast is going to be something worth listening to if you have any

00:06:58.000 interest in metabolic health, but also this last part that we talk about with respect to kids and

00:07:03.180 with respect to maybe some of the things that those of us that have kids could do better.

00:07:07.720 Certainly something that I took a lot away from that discussion and I actually look forward to

00:07:12.320 trying to implement a number of the suggestions that Ron made. So I hope you'll enjoy my discussion

00:07:17.380 with Dr. Ron Sinha. Hey Ron, thanks for making the trip up to San Francisco today.

00:07:25.240 It is great to be here. I know we chatted a few years ago, but it's finally great to meet you face to

00:07:29.320 face. I know. And I was sort of joking before, what is the commute from Los Altos up to San Francisco

00:07:33.560 today? So today it took me a good, a little bit less than an hour. Yeah.

00:07:37.580 That's incredible. Right. It could take two and a half hours if you time it wrong, right?

00:07:41.580 Exactly right. Yeah. It's funny because on the weekends when you drive off hours,

00:07:45.500 you realize that Barry is actually a very small place, but with traffic, it feels extensive. So

00:07:49.320 yeah. Yeah. I think we won't get into the who has worse traffic, LA, San Francisco,

00:07:54.200 New York. Right, right. No, this is really cool. This is the first time we've met in person,

00:07:57.320 but I do feel like I kind of know you just through so many emails and discussions over the last five

00:08:01.820 years. And you pointed out that Mark Sisson introduced us, which I had totally forgotten. I had lost

00:08:06.180 track of how we actually connected in the first place. And I actually have been remiss in needing

00:08:10.320 to catch up with Mark Sisson as well. I don't think I've seen Mark in probably about three or four

00:08:14.140 years. Yeah. And he's enjoying Southern California right now. I think he's... See, I thought he even

00:08:18.340 moved. Oh, no, no. You're right. I'm sorry. He actually moved to Florida. Yeah. Yeah. So I think

00:08:22.620 what originally connected us was I had a patient from India who had an unusually stubborn case of 1.00

00:08:33.560 insulin resistance. And it came with a slightly different phenotype. And it wasn't just one

00:08:39.420 patient. I think it was probably two patients. And there was something about it that looked a little

00:08:45.040 different from the usual hyperinsulinemia that I had seen. And it was the impressive degree of

00:08:52.400 inflammation that accompanied it. I believe that is what initially led me to your book and then to

00:08:58.100 you. So before we get into that sort of stuff, maybe tell us a little bit about what you do

00:09:05.280 medically, how you got to where you've got, and eventually, I guess, why you're interested in this

00:09:09.540 particular problem. Absolutely. So I'd say about 16 years ago, when I came out of medical training,

00:09:14.360 I came to the Bay Area. And in medical training, when we talked about diabetes and cardiovascular disease,

00:09:19.540 the types of case studies we did, we're typically older African Americans, Caucasians are smoking, 0.70

00:09:24.960 eating red meat, sort of that phenotype. And I get to basically the Bay Area, and I start seeing

00:09:29.260 patients in my clinic at that point was pretty much proximal to a lot of Silicon Valley companies.

00:09:33.740 And I started seeing a ton of people of East Asian and particularly South Asian background that

00:09:38.920 were coming in with really early diabetes and with wicked family histories of diabetes and heart

00:09:44.000 disease in almost every family member. And this is something I never knew about, Peter,

00:09:47.480 I'd kind of read anecdotally about this, but I didn't realize that this was such a common

00:09:50.700 manifestation. And then as I started digging more into the research, I realized when you look at the

00:09:55.200 UK and Canada, there is unprecedented amounts of diabetes and early heart disease in these patients.

00:10:01.320 So what I realized at that time was there was a huge gap because we didn't have any good

00:10:05.080 resources to really help these patients. I mean, you can't give an Indian vegetarian a diagram of

00:10:09.320 the Mediterranean food pyramid. That's not going to be very useful for them. So at that point,

00:10:12.780 I sort of made a commitment that I'm going to create some educational materials and nutrition that's

00:10:16.860 kind of focused on this population. But incidentally, at that time too, while I followed my own advice,

00:10:21.600 I watched myself develop metabolic syndrome. And at this point, I was lecturing to companies about

00:10:25.840 healthy lifestyles. A lot of them were asking me to come out and talk to our Indian patients about

00:10:29.740 why they're developing these conditions. And frankly, at that time, I felt like kind of a fraud

00:10:33.520 because here I'm giving the advice and I see my triglyceride shoot up to above 300. My HL is in the

00:10:37.640 20s. My ratios are way elevated. I'm like, what's going on here? And at that point, I sort of stepped

00:10:43.140 outside of nutritional guidelines and looked at, okay, really the root cause here is insulin

00:10:47.240 resistance. I can't just provide a one-stop sort of meal plan for all these patients. I've got to

00:10:52.160 do some deeper research. What advice were you giving at that point in time that you felt you

00:10:57.080 weren't able to follow or even if you were following it, it wasn't working?

00:10:59.880 I was really following more of a low-fat, low-cholesterol, caloric-based model because

00:11:03.580 that's all I basically knew. I knew a little bit about carbohydrate restriction and those types of

00:11:08.480 approaches, but I didn't really see that as being a meaningful way to approach it.

00:11:11.600 And really at that time, I was following everything to the T, five days a week,

00:11:15.280 eating the right types of diet.

00:11:17.140 Were you a vegetarian also?

00:11:18.280 No, no. So I'm from Bengala, from North India. So we eat red meat, we eat fish. That's a staple

00:11:23.100 part of our diet. So I wasn't, but still eating a lot of sort of the healthy starches at that time

00:11:27.400 and recommending that to patients as well. And you bring up a key point because at least half of my

00:11:31.360 patients were vegetarian Indians. And I noticed some of the most significant lipoprotein abnormalities in

00:11:36.560 those patients, really unprecedented diabetes. So I was like, what's going on here? These guys are

00:11:40.680 eating the Indian vegetarian diet. Why are they so sick and so inflamed, like you pointed out with 1.00

00:11:45.200 your initial case?

00:11:46.660 So I know exactly what you're referring to. You feel like, why am I doing all this stuff

00:11:50.300 correctly and it's not working? So was there kind of a aha moment or was it more of a gradual

00:11:55.160 tinkering that you did?

00:11:56.400 It was gradual tinkering with my case. So basically playing around with the macronutrient

00:12:00.360 composition of my meals and sort of following my numbers. At that time, what I was doing is I was

00:12:05.260 tracking my triglycerides every two to three weeks, basically after making changes. And that's

00:12:09.760 something I do with patients is I check at least their trigs once a month while making changes to

00:12:13.960 see how they respond. And it was amazing because as I was doing this with my first few patients who

00:12:18.700 had high triglycerides in some cases for over a decade, within weeks, we'd make some simple

00:12:23.440 changes and see dramatic numbers, which you're familiar with. But at that time, it was awe-inspiring

00:12:27.560 to realize that, wow, I don't have to put them on fibrates and fish oil. I can just make a few tweaks

00:12:31.460 to their breakfast and lunch and see these dramatic improvements in triglycerides and HDL as well.

00:12:36.040 How significant were these changes? What kind of reductions were you seeing in the triglycerides?

00:12:39.260 Within three to four weeks, we would see drops of 150 points easily because their carbohydrate

00:12:44.480 intake, my average South Asian patients, the vegetarians, 300 to 400 plus grams of carbohydrate

00:12:50.140 per day. Some of my East Asians were eating upwards of 500 to 600 grams, which is pretty typical in

00:12:55.760 areas of urban China and things. So it's really off the scales when you think of the staple amount of

00:12:59.280 carbohydrates you're taking in.

00:13:00.760 Now, it's, I think, a little counterintuitive perhaps to a listener and probably to your patients

00:13:05.960 at the time because a triglyceride sounds like fat. How would you explain to them the relationship

00:13:11.360 between carbohydrate and fat in that capacity?

00:13:14.720 Really good point. And I think that's the most difficult thing because when they have high

00:13:17.980 triglycerides, the general health information they look at is, well, triglycerides are blood fat

00:13:22.100 and blood fat is going to be reduced by eating a low fat diet. But that's where basically in my

00:13:26.940 clinic, I would show them the diagram of insulin. Basically, I'd show them the glucose sort of parking lot

00:13:31.780 glucose molecule and show the hormonal mechanisms of how glucose is basically converted into triglycerides

00:13:36.600 within fat tissue. So I wouldn't go into details, but I'd basically show them the conversion.

00:13:41.000 And now what I've developed is a lot of animations that sort of show this process because a lot of

00:13:44.900 people, it's very tough for them to logistically understand how that conversion happens. And unless

00:13:49.320 they bind to that concept, it's very tough for them to just reduce to carbohydrates and be

00:13:53.040 liberal about their fat intake.

00:13:54.560 So how many African-American patients were you taking care of at that time?

00:13:57.120 African-American patients at that time. So interestingly, when I was in Southern California,

00:14:01.220 quite a few, but here in the Bay Area, a handful at most. Yeah.

00:14:04.800 You, I'm sure, saw the stark contrast, which is African-American patients can have type 2 diabetes,

00:14:12.160 frank diabetes, and yet have normal triglycerides.

00:14:14.660 Yes.

00:14:14.820 That's quite common.

00:14:15.780 Right.

00:14:16.120 Did that throw a bit of a wrench in your understanding of the system?

00:14:19.160 A little bit, it did. That's when I started looking at these patients more from a body,

00:14:22.980 sort of a habitus type standpoint. And I started to realize that with my South Asian patients,

00:14:27.340 one thing that's very common in them is they have very slender limbs. Legs and arms are very skinny.

00:14:32.820 And compared to my African-American patients or others that develop an insulin resistance,

00:14:36.900 they've got much more leg mask and much more lean body mass. And I think that lean body mass

00:14:41.200 does provide them with the ability to process and burn those triglycerides for energy more effectively.

00:14:45.880 Whereas with my South Asians, they have such a high degree of the visceral fat. And when you look at 1.00

00:14:50.140 cross-sections of African-Americans, Caucasians, and South Asians, when you look at the ratio of

00:14:55.660 subcutaneous to visceral fat, it's remarkable what the ratios are like. And that's why South Asians 1.00

00:15:00.720 and East Asians develop such acute inflammation, insulin resistance, and low body weights, because 0.74

00:15:05.380 the proportion of that visceral fat is significantly higher.

00:15:07.680 So take a moment to explain to people the difference between visceral fat and subcutaneous fat.

00:15:12.980 Sure. So when you think about those two types of fat, I actually like to think of it in three zones.

00:15:16.900 So basically, you've got what we call the S-scat, the superficial subcutaneous adipose tissue.

00:15:22.500 You've got the D-scat, which is the deeper layer of subcutaneous adipose tissue, just right

00:15:26.560 underneath the skin. And then you've got the visceral fat. And the way I explain it to people

00:15:29.780 is think of sort of a city versus a suburb. So the subcutaneous fat is really out in the suburbs,

00:15:35.020 the superficial. The deep is a little bit further in. So this could be basically South San Francisco,

00:15:39.920 and the visceral is basically around the organs. And the way I explain it like that is because

00:15:43.500 with the suburban fat, you're basically, you've got fat cells and you've got fat structures that

00:15:48.600 are more lobulated and organized, kind of like a track home or strip mall type out in the suburbs.

00:15:53.140 And they don't have as much access to the blood supply. When you get deeper into the layers of

00:15:57.260 the deep subcutaneous fat and the visceral fat, what happens is it's more loosely organized. It's

00:16:02.080 not as lobulated, but they've got direct access to the liver and the bloodstream. And that's really

00:16:06.100 important. When we think about subcutaneous fat, often people think, oh my God, I hate my subcutaneous fat,

00:16:10.960 but really there's a subcutaneous fat. It's a safety belt for us. When you have larger subcutaneous fat stores,

00:16:16.760 it insulates you and protects you from having fat spill into those visceral fat stores.

00:16:21.840 So as much as my female patients complain about subcutaneous fat, I'm like, this is actually a 1.00

00:16:26.060 safety belt for me because we don't want this fat to get into the inner city. As we get to the visceral

00:16:30.040 fat, the other thing you want to be aware of is the concept of transmembrane flux. And what I mean by that

00:16:34.680 is the fatty acids that flow inside and outside of fat cells. In subcutaneous fat, it's relatively inert.

00:16:40.960 So you might get some fatty acid flux. You don't get many inflammatory chemicals that come out of

00:16:45.300 that fat. But as you go into the inner city fat, the visceral fat, there's all types of cross-traffic

00:16:49.420 happening. You've got inflammatory mediators, your usual oedipokines, inflammatory chemicals,

00:16:54.020 and you've got a lot of free fatty acids going back and forth. So when you see patients of that

00:16:58.540 body habitus, you realize that even though they don't have much subcutaneous fat, they've got quite a

00:17:02.960 bit of visceral. And the interesting thing is I see a lot of couples. So when I see Indian couples,

00:17:06.580 it's very obvious, it's very interesting how the women are obviously sometimes 30 to 40 pounds 0.98

00:17:11.920 overweight, but their metabolic numbers look flawless. Triglycerized, HL, everything looks

00:17:16.360 great. The husbands are real thin and skinny, and you would think that their numbers would look good, 1.00

00:17:21.560 but their numbers are much more off the charts basically. And it's because they don't have as

00:17:25.000 much of that subcutaneous fat, insulation, everything is going directly to visceral fat.

00:17:28.980 And so this is one of the great holes in the notion of using something as simple as a body mass index

00:17:35.780 calculator, which probably directionally makes sense if you're looking at a very homogeneous population

00:17:44.200 of Caucasians, but starts to really fall apart in both East and South Asians. In fact, it's probably 0.99

00:17:52.000 East and South Asians in which this term skinny fat was probably first derived. And so in the example

00:17:57.400 you just gave, the hypothetical wife in that situation gets the traditional label of, oh, 0.96

00:18:03.900 she's fat. But as you point out, she's not really metabolically in trouble. She's not at an increased 0.99

00:18:09.640 risk of diabetes, cancer, Alzheimer's disease, NAFLD, or any of these other things. But aesthetically,

00:18:16.100 of course, she would love to be more thin. Her husband, by contrast, looks fine, aside from the fact

00:18:20.880 that he doesn't have any muscle mass. But it turns out he's metabolically, at least according to the data,

00:18:26.000 probably in worse shape than the overweight individual who has comparable metabolic markers.

00:18:31.720 There was actually a study by Mitch Lazar, and maybe this is no longer the case. Maybe this has

00:18:35.580 been updated. But the last time I really looked at these data, there was a paper in science that

00:18:39.360 looked at these four phenotypes. So external versus internal. So you had lean versus not lean,

00:18:47.140 and metabolically well versus not well. So that gives you a two by two. So there are four categories.

00:18:52.240 So let's just posit that the best case scenario is to be lean and metabolically well. And when you

00:18:59.100 looked at the outcomes of all of these, the worst outcomes were in the lean individuals who were 0.97

00:19:05.120 metabolically ill. They actually did worse in the overweight individuals who were metabolically ill.

00:19:11.460 And I talked with Mitch about this quite a while ago. I mean, this paper is actually quite old now

00:19:15.580 that I think about it. It's probably 2014. But the question I asked was, is it possible that it's

00:19:21.160 their inability to actually shunt and store some of that excess energy into a safer depot of fat,

00:19:29.140 as you point out, that is actually their undoing? And at the time, I think that was sort of Mitch's

00:19:33.540 view. That sounds like you share that view. Oh, I do for sure. I mean, if we think of this tissue

00:19:38.060 overflow hypothesis, where if you think of it as a watershed type thing, it's subcutaneous to deep

00:19:43.140 subcutaneous to visceral. I've actually putting females aside, I've seen a lot of overweight South 1.00

00:19:48.300 Asians, where I would expect in the early days that they'd have numbers that are proportionally

00:19:51.880 worse, but they're actually not that bad. And so in my theory around that, and based on that study

00:19:56.740 too, is they have larger subcutaneous fat stores to insulate them. On top of that, the other thing

00:20:01.740 that's very unique about their body morphology is, again, I look at their legs. Their legs are more

00:20:05.600 muscular because they're carrying around a lot more weight. They've got larger thighs, larger calves.

00:20:10.120 So I think the combination of the increased insulation from the subcutaneous fat and the elevated

00:20:14.640 muscle stores from the legs is probably helping metabolize those lipids better.

00:20:18.300 But when I see those real skinny, we're talking BMIs of 21. Now I look at them, I can literally

00:20:23.520 predict their triglycerides. I'm like, this is probably through the roof because everything

00:20:26.700 is in that visceral store compartment. So. And then how closely do you see that association

00:20:31.580 of where their triglycerides are to some of their glycemic numbers? In other words, can you look at

00:20:37.760 that and get a sense of where they are on the spectrum towards having type two diabetes?

