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  <head>
    <title>022-02 Fuel partitioning, insulin reserve, and metabolic crisis trajectories</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Fuel partitioning, insulin reserve, and crisis trajectories">
      <outline text="Fuel selection across time">
        <outline text="Brain and red cells need continuous fuel"/>
        <outline text="Insulin signals availability, promotes storage"/>
        <outline text="Fasting: low insulin, high glucagon">
          <outline text="Liver glycogen early but finite"/>
          <outline text="Cori cycle lactate, alanine, glycerol"/>
          <outline text="Ketones gradually spare muscle protein"/>
        </outline>
        <outline text="Stress hormones free substrate for survival">
          <outline text="Inflammatory resistance causes hyperglycaemia"/>
        </outline>
        <outline text="Metabolic flexibility switches fuel oxidation">
          <outline text="Inactivity, ectopic fat, overnutrition reduce it"/>
          <outline text="Exercise raises insulin-independent uptake"/>
        </outline>
      </outline>
      <outline text="Beta-cell sensing and failure">
        <outline text="Glucose sensed through metabolism"/>
        <outline text="First phase ready granules, second recruits more"/>
        <outline text="Incretins act only when glucose present">
          <outline text="Low intrinsic hypoglycaemia risk alone"/>
        </outline>
        <outline text="Secretion cannot match resistance">
          <outline text="Amyloid, oxidative and reticulum stress"/>
          <outline text="Glucose toxicity forms a vicious cycle"/>
        </outline>
        <outline text="Atypical features prompt reconsideration"/>
      </outline>
      <outline text="Interpreting glucose markers">
        <outline text="Fasting glucose reflects hepatic output"/>
        <outline text="Post-meal glucose reflects meal and insulin timing"/>
        <outline text="Glycated haemoglobin misses variability">
          <outline text="Iron deficiency may raise it"/>
          <outline text="Haemolysis, bleeding, transfusion lower it"/>
          <outline text="Kidney disease has competing effects"/>
        </outline>
        <outline text="Fructosamine covers a shorter period"/>
        <outline text="Sensors read interstitial glucose with lag"/>
      </outline>
      <outline text="Insulin as dynamic replacement">
        <outline text="Basal suppresses hepatic release"/>
        <outline text="Prandial covers carbohydrate and protein"/>
        <outline text="Repeated correction causes oscillation"/>
        <outline text="Absorption varies with site and lipohypertrophy"/>
        <outline text="Kidney failure raises hypoglycaemia risk"/>
        <outline text="Alcohol causes delayed hypoglycaemia"/>
        <outline text="Pump interruption leaves no depot"/>
      </outline>
      <outline text="Ketoacidosis as staged physiology">
        <outline text="Lost restraint of lipolysis and ketogenesis">
          <outline text="Ketoacids consume bicarbonate"/>
          <outline text="Osmotic diuresis and vomiting deplete salts"/>
        </outline>
        <outline text="Low measured sodium, depleted total sodium"/>
        <outline text="Potassium high initially, stores low"/>
        <outline text="Fluid, insulin, then added glucose">
          <outline text="Anion gap tracks resolution better"/>
        </outline>
        <outline text="Euglycaemic ketoacidosis">
          <outline text="Low carbohydrate, pregnancy, cotransporter blockers"/>
          <outline text="Sick-day plans: fluid, ketones, pausing drugs"/>
        </outline>
      </outline>
      <outline text="Hyperosmolar crisis">
        <outline text="Insulin restrains ketogenesis, not glucose"/>
        <outline text="Glucose rises over days"/>
        <outline text="Frailty, infection, diuretics, poor water access"/>
        <outline text="Controlled fall in tonicity">
          <outline text="Rapid water entry harms adapted brain"/>
        </outline>
        <outline text="Insulin delayed until initial fluid"/>
        <outline text="Parallel potassium, thrombosis, precipitant care"/>
      </outline>
      <outline text="Hypoglycaemia and impaired awareness">
        <outline text="Falling glucose suppresses insulin, raises glucagon"/>
        <outline text="Recurrent lows lower warning thresholds"/>
        <outline text="Treat measured, avoid rebound eating"/>
        <outline text="Glucagon weaker with depleted glycogen"/>
        <outline text="Find cause, simplify regimen, restore awareness"/>
      </outline>
      <outline text="Adipose tissue and ectopic fat">
        <outline text="Expansion beyond capacity overflows">
          <outline text="Hypertrophic cells release fatty acids"/>
          <outline text="Lipid in liver, muscle, pancreas"/>
        </outline>
        <outline text="Visceral fat drains to portal circulation"/>
        <outline text="Body-mass index shows size, not composition"/>
        <outline text="Weight loss drives biological regain">
          <outline text="Treat as chronic relapsing physiology"/>
        </outline>
        <outline text="Preserve muscle with protein and resistance work"/>
      </outline>
      <outline text="Integrated metabolic plan">
        <outline text="Separate exposure, variability, hypoglycaemia"/>
        <outline text="Weigh reserve, organ risk, treatment burden"/>
        <outline text="Success is durable organ risk reduction"/>
      </outline>
    </outline>
  </body>
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