Adding Insult to Injury

I came to this blog entry on Tu Diabetes from the Diabetes Daily Headlines.

The question posed is a good one. It inspired a meander back through all the physiology, pathology and general medicine that is stored up in my brain from six years of university study, which in turn inspired this post.

And I realised once again that our bodies don't half like to add insult to injury after developing us diabetes.

This is how it works:

The liver doesn't sense blood glucose levels. Instead, it relies on knowing the level of insulin in the blood. The blood insulin levels in a non-diabetic only become low during periods of fasting. When no food is arriving in the stomach, very little insulin is being released. The liver responds by saying:

"Oooh look, there's no food around. Cells all over the body will be starving! I had better release some stored glucose and make some new glucose and dump it all in to the blood." Cue excited hand flapping and dancing.

Okay, that isn't exactly what happens, but you get the idea. All is well and good in the non-diabetic. The cells get their food. Everyone is happy.

And conversely, when the insulin level is high, the liver gets busy hoovering up all the glucose and storing it away for the next time it needs to release it.

Those of us with diabetes, however, frequently find ourselves in a paradoxical situation.

Diabetes works out fine when a high insulin level following a bolus corresponds with plenty of glucose in the blood to store away. The diabetic holy grail is matching every bolus perfectly with the amount of glucose available.

It rarely happens. The pancreas of a non-diabetic doesn't look at the food sitting in the stomach and go "Ooooh, I think that is about 30 carbs, here have a squirt of insulin <this big>", which is a representation of the way we bolus. Insulin release is much more sophisticated and, because it goes directly in to the portal circulation, the insulin acts very rapidly before being used up. This not only means that the correct amount is always delivered, but also means that insulin doesn't hang around for 2-3 hours to have a effect in the middle of a gym workout.

Our squirty bolus however, wandering slowly as it does through the jungle of the sub-cutaneous landscape, can. We may actually have too much insulin, which drives our blood glucose level low. The liver continues to respond to the insulin level and thus not only doesn't produce any glucose for us, but actually continues to take more glucose out of the blood stream, dropping the blood sugar level even lower.

Alternatively, we may have too little insulin. We may even forget to bolus entirely. In that situation the glucose from digested food builds up in the blood and then the body really adds insult to injury. The liver responds to the low insulin level and says the body must be starving. It releases stored glucose and also manufactures more glucose (gluconeogenesis) pushing the blood glucose level even higher. Like that is what we need.

The bottom line: in diabetes the liver always does the opposite of what we need. And nobody is happy.

Of course, with high blood sugar, the pancreas of a person with type 1 diabetes will never do what it needs to and spit out insulin. Which is why untreated type 1 is fatal.

The good news?

So long as you haven't had your pancreas removed, most people with diabetes can still produce glucagon. The stimulus for glucagon release is the low blood glucose level itself, so glucagon can come to the rescue even in people with diabetes.

The catch?

Well actually, there are two. Firstly the absolute level of available glucagon is not important - the ratio of insulin to glucagon is. So if you have a lot of insulin in your system, glucagon release may still be ineffectual. Secondly I've heard of studies that have shown that the glucagon response tends to wane and become less predictable after several years of type 1.

And all of that, my friends, is just another reason why diabetes really does suck.

Comments

[Colleen]

That was pretty cool - nicely done!

[Scott K. Johnson]

Caro, that was presented in a very helpful and easy to understand way. Thanks!

[Lizzie]

Oh my gosh, Caro, thank you so much for that!! It explains everything perfectly! You even answered my Part 2 question - does the natually made insulin of non-diabetics last for 4 hours in their systems, and does their "basal" drop when they start thinking "Hmm, I think I'll go to the gym in an hour" like I have to adjust my pump?

Any chance you're a practicing MD in the DC area?

[Caro]

Glad this entry was useful to you all.

Lizzie - I'm actually a practicing dentist in London, England! If you have any more burning questions though, I'll happily try to dredge through my undergraduate knowledge to give you an answer.

[Gayle]

Just started reading your blog and found this post. Wow, thanks!! So helpful!!