00:20:42.240 That's really interesting. So I see a lot of discordance in my population. So I see a lot of them

00:20:46.920 that will come in with the triglycerides. And maybe because I'm catching them at the early stage,

00:20:50.680 I don't necessarily see the glycemic impact of that. And they might be 10 to 15 years away from

00:20:55.040 that. Yes, I absolutely get the ones that come in with full blown pre-diabetes or type two diabetes

00:21:00.120 and triglycerides. But I'd say the majority of the population that I see, they've already got fatty

00:21:04.360 liver. They've got high triglycerides, but their glucose looks fine. And that is a really important

00:21:09.420 population to really educate because I'm telling them now that you don't have pre-diabetes,

00:21:13.400 you have pre-pre-diabetes. And this is where we can make the most impact at this stage because you've

00:21:19.260 probably got some preserved beta cell function. You've got some compensatory hyperinsulinemia

00:21:23.920 that's overcoming that. But if we can really make a move here and just knowing that they have pre-pre-diabetes

00:21:28.500 because they all have like at least one family member that has diabetes. So that's the one

00:21:32.260 condition they don't want. But they've never had a doctor that's taken kind of a non-glycemic

00:21:37.040 diagnosis of diabetes where your glucose is normal. You're fine. No, it's your triglycerides.

00:21:41.080 And even before that, it's just your darn waist circumference. And can we actually attack it at 0.99

00:21:44.940 that point and go from there? And what about the hyperinsulinemia? Do you see in those patients

00:21:50.120 normal glucose, but elevated postprandial insulin? So I got to be honest with you in saying that,

00:21:55.180 so in the early days, I was checking those numbers quite a bit and I would see that. I do

00:21:58.820 insulin and glucose tolerance tests and I'd see that. I'm probably not checking that as often now,

00:22:03.160 but when I do check it, usually their fasting insulin at least is off the charts. So definitely

00:22:07.220 they've got signs of early hyperinsulinemia. Yeah. Like I wish I could take a sabbatical for a year

00:22:12.300 from life because I know we've gone over this a little, we've even talked about this a little bit

00:22:16.540 through email. I really feel like I'm trying to coalesce around, I hate the term because it sounds

00:22:22.760 so stupid, but a unifying theory of metabolic disease. Of course, the problem is in physics, 0.87

00:22:28.740 unifying theories are very neat. And in biology, by definition, they're anything but unifying. So it's

00:22:34.680 actually kind of ironic that we would use the term because by definition, it's bootstrapped together

00:22:39.140 with, well, there's this subset and this subset and this subset. And sometimes you can get a

00:22:43.120 combination of these two and sometimes it's these two, but there are these different phenotypes.

00:22:47.120 I mean, there's no denying the normal triglyceride, normal LFT person who for some reason is not

00:22:54.100 getting fat accumulation in the liver and therefore doesn't seem to have an excess of fat efflux from

00:22:59.760 the liver, but they're already on the way to diabetes, if not already having diabetes. By the way,

00:23:03.760 part of the problem is I don't really like the definition of diabetes. I don't really like the

00:23:07.120 definition of type two diabetes today. I don't think that the hemoglobin A1c is particularly

00:23:11.540 helpful. So this is my soapbox. So there's two issues I have with it. One, now that about a third

00:23:16.820 of my patients are using CGM and it's being calibrated. So we're using the Dexcom because

00:23:21.960 it's much more accurate than the Libra and it can be force calibrated. So even though the FDA

00:23:26.340 says it doesn't need to be calibrated, you can still force a calibration twice a day. So you get

00:23:30.680 really accurate readings. When you put these things on patients for 90 days, you actually find out

00:23:36.680 what their average blood glucose is. You then compare that to the imputed average blood glucose

00:23:42.080 from hemoglobin A1c. And if 25% of our patients are concordant, that's pretty good. 75% are

00:23:49.660 discordant. And it could be in either direction. That's the point. In other words, for a subset of

00:23:53.320 patients, the hemoglobin A1c that you measure in their blood, which imputes an average blood glucose,

00:23:59.100 is underestimating their average. And in a subset, it's the opposite. This has led me to first and

00:24:04.620 foremost, be quite suspect of hemoglobin A1c. I first noticed this in myself, by the way, I'm

00:24:08.800 incredibly discordant. I suspect it's because of my beta thalassemia minor, which grossly overstates

00:24:14.800 my hemoglobin A1c. But again, seeing as many cases in the opposite direction, you realize this test is

00:24:21.200 helpful when comparing the difference between someone who's at 5.1 versus 8.1. It offers no fidelity

00:24:27.320 between 5.1 and 6, in my opinion. It's such an important point you brought up because I have

00:24:31.500 patients that come in and we've made incredible transformations on every metric, but they literally

00:24:36.560 look at their blood reports. These are very motivated South Asians who are very focused on

00:24:40.640 numbers and grades. And they're like, I'm still not getting that A1c down. I'm not getting that

00:24:45.020 fasting glucose down to 99. And they obsess over that, Peter. They're like, do I need to go more

00:24:49.240 low carb? Do I need to work out harder? And it's just a matter of, listen, metabolically,

00:24:52.820 by my definition, you're healthy. Let's not obsess over this number and focus on bigger things. So

00:24:57.180 interestingly, I haven't really incorporated CGM into my practice. It's something I need to do.

00:25:01.120 I've definitely prescribed it for some patients. And I know you were nice enough to actually connect

00:25:05.200 me and get me motivated to get one. And I haven't done that yet. So I think that'll be, I'm sticking

00:25:08.960 to numb fingers right now with lots of finger sticks about today. So I've got to get with the times.

00:25:12.720 I think you should. And I think you'll be really impressed with, I think, and again, maybe every

00:25:16.980 patient population is a little bit different. Maybe my patients are a bit more motivated, but who knows?

00:25:21.540 That's not necessarily the case. I think patients find it valuable on two fronts. The first is

00:25:25.980 the insights are really impressive. You just can't believe how much certain things can affect

00:25:32.440 your glucose levels, even the most benign thing, like a handful of raisins or a particularly large

00:25:38.160 Fuji apple or something like that. And then conversely, how eating the exact same amount of

00:25:43.700 glucose with something else can delay that transit and slow it down. And then of course, how what you eat

00:25:49.440 in proximity to exercise versus time of day versus how well you slept the night before.

00:25:53.460 So there's like the entire insight sphere. And what I usually tell patients is at the outset,

00:25:57.780 the first three to six months of wearing CGM is 80% new insights and 20% behavioral modification,

00:26:05.280 which is the gamification that comes from once you know what to do, actually doing it because you like

00:26:10.760 the numbers. But then you sort of get past that point and you learn most of it and you're not getting

00:26:15.080 surprised all that much. And then the benefit actually becomes the behavioral one. I've been

00:26:19.060 wearing one of these things now for probably three and a half or four years. So for me,

00:26:22.580 I'm not gaining new insights daily. Maybe every week I get a new little insight. So maybe it's 10%

00:26:28.240 insight related, but the behavioral piece, it's basically a walking Hawthorne effect.

00:26:33.100 I was going to ask you about, are you wearing it now more for behavioral? Because I think you've

00:26:36.440 gotten all the insights, but this really prevents you from digging into that bag of Cheetos or

00:26:40.380 whatever year. That's exactly right. We have pretty clear metrics with where we want to be

00:26:44.400 both in terms of average glucose, in terms of standard deviation of glucose, which we use as

00:26:48.740 kind of a proxy for insulin. And then in terms of the number of times you have excursions over 140,

00:26:54.460 that becomes kind of another metric you want to avoid. And so it absolutely curbs my behavior when

00:27:01.180 I am wearing it, which is most of the time, probably 300 to 330 days out of a year, I'm wearing it

00:27:06.660 definitely dials my behavior in. Absolutely. So now going back to this point, you've got these

00:27:11.740 different phenotypes of diabetes. And I think that the whole diagnosis of just relying on an A1c being

00:27:17.440 above 6.5 is not very helpful because one, I don't think I trust that number enough to hang my hat on

00:27:23.200 it. And secondly, why is it that somebody who's got maybe an average blood glucose of 120, which

00:27:30.060 wouldn't quite be at that threshold at a fasting level, but has these postprandial glucoses of 200,

00:27:36.660 why would we not consider that person to be at risk? And yet we don't treat that person

00:27:40.780 in the same way. So my view is basically to tell patients, I'm not remotely interested in any of

00:27:45.880 these labels. They don't mean anything. I don't actually look at hemoglobin A1c except out of the

00:27:50.680 intellectual exercise of contrasting it with this CGM. But instead it's that level of insulin,

00:27:57.240 fasting, postprandial, plus glucose, postprandial, with all of the kinetics that we can track,

00:28:03.040 and then layer it into this other stuff, which is what's the inflammatory cascade look like?

00:28:07.960 Because this is sort of what I was going to get at is you have these phenotypes, I think, where

00:28:12.140 you've got that person who's overweight, who metabolically actually looks pretty reasonable,

00:28:18.300 and they're doing a lot of the stuff correctly. But there's probably something going on at the

00:28:22.400 cortisol level. And this is another thing we see with the CGM is these very, very high nighttime

00:28:26.620 glucose levels in people who are otherwise eating pretty well. So I guess it's hard to track that

00:28:31.460 without CGM because the best, the only glimpse you get is the morning glucose level, which as you

00:28:36.400 know, can be easily 110 in someone who's metabolically quite healthy by other parameters. Do you see

00:28:42.120 cortisol as being a bigger driver of that? Inflammation? What else do you see?

00:28:45.440 So I'm going to throw some theories at you. I don't want to run this by you as well too,

00:28:48.060 because even without CGM, I noticed this pattern in myself very early on. And I started noticing in

00:28:53.080 my patients and I started really focusing on them, calming down their nighttime rituals,

00:28:58.160 getting off the devices, doing some meditative practices in the evenings, and checking their

00:29:02.520 fasting blood sugars the next day. And I clearly saw improved fasting blood sugars. And it makes

00:29:07.400 so much sense, Peter, when you think about the fact that the liver is really in charge of what that

00:29:10.900 morning blood sugar is going to be. And the liver, the cortisol is such a huge input to that. And when

00:29:15.420 you think about the process intellectually, if these are individuals who are already insulin

00:29:19.300 resistant, presumably their adipose tissues have a lot of free fatty acid release and lipolysis. So

00:29:25.080 you've already got free fatty acids going to the liver to fuel gluconeogenesis. Now, if you add

00:29:29.900 cortisol on top of that, cortisol has the exact same effect on adipose tissue, right? So you've got

00:29:34.460 two sort of lipolytic inputs, a higher pool of free fatty acids going to the liver. So that liver is

00:29:39.680 primed to produce sugar. So to me, it physiologically makes perfect sense. It's very tough to make that

00:29:44.640 case to patients because they want it to be their diet and their exercise. They're like, just tell me how

00:29:48.860 many more carbs I can cut out of my dinner, or do I need to do this workout? And I'm like, this is an

00:29:53.280 emotional metabolic issue. So I've seen that for sure. And when we actually do influence those

00:29:57.680 types of things and do those nighttime behaviors, the numbers get better. In addition to that,

00:30:01.980 what I've also noticed is sometimes when patients are too low carb with their diets, sometimes that

00:30:07.340 will trigger a reflex hyperglycemia. And the way they've tried to game that is sometimes they'll eat

00:30:11.560 some starches at nighttime. And I was going to ask you, even though that's making their numbers better

00:30:15.400 in the morning, it's sort of interrupting their fast. So I'm thinking, are we just gaming the numbers to

00:30:19.240 make your report card better? Are we physiologically really doing some good in the body? And that's where

00:30:22.940 I get a little bit hesitant about just focusing on single digit numbers like fasting blood glucose.

00:30:27.840 Yeah. It's funny you say that. I definitely have a subset of patients who are actually coming to my

00:30:31.460 mind just as we have this discussion who are really fixated on that morning glucose level.

00:30:36.160 I think it's tough. I'm very curious as to what's going on. I have reached out to a number of people

00:30:41.480 who study this and I haven't really got a satisfactory answer yet, but there's something I can't figure

00:30:46.160 out in the liver and you alluded to it. So taking a step back just for the listener,

00:30:50.260 a blood glucose of a hundred milligrams per deciliter means you have about five grams of

00:30:56.980 glucose in your bloodstream. That means if you have a blood volume of five liters, which an average

00:31:02.180 size person has at a hundred milligrams per deciliter is five grams of glucose. That's one

00:31:08.000 teaspoon of glucose. Now that's not a lot. That's a few minutes worth of metabolic fuel, especially given

00:31:14.860 that the brain is going to consume 25% of your total energy, all in the form of glucose. In other

00:31:21.260 words, the brain is taking two to three grams out of that five within minutes. So if you can do a

00:31:27.100 thought experiment and you clamp the portal vein, you prevent the liver from putting any glucose into

00:31:33.380 circulation, an organism is going to be dead in minutes. It is simply going to die of hypoglycemia.

00:31:39.600 So that's point one. Point two is how well this machine is regulated. The difference between you

00:31:46.200 sitting here now with a glucose of 100 milligrams per deciliter, which we would consider perfectly

00:31:51.040 normal. And you sitting here with a blood glucose level of 200 milligrams per deciliter, first thing

00:31:57.060 in the morning, which is Frank type two diabetes, do not pass go, do not collect $200 diabetes.

00:32:02.760 That's a difference of one additional teaspoon of glucose in your bloodstream or another five

00:32:09.560 minutes of metabolic substrate. And again, first thing in the morning, that's being regulated by

00:32:14.340 the liver. Why is it then that in the person with type two diabetes, that liver can't just back off a

00:32:21.440 little bit on its hepatic glucose output to bring that person from 200 down to 100. And if you ask that

00:32:27.840 question at an even more subtle level outside of diabetes, why is it that your patient or my patient

00:32:32.760 or me or you wake up sometimes with a blood glucose of 120 versus 90, which is, I mean, we're talking now

00:32:39.860 about milligrams of glucose in terms of difference. So how much of this is being regulated at the liver?

00:32:45.480 How much of this is being regulated at the pancreas? How much of this is being regulated at the muscles?

00:32:50.000 And I still can't really wrap my head around why this is happening. And I certainly suspect that

00:32:54.900 cortisol is playing an important role. I think cortisol is a vastly underappreciated regulator

00:33:01.460 of fat flux through the fat cell. Insulin gets a lot of attention because it's perhaps the most

00:33:07.480 potent, both on the side of lipolysis and re-esterification. And we also can't measure

00:33:12.200 things like hormone sensitive lipase easily. So we can, we have to sort of not think about that much,

00:33:16.640 but, and cortisol, because it's such a pain to measure and we can't measure free cortisol in the

00:33:20.680 blood. We, we just sort of loosely think about it, but I can't help, but wonder if that's playing

00:33:25.380 a role. Now, Jason Fung, who I spoke with about this, he has a very interesting model of insulin

00:33:31.120 resistance, which is that it's not actually resistance. It's just basically the storage

00:33:35.180 tank is full. So the elevated level of glucose is because the glycogen stores are basically tapped

00:33:41.700 out. And the elevated level of insulin is not because the insulin receptors and, or the

00:33:49.440 intracellular mechanistic transducers are themselves quote unquote resistant. It's just

00:33:55.040 trying to push harder and harder to get the glucose in. That model, by the way, makes a lot of sense

00:34:00.540 through the lens of the fact that even the most quote unquote insulin resistant person has no difficulty

00:34:05.300 putting more fat into a fat cell, which is also signaled by insulin. So what I like about Jason's

00:34:10.780 model is it gets rid of the discordance between how can you have an insulin resistant muscle and an

00:34:18.560 insulin sensitive fat cell mechanistically to which I've never had a compelling response. Have you

00:34:23.580 thought through that particular issue? It's interesting because that's exactly the model

00:34:27.220 I use when I do education for patients. It's very easy to just tell them about parking space,

00:34:31.120 muscles got a fixed amount. And I think it makes a lot of sense in that sense. I think one of the

00:34:35.600 issues is when you look at these patients early on. So if you look at the studies of normal

00:34:39.980 glucose tolerance offspring of diabetic parents, so these are normal glucose tolerance individuals

00:34:44.940 that are relatively lean, they don't have inflammatory markers, so they haven't really

00:34:48.800 shown many manifestations. But the earliest changes that you basically see is that they

00:34:53.540 already have elevated levels of free fatty acids circulating. So already you can see that in

00:34:57.640 these populations, whether they're South Asians or Hispanics, their visceral fat is already 1.00

00:35:02.040 outputting a little bit of extra free fatty acid. And we know that free fatty acid is a

00:35:05.980 chemical signal for interrupting insulin resistance sort of signaling. So at that point, I'm thinking

00:35:10.600 that yes, it probably is a capacity issue. But I think that early signal is limiting the ability of

00:35:16.160 the muscle to really store that glycogen because it's already inhibiting glycogen synthesis basically at

00:35:20.740 that level already. So I think in people that don't have insulin resistance, absolutely that parking

00:35:25.540 capacity makes sense. I think with people that have insulin resistance, it makes sense too. But we also

00:35:29.980 have to acknowledge that people that have had insulin resistance from in utero is what we're seeing in

00:35:34.640 these populations. They already have a very limited capacity and it's not necessarily physical. They

00:35:39.680 just have less because of the free fatty acid that's inhibiting the insulin signaling, if that

00:35:43.820 makes sense. Yeah. I mean, I guess the question is, which comes first is sort of the thing I'm

00:35:48.620 struggling with here. And I think of it even more upstream, which is frankly, just looking at the

00:35:53.380 liver. I don't think it's like a particularly profound statement to say that the liver is the leading

00:35:59.960 edge of the airfoil. The liver is seeing everything at a speed and at a level that transcends everything.

