The relationship between hyperinsulinemia and insulin resistance is a bit murky (Nolan and Prentki, 2019). Dr Corkey gave a good presentation on this, which Tl;dr: goes something like this — stuff in the environment, your food, etc., causes insulin hypersecretion. Not regular carb-induced insulin secretion, and not enough to cause hypoglycemia… just enough to cause insulin resistance.
I also recommend checking out some of Brownlee’s work on the microvascular and macrovascular consequences of hyperglycemia — it seems complementary to this (eg, Giacco and Brownlee, 2010; Shah and Brownlee, 2016). A lot has changed in the last decade, but there are still a lot of relevant points, or at least things to be aware of.
The Nolan and Prentki review is good – the basis is that there is no grand unifying theory underlying metabolic syndrome agreed upon by clinicians and scientists. I concur. Also, there probably isn’t one single mechanism because there are many different phenotypes/manifestations.
Definition: when I say beta cell failure in the context of T2D, I don’t mean dead failing beta cells, I mean beta cells that are trucking out more insulin than ever… but it’s not enough to keep glucose under control (due to insulin resistance). Now that that’s out of the way…
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