Baseball bats, Charles Atlas, and drunken rodeo clowns: Modern medicine for diabetes
My student taps part of the doodle with her pen, “So this is the liver, right?”
Ah. No. That’s the pancreas. The liver’s over there.
“Oh,” she says. “I thought that was the stomach.” A pause. “I’m just not quite getting this yet.”
My drawing, clearly, is not helping. On the sheet of copy paper, crudely sketched in red ink, is my pathetic attempt at depicting the elegant internal structure of the human body. Yeah, Andreas Vesalius I’m not. I mean I know what I want my illustrations to look like, but they never turn out that way.
I’m teaching a class on insulin to the Promotoras at a neighboring clinic. We’ve gotten off on a tangent about other diabetes meds that need needles. I gaze at the mess I’ve drawn. A bubbly-edged blob, on the right, is supposed to be the pancreas. It looks more like a thought balloon from the Sunday funnies. Next to it is a basketball that was run over by a FedEx truck. Right. That was intended to be the stomach. Below that is a snake that was run over by the same FedEx truck. You got it. The small intestines. Off to the left is a much, much larger pathetic sketch that was intended to be the liver. It doesn’t help that in the interest of anatomical accuracy I’ve tried to draw in all the lobes. Running down the middle is a winding road that’s the esophagus. On the top, a large open triangle. The mouth.
There are various sweeping arrows connecting this train wreck, and strange nonsense words litter the page, “GLP-1,” “DPP-4,” “counter-reg,” and “ins.”
Geesh. No wonder she’s just not quite getting this yet.
I decide to give up on the drawing and fall back on my real strengths: Words. Story telling. Analogy.
So I made up this little tale (embellished slightly for the web):
OK, I say, let’s pretend it’s first thing in the morning and Gee-el-pea, he has a funny name because he’s not from around here, is getting ready for work. It’s important that he gets to work on time, ‘cause he has a very important job. He works as Supervisor of Digestion at the Type 2 Plant over in Foodville. When he gets to work he’ll be in charge of stomach speed, shutting down the liver’s production of glucose, and calling the brain on the intercom when enough food is in the system.
So, like I was telling you, Gee-el-pea is getting ready for work. He’s got his best Khakis on. He’s had his coffee, and right on time he heads out to the bus stop. And that’s where things go bad, ‘cause Gee-el-pea lives in a kinda rough neighborhood. In fact, poor Gee-el-pea is mugged at the bus stop. A brute named Dipfour jumps out from behind a dumpster and just beats the ever-living crap out of Gee-el-pea and steals his wallet. Lying there bruised, broken, bloodied, it’s all Gee-el-pea can do to crawl home again.
So what the fuck is Dipfour’s problem? Who knows? Maybe he’s on crack. Maybe he has an anti-social personality disorder.
But a week later Gee-el-pea has recovered and is ready to go to work again. The folks he works with over in Foodville have been worried about him, so they skipped up the yellow brick road to see the Wizard of Med, who prescribed a Louisville Slugger.
So Gee-el-pea puts on his Khakis, drinks his coffee and heads to the bus stop. Sure enough, the anti-social Dipfour jumps out from behind the dumpster again, intent on great bodily harm. But this time Gee-el-pea whips out the baseball bat and smashes Dipfour over the head with it. The brawny bully collapses onto the dirty sidewalk with a thud. Yeah. It’s every bit as satisfying as the revenge of the 90 pound weakling against the sand-kicking bully in those old Charles Atlas comic book ads back in the day.
Only this is a new century. And this is diabetes. So Gee-el-pea savagely kicks Dipfour in the stomach a few times while the burglar is down, and then spits in his face for good measure.
And that, my friends, is Victoza. It’s the incretin hormone GLP-1 with a baseball bat. Able to stand up to the counter-regulatory hormone DDP-4 thanks to Charles Atlas.
Oh. Wait. I forgot to tell you about the drunken rodeo clowns.
So, if you’ve never been to a rodeo, the clowns have a job I have no intention of applying for anytime soon. I’d rather have the night shift at the sewage treatment plant, thank you very much. The job of a rodeo clown isn’t really so much to entertain the crowd as to serve as human bait to distract super-pissed off bulls so that dazed bull-riding cowboys have a chance to stagger to safety after their eight-second ride.
