Eleven pathways to hyperglycemia

Beta-cell dysfunction and death, leading to decreased insulin secretion
Insulin resistance in liver, leading to increased glucose production
Insulin resistance in fat, leading to increased lipolysis
Insulin resistance in muscle, leading to decreased uptake of glucose
Brain phenomena, ie, increased appetite, increased sympathetic tone, decreased morning dopamine surge
Increased SGLT2 effect, leading to increased glucose reabsorption
Alpha-cell defect, leading to increased glucagon secretion
Decreased incretin effect, leading to decreased insulin secretion in response to food
Decreased amylin, leading to increased rate of glucose absorption
Immune dysregulation and inflammation
Abnormal colonic microbiome, leading to decreased GLP-1 secretion (speculative)
  • Based on information in reference 3.