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.