Exercise Snacks: Can just four minutes of exercise a day improve blood sugar?

[Kristin] (0:00 - 0:14)
Wow, we are bad study participants, aren't we? Which you'd think we'd be better.

[Regina]
I think your point is excellent, though, because if you and I are not adhering to the protocol, what did everyone else do?

[Kristin] (0:20 - 0:29)
Welcome to Normal Curves. This is a podcast for anyone who wants to learn about scientific studies and the statistics behind them. I'm Kristin Sainani.

I'm a professor at Stanford University.

[Regina] (0:29 - 0:35)
And I'm Regina Nuzzo. I'm a professor at Gallaudet University and part-time lecturer at Stanford.

[Kristin] (0:36 - 0:41)
We are not medical doctors. We are PhDs. So nothing in this podcast should be construed as medical advice.

[Regina] (0:41 - 0:57)
Also, this podcast is separate from our day jobs at Stanford and Gallaudet University. Kristin, recently I had a great conversation that I totally loved, and I think you will appreciate it. It was with a veteran science journalist who listens to this podcast.

[Kristin] (0:57 - 0:59)
Yay, a listener. Hooray.

[Regina] (1:00 - 1:16)
Yeah. So he'd seen a Washington Post story about exercise snacks, but instead of just stopping there, he went and pulled up the original paper, the original study, and he said to me basically, should this have even been a story?

[Kristin] (1:16 - 1:33)
Oh, I love this, Regina. Maybe he learned from the podcast, you've got to always pull the original study, because unfortunately a lot of science news is just one paper at a time, which is often maybe not a lot of strong evidence, as we've talked about in this podcast. So we really have to ask, does this one paper deserve attention in the media?

[Regina] (1:34 - 2:04)
I know I've struggled with this as a science journalist, right? You want to cover interesting new research that's relevant to your audience, but you also don't want to oversell a single study, right? So it's a little like, how much evidence do you really need before you start telling your millions of readers about this cool new health or exercise trend?

So that's what we're going to talk about today, exercise snacks, which by the way, Kristin, is not about snacking while you exercise, sadly. This is not about eating.

[Kristin] (2:04 - 2:29)
I love that name. And this is what exercise scientists sometimes call very short bursts of vigorous exercise. Of course, it sounds cuter and friendlier if you call it an exercise snack rather than like exercise.

It's not an exercise meal, it's just a little snack. But Regina, what makes an exercise snack as opposed to an exercise meal? Like how short or little does the exercise have to be?

[Regina] (2:30 - 2:51)
I think it's a little like eating. I think there's not a hard cutoff, right? At what point does your long snacking session actually turn into lunch and not just a morning snack?

So I've seen this in the literature for as little as 15 seconds, counting as an exercise snack all the way up to five minutes.

[Kristin] (2:51 - 2:57)
15 seconds. I feel like that's like an M&M. Does that even count?

One M&M. That is a bite.

[Regina] (2:57 - 3:08)
That's like an exercise nibble. So Kristin, you and I actually tried out some of these exercise snacks ourselves, which we will talk about later. I cannot wait to hear what you thought of them.

[Kristin] (3:09 - 3:12)
Yes, I did my N of 1 experiment as you requested.

[Regina] (3:13 - 3:45)
Okay. So the Washington Post article, I want to read you the headline, a little bit of how they framed it. Headline was this, four minutes of exercise a day could help control blood sugar.

The sub headline was, a new study found short exercise snacks were practical and effective for people with type 2 diabetes. And then the lead sentence, a single minute of exercise could be enough to help people with type 2 diabetes stabilize their blood sugar, according to an inspiring new study of exercise snacks.

[Kristin] (3:46 - 4:04)
That is really positive coverage. They characterized the study as inspiring, a little non-journalistic actually, Regina. But it makes it sound really effective and that is definitely the kind of headline and lead that gets people's attention because, you know, lots of people would like to shortcut their exercise.

[Regina] (4:06 - 4:16)
They would. They very much would. So that is the claim that I chose for us to evaluate today.

It's the headline, four minutes of exercise a day helps control blood sugar.

[Kristin] (4:16 - 4:33)
I got it. So we are evaluating a claim that's really just relevant to one news story then, Regina. Yep.

But that's okay because sometimes we scrutinize just one news story in this podcast. All right, Regina, let's now back up a little bit and talk biology here. Why would we think that a minute of exercise is enough to do anything at all?

[Regina] (4:33 - 4:47)
Right. Well, there's actually a lot of research being done on this because, well, first of all, it's an easy thing to study, as you might imagine. And of course, it has this like great feel-good message.

It's intoxicating.

[Kristin] (4:48 - 5:18)
I think anything where you put snack in the title, easy to recruit for the study. They might be surprised when they come in and find out it's an exercise snack. And I guess the idea here, Regina, is that a lot of people hate exercise.

I don't actually get that because I think exercise is really fun, but I know a lot of people are reluctant to exercise for whatever reason. So I think the idea here is that if you tell people you've got to exercise for an hour, the bar is too high, right? They're just not going to ever start.

But if you say, hey, you can do it in a minute, maybe it just feels more doable, lowers the barrier to entry, right?

[Regina] (5:19 - 5:29)
I think that is absolutely it, Kristin, but I want to back up for a second because did you just say, I'm not sure I understand why people don't like to exercise? Did you just say something?

[Kristin] (5:30 - 5:34)
I mean, that's my relaxation time. I don't get it. Like, isn't that?

That's my free time.

[Regina] (5:35 - 5:49)
I love you so much for that. But yes, I think that most people, unlike you, find it painful and difficult and uncomfortable. And yes, this is completely the idea, like even four minutes is better than nothing.

[Kristin] (5:50 - 6:07)
I have this theory that if everybody actually got to the point where they could run 20, 30 minutes in a row at a decent pace, not like the jogging thing people do when they're really walking, then they would experience the runner's high and then everybody in the world would run. And the issue is that people just don't get that far. Is that a weird theory?

