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146: The Muscle Biology Behind Diabetes Risk — Transcript

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0:00Your muscles might be causing insulin
0:02resistance. [music] Most people blame
0:04diet, but your muscles play the biggest
0:07role, and not all muscle is the same.
0:11Slow-twitch fibers are highly insulin
0:13sensitive.
0:14>> [music]
0:14>> They pull glucose out of your blood very
0:16efficiently. Fast-twitch fibers, they're
0:19not as good at this, especially the most
0:22glycolytic of those fast-twitch [music]
0:24fibers. So, if you have more fast-twitch
0:27muscle, your body may struggle more with
0:30regulating blood sugar levels.
0:32>> [music]
0:32>> And those are the fibers that break down
0:34first with a poor diet and aging. That's
0:37why [music] two people can eat the same
0:39way and get very different results. But,
0:42[music] here's the upside. You can
0:44change your muscle. Simple aerobic
0:47movement like walking or cycling can
0:49shift your muscles to become more
0:50insulin sensitive. [music] So, this
0:52isn't just about what you eat, it's
0:54about what your muscle is made of.
0:57This [music] is lecture 146 of the
0:59Metabolic Classroom.
1:01Welcome back to the Metabolic Classroom.
1:03I'm Ben Bickman, metabolic scientist and
1:06professor of cell biology.
1:08In today's mini lecture, we are learning
1:11about muscle fiber types and how they
1:13influence insulin sensitivity.
1:16And why this slightly more technical
1:19topic has some very interesting and
1:23meaningful implications for
1:24understanding that diabetes risk,
1:27specifically.
1:28But, as you'll see, this has important
1:31implications for why different ethnic
1:34groups can develop type 2 diabetes so
1:36much more readily than others.
1:39I find this topic personally very
1:41interesting because it bridges some
1:43basic cell biology, as you'll see, but
1:46all in the context of a practical
1:49clinical pattern that we do see play out
1:52across populations and ethnicities
1:54globally.
1:55When we think about insulin resistance,
1:57we tend to focus on the usual suspects
1:59like liver and adipose tissue and diet
2:02and stress and poor sleep. And those are
2:04all, of course, very legitimate, very
2:06relevant. But we don't often talk about
2:09Well, even when we talk about muscle
2:11tissue, we don't talk about the
2:13differences in muscle type. As you'll
2:17see. And in order to understand what I
2:19mean by that, let's start this mini
2:22lecture by discussing muscle fiber
2:24types.
2:26Skeletal muscle is not a heterogeneous
2:28tissue. Uh it's not like fat tissue. Fat
2:31tissue is fat tissue is fat tissue. Uh
2:34you know, depending assuming we're
2:36talking about it from the same
2:37locations. But when it comes to muscle,
2:39it's a very mixed tissue. It's not made
2:42up of a single uniform cell type, but
2:45rather it's a bit of a mosaic of
2:48different fiber types, muscle fiber
2:50types. And each within these different
2:53fibers are distinct uh structural
2:56differences and contractile differences
2:59and metabolic characteristics, as you'll
3:01see.
3:02So when you look at a cross-section of,
3:05say, leg muscle, that's the most
3:07commonly studied muscle. You take a
3:08biopsy of someone's leg muscle, their
3:10quadriceps. And if you look at that
3:12under a microscope, you see that within
3:15even one person's muscle tissue, it
3:17really is a mosaic. There are some dark
3:20fiber muscle fibers interspersed with
3:23some light muscle fibers. And each of
3:26those has a different metabolic identity
3:28and activity.
3:30The classical classification system
3:33divides the human muscle type of fibers
3:36into two broad categories, type one and
3:38type two.
3:40Type one fibers are commonly called
3:42slow-twitch fibers. They contract more
3:45slowly, they generate less force, and
3:48are relatively resistant to fatigue. So
3:51they're used to being contracted for
3:53longer periods of time. These are the
3:55fibers that you use during these
3:57sustained very low-intensity activities,
4:00like you're going on a walk or you're
4:02standing
4:04in the kitchen or you are cycling at a
4:07very steady, low-intensity pace.
