The U.S. “New Patient” and “Transfer” Studies

Abstract

The large-scale clinical trials of human insulin (recombinant DNA) in the United States consisted of a "New Patient" study and a "Transfer" study. The "New Patient" study involved 101 patients (38% type I) who have never received insulin and who were treated with human insulin and followed for 6 mo using NPH insulin alone or in combination with Neutral Regular Insulin (NRI). Shortly after treatment, serum glucose and total glycohemoglobin concentration fell. No patients developed insulin lipoatrophy or insulin allergy. Two patients developed insulin hypertrophy; in one, it was transient. Intradermal tests to varying dilutions of human insulin did not change over 6 mo. In addition, there was no evidence of development of antibodies to Escherichia coli polypeptide. Two-hundred-and-forty-three patients, 91% of whom had type I diabetes, were transferred in a controlled double-blind study from mixed beef-pork or purified pork insulin (PPI) either to human insulin or back to their previous insulin treatment and followed for 3 mo. While insulin dosage did not change, there was a slight increase in fasting serum glucose and a statistically significant increase in fasting ketonuria. There was no change in the frequency of the complications of insulin treatment. These limited data are consistent with the conclusion that NPH human insulin is slightly shorter acting than its animal insulin counterparts. Overall, human insulin is a safe, effective insulin.

Prevention of Early-Morning Hyperglycemia in IDDM Patients With Long-Acting Zinc Insulin

“…The preparations were a long-acting zinc human insulin (Ultratard HM) and an intermediate isophane human insulin (Protaphane HM) having a longer duration compared with other human isophane insulins (12,13); both were mixed with soluble insulin in the evening injection before dinner. The preparations were a long-acting zinc human insulin (Ultratard HM) and an intermediate isophane human insulin (Protaphane HM) having a longer duration compared with other human isophane insulins (12,13); both were mixed with soluble insulin in the evening injection before dinner.…”

Diabetic Lipohypertrophy Delays Insulin Absorption

“…Since lipohypertrophy is due largely to the local pharmacologic (lipogenic) effects of insulin, 2 this is not surprising and, indeed, lipohypertrophy has recently been reported in patients receiving only human insulin. 3 Lipohypertrophy will therefore continue to be a side effect of subcutaneous insulin administration. In clinical practice we have noticed that the insulin requirements of patients sometimes fall abruptly when they are advised to avoid their lipohypertrophied injection sites.…”

Anaphylaxis and Immunologic Insulin Resistance in a Diabetic Woman with Ketoacidosis

“…Even human insulin has the capacity to elicit antibody formation, at least when given subcutaneously, 30 ' 31 and it has been shown that in patients presensitized to insulin (as in our patient), even the highly purified animal insulins or human insulin may result in local allergic reactions. 32 " 34 Thus, highly purified animal insulins and human insulin have not completely eliminated the potential and actual immunologic problems associated with exogenous insulin administration.…”