[Regina] (6:08 - 6:16)
Can we? I want to do a study on this now. We should do a study on this.

Yes. We could randomize. Like, oh, yeah.

Okay. We can randomize listeners to the podcast.

[Kristin] (6:16 - 6:46)
I love it. Yes. Oh, you could listen to the podcast while running.

That's how you manage to sustain the 20 to 30 minutes without stopping. I love it. Okay, Regina.

So these exercise snacks. Yeah, I guess they're better than not doing anything. And one thing I really do like is you don't have to change your clothes, right?

And that's important because it's like a lot of work to find a jog bra that's clean and socks and shoes, right? And so I like this idea that all you need to do is just get your heart rate up for one minute.

[Regina] (6:46 - 6:58)
Oh, amen to that, to not having to find the exercise bra or put on shoes. But you're right. You've got to get your heart rate up.

The intensity is important. It's got to be vigorous. Getting up to walk to the fridge does not count, sadly.

[Kristin] (6:58 - 7:05)
Ah, yes. So the exercise that you get walking to the fridge to get a snack that you can eat, that does not count as an exercise snack.

[Regina] (7:05 - 7:48)
It does not. So Kristin, you and I did the exercise snacks ourselves. I texted you the ones they used in this study, which we'll talk about in a moment.

And here's what I texted you. Your assignment was step-ups, box runs, which is running forward, sideways, and backward for approximately two meters in each direction, or running on the spot for one minute, four times a day, spaced out by at least an hour and preferably within an hour of a meal. Do this for two days and aim for a perceived effort or intensity of seven on a one to 10 scale.

So what did you think? I'm dying to know.

[Kristin] (7:48 - 8:23)
Okay. So first of all, Regina, when you were reading all of those instructions, I realized that maybe I skimmed your text and I didn't quite follow them to the letter. I got the step-ups and the block runs.

I did not get the running on the spot. I did get the one minute four times a day, but maybe that was only because you told me about that before. And I didn't get anything about preferably within an hour of a meal.

So clearly I didn't read far enough in the text. It does make me wonder whether people in the study, if I couldn't follow all those instructions or bother to read them, maybe, you know, how closely did people follow all those instructions? I did do the one minute four times a day, but the rest of it I kind of ignored.

[Regina] (8:25 - 8:28)
I love that you're human about this and that you admit it.

[Kristin] (8:28 - 8:48)
Yes. And I should also give the caveat that I tacked on a few of these snacks after doing my actual workout for the day because I was already in workout clothes. So maybe those are technically like exercise dessert instead of snacks.

And I also put on a weight vest to do my exercise snacks, Regina, because that's my new piece of gym equipment aimed at not losing as much bone.

[Regina] (8:50 - 9:01)
Okay. I'm dying over here because I love how you're like, yeah, we've got this simple little exercise snack, but no, I'm going to make it much more intense. I'm going to add some hot sauce to my exercise snack.

[Kristin] (9:03 - 9:12)
And I noticed that the minute was enough to get me breathing hard, but I didn't sweat much. So that means I did not have to change or shower afterwards. So that was very convenient.

[Regina] (9:13 - 9:43)
It was. And I kind of liked it for that reason. Like it's not a whole big thing that you do.

You stand up to take a break because you're tired of sitting in front of the computer for that long. So I managed to do mostly four, I would say. But I did not follow the instructions either because I didn't like doing the step-ups or the box runs.

It was just kind of annoying. So I ended up doing a lot of push-ups, actually.

[Kristin] (9:43 - 9:47)
Oh, you didn't give me push-ups as an option, Regina. Not that I would have done push-ups. I know.

I know.

[Regina] (9:48 - 10:17)
Yeah, that's okay. I went off protocol on this. I did push-ups because I'm trying to work on my upper body, strength building.

And I did do some body weight squats, which were also not on the list I gave you. Wow, we are bad study participants, Regina. Which you'd think we'd be better.

I think your point is excellent, though, because if you and I are not adhering to the protocol, what did everyone else do?

[Kristin] (10:17 - 10:30)
Yeah. I mean, technically, we weren't actually participants, but you'd think we'd have an appreciation for the importance of staying to the protocol, given how much we talk about that and how much we're in research. So interesting that both of us were not that great about it.

[Regina] (10:30 - 10:44)
Nope. Nope. My gym trainer had recommended push-ups or running up the stairs.

And running up the stairs just seemed unpleasant. I'm on the 11th floor in my apartment building, so technically I could have done this, but no.

[Kristin] (10:44 - 10:50)
Ooh, that would be good exercise, although your neighbors may give you strange looks. I have done this in the past.

[Regina] (10:50 - 10:55)
I've actually run upstairs in the past during COVID when it was the only place I had to exercise.

[Kristin] (10:55 - 10:56)
Oh, smart.

[Regina] (10:56 - 10:57)
That's clever.

[Kristin] (10:57 - 10:58)
And did you get strange looks?

[Regina] (10:58 - 10:58)
I did.

[Kristin] (10:58 - 11:00)
Did you stay six feet from everybody?

[Regina] (11:01 - 11:12)
No one was in the stairwell, especially not on the 11th floor. I can say, though, a minute feels so long when you're doing push-ups, like that is a long time.

[Kristin] (11:12 - 11:35)
You know, I can actually relate because my daughter has to do planks for swimming. And so one day she's like, Mom, come do my dry land workout with me. And I was like, Oh yeah, it'll be easy.

Turns out she can do a plank for like four minutes. And I made it about 25 seconds and then crumbled and it seemed like an eternity. So I get it with, you know, maybe my arm strength is not so great or my core strength.

I don't know.

[Regina] (11:35 - 11:45)
I like doing planks. I'm going to add some planks in to this. So Kristin, I kept forgetting to do them.

So it ended up me doing a lot of push-ups at night before bed.

[Kristin] (11:45 - 12:16)
So you did four together and you didn't space it out an hour is what you're telling me? Well, I would like separate it by half an hour. You are worse on violating this protocol than me.

