Insulin Therapy
Actions of insulin
Carbohydrate
metabolism
Fat
metabolism
Protein
metabolism
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Liver cells
↑Glycolysis
↑Glycogenesis
↓Glycogenolysis
↓Gluconeogenesis
↓Lipolysis
↑Lipogenesis
↓Protein breakdown
Fat cells
↑Glucose uptake
Muscle cells
↑Glucose uptake
↑Glycolysis
↑Glycogenesis
↑Synthesis of TGs & FAs
↓Lipolysis
↑AA uptake
↑Protein synthesis
Promotes tissue uptake & storage of glucose, AAs & fats
Acutely lower blood glucose
Inhibits hepatic glycogenolysis & gluconeogenesis
Increases glycogen synthesis in muscle/liver
Inhibits lipolysis
Stimulates protein synthesis
Longer term effects on growth & gene expression
Uses of insulin
 Type I DM
 Improved metabolic control in type II DM
 Oral therapies for type II contraindicated or not tolerated
 Post-MI (DIGAMI)
 Severe intercurrent illness, surgery
 Gestational diabetes (not controlled by diet)
Side effects
 Hypoglycaemia
 Weight gain
 Allergy
 Lipohypertrophy & lipoatrophy
 Transient deterioration of retinopathy
 Insulin neuritis
Insulin preparations
Short-acting
Onset
30 minutes
Peak
2-4 hours
Duration
8 hours
Intermediate
1-2 hours
4-12 hours
16-24 hours
Long-acting
1-2 hours
4-12 hours
20-35 hours
Analogue
0-15 minutes
1-2 hours
4-6 hours
24 hours
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Example
Actrapid
Humulin S
Insulatard
Humulin I
Human Ultratard
Humulin Zn
Humalog (Lispro)
Novorapid (Aspart)
Apidra (Glulisine)
Glargine, Levemir
Rapid-acting e.g. novorapid, Humalog
 Onset 10 mins
— Can give straight after meals rather than before, useful in children as can
observe to see how much eat, then adjust dose accordingly (carb count)
 Peak 1-3 hours
 Duration 4-5 hours
Rapid
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Short
Short-acting e.g. actrapid (used in DKA)
 Onset 30 mins
 Peak 1-3 hours
 Duration up to 8 hours
— Means need to snack before next meal to combat insulin
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Premixed insulin (2-dose regimen)
 Different combinations of rapid/short-acting & intermediate acting insulins
— Short-acting e.g. 30/70 mixture = 30% fast-acting + 70% intermediate
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Onset 30 mins
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Peak 2-8 hours
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Duration up to 24 hours
— Rapid-acting e.g. 25/75 or 30/70
 Can’t use long-acting insulins (don’t combine well)
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Intermediate acting e.g. insulatard
 Onset 1.5 hours
 Peak 4-12 hours; unhelpful, predisposes to hypos
 Duration up to 24 hours (realistically don’t last this long)
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Long-acting analogues (background insulin) e.g. glargine, levemir
 Take at same time each day (usually at night before bed)
 Peak-less MOA
 Takes 2-3 days for dose to build up and action to kick in
 Not very responsive as a result e.g. difficult to cut down if doing out drinking
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Insulin regimes
 Twice daily mixture
 Once daily plus long-acting
 Four times rapid-acting plus daily basal bolus
 Continuous SC insulin infusion
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Basal bolus regime
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Twice daily mixture
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Long-acting analogue: glargine or levemir PLUS
Rapid-/Short-acting analogue: novorapid, humalog, apidra (3-4x daily with meal
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Combination therapies
 Metformin
 Sulphonylureas
 Glitazones
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