T2DM can get started in a variety of ways - behavioral, overeating, body - insulin resistance, obesity.
But apparently, diabetes and high blood sugar can start completely independently of obesity and insulin resistance. It can start in the brain, in certain hyperactive hypothalamus cells. Calming those cells abolishes hyperglycemia and T2DM, even without changing food intake.
AgRP neuron hyperactivity drives hyperglycemia in a mouse model of type 2 diabetes
https://www.jci.org/articles/view/189842
“Growing evidence suggests that the pathogenesis of type 2 diabetes (T2D) involves dysfunctional central mechanisms, and, hence, the brain can be targeted to treat this disease. As an example, a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) can normalize hyperglycemia for weeks or months in rodent models of T2D. Convergent evidence implicates inhibition of a particular subset of neurons as a mediator of this FGF1 effect.”
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