Why do T1 diabetics have a decreased glucagon response to hypos?

Is it caused by too many hypos and stress on the system, or does it go away along with the insulin production? Anyone have a good explanation for this?

Glucagon is produced by the alpha cells in the pancreas. As a T1, you still have normal glucagon responses, but your liver doesn't respond to the glucagon. Insulin essentially downregulates the glucagon signal. Anybody that uses exogenous insulin has this problem.

Is it from having higher levels of insulin in our system than a non-diabetic? I'd be interesting to know whether the Dr B/very low carb types still have this issue.

Dr B's approach (love it or hate it) generally involves lower insulin concentrations and more normal BG, so those influences (and burnout) might get ruled out to some extent.

PS Thanks for pulling the quote out.

DrB mentioned in passing in one of his recent monthly messages that he recently passed out from taking too much insulin and had to be revived with IV glucose, so his approach clearly doesn't prevent this.

Regardless of the mechanism, T1 prevents the normal glucagon response, and does so rather quickly after diagnosis (diet is irrelevant): STUDY

There was a pretty good explanation in the video/Master Chat session done a while ago, on the Liver. Skip to about 6:30 to hear about low blood sugar.

The Liver's Role

I also think MM spent lots of research $ on proving that the 530G pump with the 'low glucose suspend' feature, forces BG to rise, in response to lowering the insulin.
But the video talks about a 'switch', and the complex signalling that happens, and low insulin is actually a trigger, rather than low sugar.
When there is high insulin, the body 'assumes' there must also be high/sufficient glucose in the blood, so no need for liver to dump glucose.

Actually, you and bsc don't have this right. It isn't the liver that is screwed up in a T1; its the pancreas.

If you listen to that lecture you'll hear at about 8:30 that the liver's role is to produce glucose when it receives glucagon from the pancreas. And the liver in a T1 is working fine - that's why a glucagon shot will revive a T1 who is having a serious reaction.

It isn't the liver that is screwed up in a T1 - it's the pancreas that is not producing enough glucagon. If the pancreas was able to produce glucagon when BG went too low (like it would in a non-diabetic), then the glucagon would be received by the liver and glucose would be produced, just as it is if glucagon is injected.

The question, then, that is discussed in the paper Shawnmarie cited, is why the pancreas of a T1 fails to produce enough glucagon when BG goes low.

Now she does in the Master Chat talk about a "switch" and a "fatty" and "leaky liver", but she said that applies to overweight T2 diabetics, and not thin T1 diabetics. So that isn't really part of the question of why diabetics have a reduced glucagon response. I will note, though, that it sounds from her description that liver function is just one more of the many differences between T1 and T2 diabetics.

Maybe, but Dr B has some other disorder as well, and went decades with out of control BG, so his glucogon response may have been nixed from that.

I think what MegaMinxX is saying is that the glucogon response may be working normally in a T1, but because the body's regulator system is triggered by low insulin levels, maybe it doesn't help T1s fight off a low.

But they have done studies where they artificially lower blood sugar in both people with T1 and non-diabetics (using insulin), and despite high insulin levels in both cases, the T1s still have a weaker counter-regulatory response.

So I don't think high/low insulin levels alone are the problem, I think there's something inherently screwed up in the counter-regulation system.

I think it is the glycogen response that is the issue in this hypo question, but I don't have a study to prove it. I do know from experience that my adrenaline is peaking when I have a sleeping hypo, my body is trying to fight and correct on it's own but simply does not have the metabolic ability to correct so glucose is needed ( I prefer tabs or juice ).

In a T1 hypo it is not just the liver and pancreas that are not working proper, it is the brain as well - so the thought process is sometimes off, the motor skills are affected, and they body is applying the fight or flight action - so the low is going nowhere but down! I suspect this is much the same as a marathon runner hitting the wall - they simply don't have the added brain malfunction. I am ever aware when I have had a very active day that I need to lessen my insulin dosing.

The only way to fight off lows in my life with D, is to test often and avoid them. I think one hypo is too many btw.

Scott, you should read some of the papers that have been cited where they measured the amount of glucagon that was produced by test subjects when they experience a low BG. Megaminx and bsc are indeed saying that "the glucagon response is working normally in a T1", but that isn't consistent with the results reported in the studies that have been cited here. Those studies clearly state that "the glucagon peak to hypoglycemia was reduced in the group with diabetes [and] was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis".

Please read the abstract Shawnmarie provided. "There was no correlation in response with height, weight, BMI, and HbA1c.". In other words, this does NOT occur in T1's because they have poor control.

What other disorder does Bernstein have?

I agree Jen. There seems to be consensus that the glucagon production is what is screwed up, though there isn't yet consensus on what is screwing it up.

One last question, what about the 'Chinese Restaurant Effect' where glucogon is apparently released with a big meal? Doesn't that show that glucogon is still active in our systems?

I'm not sure what else Dr B has. I don't think he disclosed it fully, but I think it is an endocrine type issue.

Thanks. I'll start doing some more reading. Seems like a lot more research is needed too.

well, I found the source of my own "thinking" of this / but I think it will be studied longer than we will be around to learn the real answer. Here:


My understanding was that there are receptors on the alpha cells that are receptive to insulin, and so insulin will prevent secretion of glucagon.

this would make sense in terms of the rescue glucagon shot works. Also the bionic pancreas trials that test with 2 pumps.

This also explains why suspending the basal insulin in hypo basal suspend would cause the BGLs to float up. The key I guess is to get faster acting insulin into pumps so that the residual effect is shorter and suspending basal would have a quicker effect.

Are there some bionic pancreas systems that only pump insulin? And rely on cutting it off to let the body's natural glucagon response bring BGLs up when they are too low?

I also wonder, that if you always have insulin (basal) in your blood, then if indeed it does suppress glucagon response, then there would be a use-it-or-lose-it result in the glucagon response, since the constant presence of insulin would mean the alpha cells never get exercised and maybe reduce capacity in response over time.

If you've ever felt symptoms of a low, you've felt a counter-regulatory response.