Insulin

Insulin:
Discovered in 1921  type 1 diabetes was no longer a fatal disease; use of insulin is mandatory in those with type 1 and its use must be accompanied by self blood glucose level monitoring. Obtained from recombinant DNA techniques

Indications for insulin – type 1 diabetes; acute complications; pregnancy; longstanding type 2 that has not responded to oral agents. Insulin does not reverse presence of established diabetes complications.

Types of insulin:
• Bovine – from cattle pancreas; used very little today
• Porcine – now used in those with reduced perception of hypoglycaemic symptoms
• Human - manufactured from recombinant DNA technology; most common type

Delivery of insulin:
injection subcutaneously in anterior abdomen, upper arms, outer thighs or buttocks; rate of absorption depends on depth, site, skin temperature, local massage, exercise, amount of lipodystrophy; administered with use of disposable syringes or pen injectors
pen injectors now make delivery of insulin easier – the short fine needles make injection more comfortable.
battery powered pump systems can be used to supply subcutaneous or IV infusions of insulin – controlled by patient. Earlier models prone to failure  rapid onset of ketoacidosis; main advantage of use of pumps is improved pharmacokinetics of insulin (reduction in variability of absorption); pumps are effective in improving glycaemic control, but are not for everyone.
inhalation – bioavailability is very low; experimental

Duration of action:
short acting – onset usually 30 minutes, peaking at 1-3 hours with a duration of 4-8 hours; half life of <5mins  need continuous infusion if want to maintain plasma levels rapid acting - onset usually 10-15 minutes, peaking at 1 hour with a duration of 3-5 hours; usually for use immediately prior to meals intermediate duration - onset usually 1-2 hours, peaking at 4-8 hours with a duration of 12-18 hours; usually used for twice daily injections long acting – acts over 24 hours; not used much today mixtures – short, intermediate and long acting insulins can be mixed in different ratios for multiple daily injectionsInsulin regimens: Various regimens are used – depends on many factors (eg patient lifestyle, self-management ability, desired level of control). Most regimens involve two to four injections of short or long acting insulin. Once daily injections are generally inadequate for metabolic control.Intensive control not consider appropriate for: • young children • those that can’t or won’t comply with self blood glucose monitoring • those with significant tissue damage (eg nephropathy) • those with recurrent hypoglycaemia • those with loss of awareness of hypoglycaemia • those with significant macrovascular diseaseSide effects of use of insulin – hypoglycaemia; weight gain (common due to physiological anabolic effects); lipodystrophy at injection sites; insulin oedema (oedema in feet and ankles after initiation of insulin – may be due to insulin affecting renal retention of sodium and water – usually resolves); transient deterioration of retinopathy; insulin neuritis (acute neuropathy that can develop following insulin – usually resolves following period of good control); postural hypotension (vasodilator role of insulin may be a factor following insulin injection)Insulin use in type 2 diabetes: failure of oral hypoglycaemic therapy in type two diabetes occurs in up to 20%, either at initiation of therapy or a subsequent deterioration  need insulin this may be due to a declining production of endogenous insulin  insufficient beta cell reserve capacity  exogenous insulin needed also indicated during major intercurrent illness, surgery, acute complications, pregnancy (usually only a temporary measure) used with metformin may help prevent the weight gain; sulphonylureas and thiazolidinedione are also being used with insulin, especially as reduced insulin dose may be neededRelated Topic: Practical Insulin: A Handbook for Prescribing Providers

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