I do think like personally, I'd rather just get all my exercise done at once in the morning for an hour and a half or whatever, because yeah, you have to keep remembering and making an effort later on. So I did do all of mine and I did because it was only two days. I made an effort.

It's like, this is for the podcast. I'm going to make sure I do it. But it did take me having to think about it the rest of the day.

Like I still got to do that. I still got to do that. I'd rather just get it done all at once.

That's just me.

[Regina] (12:17 - 12:35)
I actually like doing them because I felt so virtuous when I was done. Like, yeah, look at me. I'm pumped.

My biceps are pumped. So I think that in the future when I do these exercise snacks, and we'll talk later about whether we're actually going to do them, but I would set an alarm. I think I would need to.

[Kristin] (12:35 - 12:40)
Oh, that's super smart. And again, because you don't have to change. You can just get up from wherever you are and do them right there.

So I like it.

[Regina] (12:41 - 12:43)
Yeah. Right. Even in the middle of when we're teaching.

[Kristin] (12:45 - 12:56)
I get my steps teaching because I do flipped classroom and we do these exercises. I walk all around. I get a lot of steps.

So I could just jump up and down the steps and then they might look at me weird, but my students already look at me weird. So it's fine.

[Regina] (12:56 - 12:59)
The class that we co-teach. I say we do some exercises.

[Kristin] (12:59 - 13:24)
We should make them all get up and do exercise snacks in the middle of class. We're doing that. They won't sweat too much, but then they'll feel like all refreshed and they'll be able to add better.

So I like it. I think that's fine. We're totally doing that next time you're out here.

But Regina, this brings up all this discussion. You and I didn't really follow the protocol perfectly. These were participants in a study and so maybe they were very committed, but do we have any data on compliance here?

[Regina] (13:24 - 13:39)
They did track compliance. Yes, they did. So maybe let's just talk about the study now.

How about that? Are we ready? Yeah.

Okay. It was published in June of this year in a journal called Diabetologia. Okay, that's a mouthful.

I can't be saying that right.

[Kristin] (13:42 - 13:53)
Diabetologia? That sounds right. Yes.

Okay. Terrible name for a publication. That is not like the publication I'm going to pull off the shelf and like, yes, today I want to read Diabetologia.

[Regina] (13:53 - 14:03)
I think it's also not going to get some TV news coverage because there's no way the broadcast journalist could figure out how to pronounce this.

[Kristin] (14:03 - 14:05)
It did get Washington Post coverage though.

[Regina] (14:05 - 14:36)
So there you go. It did. And it's actually a well-known journal in endocrinology and it has a high impact factor.

Okay. Good to know. So it was a team of exercise science researchers in Canada and they had 31 adults who were relatively inactive, who had type 2 diabetes that was fairly well-controlled without insulin.

And then everyone who managed to finish this study went on to participate in a longer 12-week trial of Exercise Next.

[Kristin] (14:36 - 14:44)
Oh, now wait a minute, 12 weeks instead of two days. I like that. And do we have results from that study?

That sounds more robust, longer.

[Regina] (14:45 - 14:47)
Not published yet as far as I can find.

[Kristin] (14:48 - 14:58)
Okay. So the study we're talking about today might just be a prelude to a larger study, but some graduate student needed a publication. So they wrote up this mini study as a paper.

Is that what you're telling me?

[Regina] (14:58 - 15:18)
Could very well be. Yes, Kristin. Okay.

So study design, it was case crossover trial with an exercise snack condition and a no snack condition. And the participants did get prepared meals to eat each day. So there wouldn't be differences in their calorie intake between conditions.

[Kristin] (15:18 - 16:03)
Oh, I love that. That's a really good control to make sure, yeah, you don't end up eating so much more. You eat a bunch of ice cream after you do the exercise snacks, that's going to affect your blood sugar, right?

I like that. And also free food. Free food gets people to do things.

So that's perhaps why they joined the study. I hope it was yummy prepared meals. All right.

Crossover. So it was a case crossover trial. Crossover means that everyone got both the exercise snack condition and the control condition, hopefully randomized order.

So some people did control first, others did exercise snack first. Okay, great. And we like the crossover design.

It's more powerful because everyone serves as their own control. So it's not a huge study, 31 people, but you do have increased statistical power since everybody is their own control. Absolutely.

[Regina] (16:03 - 16:14)
So the intervention condition was this one minute exercise snack four times a day for two days. And the control condition was life as usual, which means no exercise.

[Kristin] (16:14 - 16:22)
Two days. Two days. Okay.

That's what we tested. But that doesn't seem long enough to do anything. That's eight minutes of total exercise.

Really?

[Regina] (16:23 - 16:31)
I know, right? So I did the snacks for a couple of days, more or less faithfully. I'm not sure that my blood sugar is miraculously better now.

[Kristin] (16:31 - 16:40)
Oh, that's right. You actually wear a continuous blood sugar monitor, Regina, so you could look at your blood sugar. Did it get better?

Did you track that?

[Regina] (16:40 - 16:48)
I did track it, but not to the same detail that the researchers did, which we will talk about. And no changes for me.

[Kristin] (16:49 - 16:50)
Oh, so it was a failure, N of one.

[Regina] (16:50 - 16:52)
It was a N of one failure.

[Kristin] (16:53 - 17:10)
So Regina, I don't have a blood sugar monitor, so I had no outcome in my little N of one experiment. I just did the intervention with no outcome. I'm still skeptical that eight minutes of exercise can really do anything.

And Regina, you mentioned that the researchers actually did track compliance. So how did the participants do?

[Regina] (17:11 - 17:30)
Yeah, they did sort of well. So the participants had a logbook, and they were supposed to write everything down when they ate and when they exercised. And according to the logs, at least, the participants did an average of four exercise snacks a day with a standard deviation of one.

