Type 1 Diabetes

This summary relies heavily on the podcast “The Drive with Peter Attia — Jake Kushner“. The show-notes of this excellent episode contain more relevant details, charts, book recommendations and resource links. Any mistakes in the summary below are mine.

Summary

  • Introduction.
  • Detailed Progression.
  • Role of Pancreas.
  • Diabetes Detection.
  • Diabetes Test.
  • Diabetes Treatment.
  • Role of Insulin.
  • Managing Insulin and Blood Sugar.
  • Role of (Endurance) Exercise.
  • Low Carb Solution.
  • Protein, Glucose and Insulin.

Introduction.

  • Type 1 diabetes = very little or no insulin.
    • Insulin is produced by the pancreas.
    • Low insulin results in high blood sugar levels in the body.
    • Affects approximately one in 300 people.
  • The cause of type 1 diabetes is unknown.
    • Believed to involve a combination of genetic and environmental factors.
  • Involves autoimmune destruction of beta cells.
    • Beta cells in the pancreas produce insulin.
    • Beta cells that are destroyed release their unique content.
    • This triggers an autoimmune response.
    • The autoimmune response includes certain unique antibodies.
  • The appearance of unique autoantibodies is a signal.
    • Indicates potential for type 1 diabetes:
      • Islet cell autoantibodies, insulin autoantibodies, autoantibodies targeting the 65-kDa isoform of glutamic acid decarboxylase (GAD), autoantibodies targeting the phosphatase-related IA-2 molecule, and zinc transporter autoantibodies (ZnT8).
  • Type 1 diabetes is different than type 2.
    • Type 2 diabetes is characterized by insulin resistance.
    • Type 1 diabetes is characterized by insulin deficiency, generally without insulin resistance.
      • Test for type 1 by testing for the presence of autoantibodies.

Detailed Progression.

  • Beta cells, which secrete insulin, dump off antigens.
  • Antigens begin to provoke the immune system locally.
  • Immune cells start to destroy beta cells, resulting in more antigens being dumped.
  • End result is a progressive autoimmunity, where you lose beta cells over time.
  • Adults have a greater reserve of beta cells so onset takes longer and is slowly progressing.

Role of Pancreas.

  • 95% of the pancreas serves an exocrine function:
    • Mostly there to help local digestion system.
  • 5% of the pancreas acts as an endocrine organ:
    • Secretes systemic hormones into the system (including insulin).

Diabetes Detection.

  • When a person suffers a problem that may be caused by diabetes:
    • Such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer.
  • General symptoms include:
    • Frequent urination.
    • Increased thirst.
    • Increased hunger.
    • Weight loss.
    • Or: blurry vision, feeling tired, and poor wound healing.
  • Symptoms typically develop over a short period of time.

Diabetes Test.

  • Diagnosed by testing:
    • The level of sugar or glycated hemoglobin (HbA1C) in the blood.
    • Oral Glucose Tolerance Test.
  • Varying indications of risk levels.

Diabetes Treatment.

  • Treatment with insulin is required for survival.
  • Insulin therapy is usually given by injection but can also be delivered by an insulin pump.
  • Diet and exercise are important parts of disease management.
  • Target range of blood glucose differs, but about 80-140 mg/dl.

Role of Insulin.

  • Insulin is a key factor in regulating virtually every cell in the body.
  • It’s about recognizing whether a cell is in a state of feast or famine.
    • If in feast: it takes the nutrients and parks them in the cell.
    • In a famine: it will mobilize some nutrients and make them available to keep the organism alive.
  • Insulin is a master regulator of your state of metabolism.
    • In a muscle cell:
      • In a fed state:
        • Promotes glucose uptake into skeletal muscle.
        • Insulin signal tells the glucose transporter to move to the cell wall.
        • GLUT4, a glucose transporter, translocates from the cytosol to the cell wall, which makes the muscle cell permeable for glucose to be shuttled in.
      • In a state of starvation:
        • At a cellular level, people with T1D are starving.
        • Muscle is broken down and used for gluconeogenesis.
        • It creates a profound negative nitrogen balance.
  • Insulin influences many of the major steps of protein metabolism .
    • In the presence of insulin, you’re putting more glycogen into skeletal muscle, or in the absence you’re going to break them down.
  • And IGF-1:
    • If insulin goes up, IGF-1 goes up. (see SHBG write-up)

Managing Insulin and Blood Sugar.

  • The challenge of controlling blood sugar in T1D due to variance of reaction to food:
    • Too much insulin may cause hypoglycemia, dangerously low levels of blood glucose.
    • Difficult to predict the impact of carbs.
      • Stress, sleep quality, exercise all have an impact.
    • Other things in food, like fat and protein, also alter gastric emptying and glucose conversion.
  • Potential for weight gain:
    • Hiking up insulin and overshooting blood glucose (too low):
      • Need to eat carbs to compensate.
    • End up “chasing carbs”.
    • Weight gain.
  • Blood glucose goals:
    • Target absolute levels as well as variance (standard deviation).
  • Possible future “cures”:
    • Stem cells
    • Auto-loop pancreas that would measure your glucose and administer insulin.
    • Beta cell regenerative therapy
    • Something that just shuts down the autoimmune system??

Role of (Endurance) Exercise.

  • People can use exercise can help people control their diabetes
  • Part of the mechanism is via the insulin-independent glucose uptake into skeletal muscle via AMP kinase
    • An enzyme that is sensing the energy status of the cell
    • If you alter the energy status of the cell through a tremendous amount of work (exercise), it signals the GLUT4 to translocate to the membrane of the skeletal muscle
    • So now you get insulin-independent glucose uptake into skeletal muscle
  • More likely to happen in endurance than strength exercise.

Low Carb Solution.

  • The Law of Small Numbers.
    • If you consume more carbs, you need more insulin and therefore there’s a greater opportunity to make a mistake.
    • If you consume fewer carbs, you will consume less insulin and you’ll have fewer mistakes
    • Avoid carbohydrates and apply medium and long acting insulin to cover protein and fat and basal metabolic requirements.
      • Low carb, high protein diet.
    • Use regular insulin (i.e. human insulin), not fast-acting insulin (i.e. Novolog).

Protein, Glucose and Insulin.

  • 10 grams of protein ends up being about 6 grams of carbohydrate.
    • Kinetics are not immediate.
    • You don’t get gluconeogenesis in a matter of seconds, it’s delayed over hours.

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