Variability of NPH insulin preparations.

In 1968-69 certain juvenile diabetics receiving NPH insulin began having pre-breakfast glucosuria and mid-morning hypoglycemic reactions. A mail survey of our clinic population and a study done at the Quebec camp for diabetic children in 1969 revealed that certain lot numbers were associated with poor control and that a change to new lot numbers or alternate insulin preparations resulted in better control. "Suspect" insulin preparations and non-suspect insulins were given to newly diagnosed diabetics, and plasma insulin and glucose levels were measured over a 24-hour period. The data confirmed that the "suspect" insulins were causing early hypoglycemia and failing to control hyperglycemia during the latter hours of the 24-hour period. The lower glucose levels were associated with higher plasma insulin levels. The "suspect" insulins were further found to have elevated levels of free insulin in the supernatant fluid.The requirements for quality control of modified insulin preparations are reviewed and suggestions are offered for their improvement.