[Kristin] (17:30 - 17:39)
Oh, well, I mean, that sounds pretty good. The average was four, what they were aiming for. I mean, there is some variability.

That standard deviation of one means maybe some people didn't do all four, but still not bad.

[Regina] (17:39 - 17:58)
Not bad. Now, the participants also had an activity monitor, a Fitbit, and the researchers could kind of check in on them that way. They only managed to get activity data from 18 people, but the data from those participants, at least, showed that they did an average of three snacks a day with a standard deviation of two.

[Kristin] (17:59 - 18:17)
So a little different. That's saying that when people are actually objectively tracked as opposed to self-report, they might – it might be a little bit less with a little more variability. Of course, Regina, that was only 18 of the 31 people.

Did they compare the Fitbits with the logbooks only from that 18 or just to the entire sample?

[Regina] (18:17 - 18:20)
Yeah, that would have been smart, but no. They didn't match it up that way.

[Kristin] (18:20 - 18:31)
Right. We don't know if those 18 people misreported, but it wouldn't be surprising if they fudged a little in their logbook. We've talked in this podcast before about social desirability bias.

You want to say that you did what you were supposed to.

[Regina] (18:32 - 18:41)
And, Christian, so whether or not they actually did four exercise snacks a day, the researchers analyzed them in that condition, no matter what.

[Kristin] (18:41 - 19:09)
Right. This is standard in randomized trials. It's called intention to treat.

That means you analyze people as being in the exercise condition, even if they didn't complete all of the snacks, and you count people in the control condition, even if they did the snacks on the wrong days. And we do this because if you tell people to go exercise, they may or may not actually follow through. So we're kind of evaluating the effect of the instruction more than the actual follow-through because that's very real world.

[Regina] (19:10 - 19:10)
Right. Right.

[Kristin] (19:10 - 19:17)
So what changes did they look at? You mentioned this was about blood glucose. What exactly was the primary outcome?

[Regina] (19:17 - 19:26)
Right. Primary outcome was average blood sugar over the entire two days when they were assigned to the exercise snacks versus the other two days.

[Kristin] (19:26 - 19:31)
And how did they measure blood sugar? Did they wear a continuous glucose monitor like the one you have?

[Regina] (19:32 - 19:53)
They all got one as part of the study, whether they had one themselves or not. And just for people who aren't familiar, they're the little sensors that people with diabetes wear on the back of their arm. You can see that.

And they're actually really cool. And you don't even need to have diabetes to use them and to find them cool because I use one myself. I'm not diabetic.

[Kristin] (19:53 - 20:30)
Yes. I know you do.

And you're definitely not diabetic. And I have actually threatened you to do an episode on continuous glucose monitors because this is a very popular trend. Like you wear this monitor.

I've seen a lot of people around with it, Regina. I personally, I need to look more carefully at the evidence, but I'm not totally convinced that these are really useful for anything, sorry, Regina, unless you have actual diabetes then of course it's useful. So this is on my episode to-do list to look at continuous glucose monitors used in non-diabetic populations.

And Regina, that one might be controversial. There might be a little sparring between us. We might have a little disagreement.

[Regina] (20:31 - 20:59)
I think we might disagree. And Kristin, I'm just going to say right now, you do you. I don't think that everyone needs one.

That's the thing. But I personally am a bit of a biohacker. So I love learning how my body responds to different things, exercise or food or sleep.

And I love that I get data right there to show me all the patterns. So it's good for me. I'll just say that.

[Kristin] (20:59 - 21:09)
I'm going to consider it a form of entertainment rather than a health intervention, Regina, potentially. Can you tell us though, Regina, what exactly does it measure? What are you getting from the glucose monitor?

[Regina] (21:10 - 21:32)
Yeah. So it is displaying, at least on my app, so I don't know all the science behind it, but it's displaying on my app my blood sugar level every five minutes. And I can see not only what it is now, but a 24-hour history.

I can see that. And it tells me whether my blood sugar is currently stable, steady, or if it's rising or if it's falling.

[Kristin] (21:32 - 21:37)
Oh, interesting. And then you can see, like, if you exercise or eat something, does that affect it? Yes?

[Regina] (21:37 - 21:39)
Right. I can do little experiments on myself.

[Kristin] (21:40 - 21:53)
Okay. Now I see your fascination with this. Yes.

Still entertainment, but I get it. Okay. So what did they find?

Did they, in fact, have lower blood sugar on the two days that they were exercising compared to the two control days?

[Regina] (21:54 - 22:16)
Well, not really. No. Okay.

No statistically significant difference. The average glucose level was 122 milligrams per deciliter on the snack days versus 126 on the control days. So a difference of four.

Four milligrams per deciliter.

[Kristin] (22:17 - 22:25)
Not huge, but not nothing. I mean, I think when you go in and get your blood test, your yearly glucose test, isn't it supposed to be like 90? Am I making that up?

[Regina] (22:25 - 22:27)
Yeah. That's fasting though.

[Kristin] (22:27 - 22:28)
Oh, got it.

[Regina] (22:28 - 22:50)
So this is overall. And sometimes people like to translate this into A1C numbers because that's what we get on the labs and that's how they, you know, diagnose you with prediabetes or whatever. So this works out to be an A1C of about 6% versus 5.9%. Oh, hemoglobin A1C, HbA1C.

[Kristin] (22:50 - 23:08)
We talked about this a lot in the sugar sag episode. So for anybody who wants to really understand what hemoglobin A1C is, I recommend that episode. I do want to point out that that's a measurement that actually reflects three months of blood sugar.

So however you're translating a daily measurement of sugar glucose to A1C is probably a little fudgy.

[Regina] (23:09 - 23:14)
Yeah, that was. That was just me trying to get some sort of grip on what the effect size was here.

[Kristin] (23:14 - 23:19)
6% versus 5.9%, that's a 0.1% difference. So that's tiny.

[Regina] (23:19 - 23:29)
Yeah. I looked it up. It looks like clinicians often care only when you get to about a 0.5% difference. That's the clinically important thing there.