4:10Uh the type 1 fibers are very densely
4:12packed with mitochondria. They have a
4:15rich vascularity to them, so a lot of
4:18capillaries. And no surprise with these
4:21two attributes in mind, they also rely
4:23primarily on oxidative metabolism. In
4:27other words, the oxygen-dependent
4:29production of ATP in the mitochondria.
4:32So, these are also fibers that will very
4:35readily burn fat. They will burn
4:36glucose, they'll burn ketones, but
4:38always relying on the mitochondria and a
4:42high amount of oxygen. So, you could
4:44think of them as like a diesel engine in
4:47in your musculature. They're not really
4:49flashy, they're not going to put out a
4:51lot of high rapid power and speed, but
4:54they're very efficient over the long
4:56haul.
4:57Now, type 2 fibers are fast-twitch
5:01fibers.
5:02They contract quickly. They will produce
5:04a lot of force, but they also fatigue
5:08fairly quickly. These are your sprint
5:10and power fibers, the ones that fire
5:12when you're lifting weights or you are
5:14sprinting.
5:15If the type 1 fibers are like the diesel
5:17engine, then you could say that the type
5:192 fibers are like a high-performance gas
5:21engine. This is like a race car. It
5:23delivers explosive power, but it burns
5:26through the fuel very quickly.
5:28Type 2 fibers actually do have some
5:31subdivisions, where in humans they're
5:33often further divided into type 2A and
5:36type 2X.
5:38Um and just a little bit on that,
5:39although through the through the rest of
5:41the mini lecture, I'm not going to
5:43really further distinguish them just
5:45beyond calling them type 2. But for the
5:47sake of being thorough, I'll be brief in
5:49covering them. Type two A fibers are of
5:53course fast twitch, but they also still
5:55have a pretty high degree of an
5:57oxidative capacity, so they do rely on
5:59the mitochondria. So, they're more of
6:01kind of in between the type two and type
6:04one. They're you know, they they're in
6:05type two, but they're kind of close to
6:07type one.
6:08Um, but then you have the type two X
6:10fibers, and these are the proto the the
6:13prototypical fast twitch. They're very
6:15glycolytic, so glucose burning, and they
6:18rely on a non-oxidative
6:21metabolism. So, they don't rely on the
6:22mitochondria.
6:24They're the most powerful, the fastest,
6:26but they also fatigue the fastest. So,
6:29you get a lot of action out of them, and
6:32then they're done.
6:33In a typical healthy adult, muscle fiber
6:36composition is roughly half type one and
6:38half type two, but there is enormous
6:42individual variation. The range of type
6:45one fiber content reported in human
6:48muscle biopsy studies spans from as low
6:51as 13%
6:53to as high as 98%. That's a pretty
6:56staggering biological range within one
6:59species, we humans.
7:01Genetics accounts for a large portion of
7:04this variation, but also some things
7:07like training history, age, and
7:10metabolic health can play some
7:11meaningful roles as well. Now, let's
7:15transition to talk about why the fiber
7:17type matters when it comes to this
7:19primary metabolic marker of insulin
7:22resistance.
7:24That's the heart of the lecture, after
7:26all.
7:27Skeletal muscle is, of course, the
7:29single largest site of
7:31insulin-stimulated glucose uptake in the
7:34body. When blood sugar rises after a
7:36meal, and then insulin's released to
7:38help clear that glucose, it primarily is
7:41acting on the muscle. About 80% of the
7:45glucose clearance after a meal is going
7:48into the muscle. And this has been
7:50validated with the gold standard studies
7:53of euglycemic hyperinsulinemic clamps.
7:56These the gold standard for measuring
7:58insulin sensitivity. And that's where
8:00that number was identified, the 80%
8:02uptake. Of course, the liver matters. It
8:04takes up a good a good portion. Adipose
8:07tissue takes up some but when we look at
8:09the insulin stimulated glucose uptake,
8:11but the muscle is the
8:13it takes the lion's share. So, the
8:15metabolic behavior of the muscle matters
8:18enormously when we consider whole body
8:20glucose homeostasis.
8:23And here is the central observation that
8:26motivates the lecture. Type 1 fibers
8:29appear to be more responsive to insulin
8:32than type 2 fibers.