00:36:06.200 It is the epicenter of our metabolism. At least that's my view. And when I see things like fat

00:36:14.380 flux in the liver leading in the direction of accumulation, that has to be a bad sign. But of

00:36:20.620 course, then I can poke holes in my own theory by saying, look at all the people who develop all of

00:36:25.480 the other negative symptoms and signs, but by ultrasound at least, or even by MRI, they don't

00:36:30.320 have fat in their liver and they usually have normal triglycerides. And yet they have these other

00:36:34.740 issues that you're alluding to. This is why I appreciate you saying that you truly don't

00:36:38.460 understand insulin resistance, because I think when people say they do understand it, literally I've

00:36:42.660 written diagrams of every possible thing and your heads in circles, you step back thinking, I really

00:36:47.080 don't get this at all, but it's true. And there may not be one cycle because I think I was trying to

00:36:50.780 find one process flow that would explain all these cases. There could be multiple. I mean,

00:36:54.960 we can see arrows and diagrams going in multiple directions. And I realized at a certain point that

00:36:59.700 I need to understand this process, but I'm probably not going to figure out exactly for

00:37:03.000 each individual patient. I've sort of got to go for the low hanging fruit and see what's going to

00:37:06.800 lead to the most meaningful lifestyle changes for them. That's a good point to make, because I think

00:37:11.240 if you're listening to this, you're thinking, well, if Peter and Ron are sitting here basically

00:37:15.520 acknowledging they don't know what insulin resistance is, does it matter? And more importantly,

00:37:19.940 like, what does it mean to me? And so, yeah, I emphatically say, I don't know what insulin

00:37:25.420 resistance means anymore. I have theories. The theories are plausible. If you permit me to wave

00:37:32.120 my hands a little bit and acknowledge that there are going to be different categories of insulin

00:37:37.020 resistance that will apply to different patients, but I can't give you mechanistic explanations as to

00:37:42.300 why, but it's why I do tend to focus on hyperinsulinemia because I really, when I talk to patients about the

00:37:48.060 endocrine system, I usually walk them through four of them. I say, broadly speaking, let's look at this

00:37:53.080 through the level of your thyroid system. And so again, we talk about what's happening between the

00:37:57.720 hypothalamus, the pituitary, the thyroid, and the periphery. Let's call that one system. And then I say,

00:38:01.780 let's now have the same discussion about the adrenal system. Again, same sort of connection. And then

00:38:06.800 let's have a similar discussion about your sex hormones. And then the fourth system I talk about is

00:38:11.220 this system of fuel partitioning, which of course has to do with how does the energy you consume

00:38:16.640 get stored and how do you access energy? And usually they get the first three, but then it's

00:38:21.440 that fourth one that's sort of like, what do you mean by fuel partitioning? And I say, well, first of

00:38:24.640 all, blood can only give us part of the answers here. I mean, you have to do some other metabolic

00:38:28.720 testing to get the others. But I said, if we don't have a hard time talking about hypothyroidism and

00:38:33.920 hyperthyroidism, so we can simplify this fuel partitioning problem by at least looking at one element of it,

00:38:40.600 which is hyperinsulinemia. And in some ways, that's why I still really favor the oral glucose tolerance

00:38:46.460 test. Again, whether we should be using glucola or not, the only advantage of glucola is at least we

00:38:51.820 have a standardized way for me and you and Joseph Kraft and everybody to compare our numbers. But you

00:38:59.100 could make a case that it's sort of not particularly reflective of the physiologic glucose disposal. And

00:39:04.920 maybe instead we should have the pizza test or give people carbs in a way that they normally consume 1.00

00:39:09.960 them. I actually have done this a few times. I had a patient who, I mean, she made the point, which is

00:39:13.780 this test doesn't replicate anything I do. And I said, yeah, you're right. I know. And I explained

00:39:17.720 to her all this stuff. And I said, well, what does a real cheat look like for you? What does blowing it

00:39:21.720 up mean? And she's like, it's like two margaritas and five cookies. And I was like, okay, well, that's

00:39:27.120 your next glucose tolerance test. Right. Now, of course, the problem is we still end up doing that

00:39:31.340 test in the morning, but even that's not the right thing to do. If you really want to do this test

00:39:34.960 correctly, you would do the two margaritas and the five cookies in the afternoon or whenever you're

00:39:39.520 going to do it. And in many ways, that's what the CGM has kind of allowed us to do. The CGM without

00:39:44.040 the insulin is at least allowing us to see the glycemic response to the real world challenge

00:39:50.280 of this. And while I still rely on the OGTT constantly, my hope is that eventually we're

00:39:56.340 going to be able to do more point of care insulin testing. And there is actually work in that space

00:40:01.140 being done. And maybe we're done with this sort of glucola type test. Yeah. To bring it back to

00:40:05.560 your point, I thought I kind of understood insulin resistance seven or eight years ago,

00:40:10.520 and I'm pretty sure I don't anymore. But you know, I'm finding ways to reframe insulin resistance

00:40:14.460 because I think even in the early days, since I developed it, I had sort of this toxic relationship

00:40:18.620 with glucose, triglycerides. And, and as I look at more of the evolutionary literature, you know,

00:40:23.120 there's a lot of theories including thrifty gene, the Barker hypothesis, and just to summarize for

00:40:27.900 the listeners. So when we talk about the thrifty gene, this was James Neal back in the 1960s,

00:40:32.520 who came up with the concept that insulin resistance is basically a result of us, our

00:40:37.580 primitive ancestors living in feast famine type cycles. And during feast periods, what they would

00:40:42.380 do is they'd store extra calories, viscerally, abdominally, and store calories as triglycerides 1.00

00:40:47.260 so they can survive during times of famine. And it was a very popular theory back then, but then

00:40:51.300 there was never a putative gene found for that. And then really, when you talk to experts, they say,

00:40:55.340 we never really had, if you look at sort of evolution, there were not large periods of famine that

00:40:59.900 really could explain that sort of a genetic manifestation. So that basically evolved into

00:41:03.840 this concept of a thrifty phenotype or the Barker hypothesis. And this is really based not really

00:41:09.340 on genes, but the fact that the intrauterine environment itself is what can trigger insulin

00:41:14.880 resistance and heart disease. And what David Barker found, and this was in the 1912, I think,

00:41:19.860 and what he found was he looked at 100,000 people in the UK, and he looked at records that showed that

00:41:24.740 birth weight was inversely proportional to mortality from heart disease. And literally,

00:41:29.300 when they've reproduced this, they found this in every continent. So low birth weight equals higher

00:41:33.540 risk of cardiovascular mortality and early cardiovascular mortality. And they found this

00:41:37.360 in every continent except Africa. And when you look at that, and then you look at the work of Dr.

00:41:42.180 C.S. Yajnik, and he's done incredible studies in low birth weight babies in India, particularly Pune.

00:41:47.280 And he's found that already at a very early stage, when the babies are born, they're already showing

00:41:52.020 fetal hyperinsulinemia. Their body habitus is already small, tiny fetal pot belly or visceral fat and very

00:41:57.940 thin extremities. When you check their skin fold, you basically see that they already have limited

00:42:01.960 subcutaneous fat when you compare them to Caucasians. And so this whole concept has come up about insulin

00:42:07.100 resistance. Is this really a response to stress in utero, basically? And then another theory that he

00:42:13.200 came up with is a soldier to diplomat hypothesis, which I find very interesting, where initially we might

00:42:18.400 look at this problem as being something that allowed us to preserve more glucose for brain function.

00:42:23.780 So insulin resistance really is an evolutionary adaptation that allows more glucose to be

00:42:27.840 available so our brain can use it to really thrive and survive. We always talk about our primitive

00:42:31.960 ancestors in terms of musculature, but you need to have adequate amounts of glucose reserve so you can

00:42:37.040 go up the social hierarchy and you can lead a tribe. And I spoke to Jerry Riven about this early on.

00:42:42.000 So Jerry Riven, he coined the term metabolic syndrome, the late Jerry Riven. And we talked about the fact

00:42:47.040 that what do you think is the role of insulin resistance? And he agreed that there's probably

00:42:50.600 some mechanism where it does help certain populations preserve glucose for brain function.

00:42:55.780 And when you look at the South Asian population, interestingly, they are the most highly insulin 1.00

00:43:00.280 resistant country on the planet right now. And interestingly, if you look at sort of the

00:43:04.700 metabolic shifts that are happening in terms of glucose and lipids, a lot of these are basically

00:43:08.560 trophic to the brain. So Dr. Yajnik, he saw that basically this hyperinsulinemia, we know that insulin,

00:43:14.560 and you've mentioned this before with IGF, above the neck, it does have trophic impact. So if you're

00:43:19.460 in utero and you've got elevated glucose and elevated insulin, presumably it can have some

00:43:24.220 impact on increasing IQ and intelligence in that period. And obviously, if it's an overcorrection

00:43:28.380 of the system, if you're flooding that child with lots of sugar and carbs, that could go the other 1.00

00:43:32.280 way. But it looks like there might be some adaptive qualities to insulin resistance that sort of help

00:43:36.540 with brain function and cognitive abilities.

00:43:38.300 And again, I'm more guilty of this than the next person, but we keep doing this, right, which is we use the

00:43:43.140 term insulin resistance right after we acknowledge. We don't even know what it means. And so what you're

00:43:47.680 really describing is the hyperinsulinemia with compensatory high glucose. So actually, Jake

00:43:53.300 Kushner just sent me a paper last week that I don't want to say too much about it because I'm still going

00:44:00.560 back and forth with him on sort of the interpretation. But the paper is trying to look at mechanisms for

00:44:06.680 why refeeding after carbohydrate restriction produces elevated glucose. And unfortunately,

00:44:14.720 I don't want to sort of criticize the paper too much before having gotten fully through it. But

00:44:18.740 my first reading of the paper is, God, they seem underfunded. They didn't measure, they didn't

00:44:25.220 collect urinary C-peptide. I got a lot of things they didn't do because at the first order, there's a

00:44:31.280 question, which is let's just pretend. And the paper looks at carbohydrate restriction,

00:44:35.180 but I'm actually more interested in fasting. So let's just take either one of those cases. So

00:44:38.940 either I carbohydrate restrict you or I fast you, and then I refeed you. Why do you have this

00:44:44.640 disproportionate glucose response initially? Is it because of the muscle being resistant to the

00:44:51.740 effect of insulin? Or is it because the pancreatic response is especially slow? Or is it something

00:44:57.020 else? Is it a combination of these things? These are very testable hypotheses. And certainly the first

00:45:01.660 thing I'd want to know. And again, I don't think they did it in this paper, which is sort of what

00:45:05.620 I sent back to Jake the other day, which is you'd at least want to rule out that it's not a blunted

00:45:11.260 or delayed insulin response. Insulin pancreases, you could anthropomorphize this any way you want.

00:45:17.260 So do you have a point of view on that issue of why is it that someone who's, let's just say for

00:45:23.580 the purpose of this discussion, carbohydrate restricted, or in the case of our ancestors who were

00:45:28.400 without glucose or without meals for days at a time upon reintroducing it look like they're

00:45:34.700 hyperglycemic? I mean, they are hyperglycemic. Right. I mean, this is all theoretical. And for me,

00:45:39.420 if you look at ancestral and evolutionary sort of survival, I think if you've gone through a famine

00:45:44.240 period, when you're refed, the brain is still the number one organ that you want to fuel. And we know

00:45:49.020 after feedings and carbohydrate feedings that the skeletal muscle is responsible for 80 to 90% of

00:45:53.880 glucose disposal. So to me, theoretically seems to make sense that probably the resistance is

00:45:58.380 happening at the skeletal muscle level. And that's really preserving probably an overcorrected amount

00:46:02.880 of glucose for brain function. So you would predict based on this study that if they'd measure it,

00:46:07.700 insulin would be normal. The insulin secretion would be normal. I think relatively, yes. And again,

00:46:11.980 obviously you can have mixed pictures. If this is advanced enough, you might see that. But in a pure

00:46:16.100 sense, I would say you probably would see more of that with relatively preserved insulin. We might

00:46:20.340 probably have to do a clamp study to really make that come true. So yeah, I'm working with a guy

00:46:25.940 who's got a device that can actually measure insulin and C-peptide at point of care. So one of the things

00:46:32.920 I'd like to do on my next fast is when I break a really long fast, use a standardized meal of glucose

00:46:40.340 to refeed and then see what the glucose and insulin response is to that. And after say seven days of zero

00:46:47.260 input and contrast that with the same meal given in the context of being normal fed.

00:46:53.420 Yeah, that would be interesting.

00:46:54.580 Yeah. So hopefully I'll get to that. I might even get to that before this podcast comes out. So it's

00:46:58.740 possible by the time this comes podcast, I will have already done that and maybe even talked about it.

00:47:02.600 Another point too, I'd have to look back at the study, but when you flood the system with insulin,

00:47:06.440 even in normal glucose tolerance individuals, if you flood them for 24 or 48 hours, they have a

00:47:11.660 significant diminution of their beta cell function. I mean, it already sort of has a depressant effect on

00:47:16.620 that. And I think when you study patients that have even early stage insulin resistance, they've

00:47:20.620 got somewhat fatigued beta cell function already. And coming back to those fetal studies, they already

00:47:25.280 found that even with fetal hyperinsulinemia, the beta cells were just not as developed. They're

00:47:29.680 already showing some signs of early wear and tear just from in utero hyperinsulinemia. So I think a lot

00:47:34.620 of these individuals already have sort of a second rate pancreas. And then on top of that, if you're

00:47:38.280 flooding with hyperinsulinemia, yes, it's going to cause some skeletal muscle resistance, but there's

00:47:42.040 probably some combination of some beta cell dysfunction along with that.

00:47:46.100 Was there not a study, and I don't even want to put out a year because I'm sure I'm wrong,

00:47:49.360 I think it was like 2013, that actually showed genetically that both East and South Asians had

00:47:57.080 lower beta cell density genetically, and that that feeds into what you just said as another part of the

00:48:02.540 predisposition to almost bypassing the obesity phenotype. So you go from, because again, you could think of

00:48:09.540 this as the standard Caucasian path is normal to hyperinsulinemic to obese to diabetic. And where

00:48:19.560 these Asian populations, they just seem to skip the obesity phenotype more often than not, and they end 1.00

00:48:24.540 up going metabolically dysregulated, which could be partially explained by bypassing hyperinsulinemia

00:48:29.600 if you have less beta cell either density or functionality in some way.

00:48:34.100 No, I think that makes a lot of sense.

00:48:35.420 And am I right? Is my memory correct that there were studies demonstrating this?

00:48:38.100 There was. And I remember seeing the data in the South Asians. It might've been in one study where

00:48:41.980 they combined both populations. So I'd have to look back at that. But definitely I've seen other

00:48:45.240 studies in South Asians about beta cell dysfunction that happens earlier. And there's a genetic link

00:48:49.640 with that as well.

00:48:50.500 And kind of bringing it right back to where you talked at the outset, the other study that I think

00:48:56.140 is interesting is when you looked at the liposuction study, this was in the New England Journal of

00:49:00.620 Medicine. I want to say it was 04-ish. I think Sam Klein was one of the authors. You took

00:49:06.020 metabolically dysregulated people. You did liposuction, and I think they averaged about

00:49:11.100 30 pounds of fat removal from both the superficial and deep subcutaneous space, which is all that you

00:49:16.520 can access through liposuction. And there was no metabolic improvement in the patient, which again,

00:49:21.940 makes a very compelling case that it's not fat per se that is the proxy even for metabolic

00:49:29.540 dysfunction. In general, it's this visceral pool of fat.

00:49:32.320 Exactly. If you think of that subcutaneous, like we talked about, as being your safety belt,

00:49:36.020 you're kind of removing part of that safety belt. So I would expect that that's not going

00:49:38.900 to have any impact because the visceral is where all the action's happening.

00:49:41.960 And I don't know, I doubt this is ever going to be done in humans, but in animals, has anybody done

00:49:46.720 the liposuction of visceral fat and seen if that improves metabolism? Or is it again,

00:49:52.400 the visceral fat is just a proxy for something even more sinister metabolically and molecularly?