[Kristin] (23:29 - 23:31)
And you said it was not statistically significant.

[Regina] (23:31 - 23:39)
It was not. So that p-value was 0.07, so not statistically discernible and a tiny effect.

[Kristin] (23:39 - 24:07)
So in other words, the primary outcome failed. Yep. Regina, this is like deja vu here because our very last episode, which was on the Grail Gallery Cancer Blood Test, there was a major clinical trial we talked about.

In that trial, the primary outcome also failed, but many of the headlines were still positive. And it seems like something similar is going on here. So where did that positive headline in the Washington Post come from?

Was it from secondary outcomes like in the cancer study?

[Regina] (24:07 - 24:23)
Bingo! This is where our journalist friend got annoyed because he pulled the paper and it admits right there in the abstract that the primary outcome was not significant, but nowhere in the Washington Post article did they even mention that.

[Kristin] (24:23 - 25:15)
Wait, so the reporter for the Washington Post didn't mention it in her article? Ooh, that's bad. Yeah, not good.

At least the researchers were honest and they put it right up in their abstract. But this isn't a case where the researchers did okay and the journalists got it wrong. That happens too.

Regina, I want to hear more about where those positive headlines were from, what the secondary outcomes were. But first, let's take a short break.

Welcome back to Normal Curves.

Today we're examining the claim that four minutes of exercise a day helps control blood sugar. And we were about to talk about secondary outcomes in this recent paper.

[Regina] (25:16 - 25:27)
Kristin, before we get into what the secondary outcomes are, do you want to maybe give us a little refresher about what the difference is between a primary and secondary outcome and why we care so much, why they matter?

[Kristin] (25:28 - 26:10)
Yes, this is a big point. You pick a primary outcome to be the one thing that you care most about. Secondary outcomes are things that are interesting, but don't determine whether the intervention is considered a success or not.

And the reason we want to make that distinction is because we want to control the type one error rate with respect to the primary outcome. What that means is we want to be very stringent about how many false positives we're going to allow with respect to the primary outcome. With the secondary outcomes, we're more loosey-goosey and we realize, because we might be looking at a lot of things, that there's a higher chance of a false positive.

We put the most stock in that primary outcome and it has got to be pre-specified so that we know that people aren't cherry picking.

[Regina] (26:10 - 26:31)
Exactly. You've got to put your money on one horse and you put it on that primary outcome and then you've got the secondary ones, you've got some secondary bets, but everything is going on that primary horse and that primary horse here did not win. The authors listed for those secondary outcomes, 22 of them in a table in the paper and then 12 more in a supplementary table.

[Kristin] (26:31 - 26:34)
Wow. So there were 34 secondary outcomes?

[Regina] (26:34 - 27:01)
Yep. So rather than just read you all the results from the table, which is going to put everyone to sleep, let me first read you what the Washington Post journalist said. So in the second paragraph, they said, in the study, men and women with type 2 diabetes completed four 60-second bursts of exertion called exercise snacks during the day while at work or home and improved many aspects of their blood sugar control.

Hmm.

[Kristin] (27:02 - 27:10)
So primary outcome wasn't met, but something else about blood sugar in some way was improved. Many but not all.

[Regina] (27:10 - 27:41)
Not all. Exactly. And then in the article, they get to the result way down at the bottom and they said this, the scientists analyzed everyone's blood sugar control and it was better on the days that they briefly box stepped, marched in place or speed squatted than the days they didn't.

Correct. And almost everyone's blood sugar levels stayed lower during the daylight hours when they exercise snacked with slighter, shorter after-meal blood sugar spikes. Okay.

[Kristin] (27:41 - 27:47)
So first of all, in the instructions you sent me, you didn't say I could march in place or speed squat. I didn't know that was on the list.

[Regina] (27:47 - 27:55)
That was not in the main protocol in the article, but they did say that they would adapt things if people wanted adaptions.

[Kristin] (27:55 - 28:16)
Ah, okay. So people may have come up with their own exercise just like you did, and I guess that was allowed. I noticed though, Regina, that it was pretty specific what you were talking about.

Like their sugar levels stayed lower but only during daylight hours and shorter after meals and things like this. So, you know, we worry about cherry picking.

[Regina] (28:16 - 28:17)
Right. Right.

[Kristin] (28:17 - 28:41)
So how many, you mentioned there were 34 secondary outcomes. How many of those came out to be statistically significant? 21.

Oh. Well, that's actually not nothing because if this was all just random noise, we would expect only about one or two to come up significant just by chance, and 21 is clearly higher than that. So what exactly were these other outcomes, Regina?

Were they all something about blood sugar or was it more than just blood sugar?

[Regina] (28:42 - 29:20)
Yeah. So they sliced that glucose data that I was talking about from the monitor in so many different ways. They looked at average blood sugar and like three different ways to look at variability in blood sugar, and they did that across the whole two-day time period, but then they also did it for daytime and then for nighttime separately.

And they wanted to see how much the participants stayed in their target glucose range, and they had like four ways to look at that. And then they wanted to look at the spikes that naturally happen after people eat, and we had breakfast and lunch and dinner, and they had five different ways to look at spikes there. Wow.

[Kristin] (29:20 - 29:43)
Okay. So it's one type of measure, this blood sugar level every five minutes or whatever. But since we're measuring it over a long period of time, we can find lots of things to pick out of that data, and we can do lots of subgroup analyses.

Interesting. Regina, can you tell us a little bit about what these different blood sugar measures you're talking about might represent? Like what is variability and spikes?

Like why do we care?

[Regina] (29:43 - 29:59)
Well, I'm not an endocrinologist, I just want to say that. Generally, you want your blood sugar to stay relatively steady. Like right now, I can see on my app, mine is at 86, and it's saying that it's steady.

[Kristin] (30:00 - 30:02)
86 is good, right? That's pretty low.

[Regina] (30:03 - 30:36)
Yeah. Thank you. Thank you very much.