But rodeo clowns also control the gates on the bull chutes. The idea is that once the bull-rider is ready, they yank open the gate and the bull storms out into the arena intent on bucking the rider off, and then probably goring him and stamping his head into the dirt for good measure.
What happens if the clowns are drunk? They open the gate early. Before the rider is ready. And things end badly.
In your body, DDP-4’s job is to stamp the shit out of GLP-1. After all, it is a counter-regulatory hormone. So it isn’t really the crack-crazed sociopath that I made it out to be. It’s the damn drunken rodeo clowns that are the real problem. They let the bull out of the shoot early. In dFolk, especially those of you with type 2, the DDP-4 gets out early, and wipes out the GLP-1 before it can do its job.
And, for review, what’s GLP-1’s job? Over in Foodville? Supervisor of Digestion, remember? In charge of stomach speed, and shutting down the liver’s production of glucose, and calling the brain on the intercom when enough food is in the system.
To understand how this whole process is supposed to work, we need to talk about Twinkies. Actually, it could be any kind of food, but Twinkies’ just happened to pop into my mind.
So when you eat a Twinkie, here’s what happens. As the sugar hits your mouth, red lights and alarm bells go off at digestion central. Insulin is released in those of your with functioning pancreases. GLP-1 is unleashed. It tells the liver to go smoke a cigarette and get a cup of coffee (in other words to stop releasing glucose for a while). Then it shifts the stomach into second gear, a nice digestive speed, and once enough Twinkies arrive at the stomach, GLP-1 picks up the phone and calls the brain to let it know the body has enough food. Its job done, like a poor male black-widow spider who just got laid, the GLP-1 gets eaten up by the DDP-4—the other player in this romance.
But wait a minute. What happens if the DDP-4 gets let out early by the drunken rodeo clowns? Before GLP-1 can do its job?
Let’s go back to the Twinkie and replay the scenario. The red lights and alarm bells still go off. GLP-1 is still released. But DDP-4 gets out at the same time and ambushes GLP-1 at the bus stop and GLP-1 never gets to work. So…
So no one tells the liver to go have a smoke and a cup of Joe. That means it keeps on cranking out glucose. Twinkie + sugar from the liver = twice the sugar.
But wait… there’s more.
No one shifts the stomach into second gear. In fact, it seems to be at highway speed. It’s emptying twice as fast as it ought to. And where does it empty to? Into the small intestines, of course. Interestingly, that’s where most carbohydrate absorption takes place.
So now we have Twinkie + sugar from the liver + sugar rush from the intestines. Three times the sugar we need.
But wait… there’s more.
No one telephoned the brain to tell it that the stomach really has enough Twinkies. And if that weren’t bad enough, not only did the brain not get the message the stomach has had enough, by now the stomach is empty again ‘cause it’s emptying so fast.
Can things get any worse?
Well, yes. Yes they can.
You all know what homeostasis is, right? The body’s system of input and counter input that creates a stable state? It’s like keeping the shower at the right temperature in a cheap hotel by constantly fiddling with the hot and cold handles. The body does this with blood pressure, body temperature, blood sugar (in non-dFolk), and a gazillion other things. The bottom line is: The body generally knows what’s good for it.
With one major exception.
When your blood sugar is high, you get the munchies. What’s up with that? When your blood sugar is high, the last thing in the world you need is more sugar. But it is what it is, and you all know it, because you’ve been there and done that.
So the final nail in the coffin here is that high begets more high.
Twinkie + liver sugar + excursion + empty brain + empty stomach = hunger pangs.
Hunger pangs = more Twinkies.
So many type 2s live in a metabolic state of constant starvation because of those stupid rodeo clowns. You can weigh 380 pounds, be eating like a horse, and still feel genuinely hungry all the fucking time.
The two possible solutions to this dilemma are to sober up the clowns (using a DDP-4 inhibitor like Januvia or Onglyza), or supersize the GLP-1 with a baseball bat (using Victoza or Byetta) so the native DPP-4 doesn’t stand a chance against it.
There’s a moment of silence in the clinic conference room. Then my student smiles.
“Now I get it,” she tells me. “I never understood these meds until now. Why didn’t some just explain it like that in the first place?”
I shrug. Probably because most doctors and CDEs don’t hang out with thieves, drunken rodeo clowns, or use bus stops.
Or have overactive literary imaginations.