00:49:57.740 I haven't seen that study yet. This is a little bit related, but there's a lot of interesting

00:50:02.320 brown adipose tissue. And I'm starting to really focus on this because coming back to evolution,

00:50:07.120 if you look at the patterns of migration, so if we look at our out of Africa migration from

00:50:11.420 70,000 years ago, and when populations dispersed to different parts of the world,

00:50:16.520 the ones that dispersed further north into colder climactic regions, when you look at their brown

00:50:22.140 adipose tissue and the genes that determine that, they've got significantly more brown adipose

00:50:26.340 tissue. And they've done studies to compare brown adipose tissue in South Asians versus Europeans.

00:50:31.480 And we've got significantly less brown adipose tissue. And just to sort of back up for folks

00:50:35.340 that don't know what brown adipose tissue is, brown adipose tissue is actually metabolically

00:50:40.000 active. It's brown because of increasing density of mitochondria. Brown adipose tissue in newborns

00:50:45.100 generates more heat to keep the newborn's body warm. So our populations and ancestors that migrated

00:50:50.000 to colder climates, they actually have more brown adipose tissue. Their resting metabolism is higher.

00:50:55.340 They can generate more heat. And that thermogenic metabolism can actually account for at rest

00:51:01.060 between 15 to 18% of calories burned throughout the day. It's pretty marked. And when you look at

00:51:05.960 that and you think about migration patterns and insulin resistance, the interesting thing is if you

00:51:10.960 look at native population, you look at the Inuit and Eskimos in the colder regions, they've obviously

00:51:15.260 got very low insulin resistance. But then look at the Pima Indians and others that migrated to southern 1.00

00:51:20.160 sort of areas of the world, they have much higher risk of insulin resistance. Even with India, when you

00:51:25.020 look at the country itself, in the northern parts that are near the Himalayas, you have some of the lowest

00:51:29.100 incidence of insulin resistance. So there's a place called Manipur, which is near the Himalayas. And they have

00:51:33.540 single digit, basically insulin resistance and diabetes. The highest rates of diabetes in India are further

00:51:39.020 south near the equator. So Kerala has by far the highest, I mean, the prevalence here is up to 20%. So it's all 1.00

00:51:46.000 over the world, you see this pattern and the brown adipose tissue is turning out to be really

00:51:49.280 interesting. Because number one, it's not only more metabolically active, but it actually is a glucose

00:51:54.140 disposal organ, it can actually remove glucose from the system. And they did a study coming back

00:51:58.300 to this where they took rats, and they took brown adipose tissue out of a rat, and they basically put

00:52:03.380 it in another rat. And they showed insulin resistance was completely reversed, basically just by brown

00:52:07.740 adipose tissue transplantation. And when you look at those two regions of India, what are their

00:52:11.980 phenotypic differences in body morphism composition? So the phenotypic difference is typically in South

00:52:17.760 Indians, they're shorter and vertical height, they tend to have a little bit more visceral 1.00

00:52:22.120 adiposity, so a little bit more larger pot bellies in the north, as you move further up north,

00:52:26.700 probably a little bit more lean body mass, basically a little bit taller skin type as well

00:52:31.040 to in the south, darker skin, we see a lot more significant vitamin D deficiency. And when I see

00:52:35.540 these individuals, they have a vitamin D level of maybe three or four, basically, so way down single

00:52:39.800 digits. And up north, I don't tend to see that as much either. So so there's interesting variations

00:52:44.760 between those two. And then coming back to this brain sort of hypothesis, interestingly,

00:52:48.900 even though they're more insulin resistant in South India, anecdotally, they also have the

00:52:53.420 most competent scientists and mathematicians in the south. So a lot of the brain influx into Silicon

00:52:58.520 Valleys coming from South Indian cities. So I've had this discussion with I had this with Jerry before,

00:53:02.940 and I asked him that, do you think there might be something about the fact that the most insulin

00:53:06.820 resistant part of India, somehow there's some sort of cognitive benefit they get from that insulin 0.67

00:53:11.000 resistance? And he thought it was an interesting theory, we'll have to see. But are there activity

00:53:14.520 differences between them? I mean, you'd get the sense that the folks in the northern part of

00:53:18.080 Italy near the Himalayas are also more active, like there seems like there would be so many

00:53:21.400 confounders, it would be very difficult. It'd be very tough. Yeah, absolutely. But even if you look

00:53:25.520 at the populations in Kerala and southern India, where it's more of a native sort of a village climate,

00:53:31.200 and the other thing that they have is they have increased fish and ticks, so they have a lot of

00:53:34.140 seafood. But even in studies done in more of the rural populations where they are physically active,

00:53:39.680 they still see very high levels of insulin resistance. But you're absolutely right,

00:53:42.660 there can be multiple confounders to sort of account for that. But in general, if you look

00:53:46.500 at sort of the globe, and you look at insulin resistance patterns, climate has a lot to do

00:53:50.020 with it. And it might lead to a phenotype of basically who can manage baseline adipose metabolism

00:53:55.240 better in terms of generating heat. Now you brought up vitamin D. So let's go down into that rabbit hole

00:53:59.760 for a moment. There's another topic my point of view has really started to change on. So I've never seen

00:54:04.620 a vitamin D level of three or four, that's pretty impressive. What risk is that person at? And how are they

00:54:09.780 living such that that's their, I don't mean, why are they alive? I mean, what is their lifestyle

00:54:14.160 that is producing a vitamin D level that low? A lot of it's obviously it comes down to their

00:54:18.340 skin pigment. So they're clearly not absorbing as much. And then lifestyle wise, most of them are

00:54:22.440 spending most of their time indoors. They work at high tech companies in their cars all day.

00:54:26.220 So you're not seeing this from people who are actually back in India per se, necessarily working

00:54:30.880 outside or not stuck in front of a computer all day? Even the ones that are spending time outside,

00:54:35.940 they're fully clothed. So it's kind of a taboo to be in a tank top and work out and things like

00:54:39.400 that in that population. So even my patients that are a little bit more physically active

00:54:43.160 and outdoors or runners, and they spend a lot of time outdoors, they still have pretty relatively

00:54:46.740 compromised vitamin D levels. And some of that is vitamin D resistance. Some of it is just the fact

00:54:51.620 that they're not absorbing enough. And in the early days, definitely I would replace anybody with that

00:54:56.100 sort of level you have to replace, but I wouldn't say that more is necessarily better. I don't know if

00:55:00.080 South Asians are adapted to have vitamin D levels of 60 or 80 plus, it makes sense to get them 1.00

00:55:05.160 between 30 to 40. Anecdotally, what I have seen, and this is completely anecdotally is in some of

00:55:10.360 those patients, I definitely see that C-reactive proteins do improve because vitamin D does have

00:55:14.460 some anti-inflammatory effect. I was hoping based on some of the studies that I came across, and I'd

00:55:19.180 love your input on this, that it would help a little bit with glucose disposal because vitamin D

00:55:23.360 does have some ergogenic benefits at the muscular level. I haven't seen that pan out in my patients.

00:55:27.820 The one thing I have seen as a pattern is it definitely has helped with hypertension. I've definitely seen

00:55:32.440 when I get vitamin D levels up in my resistant hypertensives. We often see their blood pressure

00:55:36.700 controls much better, but I'd love your feedback on if you've seen any patterns when you've

00:55:40.620 replenished. Again, you haven't had single digit ones, but I'm sure you see plenty of individuals

00:55:43.940 with low vitamin D. I've never seen anybody below 10. I know I'm talking to people like you that

00:55:48.060 they're walking around out there, but if I see somebody in the 10 to 20 range, that would typically

00:55:51.900 be low. Again, I used to think that sort of 40 to 60 was where people needed to be, and I would

00:55:56.940 replace people to get there. I'd no longer do that. I sort of just want people above 30 1.00

00:56:03.100 without supplementation is sort of my point of view now. So I'm generally taking vitamin

00:56:08.280 D away from people. The problem is there's a really good sleep supplement out there that

00:56:12.980 contains vitamin D, and I would love it if it contained none or much less because it's

00:56:18.680 confounding this, and I'm seeing people show up with vitamin D levels of 80 and 90, which

00:56:23.320 just doesn't make sense to me that that's a place where we want to be.

00:56:26.660 Especially if you're dealing with a patient. Again, I'd love your input on just the higher

00:56:30.300 rate of coronary calcification that we see in this population too. So it does make me

00:56:34.220 nervous to just drive their vitamin D the higher the better. So I'm pretty conservative

00:56:37.700 with that number. I don't take vitamin D anymore, and I think for years I took it. I don't supplement

00:56:42.040 anymore. And my natural place to be is probably in the 30s to 40s just based on anytime I can be

00:56:48.580 out in the backyard shooting. If I take my shirt off, I figure I'm getting my vitamin D that way.

00:56:52.400 But again, I know that's not practical for everybody. Not everybody lives in a Southern

00:56:55.880 California climate. Not everybody has the pigment that I do, which basically means I can't get a

00:56:59.860 sunburn if I try. I'm unburnable. Exactly. Yep. So I have that luxury that I don't think everybody

00:57:04.700 does. So no, I'm still really trying to wrap my head around this. But I would say the placebo effect

00:57:09.320 is huge. When somebody has a vitamin D level of three and all of a sudden it's 30, they're like,

00:57:13.780 man, I have so much more energy. I feel great, but that's more anecdotal. But I don't know if

00:57:18.020 physiologically they're really getting some benefit. Yeah. I haven't seen the blood pressure issue.

00:57:21.800 Our little sort of great trick on blood pressure is lowering uric acid. That's huge. I mean,

00:57:26.860 in fact, I take such an extreme view on this that I don't even think one should use antihypertensive

00:57:31.760 medication until uric acid is below five. So if you've got a patient walking around with a uric

00:57:35.820 acid of seven who's got hypertension, they've got to be on allopurinol first, metabolically fixed,

00:57:42.360 which by the way, may or may not correct their uric acid, doesn't necessarily do so, especially if

00:57:46.660 they use nutritional ketosis and fasting, which you'll often see raise the uric acid level.

00:57:51.500 But the effect of uric acid on blood pressure is pretty profound.

00:57:54.820 And do you think that's more of a, when you're correcting the uric acid, you're addressing the

00:57:57.980 underlying hyperinsulinemia or is there something independent about uric acid?

00:58:01.000 No, I think there's something quite independent about it because you'll even see this with just

00:58:04.120 the use of allopurinol. So yeah, if you were looking at the correction of uric acid with the

00:58:09.440 metabolic correction, I would say it's impossible to know.

00:58:12.100 But just with the independent reduction.

00:58:13.900 Yeah. And Rick Johnson actually has a paper that's in the New England Journal of Medicine

00:58:17.860 that goes through this case. Rick's done some really interesting work. You talked about the

00:58:22.220 out of Africa migration. Rick's looked at the uricase mutation that occurred after we,

00:58:29.180 so one civilization left Africa to go to Europe. It turned out that this mutation of uricase allowed

00:58:35.360 us to store much more energy in the form of fat from fructose. And one of the byproducts of that is

00:58:41.700 generating uric acid. But this became really a beneficial mutation to acquire because fruit is

00:58:47.380 at its ripest in the fall. So it's going to be sweetest. So you could actually really eat a ton

00:58:52.860 of fruit and actually store it as energy in the form of fat and you would generate uric acid along

00:58:58.140 the way. And it seems that only the subset of our ancestors or the primates that developed that

00:59:03.800 mutation were able to survive these European winters and then come back to Africa. And so he argues, 0.61

00:59:09.820 I think quite convincingly, although I haven't had him on the podcast yet to go into this in gory

00:59:13.160 detail, but talked with him about this a ton and read his papers, that it was this ability to

00:59:18.420 actually turn fructose through de novo lipogenesis into fat as a byproduct to generate uric acid.

00:59:23.540 That's actually what allowed us to come back to Africa to have survived a European winter and then

00:59:28.060 to basically proliferate. So this ability to generate uric acid is not unique to all species. It's

00:59:33.580 something quite unique to those that came from the lineage of having to survive basically a cold winter

00:59:38.880 without much food.

00:59:40.100 Hey, Peter, real quick before I forget, speaking of energy output, the other thing that you see

00:59:44.280 in insulin resistant individuals, especially South Asians, is when you compare them, when you actually

00:59:48.740 put them through exercise testing, when you take age matched, BMI matched, and you check their

00:59:53.860 submaximal VO2 maxes, typically in all these studies you look at, their VO2 max is correlated with their

00:59:59.780 level of insulin resistance, and they have substantially less VO2 max output under submaximal exercise.

01:00:04.820 And one of the things that's really interesting is with normal glucose tolerance offspring studies

01:00:10.240 before they-

01:00:10.980 So wait, you meaning the higher the degree of hyperinsulinemia, the lower their maximal VO2?

01:00:17.080 Yes. Yeah, exactly. It's hard to tell sort of what the link is, which way it goes.

01:00:21.200 Wouldn't that association be true across the board? Are you saying that it's disproportionately the case?

01:00:25.720 So I'm sorry. So there's two sets of studies. So there is one hyperinsulinemic case,

01:00:29.480 but these are young lean people before they've developed any signs of insulin resistance. So VO2 max

01:00:33.740 looks like it's already a bit of a surrogate marker for early insulin resistance in these individuals.

01:00:38.740 And one of the things that you see is in the normal glucose tolerance offspring that have no signs of

01:00:43.700 insulin resistance, if you were to measure their ATP output, the ones that just have a family history

01:00:49.080 of diabetes, their ATP output goes up by like 5%. And the ones that basically have no family history at

01:00:55.760 all, again, normal glucose tolerance, it goes up by 90%. So even the earliest stages before you've

01:01:00.760 seen any signs of insulin resistance, you're seeing significant mitochondrial dysfunction early on.

01:01:05.380 So that's another theory is, is there something at the level of the mitochondria? And it's hard to

01:01:09.880 predict, is this really something that's happening because of the increased influx of free fatty acids,

01:01:14.840 this overwhelming beta oxidation, or is there something intrinsically wrong with oxidative

01:01:20.220 phosphorylices genetic expression? So that's another theory.

01:01:23.080 This is one of my favorite topics today actually is what is our best proxy for mitochondrial function?

01:01:30.040 And right now, outside of having a laboratory where we're going to do mitochondrial biopsies and

01:01:35.600 complicated in vitro assays, what we're using is a zone two fitness test. And so rather than look at

01:01:43.720 VO2 max, which is by the time you're at VO2 max, you are both anaerobic and aerobic. You've in theory

01:01:51.440 maximized your aerobic capacity, but you've also now brought in a lot of anaerobic metabolism.

01:02:00.240 So what we're interested in is using lactate as a proxy to clamp lactate and figure out what maximum

01:02:08.860 ATP production looks like. And the higher that number, then I think we can say more comfortably,

01:02:14.080 the more mitochondrial efficiency you have, the healthier you are. So let me give you a practical

01:02:19.980 example. You basically have to do this on either a treadmill or a bike. You could potentially do it

01:02:25.460 on a rowing machine, but it's harder to sort of clamp the power. So let's just say you want to do it on

01:02:29.480 a bike. You would ride against a fixed load of power in Watts and you sample the lactate level.

01:02:37.860 And so you do long stages. So unlike a VO2 max, where you're doing typically three minute stages and

01:02:43.080 you keep ratcheting up by 25 Watts until they fail because they are, you're measuring in real time

01:02:48.680 what their VO2 is. But lactate has a bit of a lag because you're measuring it as a finger prick.

01:02:54.120 So you might do 10 or 15 minute stages and you have gradual increases. And what you're doing is

01:03:01.760 generating this lactate performance curve. And what we think, and I say, we, I mean, I'm talking about

01:03:07.160 the people who are doing this sort of testing that I'm learning from one of whom I'm actually going to be

01:03:11.040 interviewing hopefully soon on the podcast is looking at how much output can you generate while

01:03:16.520 keeping lactate in this sort of 1.7 to 1.8 millimolar range. And certainly once you're over

01:03:22.220 two, you're starting to escape the capacity of the mitochondria a little bit. It's hard to do

01:03:27.400 lactate threshold testing because even there, it's very complicated. If you develop the whole curve,

01:03:31.880 you can't really tell someone's lactate threshold until you can follow them all the way through to full

01:03:36.640 threshold, aerobic threshold. But this is below that. The point I want to make is

01:03:40.700 if your lactate threshold is sort of in the 3.8 to 4.2 millimolar range, this is definitely below

01:03:47.480 that. And this proxy really matters. So we call this, what is your zone two? And so if one person

01:03:54.240 can generate 200 Watts while keeping lactate below 1.8, and another person is generating 140 Watts while

01:04:02.200 keeping lactate below 1.8, well, that's a fundamental difference in mitochondrial performance.