I guess it was all the exercise snacks that I did yesterday. And you can see the spikes that happen after you eat, right? I talked about those.

So, like yesterday, I went from 80 to 135 within 15 minutes because I had some Chinese food, fried, spring-rolled, and white rice and stuff. And then it fell again quickly and eventually went below 70. So, again, not an endocrinologist, but I think you want to avoid being too high or too low or having too many sharp spikes.

[Kristin] (30:37 - 30:44)
Oh, interesting. But of course, when you eat, your sugar is going to go up in your blood. Right, right.

It's like a natural consequence of eating, right? Yeah.

[Regina] (30:44 - 30:47)
Right, right. But you don't want them to be too high or too spiky.

[Kristin] (30:48 - 30:48)
Got it.

[Regina] (30:48 - 30:52)
And we'll have to get into all of this on the episode that you're threatening me with.

[Kristin] (30:52 - 30:53)
I will. Yes.Okay. Attractions coming soon.

[Regina] (30:53 - 31:27)
There you go.

Coming attraction. Okay. So, for the statistics that I can see, I can see average blood sugar over an entire day.

I can see how high I spiked after meals. So, these are some of the things that the researchers here looked at. But they also calculated fancier things that I think I cannot just see based on my apps.

So, they looked at things like standard deviation of the blood sugar level and area under the curve. And I'd have to export my data to look at those. I can't believe you haven't done that yet, Regina.

[Kristin] (31:27 - 31:33)
You haven't exported your data and, you know, graphed it and calculated all the statistics. I'm so disappointed.

[Regina] (31:33 - 31:33)
Well, now I'm going to.

[Kristin] (31:33 - 31:43)
Okay. For the episode that I'm threatening, you're going to have to. Yes.

[Regina]
Yes, I will. Yeah.

[Kristin]
So, you said some of the measures were statistically significant.

Can you give us a flavor of what was statistically significant here?

[Regina] (31:43 - 32:09)
Yeah. So, the measures of variability were lower during exercise SNAP days. And they measured that through standard deviation through the coefficient of variation, which is standard deviation divided by the mean, and something called the mean average of glycemic excursions, which is looking at peaks and troughs and something, something.

But these were significant only during daylight hours and not nighttime, for example.

[Kristin] (32:09 - 32:13)
Yes. Less variability means steadier, and you're saying we want that. But only during the day.

[Regina] (32:13 - 32:42)
Okay. Only during the day. Right.

And these different ways. So, they also looked at the percent of time the participants spent within their target blood sugar range. And that was significant for a tight range that they use for healthy people, between 70 and 140.

That was significantly better on exercise SNAP days. But if you use the target range for diabetics of 70 to 180, that was not significant.

[Kristin] (32:43 - 32:58)
Ah, I see. Okay. This gives us a flavor of they're really looking at very specific things, and it matters how you parse it.

Right. And, Regina, they looked at a lot of things. Many of them came out statistically significant, but did all of these different measures show at least a consistent picture?

[Regina] (32:58 - 33:19)
Yeah, not really, sadly. Just, again, to give you a flavor, right, these post-meal spikes, they were on average lower with lower peaks for breakfast and dinner, but not lunch. But if you looked at the standard deviation, it was the exact opposite.

So, you had lower standard deviation for lunch, but not breakfast or dinner. Right.

[Kristin] (33:19 - 34:07)
We want lower standard deviation because lower variability. So, yeah, it's not very consistent because it's saying lunch is good sometimes, it's not good the other times. And we worry about lack of consistency because, again, we are weeding through a lot of variables here.

They've told us about 34. They may have looked at a lot of other things, and there's always chance findings that can pop up. So one way we can help sort of evaluate whether this looks like noise or random chance to us is to look to see whether there's a consistent pattern.

It looks like there wasn't one here. And, Regina, this reminds me a lot of our holiday guide part two episode. We went over that study on cold foods and hot foods and cold hands, and it was like only when people eat hot food in winter and they also have cold hands, then there was a significant outcome.

This seems a little similar.

[Regina] (34:07 - 34:10)
Under the full moon with a high tide. On Tuesday.

[Kristin] (34:10 - 34:26)
On Tuesday. And we're more reassured when we have a lot of secondary measures that are telling us a clean and consistent story.

And Regina, is there any biological reason to think that lunch would act differently for some measures than breakfast and dinner? Is there anything that makes sense in that?

[Regina] (34:27 - 35:01)
So clinically, my impression is that clinicians don't look at any one of these measures individually and use that to decide whether blood sugar is controlled. They integrate the evidence, right? They look at the big picture here.

But it's interesting because we see this in this study and other studies. Researchers tend to split things up like they're all separate little, you know, bits of information that you can analyze independently instead of integrating everything. And just like here, they were testing all these things like they were separate.

And I think they're not really.

[Kristin] (35:02 - 35:24)
Interesting, Regina. Now, the question is, was any of this preplanned, right? We trust it more if they came up with it ahead of time because at least there's a limited number of things they're looking at.

If they just came up with it after the fact, that may mean that they looked at, you know, a thousand different things in the data like they did in the cold hands, cold food study. So did they pre-register the study? And was there any preplanned analyses reported in there?

[Regina] (35:25 - 35:45)
They did pre-register. Clinicaltrials.gov. Oh, yay. Mm-hmm.

So it's like this is the second level of sleuthing, right? Our journalist friend who tipped us off to this, he went and looked at the study itself. And it's like, OK, now if you want to go to the next level, you go check the pre-registration to see what that shows.

[Kristin] (35:45 - 35:59)
Yeah. This is such a great tool in the statistical sleuthing toolkit because it's easy to look up these studies on like clinicaltrials.gov and you can see, did they cheat? Did they change what they said that they were going to do later?

So what did you find, Regina?

[Regina] (36:00 - 36:09)
Well, the good news, first of all, Kristin, they did report in the paper the same primary outcome that they said they would in their pre-registered protocol.