8:34Most especially when compared with the
8:36type 2X, those highly glycolytic fibers,
8:39that fast twitch extreme. Now, why is
8:41that? Multiple molecular reasons have
8:44been identified and they present a very
8:46coherent picture when you look at them
8:48together.
8:49Compared with type 2 fibers, type 1
8:52fibers carry substantially higher
8:55protein levels of the insulin receptor
8:58itself
8:59as well as GLUT4, the glucose
9:01transporter,
9:02and some enzymes like hexokinase 2,
9:05glycogen synthase, and pyruvate
9:08dehydrogenase. Now, that's a lot to get
9:11at the first pass. So, we're going to
9:12revisit that, but looking through that
9:14list that I just mentioned carefully,
9:16and you can see that
9:19you can almost you can narrate the
9:21entire story of glucose metabolism from
9:24the insulin signal to getting into the
9:27muscle to be stored or burned.
9:30More insulin receptors at the cell
9:32surface means that type 1 fibers are
9:35better equipped to detect the insulin
9:37signal and respond to it in the first
9:39place.
9:41More GLUT4 means that more glucose
9:44transporters are available to traffic
9:46that glucose from the plasma, from the
9:49blood, into the cell itself.
9:52Uh and that translocation
9:54event is of course necessary. You got to
9:56get that glucose in. Now, once the
9:58glucose is in, that's where the
10:00hexokinase comes in. Hexokinase will
10:03then
10:04phosphorylate, or you could say locks in
10:07that glucose,
10:08um the moment the glucose comes in. What
10:10prevents the glucose from coming in the
10:12GLUT4 then right back out through that
10:14same glucose transporter? It's
10:16hexokinase. It locks the glucose in.
10:18That is that first step in glucose
10:22burning, or glycolysis.
10:24And it turns it into a molecule called
10:26glucose-6-phosphate.
10:28So, hexokinase will add that phosphate
10:30group. But, that essentially locks the
10:32glucose in place and determines its
10:35fate.
10:36Then you have the other enzymes I
10:37mentioned, like glycogen synthase. That
10:40can take that glucose-6-phosphate
10:42molecule and then divert it into
10:45glycogen storage. So, a way for the type
10:481 fibers to store that glucose for later
10:51use. But then, of course, I also
10:53mentioned pyruvate dehydrogenase.
10:56That is that last enzyme that sits at
10:58the gateway of the mitochondria. So,
11:01when I had mentioned that the type 1
11:03fiber relies more on oxidative, or
11:05mitochondrial,
11:07um burning,
11:08pyruvate dehydrogenase is that critical
11:10enzyme that will take that
11:12glucose signal as we're breaking down
11:15that glucose molecule, and it will say,
11:17"I'm going to send you into the
11:20mitochondria."
11:22It turns it into acetyl-CoA, and then
11:24the mitochondria will burn that
11:26acetyl-CoA for lots of ATP.
11:29Type 1 fibers have more capacity at
11:32every single step of that pathway.
11:34They're They appear to be better at
11:35responding to the insulin signal, better
11:37at importing the glucose, better at
11:39storing it or burning it. Research has
11:41confirmed that insulin-stimulated
11:43glucose disposal rates, so the rate at
11:46which you can clear the glucose from
11:47your blood, it is strongly correlated uh
11:51with in positively correlated with the
11:53proportion of type one fibers in the
11:55muscle. So, in plain language, the more
11:58slow-twitch muscle you have, the more
12:00easily it seems the body can manage the
12:03glucose in response to insulin. Now,
12:06everything I said is true and accurate,
12:08but having said that, there is an
12:10important nuance worth understanding
12:12here. That when scientists look at the
12:14actual insulin signaling response per
12:17unit of protein within the muscle, the
12:20intrinsic um sensitivity of the two
12:24fiber types, so type one and type two,
12:26actually appears to be closer than we
12:28originally expected. It seems that the
12:31main advantage of type one fibers is
12:34largely quantitative.
12:36We They just carry more of the relevant
12:38molecular machinery. It's not that
12:40they're fundamentally more responsive to
12:42the insulin. The benefit really then
12:45comes from It's a matter of abundance,
12:47not kind of inherently anything superior
12:50with the type one.