01:04:06.820 And so I think that one training that system, which makes more sense to me than training VO2 max

01:04:13.780 training that system. Again, I'm going to do an entire podcast on this, so I don't want to go too

01:04:18.320 far down this rabbit hole, but we're using three hours a week as the magic number in that zone. So

01:04:23.600 three, one hour or four 45 minute sessions at that intensity. But again, you have to know what it is

01:04:30.380 and it's empirical. Like I test my lactate on every single one of those sessions, but of course I'm a

01:04:34.960 freak. You don't have to do that, but even every two weeks to upgrade and figure out if you're moving

01:04:39.760 in the right direction. And again, you can do it on a treadmill. Now for me on a treadmill, I actually

01:04:43.840 use a very steep incline and a brisk walk. The proxy that I've noticed for patients is if you don't

01:04:50.540 want to buy a lactate device to check your finger, like your finger sticks, a poor man's proxy is 1.00

01:04:56.300 zone two at this level is about the highest level of exertion at which you can carry out a

01:05:02.640 conversation. Yeah. That's a decent proxy actually. Yeah. It's not that far off. I sometimes take phone

01:05:07.740 calls while I'm doing my zone two bike rides because I'm on a stationary trainer and they're

01:05:12.540 uncomfortable phone calls, but not impossible. I could probably do a podcast on it because I'm

01:05:16.540 asking more questions than I'm answering. I'd like to hear that podcast. That'd be fun. Right. So

01:05:20.840 anyway, long winded way of saying, look, I think that there is definitely something to it. I wonder if

01:05:25.160 looking at zone two would be an even more sensitive indicator than VO two, because VO two, you can

01:05:31.280 train that when I used to ride a bike a lot and I knew I had a VO two max test coming up, I could game

01:05:36.460 the system, which is for about a month before the test, there are certain types of intervals you can

01:05:42.940 train that really allow you to blow up. Plus you drop a little bit of weight because it's very dependent

01:05:48.440 on your weight. And so you could go from 60 to 70 on a VO two max in a week, maybe not a week, but

01:05:53.900 probably in about three weeks, you could literally have that much of a jump in VO two max just by

01:05:58.740 managing your weight and a couple of types of workouts. But the zone two test takes longer.

01:06:04.100 It's a little more robust. And also I think it's not diluted by the anaerobic piece that comes in

01:06:09.640 VO two max. That's really eloquent. Yeah. Stepping back to lifestyle changes that I'd like to get your

01:06:14.680 input on this as well. But in my experience, I got to see in the early days, cause I was seeing so many

01:06:18.340 thin limbed Asians or phenotypes of insulin resistance and skinny folks that I was pushing 1.00

01:06:23.380 weightlifting quite a bit on them. And I think it still makes a lot of sense for them to just

01:06:26.540 generate more leg strength and more glycogen parking space. But what I've also realized over

01:06:31.220 time is many of them, although they did well initially, because they were just so focused

01:06:35.300 on weight training that they did become more deconditioned from a cardiovascular perspective.

01:06:39.600 And I think that really had an impact on insulin resistance. In some cases, they plateaued or we just

01:06:43.780 were not able to get their glucose tolerance where we wanted. So I'm finding now that I'm having to

01:06:47.660 sort of go back and say, okay, we need to incorporate some low intensity steady state cardio or some hit

01:06:53.300 training. And it's a delicate balance because one thing I would tell you is when my patients that are

01:06:57.980 really into endurance running in specifically my Asian population, I find that they're much more

01:07:03.560 catabolic when they do too much endurance training. So many of them that are racing for half marathons,

01:07:07.980 they lose a lot of muscle mass from doing that. And we know based on studies and athletes that if you do a

01:07:12.280 certain volume of endurance training, you are going to probably have AMP activated protein

01:07:16.460 kindness inhibition of mentor, you're going to see some of that happen. But I think in these

01:07:19.800 populations, that threshold is low, they go into muscle, I see it myself, if I do a lot of endurance

01:07:24.100 work, my legs, my pants start getting looser, because I lose leg mass very easily. So finding that

01:07:28.780 delicate balance of yes, we've got to build up your aerobic system, but we don't want to compromise your 0.96

01:07:32.560 muscle mass is sort of critical. So and I see that different in different ethnic groups.

01:07:36.340 Yeah, that's interesting. You would definitely have more experience than me with both South and East Asian

01:07:41.120 populations. My view is because I do get asked the question all the time, what's more important,

01:07:46.320 strength or cardio? And my first response is a glib one, which is yes. And my second response is,

01:07:52.280 I don't even know what that means. To use the term strength or to use the term cardio aren't really

01:07:57.140 helpful because they're so vague. And you have to be specific. It's sort of like saying, what's more

01:08:02.060 important, food or water? Well, it totally depends, right? So and strength does provide a lot of

01:08:08.160 cardio benefit as we know too. So it's not a black and white thing. Yeah. I mean, even just the

01:08:11.780 concept of strength training can mean so many different things to so many different people.

01:08:15.560 So my view is, if you care about living longer, and again, not everybody should, maybe not everybody

01:08:21.820 does. I don't want to shove my framework down everybody's throat. But if you want to take the

01:08:25.540 long view, and you actually care about making it to your 80s and 90s and performing really well,

01:08:31.400 being a super functional member of your family, your community, or whatever it is that matters to

01:08:37.480 you, you absolutely have to be visiting at least four different components of exercise. The first

01:08:45.360 being stability. So this is the one that's most sorely missing. And it's the one that is the root

01:08:50.660 cause of most injuries that people have. And it's the one that is actually the most interesting to me.

01:08:56.140 So it's basically the ability, it's restoring the body to its natural ability to transmit load

01:09:01.060 across the muscles, preferentially and not the joints. But doing that is, that's a whole new

01:09:05.440 way of training that we won't get into today. The second is strength. But again, what does that

01:09:09.860 mean? And it's because you can have different types of strength, but the most important ones are

01:09:14.800 going to be the simplest ones, which is the ability to hip hinge, the ability to pull and the ability

01:09:20.000 to push. And all of those things require enormous stabilization. So if you do those things without being

01:09:25.900 stable, you get injured. So anyone who's doing those things and is hurt by them,

01:09:30.640 means they're, they're not stable enough to be doing them yet. So you have to go back to square

01:09:33.940 one, which is build the stabilization, but everyone should be hip hinging, pushing and pulling and

01:09:38.820 everything else is gravy. If you want to do some bicep curls on top of that, knock yourself out.

01:09:42.480 But at the end of the day, it's push, it's pull, it's hip hinge. And those things have to be done

01:09:46.240 in my opinion, by everyone. Then you move over into this quote unquote cardio world. And there are many

01:09:51.600 energy systems. And this is where I think people confuse the difference between athletic performance

01:09:58.480 and training for life. So if you're training for a 5k at the elite level, that's a 15 minute race.

01:10:07.400 That's an energy system. That is a person who is running slightly above lactate threshold and then

01:10:14.580 well above lactate threshold. That's basically what that race looks like. If you're running a marathon, 0.98

01:10:18.600 which again, at the elite level, you're talking about two hours and 20 minutes, two hours and 30 minutes

01:10:25.400 would be incredibly elite. That's a person who's running below lactate threshold until the very end.

01:10:31.300 The question is at the level of quote unquote, normal people, people who aren't getting paid

01:10:36.320 to run 5k's and getting paid to run marathons, which I think is pretty much everyone listening

01:10:41.360 to this. You have to ask yourself what matters the most. And in my view, at that point, you can

01:10:45.980 simplify the problem greatly. You have to be very aerobically efficient, which comes back to this zone

01:10:51.380 area. And then you have to have some anaerobic performance. And that's where the high intensity

01:10:56.780 interval training comes in. You don't actually need much of what's in between because the what's

01:11:01.720 in between is very sports specific. So I think aerobically and anaerobically at peak, I'm in

01:11:09.220 reasonable shape today, but my middle zone, what would be called my functional threshold power

01:11:14.700 or in cycling, they call it sort of sweet spot around that zone. For me, it's deplorable today,

01:11:20.160 but it doesn't really matter because I'm not interested in doing a race that's one hour

01:11:24.780 long anymore. I'm not racing at anything, but I don't need to train the system that is

01:11:29.400 geared towards that. Now, there are going to be people who push back and say, no, you

01:11:32.400 need to be robust across every one of these energy systems. And maybe that would be true

01:11:37.080 if we had infinite time. But if you have finite time and you have to prioritize, and one

01:11:41.380 of the things I do with any of my patients who are interested in this exercise, and several

01:11:45.100 have taken me up on the offer, is I like to do an inventory of time in your life, which

01:11:49.040 is they're 168 hours in a week. Let's talk about how many of them you're sleeping. How

01:11:53.680 many of them are you thinking about and or preparing meals, all things that have to do

01:11:57.800 with food? How many of them are you meditating? How many of them are you exercising? And how

01:12:01.620 does each hour of exercise fit into those four buckets of stability, strength, aerobic, and

01:12:05.720 anaerobic? And again, for most people, it's like 12 to 14 hours would be the upper limits

01:12:11.420 of what they can put into exercise. And if that's the case, then I feel like you've got to

01:12:15.420 be laser focused on that. But I definitely want patients to accept the fact that it can't

01:12:20.580 be one or the other. You can't just go down one path or the other. And there, I think you

01:12:25.180 do have phenotypes. I think there are some people who just doing strength training can

01:12:29.340 do pretty well. Some people who are just doing, and again, I hate the term cardio, but just

01:12:33.580 to make it a simple term, who can do pretty well. But I've never met someone who doesn't do

01:12:38.720 better when they're putting them together.

01:12:40.380 Yeah. In these Silicon Valley companies where I go, a lot of these individuals that have come

01:12:44.060 from other countries, I mean, they have never even grown up doing organized sports. So they 1.00

01:12:48.140 don't have any infrastructure of balance or stability. And then they'll join some sort

01:12:51.620 of corporate bootcamp class. And I've seen Achilles tendons get ruptured. I've seen

01:12:55.740 rhabdomyolysis. It's just, and I've talked to HR about the fact that these individuals are

01:12:59.840 not ready for this. And it's an intensely competitive environment. You're next to European and African 1.00

01:13:04.340 American, someone that's got an athletic background, you're trying to stay up with them, but it can

01:13:07.820 create all types of joint dysfunction. So coming back to your point about just stability and

01:13:11.620 core and these things, got to look at the picture holistically. One issue I see is with

01:13:15.980 aging in the Asian population. It's a pretty fatalistic outlook. When you look at individuals 1.00

01:13:20.620 that reach age 50 or 60, because their leg strength is so compromised, they're already

01:13:25.140 walking slower. They're using a cane. They don't even think about the possibility of how they can be

01:13:29.920 so much more independent if they were able to train that system. But you think, again, coming back to

01:13:33.980 our issue about how ethnically they've already got smaller limbs. And then if you've got insulin

01:13:38.080 resistance on top of that, I kind of think of insulin resistance as also being anabolic resistance,

01:13:42.300 because you're not able to really accumulate muscle mass as well as you could, it really creates a

01:13:47.140 pretty depressing picture of how individuals age and become depressed later on in life. So one of my

01:13:51.820 things that when I give talks to multi-generational sort of audiences is really focusing on leg strength

01:13:57.100 and balance. I mean, if they could just spend their time doing that. And then with my busy execs in

01:14:01.100 Silicon Valley types, the ones that just will not add time to their schedule, I'm like,

01:14:05.800 how do you integrate these activities while you're at work? So can we get you in? There's apps and

01:14:10.460 tools that I use that can measure your squats. You know, I kind of measure that as a vital sign.

01:14:13.900 Can we do this many squats by 12pm? Can you do this sort of stretching? Or can we do some balance

01:14:18.740 exercises then? For stress management, a lot of them refuse to meditate, they're not going to spend

01:14:22.860 the time to do it. So what I do is with my Apple Watch, a lot of them wear Apple Watches, or they've got

01:14:27.400 a Fitbit where they can track their heart rate. And I teach them how to breathe in ways that can

01:14:31.600 actually bring down their heart rate. So I sort of call this active meditation. When you're in a

01:14:35.200 meeting, what is your average resting heart rate? And I don't know if you've done this before. But

01:14:38.720 it's interesting when I commute to work, or I'm sitting in meetings, I think I'm calm. And I look

01:14:42.820 at my heart rates like 20 points above my resting. And then I just breathe through that. And all of a

01:14:47.120 sudden, the number comes down. A lot of my patients that have done that throughout the day, they brought

01:14:50.640 their blood pressure down dramatically, because now they're breathing their diaphragm doing a lot of

01:14:53.940 things like that. And once they get that concept, they're like, this is something that makes a

01:14:58.060 difference. Maybe it is worth me doing some mindfulness, or maybe it's worth me doing more exercise. So it's

01:15:02.720 kind of a hack that I use for the individual. You've got these patients who are like, there's

01:15:06.000 no way in hell I'm going to be able to add 20 minutes to my day. Well, I'm like, what can we

01:15:09.440 do during your day that can actually be more impactful that might prove the case that this

01:15:12.940 is meaningful? Yeah, a lot to unpack there. So it's funny, there's a guy I follow on Instagram.

01:15:16.900 I don't know him. His name is Ben Bruno, though. And he's completely, he might be like one of the

01:15:19.740 best Instagrammers ever. He's just so funny. And I saw that he had a t-shirt that said,

01:15:25.540 every day is leg day. And I was sort of bummed because that's something I like to say. And I was

01:15:29.120 like, oh, I would have loved to have made a t-shirt of that, but he already thought of it. So I should just buy

01:15:32.540 his t-shirt. But I kind of agree with that ethos, which is every day is leg day. So for me, it's

01:15:37.600 like, I'm going to lift three days a week and I'm going to be on my bike or a treadmill four days a

01:15:41.340 week. So seven days a week, I am deliberately doing something that is working my legs. I'm either

01:15:46.160 climbing hills on a bike and I'm always hip hinging. So every one of those three days in the

01:15:51.300 weight room has a hip hinge. It's a deadlift, a leg press, a Bulgarian or something like you just 1.00

01:15:56.600 have. I wish I had less strong legs said no one ever at the end of their life. So completely agree

01:16:02.780 with you on that. But again, I want to reiterate, if you try to do that stuff without cylindrical

01:16:08.420 strength in the middle of your body, your host, your host, you're just going to get hurt. So

01:16:13.020 you're going to hurt your back. You're going to hurt your hips. You're going to hurt your knees.

01:16:15.360 It's interesting. Again, I think what you're describing vis-a-vis the heart rate is kind of a

01:16:19.880 poor man's biofeedback. Some people that are more slick will use heart rate variability,

01:16:23.800 but heart rate is a first order approximator of that. And certainly if you can lower your heart

01:16:28.720 rate from 80 to 60 sitting in a meeting, you're doing something correct. Right, exactly. And it's

01:16:34.020 actually an elegant way that you do it, which is you use that as the thin end of the wedge to make

01:16:37.760 the broader case, to make change. I've never really personally looked at meditation. I shouldn't say

01:16:42.560 that. I think I used to look at meditation as a tool to reduce stress. Again, I have a bit of an

01:16:47.940 issue with that terminology because I don't know what that means anymore. Is stress the external

01:16:53.420 things that are stressors to me or is stress how I'm responding physiologically to those things?

01:17:01.080 And while I think certain types of meditation, specifically mantra-based meditations,

01:17:05.980 probably do more in the moment to improve those things, my internal bias is really towards

01:17:13.120 mindfulness, which is, I view mindfulness like I would view going to the gym. It's just a training

01:17:18.360 tool that often is uncomfortable and oftentimes is unpleasant, but it teaches me a tool that I carry

01:17:25.500 with me when I go elsewhere. So sometimes I don't want to deadlift, but deadlifting makes it easier

01:17:30.420 for me to pick things up when they fall down in my backyard. And similarly, sometimes I don't want

01:17:35.900 to meditate, but the deliberate practice of this ability to observe thought and not react to it and

01:17:42.320 instead examine it more closely and distance myself from it to see the thought rather than to be the

01:17:47.440 thought. That just turns out to be a more valuable tool to being less miserable in my life. My

01:17:52.100 predisposition is just to be a miserable human being. So then meditation becomes a tool out of that. And I 0.92

01:17:57.480 think that's where a lot of people miss the point on meditation is it's mostly just a tool to be less

01:18:02.720 unhappy. Yeah, agreed. And as much as that's desirable. Yeah, absolutely. And I think you brought up a key

01:18:07.620 point. A lot of individuals think stress reduction means that you're magically going to eliminate

01:18:11.880 external stress. So when I do a lot of seminars, I talk to individuals and about the fact that all

01:18:16.680 of us sitting in the room have X amount of stress, but a certain percent of the individuals in this

01:18:21.400 room are going to get high blood pressure, glucose abnormalities, some sort of chronic health

01:18:25.040 condition as a result of that. So if we can train our systems to not be as reactive and responsive to

01:18:30.220 that external stress, that's really what we're looking for. And the heart rate I know is a blank. I used

01:18:34.160 to do a lot of HRV monitoring early on, but the heart rate just makes the case that my God, you can do

01:18:38.900 something and actually influence your own physiology. And there's other ways. I mean,

01:18:42.320 when you wear a continuous glucose monitor, I don't know if you've ever tracked the fact that

01:18:45.180 when it's elevated, have you ever noticed after mindfulness or doing something that's meditation

01:18:49.620 based, have you been able to influence your glucose? No, but the opposite is absolutely correct.

