Pharmacy Diabetes

DPR-session-2-Physiological mechanisms: overweight, obesity and impaired glucose metabolism

Physiological mechanisms
  • Evidence suggests that obesity accounts for up to 90% of the risk of developing type 2 diabetes.
  • Not everyone with type 2 diabetes is overweight or obese as defined by Body Mass Index (BMI).
  • E.g., indigenous people, South Asians, etc…
  • Central adiposity (i.e., intra-abdominal fat) is the underlying issue.
  • Adipose (fat) tissue stores much of the excess energy
  • Excess fat accumulates in other organs → liver, pancreas, and muscle.
  • In these non–adipose tissues, excess energy leads to lipotoxicity, meaning the excess fat stored in these cells inhibits their proper functioning.
  • This disrupts normal glucose and insulin metabolism.
  • Muscle lipotoxicity inhibits glucose uptake.
  • This produces peripheral insulin resistance, requiring greater amounts of insulin to “push” glucose into the muscles.
  • This resistance is reduced with physical activity as muscle tissues consume energy (e.g., glucose) and become more responsive to insulin.
  • Pancreatic lipotoxicity inhibits β-cell insulin production, reducing the amount of insulin available to overcome the insulin resistance in muscles and other organs.
  • Significant energy restriction removes triglycerides (fat) from the pancreas in a matter of days, restoring β-cell insulin production.
  • This occurs before significant weight loss occurs in other organs and tissues, indicating it is not just excess body fat, but excess energy, driving insulin resistance and type 2 diabetes.
  • MRI scans of the pancreas in nearly 33,000 people in the UK.
  • Higher pancreatic fat content is associated with a 42% increase in risk of developing type 2 diabetes.
Assessing adiposity
  • BMI is not the best measure of excess body fat (adiposity):

    – Waist circumference;

    – Waist : height ratio;

    – Bioimpedance analysis;

    – Fat Mass Index =
    Fat Mass (kg) ÷ height² (m²).
    are much better indicators