A few patients with diabetic ketoacidosis may show extreme insulin resistance. In most cases the insulin resistance may have contributed to the ketoacidosis.

Extreme insulin resistance indicates the requirement for very high doses of insulin (may be over 1,000 units per hour) often with no or minor changes in blood glucose concentration). A definition is the need for > 3 units per kilogram per day (Ovalle).


Causes of the extreme insulin resistance may include:

(1) Type A insulin resistance (mutations of insulin receptor)

(2) Type B insulin resistance (antibodies to insulin receptor)

(3) antibodies to insulin

(4) systemic cytokine release (triggered by Brentuximab therapy, other)

(5) drug-induced (isoproterenol, other)

(6) extreme shock (transient)

(7) possibly severe hypophosphatemia (if all other causes ruled out)


If antibodies are the underlying mechanism, then patients have been managed by:

(1) corticosteroids

(2) plasmapheresis


If the cause is transient and if high dose insulin is continued, then hypoglycemia may occur.

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