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These mechanisms further activate the hypothalamic-pituitary-adrenal axis, hepatic glycogenolysis, hyperglycemia, hyperlipidemia, and insulin resistance, contributing to core depressive features of anhedonia, emotional dysregulation, and cognitive slowing ( The complex etiopathogenesis of T2DM has been explored in detail and includes insulin resistance (in the liver, muscles, and adipose tissue), impaired insulin secretion, -cell dysfunction, immune dysregulation and meta-inflammation, hyperglucagonemia, disrupted gut microbiota, increased gastric glucose absorption, renal adaptation with enhanced glucose reabsorption and gluconeogenesis, decreased dopamine, and heightened sympathetic tone in the brain ( via cells of the circumventricular organs located around the third and fourth brain ventricles, transmitting signals to deeper brain structures

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In the osteoarthritis trial, participants lost up to an average of 71.2 pounds