Diabetes Pathology

• WHO (2019) defines diabetes as:

  • “A group of metabolic disorders characterized and identified by the presence of hyperglycaemia (increase glucose in blood) in the absence of treatment”
  • The aetio-pathology includes defects in insulin secretion, insulin action (or both) and disturbances of carbohydrate, fat and protein metabolism
• Visceral adipose tissue:

  • endocrine organ that secrete inflammatory and antiinflammatory mediators
  • adipokines (bad) are increased and adiponectin (good) is decreased during sedentary behaviour
  • increased adipokines causes release of resistin
  • resistin increase risk of insulin resistance - promotes LDL cholesterol
  • increased adipokines also causes release of c reactive protein, interleukin 6, tumour necrosis factor
  • pancreas releases insulin to counter this, but over a long term, there is a burnout/decrease in insulin production

  
• Key words:

  • adipocytes are fat cells - primarily compose adipose tissue
  • adiponectin - protein hormone which helps to regulate blood glucose
  • adipokines (aka adipocytokines)
  • examples include leptin, adiponectin, resistin, interleukin 6 and tumour necrosis factor alpha (TNF), c-reactive protein
  • hyperinsulinemia - excess levels of insulin circulating in the blood relative to the level of glucose
• Insulin resistance:

  • At rest GLUT4s are predominantly within the cell
  • In the presence of insulin, glucose uptake into skeletal muscle occurs due to increased GLUT4 activity
  • Insulin stimulates the translocation of intracellular GLUT4s to the T-tubules or plasma membrane of the muscle cells
  • Via the GLUT4s the glucose is transported from the circulation into the muscles for utilisation or storage

  
• Summary of contributions of T2 diabetes Pathophysiologies over time (1-3)

  • NGT = normal glucose tolerance, IGT = impaired glucose tolerance, T2D = type 2 diabetes
  • Both beta-cell dysfunction + insulin resistance start many years before diagnosis
  • Those who develop diabetes have typically lost ~50% of beta-cell function
  • Beta-cell dysfunction ultimately determines the onset of hyperglycaemia and is a major factor associated with progressively rising plasma glucose levels and disease progression