--- module: 022-02 language: en chapter: 22 title: "Diabetes, Energy Metabolism, Obesity, and Metabolic Emergencies" module_title: "Fuel partitioning, insulin reserve, and metabolic crisis trajectories" source_sha256: 8fb0e6cc1a6c106fbc41b8d9bf04c2ed381bfb66eeb451924d749aa6624ce8b5 --- # Fuel partitioning, insulin reserve, and crisis trajectories ## Fuel selection across time ### Brain and red cells need continuous fuel ### Insulin signals availability, promotes storage ### Fasting: low insulin, high glucagon #### Liver glycogen early but finite #### Cori cycle lactate, alanine, glycerol #### Ketones gradually spare muscle protein ### Stress hormones free substrate for survival #### Inflammatory resistance causes hyperglycaemia ### Metabolic flexibility switches fuel oxidation #### Inactivity, ectopic fat, overnutrition reduce it #### Exercise raises insulin-independent uptake ## Beta-cell sensing and failure ### Glucose sensed through metabolism ### First phase ready granules, second recruits more ### Incretins act only when glucose present #### Low intrinsic hypoglycaemia risk alone ### Secretion cannot match resistance #### Amyloid, oxidative and reticulum stress #### Glucose toxicity forms a vicious cycle ### Atypical features prompt reconsideration ## Interpreting glucose markers ### Fasting glucose reflects hepatic output ### Post-meal glucose reflects meal and insulin timing ### Glycated haemoglobin misses variability #### Iron deficiency may raise it #### Haemolysis, bleeding, transfusion lower it #### Kidney disease has competing effects ### Fructosamine covers a shorter period ### Sensors read interstitial glucose with lag ## Insulin as dynamic replacement ### Basal suppresses hepatic release ### Prandial covers carbohydrate and protein ### Repeated correction causes oscillation ### Absorption varies with site and lipohypertrophy ### Kidney failure raises hypoglycaemia risk ### Alcohol causes delayed hypoglycaemia ### Pump interruption leaves no depot ## Ketoacidosis as staged physiology ### Lost restraint of lipolysis and ketogenesis #### Ketoacids consume bicarbonate #### Osmotic diuresis and vomiting deplete salts ### Low measured sodium, depleted total sodium ### Potassium high initially, stores low ### Fluid, insulin, then added glucose #### Anion gap tracks resolution better ### Euglycaemic ketoacidosis #### Low carbohydrate, pregnancy, cotransporter blockers #### Sick-day plans: fluid, ketones, pausing drugs ## Hyperosmolar crisis ### Insulin restrains ketogenesis, not glucose ### Glucose rises over days ### Frailty, infection, diuretics, poor water access ### Controlled fall in tonicity #### Rapid water entry harms adapted brain ### Insulin delayed until initial fluid ### Parallel potassium, thrombosis, precipitant care ## Hypoglycaemia and impaired awareness ### Falling glucose suppresses insulin, raises glucagon ### Recurrent lows lower warning thresholds ### Treat measured, avoid rebound eating ### Glucagon weaker with depleted glycogen ### Find cause, simplify regimen, restore awareness ## Adipose tissue and ectopic fat ### Expansion beyond capacity overflows #### Hypertrophic cells release fatty acids #### Lipid in liver, muscle, pancreas ### Visceral fat drains to portal circulation ### Body-mass index shows size, not composition ### Weight loss drives biological regain #### Treat as chronic relapsing physiology ### Preserve muscle with protein and resistance work ## Integrated metabolic plan ### Separate exposure, variability, hypoglycaemia ### Weigh reserve, organ risk, treatment burden ### Success is durable organ risk reduction