01:18:53.540 So it's very easy because I think it's much easier to raise glucose than to lower it.

01:18:58.480 True. Yeah. So there's no question that I can be in a distressful situation, get angry about

01:19:06.900 something and then watch my glucose go from 90 to 120 in a matter of two minutes. I mean,

01:19:12.940 that is not at all an uncommon finding. And that is again, yet another awesome feedback tool for me to

01:19:20.400 be reminded of, oh, wow, you let that whole thing get to you and look at the price you're paying for it.

01:19:25.680 Exactly. Because most of my patients are left brainers. I mean, I can't go through the usual 0.89

01:19:29.540 sort of meditation mantra based talk, but first I'm like, what are left brain things that we can

01:19:33.560 do? Is it glucose? Is it your heart rate, your HRV? And once you make that case, then you can sort

01:19:38.480 of buy them into other types of practices. So you've written quite a bit about sort of energy,

01:19:42.700 fatigue, stress management. You have something, the five S's that you've talked about.

01:19:46.820 Yeah. So basically if we focus on and things like stress, sedentary activity, sleep, these core habits,

01:19:53.040 because many of my patients that come in that have been exposed to my work, they're very focused on

01:19:57.140 sort of the diet exercise axis, but the other elements have been sort of ignored.

01:20:00.780 Meaning they're interested in those things even before they come to you. That's sort of their bias.

01:20:04.460 Well, it is because a lot of them have read my book or they've watched my videos. So that's the

01:20:08.200 part that they can focus on the most. The ones that have not been exposed to my work at all,

01:20:12.000 I've got to start from scratch. But many of the individuals that have at least got that down to a

01:20:15.700 foundational level, they tend to put the stress and sleep on the sideline. And I'm sure you've had

01:20:19.980 patients before too, where they literally just want you to add an exercise or tell them what to eat.

01:20:24.960 But the minute you bring up the stress where their eyes glaze over, right? They don't want to even

01:20:28.140 hear or deal with that at all. So I've had to find sort of innovative ways and practices that they can

01:20:33.320 use to sort of incorporate that in their lives so they can make more of a meaningful impact.

01:20:37.620 And so focusing on those other S's has been sort of key. And one thing that has really happened in

01:20:42.440 my practice is a lot of my patients bring their family members in. So one thing about Indians in 1.00

01:20:46.460 particular, they don't like to come alone to their visits. They'll bring their spouse.

01:20:49.300 They'll often bring their parents or their in-laws. So I sometimes have four or five people in the

01:20:53.160 room. And man, Peter, those can be some pretty intense sessions because initially it starts

01:20:57.220 up quiet. I hear about what the issue is and then ask a couple of probing questions. And all of a

01:21:02.040 sudden, all the family tension comes out. Because what I'm not realizing is when I see a patient

01:21:05.760 individually, they come out nodding their head, they've got my prescription and plan. But what I

01:21:10.120 realized on the back end is there's a mother-in-law at home that's doing all the cooking or a nanny, 0.99

01:21:13.860 or there's a family member that's visiting for six months that's causing tremendous amounts of stress.

01:21:18.080 So when you see all the generational elements, you realize that, wow, this is much more challenging

01:21:23.480 than just looking at one individual. And if you can engage that whole family unit, and it's

01:21:27.860 interesting because of all the multi-generational issues, I can talk about the fact that, you know

01:21:31.900 what, this daughter, this teenage daughter's got PCOS. Dad's got coronary artery disease. You've got

01:21:36.820 prediabetes. This is a spectrum basically, right? This is insulin resistance across different lifespans.

01:21:41.820 And it's pretty powerful because when they get that concept and how it manifests with these

01:21:45.280 different conditions, they realize that they've got to make multi-generational changes. Otherwise,

01:21:49.160 if you just focus on one individual, it sort of gets lost in them.

01:21:52.780 And how often are you seeing PCOS?

01:21:54.360 So I don't see many teenagers in my practice, but the interesting thing is when I talk to parents,

01:21:58.880 adults, and I mentioned PCOS, A, either their daughters got it, or when I go through sort of

01:22:03.800 the checklist of symptoms, they're like, they probably have it. And I've talked to some

01:22:06.900 endocrinologists who've said in different parts of the Bay Area, in Fremont in particular,

01:22:10.120 they're seeing probably 25 to 30% of Asian Indians probably have some manifestation of PCOS.

01:22:15.340 What do you think is the root cause of it?

01:22:16.720 So again, coming back to insulin resistance, I actually, just like you hate the word type 2

01:22:20.420 diabetes, I hate the term polycystic ovarian syndrome because I really think insulin,

01:22:24.700 it should be called insulin resistant ovarian syndrome because I think really it's coming from,

01:22:28.500 again, hyperinsulinemia. So really the effects of insulin on the ovaries, particularly the fecal

01:22:33.940 cells is causing the testosterone release and that's leading to all the different manifestations.

01:22:37.800 And for a teenage girl, aside from all the issues with type 2 diabetes and heart disease later on,

01:22:43.520 for these teenage girls with facial hair, with obesity, with acne, with emotional disorders from

01:22:49.000 this condition, it's absolutely devastating. And when I look back at my childhood, I kind of remember

01:22:53.500 having family friends that a lot of guys would make fun of because they had facial hair. And

01:22:57.680 looking back, I can already peg in my memory at least a half dozen girls that I grew up with that 0.96

01:23:02.080 probably had PCOS, but they had no idea they had it.

01:23:03.960 But no one knew what it was called.

01:23:04.960 Nobody knew what it was called. Yeah.

01:23:06.240 And how much of it do you think is insulin versus IGF's effect? I don't see it in my practice very

01:23:12.940 rarely, but it's one of those things that always somebody in your practice has a friend or a

01:23:17.460 relative. So it sort of tangentially comes across my radar, but I'm quite naive.

01:23:21.960 I mean, basically when we implement the insulin sort of management strategy through lifestyle,

01:23:26.880 in many of these cases, we see it reverse. So I think IGF definitely plays a role. But again,

01:23:30.960 if you implement a lifestyle that's going to lower insulin levels and improve insulin resistance,

01:23:34.660 many times we see them get off medications. It's so reversible in so many of these cases,

01:23:38.620 which makes it even more convincing to me that insulin resistance is really a major root cause.

01:23:42.420 But I'd have to look deeper in the literature to sort of look at, is it more insulin or IGF?

01:23:46.160 There might be some overlap between both.

01:23:47.520 There's another phenotype. Here's this idea I'm sort of working on, which is you have one category of

01:23:52.540 adiposity, which is pure excess energy intake. It gives someone access to unlimited food

01:23:58.440 and give all the hedonic pleasures that come with it. There's a phenotype of adiposity.

01:24:03.900 There's a subset of people whose bodies will auto-correct and reduce intake. And I suspect most of us would not.

01:24:10.860 In other words, if you put me in an office with unlimited or put me in the rat cage with unlimited food,

01:24:16.940 I'm just going to get obese. And it won't matter a whole heck of a lot what macronutrient composition

01:24:21.360 you're giving me. By the way, I don't know that that's necessarily true for me because

01:24:25.320 I know from being on ketogenic diets, if I eat an unlimited quantity of purely ketogenic food,

01:24:32.660 I actually get leaner. So in other words, there's something regulating in me that will

01:24:36.140 sort of control intake, but that goes out the window if you give me unlimited access to M&Ms.

01:24:40.220 I can't regulate that. So then you have sort of, let's just loosely call that sort of the

01:24:45.760 diffuse energy abundant intake. We're not going to go into that. Lots of people have talked about that.

01:24:50.100 The second phenotype, these are the people that really respond well to carbohydrate restriction.

01:24:54.300 They are generally the hyperinsulinemic phenotype. So you take someone who has adiposity coupled with

01:24:59.680 hyperinsulinemia, even though, by the way, I think a follow-up study by Christopher Gardner did not

01:25:06.240 find this, though his first study, A to Z study, did find this. I could offer reasons or critiques of

01:25:12.440 why I think the follow-up study did not find this. Clinically, I still see it. Hyperinsulinemic people 1.00

01:25:18.220 respond very well to true intermittent fasting, which is real periods of fasting and carbohydrate

01:25:23.580 restriction. They respond really well. Then you have another group of people who don't seem to

01:25:28.580 respond to either of those two. They're usually female and not male, by the way. And you reduce

01:25:34.700 calories and or carbohydrates and or add fasting. And it doesn't matter. Their metabolic rate continues

01:25:41.980 to slow to match whatever you do. Now, the PCOS throws in another layer of complexity, but let's assume

01:25:48.920 you've already, this person does not have PCOS. This phenotype I find is the, at the risk of

01:25:55.260 oversimplifying, they're the sleep stress dysregulated group. And the only way I've been able to move the

01:26:02.880 needle for that type of patient is the following. You still have to do all the blocking and tackling on

01:26:08.400 all the nutritional stuff. You can't back off that. So you're still doing some amount of time-restricted

01:26:13.640 feeding, some periodic fasting, carbohydrate restriction. You're doing all of the right

01:26:18.040 nutritional things. Oh, we're also sort of loading them up with monounsaturated fats,

01:26:22.060 reducing saturated fats, but they have to sleep eight hours a night. They have to exercise every

01:26:26.740 single day. And you have to figure out what it is that is driving their stress. And sometimes it

01:26:33.260 doesn't even manifest overt hypercortisolemia. And then on top of that, it takes a long time. So then

01:26:38.600 you have to get them to buy into that strategy because if they don't get results in a month,

01:26:45.080 the tendency is to give up. But if you look closely, they've lost four pounds in a month.

01:26:48.980 And they might on the surface think, well, it's only four pounds, but you realize, no, no, no,

01:26:52.560 you don't understand. You're going to potentially lose 25 pounds in a year if you keep this up,

01:26:57.020 but you have to stay the course. It's a very stubborn. Oh, and then the other thing is they

01:27:00.880 generally have high inflammation. Yes. And it's not sky high. It's just fibrinogen is a little

01:27:05.660 elevated. CRP is not normal high. Right. And there's some thyroid dysfunction usually that

01:27:10.380 goes along with that. Yeah. Interesting. And you're seeing that more at the TSH level or?

01:27:14.520 Even pre-TSH. So if you're just checking antibodies already, you're starting to see

01:27:18.380 thyroid autoantibody use. And to me, that's already a marker. So you're right. You sort of break it down.

01:27:22.680 Is this really more insulin resistance? Is it more autoimmune inflammation? And it's tough to sort of

01:27:27.180 make that out, but sometimes those thyroid antibodies can be very early marker of autoimmune.

01:27:32.060 And which ones are you looking at? And so I'm looking at your typical anti-TPO.

01:27:35.660 Antibodies and thyroglobulin as well, too. So you can pick up on that quite a bit.

01:27:38.980 And are they, when you say elevated, do you mean elevated even at the level of what the lab says,

01:27:43.000 or even are you looking at upper limit of normal would still be elevated?

01:27:46.280 I'm looking at upper limit of normal. So, and sort of tracking that. And it's interesting because

01:27:50.200 many of my female patients, because they've been aware of this, have sort of followed that over time.

01:27:54.520 So we can see the trends sort of go up before the TSH goes up. So that might be sort of a marker.

01:27:59.740 Other things we see are just GI dysfunction, a lot of eczema in these patients too. So these are

01:28:05.160 other sort of autoimmune manifestations. So you're right. When they have that inflammatory

01:28:08.560 component, it makes it very difficult because insulin resistance alone, just fixing that problem

01:28:12.980 individually is not necessarily going to protect them from weight loss. And a lot of that inflammation

01:28:17.820 causes those fat cells, especially the subcutaneous fat. It looks like it has, inflammation looks like

01:28:22.240 it has a direct impact on subcutaneous fat in terms of the ability of subcutaneous fat to really

01:28:26.600 release free fatty acids.

01:28:28.160 Why do we see this more in females? So if I picture every patient I know that fits the 1.00

01:28:33.880 phenotype of that last bucket, they're all women. And it's tempting to say, well, it must be an 0.99

01:28:39.500 estrogen and testosterone access issue, but I'm not convinced of that. I think those things play a

01:28:45.820 role, but there's something else. And I can't understand why I'm just, it could be just small

01:28:49.220 N and I'm being fooled by the relative small sample size. But why do you think you're seeing this,

01:28:54.160 or I'm seeing this disproportionately? I've asked myself this question so much, but I think it comes

01:28:57.960 back to evolutionarily. If we think about women's sort of procreation purpose in terms of being able 1.00

01:29:03.020 to store fat and not having fat stores basically for lactation, I think there is sort of a larger

01:29:07.800 amount of subcutaneous safety belt for women. And the issue is you're right after menopause. I think

01:29:12.700 that the big problem is before menopause, we're not seeing the manifestations with insulin resistance,

01:29:17.700 but after menopause, all of a sudden it catches up right away. So we sort of lose that protection.

01:29:21.760 But in the early stages, when you're in those fertility years, I think that subcutaneous fat

01:29:25.640 is really helping to propagate basically reproduction. I think that's the main purpose.

01:29:29.840 But coming back to, I'll tell you why I'm convinced about the stress axis

01:29:32.860 as being a major target here is many of my women that have been doing ketogenic diets, 0.91

01:29:37.020 they're working out like crazy. They're seeing no results. Oftentimes they'll go back to India 1.00

01:29:41.540 for three or four months. And I tell them while you're in India, just forget all the rules, 1.00

01:29:45.400 do your best to sort of stick to the plan that you can, but let's just monitor maybe your blood

01:29:49.340 sugars a little bit and your body weight. And I can't tell you how many people, Peter,

01:29:52.940 when they've gone back to India to sort of be in their family, they've lost weight and they're

01:29:56.600 eating double the amount of carbohydrates. What's the main differentiator? Well, they're back to their

01:30:00.760 tribe, their family. They're probably sleeping better. They're eating a little bit less processed

01:30:04.360 foods, but more carbohydrates, but they're just in their native place now. Whereas when they come back

01:30:08.520 here, they're isolated. They've come back from a huge family. They're here with all the independent

01:30:12.260 stressors of Western life. And that is just so more obesogenic. And I've seen so many cases that

01:30:17.120 I'm basically convinced that that stress access is a huge part of obesity.

01:30:20.940 If you had shared with me that story, which by the way, now I've seen myself. So if I had seen

01:30:25.180 that story and, or heard that story five years ago, I would have come up with 10 other plausible

01:30:31.460 explanations for it. And today I think the one you have offered is by far the most compelling. I mean,

01:30:38.420 and I don't know why I would have rejected that five years ago. It's just, it's too touchy feely.

01:30:43.420 I can't measure it enough. I don't know what it is, but I do agree that the effects of how we

01:30:49.720 internalize stress do more damage than I've ever understood. And perhaps part of why I've rejected

01:30:55.640 it is it's not measurable because it's not just about cortisol. And maybe if we could have real-time

01:31:01.380 measurements of catecholamines, we might see other signals there, but yeah, I couldn't agree enough.

01:31:07.360 And the other thing is now that we are tracking sleep so much more closely, we use the aura ring,

01:31:12.120 which is I think very good at measuring duration and probably reasonable at measuring stage.

01:31:19.000 Just looking at duration, just forget the staging. And by the way, for that matter, I think many of

01:31:23.940 the sleep devices, you don't have to be your Apple watch. It could be your Fitbit. It could be

01:31:27.440 whoop or any of these things. They're all pretty darn good nowadays at measuring the duration of sleep.

01:31:32.140 There is a fundamental difference between a patient who is sleeping six hours a night and a

01:31:37.020 patient who is sleeping eight hours a night. And what I find really amazing, I saw a patient yesterday,

01:31:41.420 actually, who we were reviewing his numbers and we do it in monthly blocks. So we say, okay,

01:31:48.040 so for the last 30 days, you average six hours, 12 minutes of actual sleep. And he's thinking,

01:31:54.340 that can't be right. I'm in bed. Like, and I said, let's go through your routine. Tell me everything.

01:31:59.220 What time do you get into your bed on? Tell me two nights ago. What time did you get into bed? Okay.

01:32:03.300 What did you do? What time did you get up? And you realize, actually, you think you're in bed eight

01:32:08.720 hours? You're not. Because part of that time in bed, you're putzing around reading. You're

01:32:12.540 trolling your phone. Sleep efficiency is horrible, right? Yeah. So, yeah.

01:32:15.860 So that person who's truly getting six hours of 12 minutes of sleep a night, you get that person up

01:32:20.160 to eight hours of sleep a night and make no other change, it's mind-boggling the difference.

01:32:26.420 Especially if you could do that, let's see what that looks like after three months.

