What Eades is saying doesn’t really make sense. If a type 1 diabetic (ie, complete lack of endogenous insulin) consumes 15g of glucose or 150g, the change in serum glucose will be wildly different, and commensurate with the amount ingested. If what he’s saying was correct, that insulin-independent glucose disposal can account for even large boluses in the form of a meal, then the change in serum glucose in a T1D would the same regardless of intake, as that change would be from hepatic output, not from the meal, which in the absence of insulin will be the same whether you’re eating a bowl of pasta or arugula with salmon. As someone who’s last endogenous secretion of insulin was about 26 years ago, I can pretty confidently tell you that is not the reality. I can eat a turkey sandwich before a 20mi bike ride no problem, but a 16oz soda with 70g of sucrose is going to put me past 500mg/dL even with the same exercise.

It is true that the effect of insulin on serum glucose in the advanced T2D patient specifically seems mostly based on suppressing hepatic output, and not entirely on opening GLUT4 channels in skeletal muscle as was thought before, but that doesn’t mean it’s black and white. GLUT4 exists, and is activated via IRS1, and GLUT1 is virtually unexpressed in skeletal muscle after the first year of life (Gaster et al, 2000). That is beyond contestation at this point. If Eades has a good argument as to why this exquisitely architected system of insulin-dependent glucose uptake into muscles that are perfectly prepped for its immediate oxidation would all exist for no reason, I would love to hear it. In fact, we have a version of what Eades is describing, in the form of AMPk activated GLUT4 translocation, skipping IRS1 and the need for insulin, but that’s in situations where the myocyte senses energy deficiency, not at rest. You probably know as well as I do how inefficient exercise is for disposing calories, so unless Eades expects us all to take 6 hour zone 2 jogs after every meal, at some point insulin-mediated glucose disposal has to be accepted.

Plus, we and our predecessors in Homo have been consuming starches for hundreds of thousands of years, there is evidence of strong selection on regions like AMY1 that extends long before our genus, etc. It’s clearly just as native to us at this point as any other nutrient. What’s not native is—like I said before—the context. The liver obviously can’t handle 3 100g boluses of refined glucose per day, for 30 years, especially in a sedentary person. That doesn’t mean glucose, or insulin, is a thing to be suppressed at all costs, just like the mechanistic connection between fatty acids and cardiovascular disease doesn’t mean fatty acids should be suppressed at all costs. IMO, an insulin sensitive person who exercises 4-6 times per week can eat whatever combination of whole foods they like and have basically zero fear of MetS or accelerated atherosclerosis. Remember that JAMA paper in Jan 2021 that computed the WHI biomarkers HR for CVD? LDL was like 1.6, lipoprotein insulin resistance was higher, near to obesity, and T2D was like 10.5. To my mind, insulin resistance is the smoking gun, whether it’s the initial causative agent or not, it seems pretty clear that if you’re weight stable and insulin sensitive, you’re safe.

Plus, I feel like he of all people shouldn’t be relying entirely on rodent data. Isn’t that usually his thing? That metabolic observations from rats shouldn’t be extrapolated to humans?

> If blood glucose was stable and it went up 18mg/dl (1 mmol) wouldn’t that indicate the intake was too high ?

I mean, maybe in an absolute sense it means intake was greater than the ability of basal glucose disposal to completely account for, but “too high” seems like it suggests pathology, and I don’t see that small of a disturbance to serum glucose being anywhere near such a threshold. Any healthy person’s glucose will rise more than that simply by waking up, or lifting weights for a bit.

Plus, insulin shuttling glucose into muscle and adipose tissue isn’t bad. It’s a normal physiological process. Provided both of those tissue categories remain sensitive to insulin and the person is at stable weight, I don’t see how you could sneak your way into MetS.