[Kristin] (36:10 - 36:21)
Excellent. So they didn't do any outcome switching on the primary outcome, meaning, you know, changing the primary outcome after the fact. That's good.

We talked about outcome switching, Regina, back in that alcohol episode.

[Regina] (36:21 - 36:44)
Right. So that's something, at least. But, Kristin, in the protocol, they listed only nine secondary outcomes.

And then somehow in the paper, you had 13 more secondary outcomes magically appearing. And then they started breaking things into, you know, daylight and nighttime. And then before you know it, we're at 34.

Right.

[Kristin] (36:44 - 37:02)
So there was outcome switching with regards to the secondary outcomes because it sounds like those 13 were not in the pre-registration. Regina, question for you. Did those 13 added outcomes magically come out statistically significant, by chance?

Just by chance.

[Regina] (37:02 - 37:27)
All of the added 13 secondary outcomes were significant in at least one subgroup. So they were able to report it as a significant effect in their paper. Yeah.

Now, just to be fair, Kristin, of course, we don't know when they added these outcomes, whether it was before they looked at the data, right, or after they had started analyzing and poking around the data.

[Kristin] (37:28 - 38:44)
To be totally fair, maybe they just forgot to put these in their original protocol posted on clinicaltrials.gov because we don't always get everything right there. And then they had them in their analysis plan that we can't see as the public. But I'm a little skeptical, Regina, because the fact that they're all statistically significant also suggests another possibility that could have happened.

I'm not saying it did happen, but it could be that they started peeking around in the data and looking at all the ways you could take this continuous glucose monitoring data and parse it and all the ways you could divide it into subgroups. Maybe they looked at daylight and nighttime, but also looked at morning, afternoon, and evening, and we didn't see the morning, afternoon, and evening, right? So they could have rummaged through the data, found significant things, and then only then declared them secondary outcomes and reported them in their paper.

And that means it might not have been 34 things that they looked at. Maybe they looked at 1,000 things, and the fact that 21 are coming out significant isn't so impressive anymore. And again, it's not horrible to add secondary outcomes after the fact.

It happens all the time. But you need to be transparent about it, and you should label it as exploratory. So Regina, did they label these as exploratory, the ones that weren't in the protocol, or did they label them as secondary?

[Regina] (38:44 - 39:04)
They did not. They did not. They lumped them all in as if they were all preplanned, preregistered, all listed as secondary outcomes.

That's not good. Yeah. So it's good, right, that they didn't lie about the primary outcome.

They didn't switch that. But we really like it when researchers are transparent and let us follow all of their steps.

[Kristin] (39:05 - 39:15)
Yeah. I don't like it when they add a bunch of secondary outcomes, especially when that primary one wasn't significant. It seems like, gee, I got to make something out of the data, so let me keep hunting.

Again, we don't know what happened, but yeah.

[Regina] (39:16 - 39:30)
So Kristin, one other cool thing about clinicaltrials.gov that you and I like is that it has this little feature where you can see if there were any changes to the protocol since the first posting.

[Kristin] (39:31 - 39:39)
I love this. You can't just go in and change it secretly. There's no way to do that.

It forces you to be transparent on any changes. And Regina, were there changes? Yep.

[Regina] (39:39 - 39:54)
So they updated the preregistration after the trial started, first of all, and that's where they changed their planned sample size. They were originally aiming for 40, but then after the trial started, they changed it to 30.

[Kristin] (39:54 - 40:11)
Oh, so this makes you worry that they calculated things. They thought they needed 40 to have ample statistical power, but then they couldn't get that many. So they said, oh, let's just go back and say we wanted 30.

So did they tell us in the paper that they were aiming for 40, but then they had to reduce it to 30 because of logistics or whatever?

[Regina] (40:11 - 40:25)
No, they did not. And actually in the paper, they said that they calculated they only needed 24. And then I looked at their math and their math for the 24 wasn't entirely clear.

So yeah.

[Kristin] (40:25 - 40:41)
I mean, it's OK if you have to update, change your targeted sample size. Recruitment is sometimes harder than expected. But again, you need to be upfront about it.

So don't pretend that your sample size target was always 24 when it really was 40. That's sneaky. I don't like it.

Yeah.

[Regina] (40:41 - 40:54)
I feel like we say that a lot in this podcast, Kristin. Even if things don't go perfectly as planned, it's OK. Just be transparent about it.

And it's kind of a good life lesson, right, in general.

[Kristin] (40:54 - 40:55)
Oh, for sure. Yes.

[Regina] (40:55 - 41:02)
Yeah. Is there a way we can make it about sex? We've gone so far without sex in this episode.

I feel like we could make it about sex if we tried, if we tried really hard.

[Kristin] (41:03 - 41:14)
Good effort on trying to get the sex in. What I'm now thinking, though, of, Regina, is sex snacks, because we're talking about exercise snacks. I don't know what that would be, but that just popped in my head.

[Regina] (41:15 - 41:20)
So is there such a thing? One minute. One minute sex snacks.

I am not going there at all.

[Kristin] (41:20 - 41:38)
I wonder if that would improve your blood glucose. But you were talking about transparency and sex. I do think there is a theme there, potentially, right?

Non-transparency and sex. There's a lot of directions you could go with that. People are sometimes secretive when it comes to things about sex.

[Regina] (41:39 - 41:45)
This is true. We're going to leave that whole thing, though, as like an imagination exercise for the audience.

[Kristin] (41:45 - 41:49)
Perfect. But we have gotten sex into the episode. Good job, Regina.

Yes.

[Regina] (41:50 - 42:12)
Okay, Kristin, one of the things that the researchers did do well, I think, is acknowledge that the effect sizes were small overall. But they said something in the discussion that puzzled me a little bit. They said, well, these effects are probably just small because there was, quote, a low volume of exercise, which kind of confused me.