12:51This matters because it tells us that
12:53the fiber type effect on insulin
12:55sensitivity is primarily about the scale
12:58of the glucose handling uh
13:00infrastructure, the molecular machinery.
13:02It's not something intrinsic about the
13:05type one fibers being superior to the
13:06type two.
13:09Research on people with metabolic
13:10syndrome, so insulin resistance, has
13:13confirmed this picture in a very
13:14compelling way. When sedentary
13:16individuals with metabolic syndrome were
13:19compared to healthy sedentary controls
13:21using the clamp technique I mentioned
13:23earlier, those with metabolic syndrome
13:26had significantly fewer type 1 fibers
13:29and relatively,
13:31that word is important, relatively more
13:33type 2 fibers.
13:36Insulin responsiveness correlated
13:38tightly with the proportion of type 1
13:41fibers. Critically, this was true in
13:43pre-diabetic individuals before they
13:46were ever diagnosed with type 2
13:47diabetes. This is important because it
13:50tells us that the fiber composition
13:52shift is more than
13:54um just a downstream consequence of
13:56having diabetes. It's present earlier.
13:59In fact, it precedes it. So, it might be
14:01a genuine contributing factor to insulin
14:04resistance and not just a consequence of
14:06it.
14:08Perhaps the most striking data in this
14:10field comes from studies that
14:12deliberately recruited subjects with
14:14extreme differences in fiber type
14:16proportions. So, comparing individuals
14:19with about 60% type 1 fiber
14:22um against those with about 36%
14:26All of them otherwise healthy young
14:27adults with normal fasting um glucose
14:30and normal fasting insulin. Now, despite
14:32appearing metabolically normal and the
14:35same by these standard markers, the
14:37group with lower type 1 fiber proportion
14:41showed whole body insulin sensitivity
14:43that was decreased by approximately 50%
14:46compared to the high type 1 group.
14:49That, of course, is not subtle. A 50%
14:52reduction in insulin sensitivity is the
14:54kind of magnitude that we often
14:56associate with and we see with uh
14:59pre-diabetes.
15:00But, remember, this was in young,
15:02apparently healthy people whose blood
15:04work would not have raised any alarms
15:06whatsoever.
15:08The cardiometabolic implications do
15:10extend beyond glucose handling, which is
15:12just further testament to the relevance
15:14of insulin resistance.
15:16Research examining premenopausal women
15:18found that the percentage of type 1
15:20fibers positively correlated not only
15:23with insulin sensitivity, but also with
15:25favorable arterial elasticity and lower
15:29blood pressure.
15:31While type two fibers negatively
15:33correlated with insulin sensitivity and
15:35this arterial elasticity. So, you know,
15:37just touching on the risk of having a
15:40higher or lower blood pressure.
15:42A fast-twitch dominant muscle fiber
15:45profile appeared to link across multiple
15:48cardiovascular risk factors
15:49simultaneously. Now, there's more nuance
15:52than this and I hate the thought that I
15:54might be sounding like I'm vilifying
15:57type two. Remember,
15:59the difference between them is probably
16:01that people that type one fibers tend to
16:04be bigger than type two fibers in the
16:06average person. That's the critical
16:09thing to keep in mind.
16:12Now, what happens when you challenge the
16:16organism with a diet? Well, there's some
16:18animal research that we have to rely on
16:20here.
16:21Some animal studies that use
16:22diet-induced obesity models, so they
16:25make them fat with high-fat, high-sugar
16:27diets.
16:28They've shown that this this
16:30diet-induced insulin resistance develops
16:32specifically um
16:34in in the type two fibers with most with
16:38the most glycolytic fibers showing
16:40reduced GLUT4 protein expression
16:42compared to GLUT1 or compared to the
16:45type one, rather.
16:47So, this this compounds the risk in
16:49individuals who already carry a
16:51fast-twitch dominant fiber profile. So,
16:53that's what's important. If someone has
16:55naturally more fast-twitch, they might
16:58be starting from a bit of a
17:00disadvantageous
17:01position metabolically that they may
17:04they may be more susceptible to
17:06diet-driven
17:08metabolic problems. That's what the
17:09animal studies suggest.
