Triabolical_ t1_j17d7m9 wrote on December 22, 2022 at 5:04 AM

There is no consensus on insulin resistance, but this is what I think is going on...

The best measurement for insulin resistance is known as a "hyperinsulinemic euglycemic clamp". It's a fairly invasive procedure and is therefore only used sometimes in research settings.

Therefore much of the research uses measures that correlate well with the euglycemic clamp technique. A commonly-used one is known as HOMA-IR, and it is calculated using fasting insulin and fasting glucose. Because of the way the formula works, it is more of a measurement of insulin, and therefore high values are an indication of hyperinsulinemia, or constant elevated insulin.

This makes it a far better measure of metabolic health than HbA1c, which is what is commonly used to diagnose prediabetes and type II diabetes, but it's not often used.

The hyperinsulinemia is responsible for a lot of issues that come from prediabetes or type II - it makes is harder to metabolize fat and that leads to elevated weight gain and high triglycerides.

As for what causes the hyperinsulinemia, that's where there's a lack of consensus.

My opinion is that excess fructose leads to fat accumulation in the liver, which leads to NAFLD, which leads to the liver making too much glucose (disregulated gluconeogenesis), and that is what leads to the hyperinsulinemia - the constant supply of glucose means insulin levels cannot go back to normal.

To fix insulin resistance, you need to get rid of the hyperinsulinemia. From a mechanistic standpoint, that would mean somehow dealing with the disregulated gluconeogenesis. You could either fix the fat accumulation in the liver - somehow - or you could make the glucose wanted rather than unwanted.

In other words, you need to be in ketosis - a state where gluconeogenesis is normal. Which means either a very-low-carb diet, a very-low-calorie diet, or a fasting diet.

If you look at the clinical evidence for treating type II diabetes, the only real effective treatments are gastric bypass (forced low calorie diet), low-calorie diets (<800 cal/day), or keto diets. There is also some evidence for fasting, though that is less studied.

The other common diets significantly underperform these options.

derpderp3200 OP t1_j17unj9 wrote on December 22, 2022 at 8:30 AM

I've only had it checked twice, but curiously enough I don't have hyperinsulinemia, but still have elevated fasting glucose and huge spikes after food(on OGTT had a drop below fasting values instead). I'm also on the verge of being underweight, what I struggle with is persistent lack of appetite rather than weight gain.

I'm also a young person with "treated" sleep apnea. Quotes because my impression is CPAP et al largely just convert apneas into subtler microarousals that have milder physiological consequences but comparable effects on sleep quality.

About T2DM, my impression from reading literature has been that while full blown diabetes are fairly similar to each other, earlier dysglycemia has a number of phenotypes that only start to converge after beta cells begin failing.

Triabolical_ t1_j1986ba wrote on December 22, 2022 at 4:33 PM

What do you get from HOMA-IR?

Note that OGTT is *not* a measure of insulin resistance, it's a measure of carbohydrate tolerance, and there are a number of things that affect carbohydrate intolerance.

If you are carb intolerant, eating a lot of carbs is not a great idea in my opinion. What does your diet look like?

WRT sleep apnea, it is associated with insulin resistance but there's not agreement on which way the association goes.

derpderp3200 OP t1_j1aggp8 wrote on December 22, 2022 at 9:22 PM

Oh, sorry. I'm trying to build a working model of this whole thing, but have been struggling with substantial brain fog that in retrospect has roughly correlated with my fasting insulin and postprandial fatigue getting worse over the past few years...

Early in the year had a HOMA-IR(glucose, insulin) of 0.51(94mg/dl, 2.2 uIU/ml), more recently 1.2(105mg/dl, 4.6uIU/ml). OGTT at both timepoints showed a glucose drop below fasting, with reasonable insulin numbers, which I suspect is rapid gastric emptying that sometimes occurs in prediabetes/T2DM, and is often associated with largely the same set of postprandial fatigue/brainfog symptoms I get(going by Sigstad’s score criteria). Glucose peak likely occurred before 1h mark. On a glucose meter, my fasting glucose is consistently ~105, which very easily jumps to 150-170 even with a single sandwich or some lowish-glycemic-index buckwheat, and to 180-220 with what I'd consider "a normal meal".

I thought that impaired glucose tolerance was a consequence of impaired first-phase insulin secretion, which in turn strongly correlates with fasting insulin levels, which I thought was a function of insulin resistance... I don't know, I just hope so badly that treating this stuff will fix the brain fog that's been getting worse and worse for years now :(

About apnea, it's likely apnea->dysglycemia- glucose metabolism follows a diurnal cycle susceptible to disruption even by sleep restriction, and sleep disordered breathing as a spectrum causes abnormal autonomic tone, while much less of a case can be made for dysglycemia->apnea. Maybe damage to upper airway dilator muscle innervation, airway edema, or tongue base fat deposition... though most likely each of these would require anatomically compromised airway just like most cases do.

Triabolical_ t1_j1aq9t2 wrote on December 22, 2022 at 10:30 PM

Interesting.

Your HOMA-IR would suggest that you are mildly insulin resistant, though opinions differ on what a good threshold is.

I believe the symptoms you are getting and the low blood glucose is a sign of reactive hypoglycemia. I don't have enough knowledge about dumping syndrome to have any opinion on it.

I can tell you that I had pretty significant reactive (or postprandial) hypoglycemia - I'd get back from lunch and 90 minute later I'd really want to go to sleep.

For me, the fix was to switch from the sandwiches and burritos I was eating to something that was much, much lower in refined carbs - salads and burrito bowls without the carbs. I ended up full keto and these days I'm what I would call "keto adjacent".

Given that you are having issues with carbohydrate intake, going low-carb for a while would be an interesting experiment.

derpderp3200 OP t1_j1cpaij wrote on December 23, 2022 at 9:11 AM

I never really had hypoglycemia after an actual meal(I know you can get the adrenergic subset of hypoglycemia symptoms without objective hypoglycemia, but it doesn't seem to fit the bill), and my fatigue seems independent of glucose levels- sometimes it hits while they're still high, sometimes after they go back down, sometimes minimal symptoms start before it reaches the peak. I get hours of horrid brain fog, restlessness, anxiety, overwhelming desire to lie down, spend 45-90min in a food coma, and be groggy for several hours afterwards. It gets lighter in the evening, and it's bad enough that I'm afraid of eating during the day. But I'll have to force myself since science suggests that skipping breakfast and one meal a day worsen glucose tolerance, which tracks with my symptoms getting worse after I switched to this.

I'm trying to limit my carb intake, but it's very difficult. For one I'm vegetarian, for two, between ADHD, Sleep Disordered Breathing, and the part of fatigue I now presume to by dysglycemia related, I'm an extremely low functioning person and taking care of myself stretches my capacity very thin.

A lot of the time it's a choice between having some bread and going hungry, and I've been going hungry for a longer time now, which is also bad for my energy levels.