--- module: 022-01 language: en chapter: 22 title: "Diabetes, Energy Metabolism, Obesity, and Metabolic Emergencies" module_title: "Foundations" source_sha256: d714706d809400de44765941f3f065549b22439a356fcd9476302575d166f42a --- # Diabetes, energy metabolism, obesity, and emergencies ## Fed, fasting, and stress states ### Insulin dominates the fed state #### Adenosine triphosphate closes potassium channels #### Incretins amplify glucose-dependent secretion #### Promotes uptake, glycogen, lipid, protein, potassium entry #### Suppresses hepatic output, lipolysis, ketogenesis ### Glucagon rises as glucose and insulin fall #### Liver glycogen first, then gluconeogenesis #### Ketones fuel brain and muscle, spare protein ### Stress hormones oppose insulin action #### Expose limited beta-cell reserve #### Recurrent lows blunt warning, cause unawareness ## Diabetes classification and pathogenesis ### Type 1: immune beta-cell destruction #### Absolute insulin deficiency, insulin essential #### Autoantibodies classify but do not injure ### Type 2: resistance plus beta-cell dysfunction #### Compensation fails through gluco- and lipotoxicity #### Heterogeneous: resistance or secretory failure ### Monogenic, pancreatic, endocrine, drug, gestational ### Type changes treatment, inheritance, ketosis risk ## Diagnosis and monitoring ### Fasting glucose, tolerance test, glycated haemoglobin ### Confirm abnormal results unless clear ### Glycated haemoglobin misleads if red-cell lifespan alters ### Sensors show direction, variability, time in range ### Ketones in deficiency, illness, pregnancy, inhibitors ## Chronic tissue injury ### Hyperglycaemia damages microvessels #### Retinopathy: leakage, ischaemia, neovascularisation #### Kidney disease: albuminuria, filtration loss #### Sensory, painful, and autonomic neuropathy ### Accelerated atherosclerotic cardiovascular disease ### Foot ulcers from neuropathy, pressure, ischaemia ### Prevention goes beyond glucose treatment ## Glucose-lowering therapy ### Lifestyle foundations and individualised goals ### Metformin lowers hepatic output, little hypoglycaemia ### Sulfonylureas: hypoglycaemia and weight gain ### Thiazolidinediones: oedema, fractures, heart failure ### Glucagon-like peptide one agonists slow emptying, appetite ### Cotransporter two inhibitors: heart and kidney benefit #### Ketoacidosis without extreme hyperglycaemia ### Basal restrains fasting output, prandial covers meals ## Hypoglycaemia ### Usually insulin or secretagogue exposure ### Adrenergic warning versus neuroglycopenia ### Oral carbohydrate if able to swallow ### Intravenous glucose or glucagon if severely impaired ### Sulfonylurea lows may recur ## Diabetic ketoacidosis ### Insulin deficiency plus counter-regulatory excess #### Hyperglycaemia drives osmotic diuresis #### Ketones consume bicarbonate, high-gap acidosis #### Potassium shifts out, total stores depleted ### Glucose may be only moderately raised ### Fluid, insulin, potassium, then added glucose #### Continue insulin until ketosis resolves ### Seek infection, omitted insulin, infarction ## Hyperosmolar hyperglycaemic state ### Enough insulin to restrain major ketogenesis ### Osmotic diuresis causes water loss, hypertonicity ### Slower onset in older or vulnerable people ### Gradual fluid, cautious tonicity correction #### Rapid shifts worsen neurological injury ### Mixed presentations are common ## Obesity and metabolic dysfunction ### Leptin and hypothalamus integrate weight signals ### Weight loss raises hunger, lowers expenditure #### Biological resistance, not personal failure ### Visceral and ectopic fat drive complications ### Assess beyond body-mass index ### Combine diet, activity, drugs, selected surgery ## Dyslipidaemia and fatty liver ### Insulin resistance raises triglyceride-rich particles #### Lowers high-density lipoprotein cholesterol ### Statins cut synthesis, increase receptor clearance ### Steatotic liver disease from fat to cancer #### Normal aminotransferases despite fibrosis ### Weight, activity, lipids, alcohol, prevention