17:12Now, you're wondering what you can do to
17:14shift your fiber type.
17:17Although it's should be more a matter of
17:22increasing the fibers in general, which
17:25I'll come back to in a moment. Now, when
17:27it does come to fiber type, genetics is
17:29the dominant factor
17:31that determines it. Twin studies suggest
17:34that about 40 to 60% of fiber type is
17:37heritable. But that still does leave, of
17:39course, about 40 to 60% that can shift
17:42due to lifestyle.
17:45Now, before discussing fiber type
17:47shifts, it is worth stepping back and
17:49asking the more fundamental question.
17:50Given that type one fiber
17:53given that the advantage, as I noted a
17:54moment ago, is primarily a matter of
17:56quantity, you just have more of these
17:59proteins in larger type one fibers. What
18:03I think the better strategy is not to
18:05necessarily convert fast-twitch fibers
18:08to slow. I don't think that's relevant
18:10at all, but it's really more a matter of
18:13just building more muscle. A larger
18:16muscle and larger fast-twitch fibers
18:19will just carry more total metabolic
18:21machinery than a smaller one. This, I
18:23think, is the most underappreciated
18:25argument for resistance training as a
18:28metabolic health tool.
18:30It It does not, just, of course,
18:32influence fiber type. If you resistance
18:34train, you end up having more type two.
18:37Um but it's it's because you have larger
18:39type two.
18:40That's the critical thing, that it
18:42expands the overall size of the fiber.
18:45And so you just have more glucose
18:47disposal potential.
18:49With that in mind, I strongly maintain
18:52that resistance training is essential.
18:55Beyond fiber type effects, the more
18:56important metabolic benefit is the
18:58absolute increase in muscle mass itself.
19:01More total sites for insulin-stimulated
19:04glucose disposal, regardless of fiber
19:07type. Importantly, this is something
19:09endurance exercise simply doesn't really
19:12do. As much as endurance exercise can
19:14shift you to have more of a population
19:17or volume of type 1,
19:19uh
19:20it will not You don't look at an
19:22endurance athlete and see big muscles.
19:24Uh more Remember, more muscle is
19:27generally going to be a better thing
19:28here.
19:29But in this regard, aging does work
19:31against us, whether we want it to or
19:34not. Fast-twitch fibers atrophy the most
19:37readily
19:38um more than the slow-twitch. We just
19:40continue to use slow-twitch fibers more
19:42as we age. And as we become sedentary,
19:45it's the power fibers that we start to
19:47lose the most. And so, I feel very
19:50strongly that we need resistance
19:51training to defend muscle mass and keep
19:54total um glucose disposal capacity as
19:57large as possible.
19:59Now, let's shift into a topic that you
20:02might not expect to focus on when we
20:05just talk about fiber type. And that is
20:06the ethnic differences.
20:08Because across the different ethnicities
20:11globally, we do see very different
20:13diabetes risk. And some of this is
20:18attributed to muscle fiber type.
20:20So, let's talk about ethnicity. Because
20:23I think this gives a very interesting
20:25and kind of beautiful nuance as we look
20:28at globally.
20:29Because as I noted, type 2 diabetes does
20:31not affect all populations equally. And
20:34muscle fiber type and its composition
20:36is, I think, one of the more
20:37underappreciated contributors to these
20:39disparities.
20:41Now, I'm going to talk in very gen- um
20:43general broad terms, which is always
20:45dangerous. Please appreciate that within
20:48each ethnicity, I am painting in very
20:51broad strokes.
20:52Um where within the ethnicity, it's
20:54very, very possible to have these
20:56individual differences. You know, you
20:58are more than just your ethnicity, of
21:01course.
21:03With that in mind, black and Hispanic
21:06groups tend to have higher rates of
21:08diagnosed diabetes. Now, I'm presenting
21:09this of course from an American US
21:12perspective here, where most of the
21:14research has been done.
21:16So, here with with black and Hispanic
21:18groups, you see rates of diagnosed
21:20diabetes of about 11 to 12%. But, that's
21:23interesting because compared to whites,
21:27you see about 7%. So, that's quite a bit
21:29different. Now, lest the black and
21:32Hispanic groups
21:34feel very disappointed in these numbers,
21:37unfortunately, it can get much worse.