01:32:29.840 And so, yeah, this sleep stress thing is kind of crazy.

01:32:32.700 One quick thing on sleep too, I just want to mention is the correlation that I see,

01:32:36.120 especially in Asian patients and South Asians, between insulin resistance and sleep apnea.

01:32:41.260 That's been a huge factor. And a lot of what we face, even when you screen for sleep apnea,

01:32:45.320 often you are using body mass index criteria, but you often will find overt sleep apnea with a BMI

01:32:50.840 of above 23. It's a chicken or egg thing. Like, is it the sleep apnea that's triggering insulin

01:32:55.020 resistance or vice versa? But clearly sleep apnea and intermittent hypoxia is a major inflammatory

01:32:59.940 stimulus. And often when that has been corrected, whether it's through lifestyle changes or through CPAP,

01:33:05.760 we often see glucose numbers get so much better. So all along was really intermittent hypoxia during

01:33:10.680 the night. Do you think that hyperinsulinemia per se plays a causative role in sleep apnea?

01:33:17.660 That's the controversial question. Nobody knows really what starts what. My theory would be that

01:33:22.460 it probably does have somewhat of a causative link, but yeah, it's very tough to say. There's a lot of

01:33:27.620 people that argue on both sides of that. So I lived in the Bay Area 12, no, 11 years ago. I spent six

01:33:34.180 years of my life in the Bay Area. I've been gone for 11 years. I don't recognize it anymore.

01:33:38.740 So when I'm here, it's just, it's not the place it was over 20 years ago when I first came here for

01:33:44.440 medical school. It's clearly one of the most exciting places in the world if you're bent is 1.00

01:33:51.040 innovation and all the things that come from here. But it strikes me as a really hard place to raise

01:33:55.960 kids, probably a lot like New York would be, and maybe to some extent like Southern California is.

01:34:00.560 What's the trickle-down effect of what you're seeing on your patients, on their kids?

01:34:04.860 The way I sort of came about this was, I still remember a patient family encounter where I had

01:34:09.620 a woman who was 47 and she had a first heart attack and she read my book, came to see me with

01:34:14.800 her parents and her child. By the way, can I interrupt for one second? I do want to come back

01:34:18.180 to this story, but this reminds me of something you said 20 minutes ago and I forgot to ask you about it.

01:34:22.700 Are you seeing an association between the LP little a of your patient population, which is

01:34:27.500 much higher than the general population and any of these other metabolic dysregulators? Or is the

01:34:33.640 higher prevalence of LP little a in your patients and the higher prevalence of hyperinsulinemia

01:34:38.320 uncoupled? Even though when you look at worldwide studies of instance of LP little a in South Asians,

01:34:43.280 it looks like they are a population that's at risk for elevated LP little a, but I clearly see quite a

01:34:47.920 bit of uncoupling. I checked that number quite a bit because some of my patients have a family history

01:34:51.980 of coronary artery disease, but many of them have normal LP little a's and still sky high insulin

01:34:56.360 resistance. Definitely there are those that have elevated LP little a and the risk is multiplied by

01:35:01.080 that. But I see plenty of cases where LP little a is not linked to it at all. So you're not, you're

01:35:04.420 seeing those as uncoupled independent risk factors. I do. Yeah. And this woman who's 47 with an MI was

01:35:09.580 elevated LP little a? She was not actually. She had a family history. Her LP little a was perfectly fine.

01:35:14.260 Oh wow. Yeah. But the reason that the sort of emotional axis came up was her parents were in the room

01:35:19.080 and they basically told us that our daughter, she just cannot slow down. She had this heart attack. She did six

01:35:24.220 months of cardiac rehab and she's back to where she was before. And the parents are like, we don't

01:35:29.040 understand how we can slow her down. She's a workaholic. She's just burning both ends of the 1.00

01:35:32.480 candle. And then it was interesting because she made a comment during that visit that mom and dad,

01:35:37.200 you guys always taught me never to slow down when I was growing up. You told me to be the best in

01:35:40.840 everything that I did. Maybe if you taught me to slow down then I'd have an easier time now. And that

01:35:45.340 was like a moment where I sort of sat back and thought, wow, I've never thought of it that way, that the way we

01:35:49.440 raise our kids early on might actually set a pattern for how much of an accelerated life or

01:35:54.380 how much of a stressed out nervous system they might have later on. And as I've talked to more

01:35:58.660 and more families here in Silicon Valley, I'm realizing that it is a lot of the behavioral

01:36:03.460 patterns that we're instilling in our kids are kind of setting the foundation for insulin resistance

01:36:07.160 and inflammation early on. We see so much fatty liver. I'm starting to see hypertension, adult

01:36:12.500 hypertension in teenagers that are just going through their junior year. And that's something I'd never seen

01:36:16.460 before. And we just realized that a lot of our parenting patterns out here in Silicon Valley

01:36:20.400 are kind of instilling these sorts of behaviors. And they're already manifesting with adult health

01:36:24.120 conditions early on in life. So that's something I'm really, that's why I'm very open to having

01:36:28.020 people bringing in their kids, bringing the parents and trying to wrap our heads around what is it that's

01:36:31.860 happening here. And that academic drive for excellence, the high expectations they set. There's one

01:36:36.300 concept I call pyramid parenting, where a lot of people that immigrate to this country, they feel like,

01:36:41.240 okay, if I made it from India to basically work here for a high tech company, my child with these

01:36:46.180 opportunities should be able to outdo that they should be running that company. And that's kind of

01:36:50.080 ingrained. Even my dad, when he came here from a village in India, he was like, you know, if I made it 0.87

01:36:53.780 here, and I'm a pulmonary critical doctor, you should be running your own hospital like that pressure is

01:36:57.680 always there. But we don't realize how much pressure and what damage that can do. And even the Asian and Indian 1.00

01:37:03.460 population, now that I'm exposed to them more, we're seeing opioid abuse, we're seeing all types of

01:37:08.220 substance abuses, because they cannot deal with the pressure that's being put on their shoulder. So it's

01:37:12.780 turning into quite a crisis. My wife and I now give a talk to high tech companies in schools,

01:37:16.720 and it's called basically, Is Your Child a Startup? Because we often give the analogy that we often

01:37:20.800 treat our kids like startup companies, we back them with resources and funding, we expect them to do

01:37:24.900 great things, go to Stanford, run this company. And we don't realize that we're not even giving them

01:37:29.560 the opportunity to grow up and just be a normal child. And it's having a toxic effect. And as we've

01:37:33.540 given this talk, I get emails from so many teenagers about the fact that they feel suffocated.

01:37:38.180 My dad keeps showing me TED talks on resilience. I don't know if I can handle this anymore.

01:37:41.060 I just want to, you know, it's like, where do we sort of draw the line? And it's really had a major

01:37:45.680 impact on my parenting, because it's a little bit in my DNA. How many kids do you have? I've got

01:37:49.380 identical twin boys, and they're 15. So they just they're literally finishing up their freshman year

01:37:53.640 in high school. So it's amazing how many stories you hear about what's happening. So I just finished

01:37:58.340 reading The Coddling of the American Mind. Have you read it? No, no. It's a great book. And of course,

01:38:03.200 it's dealing with a slightly different issue, which is the title of the book suggests is how we're

01:38:10.280 basically producing a very fragile Gen I. So their thesis is that a lot of this sort of ridiculous 1.00

01:38:19.880 over the top political correctness that we're seeing at a handful of elite institutions that's,

01:38:25.860 I mean, I had to actually skip some of the stories in the book, because they're so upsetting of the

01:38:30.420 completely extreme responses that some of these students have had towards relatively normal behavior.

01:38:37.640 They're talking about this as being this sort of Gen I. So it's not the millennial. It's the,

01:38:42.060 I think it's the kids born post 95, actually. And they tie it into a lot of the helicopter

01:38:47.820 parenting sort of stuff and this sort of overly protective stuff. But what you're describing is

01:38:53.780 a slightly different variation on that, which is not just that they're being overly protected or

01:38:58.480 coddled, but overly pushed. Do you think that is just unique to the Silicon Valley or other areas

01:39:03.840 of equal prominence? No, I think it's pervasive. Silicon Valley is a bit of sort of a phenotype,

01:39:08.720 but I think it is pervasive. Because if you think about how we look at our kids, for many

01:39:12.120 individuals, the kids are an extension of their ego. Like even if you talk to the most modest

01:39:16.420 individual, you get them talking about their kids, and they can go on for hours, right?

01:39:20.300 And it's funny, as my kids are going through high school, I'm having direct flashbacks into certain

01:39:24.140 moments and stages I went through in high school. And I think consciously and subconsciously,

01:39:28.300 sometimes we might push our kids to do things because we might have suffered something like

01:39:31.800 maybe not being athletic in high school didn't get me to be more popular. So now I'm going to push

01:39:35.480 that down my kids. And we're doing it with good intentions in mind. But if we don't realize the

01:39:39.820 fact that maybe this individual is not inclined to doing organized sports and athletics,

01:39:44.020 me making them feel less because I'm pushing them so hard to do that can have really devastating

01:39:47.980 impacts. So I think this problem exists everywhere. But here in Silicon Valley, that problem's on

01:39:52.700 steroids. And I'll give you another anecdote. I had a teenager reach out to me who is not

01:39:56.840 motivated by school at all. He's like a junior. There's a concept of not helicopter parents,

01:40:01.020 but they call them snowplow parents. The New York Times did an article on this. And

01:40:04.060 snowplow parents just pave the way for their kids so they can go to whatever college. 0.94

01:40:08.660 And this student told me that one of his friends, who's a total slacker, what basically has happened

01:40:12.580 is his parents being entrepreneurs, they use the designers and the software architects in their

01:40:17.140 company to build an app for him. So we can put on his resume that he basically ran his own startup

01:40:21.900 company. So these sorts of things are happening. So literally, people are creating pseudo profiles.

01:40:26.300 And when all this news came up about the Lori Loughlin case, and everything that happened,

01:40:30.840 I know it enraged everyone. But here in Silicon Valley, I see that many of us are creating pseudo

01:40:35.040 profiles of our kids. They're just kids, but we want them to look like they're early entrepreneurs,

01:40:39.460 or they're stellar athletes, but they're just kids. And many of us are pulling out the snowplows and

01:40:43.740 sort of creating these expectations. And I think it's just not a healthy way. I think the whole

01:40:47.600 college admission process is a complete mess. It really brings out the worst in individuals and

01:40:51.800 puts too much pressure on the kids.

01:40:53.400 I couldn't agree with that more. I guess with my youngest turning 11 this year, I'm

01:40:57.660 hoping we got a few more years for it to work out some of the kinks before we have to 0.98

01:41:01.160 sort of deal with that stuff. It's pretty tough. Now, what part of the country did you grow up in?

01:41:05.160 I was born in New York, and then I spent two years there, seven years in Philly,

01:41:08.860 and then came over to California after that.

01:41:11.200 And so you alluded to the fact that you already sensed this from your dad. Your dad's an immigrant,

01:41:16.460 and he could still figure out a way to become a doctor in the United States. So you becoming a

01:41:21.760 doctor would not be considered an equal achievement. It had to be one better than

01:41:26.060 that. Do you think that that dynamic has been amplified today, or we're just more aware of it

01:41:32.660 today?

01:41:33.260 I think it's amplified because the possibilities are endless. Literally for my dad, it was like

01:41:36.920 me being a physician. That was probably enough. Of course, he wanted me to specialize. I did general

01:41:41.200 internal medicine. He was pulmonary critical care. He was like, Ron, you should be a cardiologist.

01:41:44.340 You're going to make more money and do fine. But here in Silicon Valley, it's not even enough to be

01:41:48.400 a doctor. It's like doctors here are blue-collar workers. When I went looking for a house, when my

01:41:52.400 real estate agent found out my wife and our physician, she's like, you're not going to be

01:41:55.200 able to find a house. I'm like, what are you talking about? We're both doctors. She was right.

01:41:59.060 We're getting outbid by all these high-tech employees and things. So here I think the scale

01:42:02.780 for greatness is so much higher. And I had a neurosurgeon come see me in the clinic, and we

01:42:07.260 were talking about this, and he's a patient of mine. And he told me that you would think that being a

01:42:11.260 neurosurgeon would be enough. But my dad sometimes is like, why can't you be more like Sanjay Gupta?

01:42:15.480 He has his own TV show, and he's written a few books. I'm like, shit, seriously? 0.99

01:42:19.320 This guy spent so much of his life doing brain surgery, and still his dad's giving him a hard 1.00

01:42:23.900 time. I'm sure there's a lot of Atul Gawande stories out there, too. Are you just a surgeon?

01:42:28.920 Why can't you be like Atul?

01:42:30.960 And do you think this is specific to either Asians, Southeast or East Asians? Do we see this

01:42:38.020 with Caucasian families the same way?

01:42:39.720 We do. When I used the word Asian, I should put air quotes around it. We can call it an Asian

01:42:44.560 form of parenting. But here I see it, for example, with a lot of individuals of other

01:42:48.620 backgrounds in sports. They invest so much time and hours and resources into their kids

01:42:53.260 doing sports. And what we see, and often I see this in the clinic and during talks, is

01:42:57.440 a lot of these kids, they're not really growing adequately because they're spending so many

01:43:00.840 hours of their day training. They eat a garbage diet because they're running between math,

01:43:04.720 tutoring, sports, and all this. So I think everybody has sort of their own dream. Like for some

01:43:08.920 people, it's their dream to have their kid win the spelling bee. And for others, it's to be

01:43:12.480 like a top-notch runner, soccer athlete. And if they've got the motivation, the resources,

01:43:16.940 and you can do that in a balanced way, great. But many times what we're seeing in high school

01:43:20.700 is they have so many activities that by the time they come home and they're doing their homework,

01:43:24.860 they're going to bed at like one or two in the morning. And that's something for us,

01:43:27.980 we do not compromise bedtimes. Like we hear from other parents that, you know what, in high

01:43:31.700 school, your kids are going to have to go to bed at two in the morning. But so far, they're just

01:43:34.480 freshmen. Maybe that'll happen. But I'm like, usually those kids are going to bed that late.

01:43:38.080 They are having other issues. They're not able to organize themselves. They're not able to focus

01:43:41.580 on their task. They've got their cell phone next to them. And they're looking at, well,

01:43:44.760 my kids have affirmed this. I said some of their friends are watching an episode of Game of Thrones

01:43:48.500 at one in the morning, just as a study break. And then they jump back in their books at two in the

01:43:51.980 morning. So when their parents tell me, oh, he's got so much homework, I'm like, is he really doing

01:43:55.820 a lot of homework? Is there a lot of other ancillary activities happening? So.

01:43:58.880 Yeah. One of the other things that sort of jumped out at me from the book I mentioned a while ago,

01:44:02.080 The Coddling of the American Mind, is the dramatic reduction in playtime that kids have. And I don't know,

01:44:07.220 I just think about when I was a kid, I don't think my parents knew what the hell I was doing anytime.

01:44:10.900 All we did was screw around. You were always playing. We played, you know, I grew up in

01:44:14.320 Canada, so hockey was sort of the only thing that mattered. So all we did was play hockey all the

01:44:19.320 time. You were always playing street hockey. You were always playing ice hockey. You were always

01:44:23.840 sort of, or foot hockey. So at recess, you were playing foot hockey, which is just kicking a

01:44:27.860 tennis ball around, pretending you're playing hockey, but really you're playing soccer with a

01:44:30.500 tennis ball. And then you'd come home and you'd play street hockey, and then you'd go out and have

01:44:34.060 ice hockey, organized hockey in the evening. And we never had tutors and we never had.

01:44:40.980 I don't know. We just-

01:44:41.680 You know, you're bringing up a key point because you did sports for fun. And many of the teenagers

01:44:46.180 are getting so much pressure. We must have patients like this that were former athletes. Many of them

01:44:50.600 don't know how to exercise for fitness. And the minute they leave high school, they're not going

01:44:54.680 to exercise. They're like so burned out on the structure and the pressure from playing organized

01:44:58.960 soccer, basketball, football. They just can't deal anymore. It's not even a source of pleasure. And I want

01:45:03.540 to bring up the other issue, because I think this is key, is instilling hobbies. So for example,

01:45:07.400 our kids were into music very early on. We got them a recommended piano teacher. And this piano

01:45:12.580 teacher basically had a very structured approach to music. And literally she kind of told us that

01:45:17.180 if they follow this certification process for piano, they can put that on their college resume.

01:45:22.220 And I didn't even realize that this even existed. And then we're like, you know what? They're not

01:45:25.940 even enjoying it. Let's just get rid of her and let's get them like a rock keyboard instructor or 1.00

01:45:29.620 somebody else. And literally we brought somebody else in. They taught them how to play Star Wars,

01:45:33.460 music, anime. They love all this stuff. And now for their study breaks, they love playing piano.

