Incomplete notes. For more info, read up David Chong’s lecture.

Insulin types

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Older types

  • Soluble
    • quick onset
    • short duration
  • NPH, ‘Lente’ & biphasic
    • intermediate onset
    • intermediate duration
  • ‘Ultralente’
    • slow onset
    • long duration

Newer types (recombinant analogues)

  • Lispro Aspart Glulisine
    • slow onset
    • long duration
    • Mimics pulsed secretion (give with meals)
  • Glargine Detemir
    • long duration
    • Mimics basal secretion (give during bedtime)

Unwanted effects of insulin

  • Hypoglycemia
    • didnt eat / too large dose
    • lightheadedness
    • tachycardia, sweatiness
    • skeletal muscle tremor
    • loss of consciousness, seizures
    • give glucose + glucagon
  • Insulin allergy
    • IgE antibodies to non-insulin protein contaminants
    • rare now, because now follow highly purified insulin preparations
  • True insulin resistance
    • IgG mediated
  • Hypertrophic Lipodystrophy
    • hypertrophy of subcutaneous fatty tissues at injection sites
    • avoid by using different injection sites

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Insulin pump

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Treatment strategies

Enhance incretin effects

  • GLP-1 analogues
    • Liraglutide
      • longer half life
    • Exenatide
    • Mechanism of action:
      • glucose dependent insulinotropic effect & reduction in glucagon secretion.
      • improves beta-cell function.
      • reduces rate of gastric emptying and promote early satiety –> weight loss
      • mild nausea,
      • transient hypoglycemia inhibitors
  • DPP-4 inhibitors/’Gliptins’
    • Reduces HbA1c
    • Mild hypoglycemia
    • No effect on satiety & gastric emptying –> weight neutral
    • No effect on beta-cell function

Enhance insulin secretion (using secretagogues)

  • Sulphonylureas
    • mimics glucose stimulated insulin secretion
    • 1st generation obsolete
    • 2nd generation (gliclazide)
      • care in the elderly
        • dose dependent hypoglycemia
        • care in renal impairment if serum cretinine is high
      • eventual treatment failure due to complete loss of beta-cell function
      • extra pancreatic effects
  • Meglitinides
    • similar to above
    • modulate K+ channel closing
    • quicker action & shorter duration than sulphonylureas
      • effective if taken after meals
    • adverse effect: hypoglycaemia

Enhance insulin action/sensitivity

  • Metformin (biguanide)
    • important for type 2 diabetes
    • stimulate tissue glycolysis
    • reduces hepatic & renal gluconeogenesis
    • slows GI glucose absorption
    • Reduces glucagon levels
    • Indications:
      • overweight patients (Can lose weight)
      • type 2 diabetes on insulin (lower futher HbA1c)
      • UKPDS lowers mortality
    • Adverse effects
      • Abdominal discomfort, nausea, diarrhea
      • severe lactic acidosis
    • Will not cause hypoglycemia
  • Thiazolidinediones (TZDD)
    • Nuclear Peroxisome Proliferator- Activated Receptors (PPAR)
      • activate transcription of genes affecting glucose & lipid metabolism
      • adipocyte differentiation
    • Binds to PPAR-gamma
      • Pioglitazone & rosiglitazone
    • Effects:
      • increase tissue sensitivity to insulin
      • lowers glucose, FA and TG
      • Decreases HbA1c)
    • Adverse effects
      • Weight increase
      • Redistribution of fat
      • Fluid retention
    • Rosiglitazone
      • increases risk of heart failure
      • idiosyncratic hepatic failure

Reduce glucose absorption

  • Alpha-glucosidase inhibitors (Acarbose & Miglitol)
    • Inhibit glycoside hydrozylase (carbohydrate digesting enzymes)
      • suitable for prevention in prediabetes
    • Taken with meals
    • Adverse effects:
      • more undigested carbohydrate available to colonic flora
      • flatulence
      • diarrhea

Replace islet cells/transplantation

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Summary

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Mnemonic: GMT S MR AD

For glycaemic control

  • alpha-glucosidase inhibitors
    • lowers  HbA1c more than the others

For better lipid profile

  • Metformin
    • lowers LDL
  • Thiazolidinediones (TZD)
    • raise HDL & LDL

For weight loss

  • Metformin
  • GLP-1

Causes weight gain

  • Sulphonylureas
  • Metiglinides
  • TZD

Weight neutral

  • DPP-4

Enters hypoglycemia

  • Sulphonylureas
  • repalinide

Adverse effects

  • Metformin
    • lactic acidosis
    • GI upset
  • TZD
    • risk of heart failure (Rosiglitazone)

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Extras:

Anti-obesity agents

  • Orlistat
    • inhibit intestinal lipases
    • fat remains in gut –> steatorrhoea & fecal incontinence
  • Sibutramine
    • enhances satiety
    • raises BP & heart rate –> hypertension

Hyperosmolar Nonketotic Hyperglycemia (HONK)

  • Severe hyperglycemia without ketosis
  • In type 2 diabetes
  • Absense of ketosis because enough insulin secretion to inhibit ketogenesis
  • Mortality high in elderly
    • plasma osmolality high
    • dehydration
    • depressed consciousness
    • risk of arterial thrombosis
  • Treatment
    • adjust osmolality
    • fluid replacement
    • carefull insulin use
      • sensitive to insulin action
    • anticoagulant

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