21:39Native Americans face rates as high as
21:4133%
21:43in some communities within the United
21:46States. And South Asians show rates that
21:49often will rival or exceed those of
21:51blacks, despite having considerably
21:53lower rates of clinical obesity.
21:56And when we look at the skeletal muscle
21:58physiology data,
22:01um we start to see, I think, a picture
22:03that is worth noting. All right. So,
22:04let's just start as I want to go through
22:06these different ethnic groups. Of
22:08course, I am presenting this primarily
22:10from the American perspective, where not
22:12only am I located, but where most of the
22:14research on this topic has been done.
22:17The primary ethnicity in the United
22:19States is white Europeans. So, white
22:21Europeans have served as the reference
22:23population in most of the fiber type and
22:26insulin sensitivity research.
22:28I don't think that is anything more than
22:30the fact that
22:32the research has been conducted in
22:34communities in areas with predominantly
22:37white participants. So, that became the
22:40sort of standard or the reference point.
22:43Now, with that context in mind, white
22:45Europeans will show a relatively
22:46balanced slow-twitch to fast-twitch
22:49ratio. It really is about 50/50 on
22:51average. Of course, there's wide
22:53individual variation. There always is in
22:55every ethnicity.
22:57Insulin resistance in this group has
23:00been most consistently linked to
23:02mitochondrial dysfunction and
23:05and intramuscular lipid accumulation
23:07within type 1 fibers.
23:10Um so, remember, this is the reference
23:12point. That's And then let's move into
23:14the other ethnic group. So, let's turn
23:15to blacks first.
23:17The I think the next most dominant group
23:19within the United States.
23:20Uh the research has found that this
23:22group has on average a greater
23:24percentage of type 2 skeletal muscle
23:27fibers and lower maximal aerobic
23:31capacity compared to whites.
23:33Direct fiber type biopsy studies found
23:36that African-American women showed
23:38significantly higher proportion of these
23:41type 2X, the most glycolytic fibers, and
23:45fewer type 1 fibers compared to
23:49comparably obese white women.
23:51That further correlated with higher
23:53rates of obesity, reduced rates of fat
23:56oxidation, and greater insulin
23:58resistance. This study, in fact, that I
24:01am citing here was actually conducted
24:03where I earned my PhD at East Carolina
24:05University. So, again, just to paint
24:07that picture cuz it was a very
24:08compelling study. I remember when the
24:10work was being done. They looked at
24:12white women, black women of generally
24:15equal obesity levels, and found that the
24:17muscle biopsy in the black gals had much
24:21higher rates of these the most extreme
24:23power glycolytic um muscle fibers,
24:27a muscle fiber type, and they tended to
24:28have much higher rates of type 2
24:32diabetes and or risk and very and much
24:35lower rates of fat oxidation, fat
24:37burning.
24:38The studies of the um skeletal muscle
24:41enzymatic activity, so how how well
24:44these enzymes are working, really
24:46reinforces this, showing much higher
24:48glycolytic activity compared to the
24:51oxidative um capacity. So, that's that a
24:53kind of a biochemical signature that's
24:56very consistent with a muscle that runs
24:59more on a glycolytic metabolism at
25:00baseline.
25:02All right, now let's shift to South
25:03Asians. This is people from India,
25:05Pakistan, Bangladesh, Sri Lanka, and any
25:09other kind of neighboring countries.
25:11They present one of the most clinically
25:13important and scientifically puzzling
25:15cases of ethnic diabetes disparity.
25:19They have remarkably high rates of type
25:212 diabetes relative to their degree of
25:23obesity.
25:25And lifestyle factors alone can't really
25:27account for this. One contributing
25:29factor may be actually detectable from
25:32birth. South Asian newborns have much
25:36lower skeletal muscle mass
25:38and higher trunkal fat compared to white
25:42European newborns.
25:44Um this is sometimes referred to as the
25:46thin fat phenotype. Remember, of course,
25:50since skeletal muscle is the primary
25:52site of insulin-stimulated glucose
25:54disposal, entering life with less of it
25:57may
25:58be a metabolic disadvantage um that can
26:02compound over time.
