Does a healthy ketogenic diet cause irreversible insulin resistance?

[SomeGuy]

This would have been my expectation, except that the study seems to be claiming the opposite, that gluconeogenesis was less on the carb-free diet.

Am I reading this incorrectly?

"… As a result, absolute gluconeogenesis tended to be higher when subjects were in the H condition than when subjects were in the N condition."

[PaulL]

Interesting. I read this in the abstract: “Results: EGP [endogenous glucose production] was lower in the H [intervention] condition than in the N [control] condition.” And the same remark is repeated later. I obviously missed the part you quote. Will have to go back and re-read more carefully later. Though it is surprising that the abstract would contradict the body of the paper. Perhaps they are defining their terms in a non-obvious manner?

[PaulL]

The observation that ‘β-hydroxybutyrate and acetoacetate replaced glucose’ as the primary fuel for the brain supports Bikman’s assertion that ketones in sufficient quantity could provide 100% of the brain’s fuel requirements. This, in turn, may be a reflection of the observed RQ.

I think it was you who posted a link to a paper by Cahill stating almost that, but interestingly, Cahill is also the source of the estimate that the brain needs a minimum of 130 grams of glucose a day. Cahill’s experiment on fasting subjects using a euglycaemic hyperinsulinaemic clamp would tend to support the notion that the brain doesn’t actually need glucose at all, if ketones are providing sufficient energy.

[SomeGuy]

Will have to go back and re-read more carefully later.

The part I quoted above is just the rest of the same sentence after a semicolon. FWIW, I didn’t find it to be contradictory but I did have to read it a few times to digest the nuance being drawn between fractional and absolute. (And “endogenous” includes two sources of non-dietary glucose production, further complicating interpretation.)

[Naghite]

Just read the linked paper by @Belisarius, and it is interesting. I really wish they had measured glucagon and not JUST insulin, that may have given a different story. Of course, without being fat adapted, that also kind of throws a wrench in the numbers, with ketone production not being efficiently used with (some?) of those involved and energy being wasted as ketones in the urine.
Another thing that might have helped was measuring (at least in the liver), the glycogen stores at the end of the 3 days. Since the carb eaters would have re-filled their glycogen reservoirs easily and thereby reduced their need for GNG over continued dips into their glycogen stores, this result is not too surprising really - but might have been more valuable with fat adapted participants.
Here is a summary for those who are confused by the statements
H (no carbs) - glucose produced = 181 g/day (of which 172 from GNG and 9 from glycogen)
E (carbs) - glucose produced = 226g g/day (145 from GNG and 81 from glycogen).
Carb eaters re-fill their glycogen stores faster and higher and are able to use their quick-access sugars more easily, while the H group would not have the stores and decide to use GNG to stop from completely depleting the glycogen stores. This should not surprise anyone on these forums and is completely logical.

Separately, not ONE response to the paper/article noting that eating Fat produces GNG based solely on fat intake. A steady increase (straight line) based on food intake. This is a pure study with type I diabetics and (to my mind putting protein aside) makes it pretty clear that GNG is not purely demand driven. Obviously demand does influence production, but not solely.

@SomeGuy But I can change my average glucose level from (approximately) 5.6 mmol/L average for one day, eat twice as much protein the next day and have an average that day of 6.2 and then eat less the next day and have my average (with a continuous glucose monitor) fall back to 5.6. All from diet, eating the same foods but a different volume. Does my bodies demand for blood glucose rise by 0.6 mmol/L just because I ate more that day? How would this work and make sense to you?

[SomeGuy]

@SomeGuy But I can change my average glucose level from (approximately) 5.6 mmol/L average for one day, eat twice as much protein the next day and have an average that day of 6.2 and then eat less the next day and have my average (with a continuous glucose monitor) fall back to 5.6. All from diet, eating the same foods but a different volume. Does my bodies demand for blood glucose rise by 0.6 mmol/L just because I ate more that day? How would this work and make sense to you?

Makes perfect sense to me. I don’t recall disputing the notion that serum glucose is both demand-driven and supply-driven, along with other hormonal factors.

The amount & source of dietary energy and to extent to which you expend that energy are relevant variables - along with how insulin is released and how responsive one’s tissues are to that insulin - in determining serum glucose levels at any particular moment.

Sorry if I’ve posted anything confused on such matters 'tho I don’t recall doing so.

[PaulL]

Carb eaters re-fill their glycogen stores faster and higher and are able to use their quick-access sugars more easily, while the H group would not have the stores and decide to use GNG to stop from completely depleting the glycogen stores.

This appears to be an artefact of not being fat-adapted. Volek’s team showed that fat-adapted athletes who’d been on a ketogenic diet for two years or more had glycogen stores indistinguishable from those of carb-burning athletes.

[PaulL]

But I can change my average glucose level from (approximately) 5.6 mmol/L average for one day, eat twice as much protein the next day and have an average that day of 6.2 and then eat less the next day and have my average (with a continuous glucose monitor) fall back to 5.6.

It would be interesting to know if this fluctuation represents a real change, or is simply an artefact of the margin of error. Most home devices are not all that precise. On the other hand, if this is repeatedly reproducible, then it probably is real, even though the results fit within an accuracy of ±0.2.

[Naghite]

It is reproducible (I have repeated multiple times) both within the same week (back and forth) using the same CGM and then again on a different weeks using a second CGM to reproduce. Again, I can raise and then lower and then raise again based on food intake (carnivore so all fat and protein, with the linked paper on fat showing the results could not be caused by just fat in a person who can produce insulin).

[Naghite]

Here is Ben Bikman repeating it all in one video as I had described above. I do not have time now, but I am going to start a separate thread since I have found the original papers demonstrating most of what Ben describes. https://www.youtube.com/watch?v=MEzAvos1jak

[Belisarius]

I think this relevant here:

Long Term Ketosis - Good, Bad, Ugly?

But insulin resistance (or maybe more accurately described, glucose intolerance) when in the ketogenic condition doesn’t indicate metabolic inflexibility at all. It would be inflexibility only if glucose tolerance didn’t return after a few days eating high carb. During a ketogenic diet, multiple mechanisms make fat uptake efficient at the expense of glucose. And during a high carb diet, the reverse is true. The fact that it takes someone a few days to keto-adapt or glucose-adapt is not inflexib…