Insulin Action Time and Insulin Resistance

  1. Did any of you experience rapid (i mean daily/weekly) changes in insulin action time? e.g. one day humalog acting for 2,5h & the other for 5h given the same amount of activity / food?

Do you have any ideas what may be the underlying physiological reasons?

  1. Did any of you experience radical shifts in insulin resistance on a daily basis? e.g. one day all is standard but the next - same amount of insulin makes you plunge and eat twice as much to keep glicemia stable.

What may be the reasons?

Here’s my theory. Insulin action time is a fixed value. It doesn’t change. Since insulin is injected into an environment that includes factors that “push back” the effect of insulin, it’s not so easy for us to measure.

You can’t simply observe the movement of blood glucose and then attribute that effect to insulin alone. There are a host of other things that interact with insulin including cortisol and adrenaline.

Diabetes is a dynamic disease. It’s simplistic to only rely on fixed formulas to dose insulin. Insulin resistance goes up and down, even in non-diabetic individuals. One poor night’s sleep, for instance, will raise insulin resistance in all people, including non-diabetics.

No, I don’t experience radical shifts in insulin resistance but I do live with small changes day to day and milder trends over a few weeks that causes me to make regular changes to my basal rate and insulin sensitivity factor settings in my automated insulin dosing system.

You have not shared any of the context for your questions. Are you diagnosed T1D or T2D? How long have you lived with diabetes? How old are you? Is it possible that you are experiencing a slow onset form of T1D known as latent autoimmune diabetes in adults or LADA?

What kind of diet do you consume? Does your diet include bread, noodles, rice, potatoes or highly processed foods like breakfast cereals or “energy” bars? Do you drink carbohydrates like carbonated beverages or juice? Do you eat three meals a day? What about snacks?

What is your exercise regimen, if any? How well do you sleep? What stresses do you live with every day?

Have you asked a doctor or other medical professional these questions? If so, how did they answer?

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I think I know what your getting at, and yeah, I think I have been seeing that of late.
I call it "system instability,’ or “fluctuating system control,” or “system variability.”
I have no idea what the cause it. It just finally went away on its own.

I agree with Terry that the insulin action should be constant, its your body’s response to it that changes.

I was having a horrible time with the system behaving in a very dynamic way for months. Now, things are ok, other than some bedtime lows. Like, its pretty ‘well behaved,’ and flatline. I changed NOTHING. Some internal and physiological variable shifted.

@Terry4 You are right, insulin parameters are fixed. it’s all about the system/environment. I am T1 diabetic and I have looked at all these issues extensively with my medical team. we did not find straightforward answers.

Maybe my question should be a bit different…
Most of professionals and diabetics are quite used to the fact insulin sometimes simply does not work as long and hard as expected (e.g. 30% of standard system impact due to hormones, inflammation, stress, etc. etc.).

But what about the other end? What if in your relatively stable system with moderate daily changes and comparable key parameters (time of the day/activity/dose/nutrition/stress/stacking/injection site, etc.), suddenly in a form of a singular event insulin turns out to have exponentially (let’s say 2x and above) stronger effect on your system? Did you have such experiences? What could have caused such a situation on a physiological level?

I can get Humalog to REALLY KICK IN by going for a brisk 3000+ step walk after taking the shot.

If I don’t go for the walk it will lazily work over 4-5 hours.

The effect is consistent and walking without recent insulin doesn’t do much to my bg.

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Could you be injecting into either a muscle or a blood vessel of some sort? Are you on MDI?

No, I haven’t experienced this. Smaller increases in insulin sensitivity can have dramatic effects, however. Sensitivity increases, say from 1:30 to 1:40, can often express themselves in a series of hypoglycemic events requiring emergency glucose treatments and an increased vigilance.

As to the cause of increased insulin sensitivity, many factors are related. An increase in exercise, improved sleep, losing weight, and a reduction of carb consumption all can increase sensitivity.

One factor that has surprised me and took me a while to understand is when I reduce insulin delivery through reductions in my basal rates or increases in my insulin to carb ratios, it can often lead to increases in sensitivity. It’s paradoxical and puzzling. Usually, when insulin is reduced, glucose goes up. But many times I’ve observed a reduction in insulin leading to lower levels of glucose, even hypoglycemia.

This trend is naturally limited but it makes sense if you accept that insulin itself is the main driver of insulin resistance. In T2D, for example, hyperinsulinemia (too much insulin in the blood) is closely related to an increase in insulin resistance.

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Thank you for sharing this. This is such an interesting observation.
If you go down with basal - this obviously should increase your glucose levels, but if you add to that higher insulin to carb ratios for meals - one guess / idea would be glucogenesis. insulin facilitates the process of glycogen synthesis from glucose. so maybe higher concentrations of insulin give it an additional push. as a consequence your glucose would drop more than expected as larger percent of glucose would end up attached to glycogen chains.

It would be useful to have some analysis/research regarding the magnitude of effect of glucose / insulin on the processes of gluconeogenesis, glucogenesis, glucogenolysis. How do these processes look like in a diabetic patient? What is their magnitude? How do they look like for a diabetic patient who depleted his/her glycogen levels (e.g. due to low carb diet)? Can they be more aggressive and… push you to very hard hypo? For a healthy person, when sugar drops he/she stops releasing insulin, so the process of glucogenesis stops. but in a case of a diabetic when sugar drops, there may be still plenty of active insulin… does this process continue?

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The body responds to not only insulin, but also the ratio of insulin to glucagon, since they are both active all the time (in non-diabetics) in various amounts.

These are hard to memorize, but they are easy to process mentally and determine the effect when thinking about it in terms of how the non-diabetic’s body would respond. When would there be insulin (a fed state), and when would there be glucagon (a low BG state).

(When I refer to insulin or glucagon here, I am actually meaning the ratio of insulin to glucagon.)

Gluconeogenesis - making glucose from non-carb sources. Why would the body do this? Because it does not have enough available carbohydrates. So gluconeogenesis happens during glycogen depletion.

  1. This process is stimulated by glucagon (Oh no! There is glucagon in our system, that means our BG must be low! Let’s make some glucose!)
  2. It is stimulated by epinephrine (Oh no! Stress! We need some carbs to help combat whatever is causing the stress!)
  3. And it is inhibited by insulin. (There is a lot of insulin in our body. Whenever there is a lot of insulin in our body that means we have just eaten a meal, so we don’t need to create glucose now.)

Glucogenesis - the process of storing glucose molecules as glycogen. When would a body store glucose? In a fed state. And what happens in a fed state? A higher amount of insulin.

  1. This process is stimulated by insulin (There is a lot of insulin in our body. That means we just ate. Now is a good time to store glucose!)
  2. And it is inhibited by glucagon. (We are low, so now is not a good time to be stashing glucose away for later, we need it now!)

Glycogenolysis - the opposite of glucogenesis. Instead of storing glucose as glycogen, glycogenolysis is the breakdown of the glycogen back into glucose. When would a body do that?

  1. Insulin inhibits glycogenolysis. (If there is a lot of insulin, that means we just ate. We just don’t need to release glucose now!)
  2. Glucagon increases glycogenolysis. (We have glucagon in our body, that means we have low BG. So we need to release some of the stored glucose right away!)