26:04The South Asian picture carries a
26:06striking paradox, even at the
26:08mitochondrial level, where both diabetic
26:11and non-diabetic South Asians have
26:14higher skeletal muscle
26:16um mitochondrial oxidative capacity than
26:19non-diabetic um white Europeans.
26:22And yet they are substantially more
26:24insulin resistant. So this suggests that
26:27it is more complicated than just having
26:28more type 1. As much as I earlier
26:31presented a general overview that more
26:34type 1 tends to be an advantage, this
26:37point, now that we see in South Asians,
26:39comes back to the idea of quantity. So
26:41again, the primary driver here appears
26:44to be the quantity of muscle rather than
26:46its quality. More type 1. Of course,
26:49alongside a different sort of fat
26:52distribution where South Asians tend to
26:54have much more
26:55fat cell hypertrophy. But I don't want
26:57to get into all that because remember, I
26:58wanted this topic to focus just on
27:02muscle. But remember, there are
27:04additional inputs that go in here in in
27:07the South Asian population that's very
27:09very relevant.
27:11Okay, now let's go from South Asian to
27:13East Asians.
27:14Um overall, East Asians have
27:17among the lowest obesity rates globally,
27:20but their metabolic status is still
27:22problematic because they will tend to
27:25have higher rates of abdominal and
27:28visceral obesity at any given BMI
27:31compared to white Europeans. And this is
27:33something evident even in childhood. So
27:35I'm going to say that again. You can
27:36have say an East Asian child and a white
27:40European
27:42descent child of the same overall body
27:45fat and the East Asian will tend to have
27:47more of that stored abdominally and
27:49viscerally.
27:51Um the evidence also suggests that
27:53there's a lower absolute skeletal muscle
27:56mass on average in East Asians. The
27:58result is a population that does have a
28:00metabolic risk that challenges the
28:03standard Western BMI thresholds. Once
28:06again, this is an issue where a lot of
28:09these
28:10baseline metrics were identified in
28:12white Europeans including BMI here where
28:15East Asians tend to just have yes, both
28:18less fat mass, but also less lean mass.
28:22And so you need to have a different BMI
28:24threshold for East Asians than you see
28:26in other ethnicities. And indeed you do.
28:28You you start to see more and more
28:30revised BMI cutoffs that have been
28:32proposed specifically for East Asian
28:34populations.
28:35Now, let's come back to the Native
28:37Americans that I mentioned earlier. We
28:39do see within the United States the
28:41highest diabetes prevalence in this
28:42community by far.
28:45Well-studied populations such as the
28:47Pima Indians have been documented to
28:50have muscle fiber profiles with
28:52relatively low type 1 proportions, which
28:55of course correlates with profoundly
28:57elevated insulin resistance measurable
28:59in children and young adults
29:01um long before the diabetes is formally
29:04diagnosed. But having said that, the
29:06earliest recorded instance of fully
29:08diagnosed type 2 diabetes that I'm aware
29:10of was a 4-year-old Pima Indian.
29:14So this is a population that is very
29:15susceptible to insulin resistance and
29:18its consequences. This
29:21population is the origin of the thrifty
29:24genotype um
29:26theory or hypothesis. The idea that
29:28ancestral populations um in different
29:31regions adapted to feast famine cycles
29:34and that this adaptation resulted in a
29:37metabolic phenotype that wants to store
29:40energy more efficiently. That that idea
29:43does have some merit. Um but that same
29:45phenotype, of course, that body type
29:48becomes very pathological under our
29:50modern conditions of constant
29:53caloric abundance and I would say
29:55overconsumption of carbohydrates.
29:57The hypothesis does have its critics and
30:00they are um
30:01the criticisms are very valid. So this
30:04is a very kind of general theory that
30:08sounds good um but has people have poked
30:11some holes in it. But just so you're
30:12aware of it that that's the origin of
30:14that viewpoint that you might have heard
30:15of.
30:16Now the last group I want to mention is
30:17Pacific Islanders in part because of
30:19where I am in recording this in the
30:21state of Utah. We have a high Pacific
30:23Islander population, which I love. Um
30:26this group will include Polynesian, um
30:29Micronesian, and and other just Pacific
30:32Island populations.