01:45:38.100 And I know that going forward after college, anytime they're stressed, they're going to play

01:45:41.660 music. My roommate in college, he went the track of falling piano for college admissions. He's never

01:45:47.380 touched the piano since because all he has memories of is just the pressure of performing, having to

01:45:52.340 fill out these evals and scoring on exams for piano. It's like we're taking the joy out of a lot of

01:45:57.240 things that should be hobbies that we use for stress reduction later. We've got to really be aware of

01:46:01.340 that. Yeah, I get pretty stressed out actually just thinking about being a parent. I think it's

01:46:04.900 I probably need to visit this topic more on the podcast because there are lots of books I'm reading

01:46:09.760 on this topic and they're kind of depressing actually because of a lot of these trends that

01:46:14.460 you see. So you'd have to separate out the sort of societal trends that we're seeing, which almost

01:46:20.520 without exception are in the wrong direction. There are some exceptions to that. And then balance that

01:46:25.400 with, well, what do you do as a parent? Because in the end, all I've got is control over some

01:46:29.860 control, not even complete control, of course. I have some control over three kids. And then

01:46:33.840 there's this piece which says, well, you can ironically screw that whole thing up by trying

01:46:38.440 too hard to do the right thing. Like, okay, guys, it's time for more unstructured play. Let's go

01:46:43.780 outside and not play in a structured way and go. You know, so it's like you're right. So one skill

01:46:49.780 that we know that we need to teach kids that's going to lead to their happiness is their ability

01:46:53.500 to look internally and sort of cognitively reframe situations. So when they're dealing with stress,

01:46:58.420 so one key thing is when I've talked to therapists here in Silicon Valley, they tell me that watch out

01:47:03.920 for the kids that are quiet when they're too quiet. If they're not really interacting, they're not

01:47:08.260 talking to you, they're just following the rules compliantly. Those are the ones you have to watch

01:47:12.780 out for. And what's the reason? Because they're ruminating. They have nobody to express their emotions

01:47:16.380 to. So they're internally thinking about these things day and night. Having two boys, both of my kids,

01:47:21.420 they naturally sort of had that habitus of being more internalizers. So we've had to instill activities

01:47:26.160 and again, do it in sort of an undercover fashion to make sure that they're expressing their emotions.

01:47:30.440 So one exercise we often do sort of covertly is called roses and thorns, where we sit around the

01:47:35.180 table and we'll sort of go through and talk about a few good things that happened, a few bad things

01:47:38.920 that happened. So I read about this. And again, I sort of tried the exercise. My kids are like,

01:47:42.960 oh my God, dad, you're just doing another one of these things. But then what I started doing was

01:47:46.300 they weren't really coming out. I started really sharing my frustrations. Like I'm like, you know what?

01:47:50.240 I had this situation at work that was really tough. I've got this coworker. I've got this boss. And they saw

01:47:55.320 me just unload stuff. And then all of a sudden, my boys were like, I got a teacher just like that.

01:47:59.440 Or I got a coach just like that. So one really powerful thing is the more you can express your

01:48:04.140 emotions, your kids find out that, okay, you're not this dogmatic top-down dad just telling you,

01:48:08.680 okay, watch this TED Talk do this. You've got your own issues that you're struggling with. And now there's

01:48:12.940 so much more comfortable sort of open up. And from an early age, I've actually seeked out the advice

01:48:16.580 of my kids. And I'm like, what do you think I should do in this situation? I've got this challenge

01:48:20.200 coming up. What should you do? And you get some really insightful advice. But it also makes them

01:48:24.040 feel like this is a company and we're equals. A lot of parents that struggle with their kids,

01:48:28.260 they come to you saying, my kids don't listen. I'm like, do you like working in a company where

01:48:31.520 your manager tells you what to do 24-7? Would you like to work in that company? And they're like,

01:48:35.240 hell no. I'm like, well, that's how your kid feels. Because day and night, you're telling them,

01:48:38.660 don't do this, do this. Give them some ownership. Tell them that how can they participate in these

01:48:43.100 decisions? And how can they help you as well too? And it's just much more empowering.

01:48:46.640 And it's an undercover way. You don't have to have these forced rituals, like you said,

01:48:49.820 where you can get eye rolls from teenagers. But you can sort of do this throughout the day.

01:48:53.200 Do you have a point of view on phones and at the age at which that starts to become

01:48:58.220 less harmful? To be clear, I wish I didn't have a phone. I'm convinced that it is,

01:49:04.360 although it comes with tremendous benefit. And obviously, I can't imagine not having one,

01:49:07.980 or I wouldn't at this point. But I think it's a very harmful thing that I bring with me.

01:49:12.000 And my view is I want to delay my kids having that as long as possible. Do you have a view on that?

01:49:18.940 So I don't have a hard number for it. But I look at the phone as literally being a drug

01:49:22.480 or a toxin. And you have to see that basically, if your kid is the type that is really consuming

01:49:27.620 a lot of media and other forms, I'm not going to give him a pack of cigarettes. This is just

01:49:31.040 something you need to delay as much as you can. Luckily, and honestly, this is not, I mean,

01:49:35.020 we sort of got lucky because we sort of didn't expose them to much media early on. We focused

01:49:39.320 more on hobbies and playing, things like that. So they don't really get much stimulation from

01:49:43.240 digital devices. But we did eventually end up sort of giving into it around middle school,

01:49:48.620 around seventh or eighth grade, because what we realized is a lot of their kids are talking about

01:49:52.220 stuff. And unfortunately, the school they were at, they had an open phone policy. So many of them

01:49:55.960 are looking at stuff and they're socializing using their phone. And we didn't want our kids to be

01:50:00.240 standing sort of isolated and not be sort of part of that. So we had a very long discussion about

01:50:04.800 what the phone's for. And we sort of introduced it at that point. And at least there's a lot of

01:50:08.520 stuff that's probably going on, Peter. I don't know about, but, but I feel like when they're

01:50:11.420 doing homework, their phone's on the charger, they're not using it at all. But for some of

01:50:15.500 their friends, I mean, literally we carpool with some of them and they cannot keep their fingers

01:50:19.020 off the device. If that was my kid, I would either take the phone away or implement some more harsh

01:50:23.320 restrictions on that. So I think you have to customize it rather than go by, okay, by this age,

01:50:26.760 you should introduce it. So if you're providing advice to some of your patients, what does that spectrum

01:50:31.340 look like of, because I'm guessing that given how thoughtful you are about all these things,

01:50:35.460 your patients are just as interested in your views on parenting as they are on hyperinsulinemia.

01:50:40.260 Yeah. So if I do seminars and talks on this, I'm very hard nosed about this, Peter. I think we're

01:50:44.560 living in a world right now where we're just sort of, we've kind of normalized this whole thing.

01:50:48.260 It's kind of like back in the days, I think you've talked about this where we knew cigarettes were bad

01:50:52.260 for us, but hell people were smoking. My dad was a pulmonologist who smoked. I remember going to lung

01:50:57.520 cancer conferences where in the hallway pulmonologists were smoking cigarettes after looking at slides of

01:51:02.860 lung cancer biopsies. I mean, that's how it was. This is just a few decades ago. And I feel like

01:51:07.420 we're living in an era right now where people just casually talk about, yeah, my kid was on

01:51:11.020 this social media platform till two in the morning. They just kind of joke about, oh yeah,

01:51:14.260 he's hooked on the device, but it's scary what it's doing. I mean, we definitely, when I really dig

01:51:18.620 down in these family sessions, they always identify the phone as being a major cause of just conflict in

01:51:23.840 the family, attention deficit stuff, so many issues. So I lay it out. I'll show them the

01:51:28.240 neurochemistry. I'll show them the dopamine pathways, the fact that what's happening,

01:51:31.860 social comparison. You talk to Dr. Pasevulski about this and the impact of what's happening

01:51:36.540 there. When you talk to these kids, especially girls in particular, the social comparison that

01:51:41.220 happens at that level is just amplified to a different level altogether in terms of

01:51:44.900 subtle messaging like, oh yeah, we showed up at this party. And then all of a sudden you're not

01:51:48.340 included in that. It's really a difficult line we're treading right now. So the parents need to be

01:51:52.540 aware of that and we need to sort of set some boundaries. And when parents give me pushback

01:51:56.540 and they're like, you know what? I have no control of it. I tell them, well, let's say your kid's

01:52:00.020 sitting at home and they decide to light up a cigarette. Are you just going to sit there?

01:52:03.320 And they're like, no, of course not. And I'm like, well, you have to look at this as being

01:52:06.260 pretty analogous to that because because of this device, they're going to bed late. They're having

01:52:09.900 social issues. This is something we need to take seriously. So you've got to kind of reframe it

01:52:13.700 because like I said, the normalization of this digital media use has made it something that people are not

01:52:17.880 taking seriously enough. And I was actually in the process of starting a not-for-profit called Data.

01:52:21.940 So doctors against tech addiction, like I wanted to get CEOs and entrepreneurs from high-tech

01:52:26.800 companies, physicians. It's on my to-do list, but it's something my wife and I are totally

01:52:30.340 passionate about. I feel like we need to expose this more. Man, well, I hope at least one person

01:52:34.040 listening to this can bring something to help you guys on that. Yeah, I'd love that. We'll make it

01:52:38.240 easy for people to reach out to you. But going back to this point, because again, I'm obviously very

01:52:41.980 personally interested in it, but I just know from, because our kids aren't there yet, but I have so many

01:52:46.580 patients whose kids are there. How much of this is a substitution effect versus a regulation of the

01:52:54.320 thing? Let me give you an example. If you have someone who's smoking, there's the regulatory

01:52:59.100 environment around making it harder to smoke. Like we're going to charge more money. We're going to

01:53:04.560 place restrictions on where you can smoke. But the other side of that is what's the root cause of why

01:53:10.120 you're smoking? Oh, there's a bit of anxiety. Well, look, why don't we give you something else to do

01:53:15.260 that's scratching the itch of that? So I don't know if that's the right analogy, but when you think

01:53:19.060 about the quick hits that we get from social media, the sort of, I don't know, I think there's more

01:53:25.160 reasons than I can count as to why we find these things so addictive. If you're dealing with your

01:53:29.960 kids, and let's say your kids were really struggling to put that phone away, how much of it would come

01:53:36.260 down to just restriction versus bringing other things into bear? I think the latter point, you're right.

01:53:41.800 Once you develop a confrontational relationship with that kid, then obviously them using the

01:53:46.700 phone as a way for them to rebel, they're going to want to consume that media even more. So I think

01:53:50.860 these are the areas where if you've got a bit of a combative relationship with your child already,

01:53:55.060 this is where you've got to introduce and add things. So this is obviously if their idle time

01:53:59.320 is focused on a media device, what are the things can they do with their idle time? Like what are the

01:54:03.160 other hobbies? What are the other things we can instill? And I'm not saying that you're going to cut

01:54:06.460 out the phone completely, but this might be a sign that all of us in the house need to sort of

01:54:10.460 address this. And as you know, a lot of these kids have got parents that can't get off their

01:54:13.600 phones either. And we say that, oh yeah, it's for work all the time, but it's rarely ever anything

01:54:17.720 life-threatening. A lot of us have to sort of model that. I've had some parents come to see me and I've

01:54:22.100 told them, you know what, just don't even limit their time. But for 10 or 15 minutes, can you guys

01:54:27.080 do this sort of activity? Can you go for a walk? Can you do a hike? And just kind of naturally

01:54:31.320 compress the time that they're on the digital media device because you've introduced other types of

01:54:35.140 activities. Because then at least their brain's not being exposed to the media as much. And they're finding

01:54:39.440 that, wow, there are certain things that we're doing that are actually enjoyable that don't

01:54:42.580 involve a device. Just a weekend to go camping sometimes, when you get their friends together,

01:54:46.900 we tell our friends, usually when we gather, let's have a rule already that no devices during the next

01:54:51.440 12 hours when we're out at this camp. And it's good to find, this is the other thing Peter will find is

01:54:55.480 if you've got some friends in your circle that sort of agree with that approach, it makes it much

01:54:59.700 easier. Because then you can have dinners, you have friends come over and you're like, guys, let's just have

01:55:02.660 the kids not bring their phones or put in a basket and let them just play outside. Does everybody agree?

01:55:06.580 And usually people will. There might be a couple that are like, okay, why? It's their own life.

01:55:10.620 But you want to surround yourself with more and more of those types of people.

01:55:13.660 I can't think of a better way to end this podcast than on that note. Ron, this has been really

01:55:17.460 interesting. I think we've talked about this before, but your experience is disproportionately

01:55:23.440 with a group of people who are under a lot of stress, who have a genetic predisposition that

01:55:28.900 doesn't enable them to, at a metabolic level, tolerate the insults that maybe others do.

01:55:37.000 But that gives you a window into what we would call a model system in biology that I think the

01:55:42.240 applications of which are much broader. I think the work that you're doing and the way that you're

01:55:46.380 communicating and sharing it is just an incredible value. It's a resource to me personally.

01:55:50.040 Thank you.

01:55:50.420 And therefore, by extension, my patients. But I think given that I'm kind of a nobody with a

01:55:54.420 very small practice, I think more broadly, that's a huge application. And in fact, to people who can

01:55:59.880 take care of themselves, the reality of it is so much of what you do and what I do, you don't really

01:56:04.700 need a doctor to do for you. A person who there are now resources out there, whether it be podcast

01:56:10.180 books that allow a person enough information to work on their sleep, to work on their management of

01:56:16.540 their own distress, their nutrition, and these other things that in some ways, people like you and I

01:56:21.520 are more there for accountability. And then some of the nuanced stuff around the diagnoses and maybe

01:56:27.180 ordering the interventions a little bit.

01:56:30.060 But actually, I wanted to highlight, I think you bring up a key point because I have a lot of

01:56:33.160 patients to see me who are engineers and they often tell me, I wish I went to medical school

01:56:37.100 because I could do what you could do. And then I kind of remind them, you know, the burnout rates

01:56:40.360 of medicine are about 50%. So it's like, it's not that going to medicine would solve this problem,

01:56:44.800 but you can still make a huge impact on the lives of your coworkers, your family, just with the

01:56:48.920 knowledge you've gained. And that's been one of the most rewarding thing. I think

01:56:51.400 you know from your audience too, that many individuals have gone out and they've made

01:56:55.000 an impact on their community. They've become sort of the evangelists for health and you don't need

01:56:59.180 an MD, a PhD for that. You can do that. And that to me, as much as I do all these activities,

01:57:03.660 I get no more gratification. The most gratification is if I have a one-on-one interaction with the

01:57:07.900 human being and I can make an impact on their life. And you don't need special fancy degrees.

01:57:11.840 Anybody at any stage can do that. So, so I'm glad you called that out. You really don't need to

01:57:15.480 have advanced degrees to have this sort of meaningful interaction.

01:57:18.200 Well, thanks so much, Ron. I really appreciate it. And again, look forward to it. Where can

01:57:22.500 people find you? What's the easiest place for people to find you? Do you spend much time on

01:57:26.340 social media that we've just talked about? Is it easier for them to look at your books? Do you have

01:57:30.100 a blog?

01:57:30.560 So the best way is through the blog and just click on the email icon and I answer all my emails.

01:57:34.960 And the blog is?

01:57:35.740 So definitely reach out to me. Just put my name, ronishsinha.com, R-O-N-E-S-H-S-H-S-H-N-A.com.

01:57:40.720 And we'll link to all of that stuff.

01:57:42.140 Awesome. It's been an honor to be here with you, Peter. Thanks so much for all the work you're doing.

01:57:45.140 Thank you, Ron. You can find all of this information and more at peteratiamd.com

01:57:51.620 forward slash podcast. There you'll find the show notes, readings, and links related to this episode.

01:57:57.280 You can also find my blog at peteratiamd.com. Maybe the simplest thing to do is to sign up for

01:58:02.680 my subjectively non-lame once a week email, where I'll update you on what I've been up to,

01:58:07.300 the most interesting papers I've read, and all things related to longevity, science, performance,

01:58:11.940 sleep, et cetera. On social, you can find me on Twitter, Instagram, and Facebook,

01:58:16.780 all with the ID, Peter Atiyah, MD. But usually Twitter is the best way to reach me to share your

01:58:21.300 questions and comments. Now for the obligatory disclaimer, this podcast is for general informational

01:58:26.200 purposes only and does not constitute the practice of medicine, nursing, or other professional

01:58:30.780 healthcare services, including the giving of medical advice. And note, no doctor-patient

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01:58:51.460 advice for any medical condition they have and should seek the assistance of their healthcare

01:58:55.600 professionals for any such conditions. Lastly, and perhaps most importantly, I take conflicts of

01:59:01.400 interest very seriously. For all of my disclosures, the companies I invest in and or advise, please visit

01:59:07.400 peteratiyahmd.com forward slash about.

The Peter Attia Drive - September 02, 2019

#69 - Ronesh Sinha, M.D.： Insights into the manifestation of metabolic disease in a patient population predisposed to metabolic syndrome, and what it teaches us more broadly

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