[Kristin] (42:12 - 42:21)
I mean, low volume of exercise. Isn't that the whole point of the exercise snacks, right? That you don't have to do too much and you can still see a meaningful effect.

[Regina] (42:21 - 43:01)
Yep. Yep. That is the whole point.

I feel like they just undermine the whole premise of exercise snacks right here. I agree. So the Post article also has the authors acknowledging that they basically have no idea how many snacks you should have in a day and how long each exercise snack needs to be.

And they have a quote from the head researcher, we had to make somewhat arbitrary choices about the length and number of snacks. We don't think that there's anything magical about precisely one minute of exercise or four minutes a day, 70 seconds at a time might be better, or five daily snacks. Find what works for you.

[Kristin] (43:01 - 43:19)
Well, I like that last part, right? Yes. It might be a lot of what you're actually willing to do.

Maybe this is the most important thing, because isn't this at the bottom of this all is like what exercise are you going to actually tolerate and be able to keep up on a regular basis? My opinion is maybe 60 minutes a day might be better for you, but you know, that's just me.

[Regina] (43:21 - 43:23)
If you're like me, it's more like one second.

[Kristin] (43:23 - 43:25)
Oh, come on. You're good about exercise.

[Regina] (43:25 - 43:37)
Five seconds. I do like it, but oh, it's so painful. I hate it.

But I do feel better having done it. I like that at least they're honest about not knowing.

[Kristin] (43:37 - 44:23)
Yeah. I like the quote. I think it's very good, actually.

On that note, Regina, let's wrap up this episode and we're going to rate the strength of evidence for the claim. And I'll just point out that the claim that we're looking at today is from one news story. And sometimes we look at all the evidence around something.

We are not today looking at all the evidence around exercise snacks. I'm going to put that out as a challenge for you, Regina, for a future episode. We are narrowing to one claim in one news story.

So here's the claim for today. Four minutes of exercise a day helps control blood sugar. And how do we rate strength of evidence in this podcast?

With our famous highly scientific one to five smooch rating scale, where one smooch means little to no evidence for the claim and five means strong evidence for the claim. So Regina, kiss it or diss it?

[Regina] (44:23 - 45:08)
I'm going to go three smooches on this. That might surprise you here. I feel like there might be something, right?

It was 21 things that came up significant. I can see why the Washington Post journalist got excited about this. It's a fun study.

I can see why our journalist friend was kind of skeptical of the whole thing. What I really wish is that the Post article said that the primary outcome failed. I really want that.

They didn't point that out. They didn't point out that the picture was kind of mixed. And of course, that journalist didn't look behind the scenes to see, oh, there's not a whole lot of transparency there.

But I don't know. I like exercise snacks. I think I'm going to keep doing them more just because they're fun.

[Kristin] (45:09 - 45:54)
I'm in like a skeptical bad mood. So I'm going to disagree with you a little and go one smooch on this one. If we're just looking at this one claim, like that study failed and anything they saw seems pretty p-hacked, data fished, whatever you want to call it.

Four minutes, two days, changing blood glucose. I'm not believing it. And there was enough red flags in that study.

So I'm going to go the dead last one smooch. I have to say the exercise snacks were fun. And I like the fact that I didn't have to shower and I could do them barefoot and without a jog bra sometimes.

But I'm probably going to be sticking to my normal exercise routine and not changing it up because it works for me. Maybe that's the moral, right? Whatever works for you on exercise.

[Regina] (45:55 - 45:56)
Right. One smooch.

[Kristin] (45:56 - 45:57)
I'm the Grinch today.

[Regina] (45:58 - 46:01)
Yeah. Got you. Okay.

What about methodological moral?

[Kristin] (46:02 - 46:14)
So I think the transparency thing is really important. We keep emphasizing this on the podcast, but I'm going to do a methodological moral on it today. It's good relationship advice to be transparent.

It's also good research advice.

[Regina] (46:17 - 46:32)
I love this. I love that we've now broadened it out. This is super important.

And I think you're right. It's important throughout life and especially in research. If we can't trust the other person, the other party, what do we have?

[Kristin] (46:32 - 46:33)
Yeah. How about you, Regina?

[Regina] (46:34 - 46:39)
Oh, I think I'm going to go with this one. If the primary outcome is not significant, say it up top.

[Kristin] (46:40 - 46:44)
Ooh, I love that. I'm surprised we haven't done that one before, actually. That's great.

Yeah.

[Regina] (46:44 - 46:51)
Just put it up top. Just admit it. And then go on and then talk about all the other exciting things, but just put it up there.

[Kristin] (46:51 - 46:59)
That could have been a methodologic moral for our very last episode on the Greyhall Gallery blood test trial. Absolutely. Same thing.

Yeah. Really important. Right.

[Regina] (47:00 - 47:05)
But on a personal note, I found the exercise snacks fun, so I think I'm going to keep doing them.

[Kristin] (47:05 - 47:12)
All right. Keep doing them. Monitor your glucose and report back.

Maybe if you do it for 12 weeks, it'll affect your actual blood sugar level.

[Regina] (47:12 - 47:15)
Maybe it will. And maybe you'll do them with me next time I visit.

[Kristin] (47:15 - 47:23)
Maybe when you're out. If I'm going to do them, I'm going to be tacking them on the end of my regular routine. So I think that kind of defeats the purpose.

[Regina] (47:23 - 47:31)
Well, how about if we reward ourselves, minute of exercise, snack, and then ice cream sandwich? Oh, I like that.

[Kristin] (47:31 - 47:38)
So for every snack of exercise, we get a snack of food. And yeah, I'm all in on the ice cream sandwiches.

[Regina] (47:38 - 47:39)
Absolutely.

[Kristin] (47:39 - 47:43)
All right. Deal. One minute of exercise for one ice cream sandwich.

Seems about right.

[Regina] (47:44 - 47:52)
It's a good exchange, right? Absolutely. All right, Regina.

This has been really fun. Thank you so much. Thanks, Kristin.

Thanks, everyone, for listening.