Insulin Resistance

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Chapter: Essential pharmacology : Insulin, Oral Hypoglycaemic Drugs and Glucagon

When insulin requirement is increased (conventionally > 200 U/day, but physiologically >100 U/day), insulin resistance is said to have developed. However, it may be of different grades.


INSULIN RESISTANCE

 

When insulin requirement is increased (conventionally > 200 U/day, but physiologically >100 U/day), insulin resistance is said to have developed. However, it may be of different grades.

 

1.     Acute


 It develops rapidly and is usually a short term problem. Causes are—

(a) Infection, trauma, surgery, emotional stress; corticosteroids and other hyperglycaemic hormones may be produced in excess as a reaction to the stress oppose insulin action.

 

(b) Ketoacidosis—ketone bodies and FFA inhibit glucose uptake by brain and muscle. Also insulin binding may increase.

Treatment is to overcome the precipitating cause and to give high doses of regular insulin. The insulin requirement comes back to normal once the condition has been controlled.

 

2.     Chronic


This is generally seen in patients treated for years with conventional preparations of beef or pork insulins. Antibodies to homologous contaminating proteins are produced which also bind insulin. Very high grades of insulin resistance may be produced in this way. It is more common in type 2 DM.

 

Development of such insulin resistance is an indication for switching over to the more purified newer preparations. Some patients may be selectively resistant to beef insulin and respond well to pork or human insulin. After instituting highly pure preparations, insulin requirement gradually declines over weeks and months, and majority of patients stabilize at ~ 60 U/day.

 

Pregnancy and oral contraceptives often induce relatively low grade and reversible insulin resistance. Other rare causes are—acromegaly, Cushing’s syndrome, pheochromocytoma, lipoatrophic diabetes mellitus. Hypertension is often accompanied with relative insulin resistance as part of metabolic syndrome.

 

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