30:34Of course, this is a group that has
30:35within itself a lot of variations. So
30:38please once again remember I'm not
30:40trying to create um,
30:42these siloed populations that within
30:45each ethnicity you do continue to have
30:47individual variations. But this group
30:50deserves some mention here because they
30:52carry some of the highest rates of
30:53obesity and type 2 diabetes in the
30:55world. With some Pacific island nations
30:58reporting diabetes prevalence well above
31:0140%. Indeed, the most diabetic countries
31:04on the planet are the Pacific are
31:06countries within the Pacific Islands.
31:08What makes this population particularly
31:10interesting from a body composition
31:12standpoint is that they tend to have
31:14greater
31:15muscle mass and bone density than white
31:18Europeans at the same BMI. So once
31:20again, we have a group here where the
31:22standard BMI thresholds tend to
31:24underestimate the metabolic risk rather
31:27than overestimate it. So it's kind of
31:29opposite of the East Asians. East Asians
31:32need BMIs that are lower.
31:34Pacific Islanders need, um, BMIs that
31:37are generally higher. Now, despite the
31:40relatively higher muscle mass, insulin
31:42resistance and diabetes remain
31:45strikingly high, which points to
31:48something it's a combination of factors.
31:50Of course, very heavily related to diet
31:53and dietary changes, but also more
31:55central fat, but also possibly
31:59possibly more type 2 fibers. Now, why am
32:03I saying possibly? Because of all the
32:05populations that I mentioned, this is
32:07the group with the
32:09least amount of muscle biopsy data. We
32:12just there are just huge gaps, um, here.
32:15So a very limited amount of data here
32:17that my hope is that this important gap
32:20will be, um, closed soon. Um, but as
32:24much as I'm bringing in the Pacific
32:26island population in this lecture on
32:27muscle fiber type,
32:29oddly enough, um, we don't have a lot of
32:32data when it comes to muscle fiber. In
32:34fact, I'm unaware of any, um, looking in
32:36Pacific Islanders. I strongly speculate
32:39that there's going to be much more type
32:40two, that this is going to be a muscle
32:42fiber profile that will be more similar
32:44to what I described in the black
32:46populations earlier.
32:48All right. Now, let's wrap this up. Let
32:50me bring it all together.
32:52The fiber type composition of your
32:53skeletal muscle is a biological input
32:56that will and does appear to affect your
32:58baseline insulin sensitivity.
33:00The general overview is that having a
33:03higher proportion of the slow twitch
33:06type one fiber appears to be
33:08metabolically advantageous because those
33:11fibers express more of all of the
33:13enzymatic machinery at almost every step
33:17to respond to the insulin and to clear
33:19that glucose.
33:21And a shift toward or someone having
33:23more fast twitch glycolytic fibers
33:26um
33:27will it tends to correlate with a muscle
33:30that is less responsive. But remember,
33:33the difference is in the amount that we
33:37have. That's the critical thing to keep
33:39in mind here. And And as I elaborated
33:42the differences across ethnicity, which
33:44are very real, we see very real
33:46differences in risk of these metabolic
33:48diseases associated with very real
33:50differences in muscle fiber type, it is
33:52not the complete story. As I've alluded
33:55to, there's differences in fat cell
33:57size, there's differences in visceral
33:59adiposity, beta cell function in in
34:02blacks and East Asians, for example.
34:04And of course
34:06um at the end of it all, I would say
34:07it's the dietary patterns that will
34:10matter most. So, regardless of how you
34:13go into this with what you think your
34:15muscle fiber type may be,
34:18genetics is not your um destiny here.
34:21That it's going to be your lifestyle
34:23variable that matters most. That to me,
34:24I think I hope is the most important
34:26message.
34:27But within the midst of these important
34:29messages, I hope you appreciate that
34:31fiber type
34:32is not necessarily fixed that with more
34:35aerobic exercise you can push a little
34:37more type one with more resistance you
34:40can push more type two
34:42regardless of ethnicity and remember
34:44it's the volume or the amount of the
34:47fibers that matters most less [music] so
34:49it's type that's it class dismissed
34:52until next time [music]
34:54more knowledge better health.

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