Effect of Puberty on the Pharmacodynamic and Pharmacokinetic Properties of Insulin Pump Therapy in Youth With Type 1 Diabetes

Development of biosynthetic techniques for production of human insulin enabled the pharmaceutical industry to produce rapid-acting insulin analogs that are more rapidly absorbed following subcutaneous injection than regular insulin (1–5). These analogs may be especially useful in treating adolescents with type 1 diabetes who require large premeal bolus doses due to the peripheral insulin resistance of puberty (6). When used in large doses, the peak action of regular insulin is delayed (to 3–4 h) and the duration markedly prolonged (to 8 h or more) (7). The pharmacokinetic and pharmacodynamic properties of the rapid-acting insulin analogs have not been well studied in pediatric patients or when administered by continuous subcutaneous insulin infusion. This study was undertaken to examine the effect of puberty on the pharmacokinetics and -dynamics of aspart insulin in pump-treated patients. A total of 21 healthy nonobese subjects with type 1 diabetes ranging in age from 8 to 17 years were studied. All were receiving continuous subcutaneous insulin infusion therapy and had A1C levels between 6.5 and 8.9%. The Yale Human Investigation Committee approved the study; written informed consent was obtained from the parents and assent from the subjects. Subjects were divided into two groups: prepubertal (Tanner stage I, n = 9) and pubertal (Tanner stages II–V, n = 12). The two groups did not differ significantly in A1C levels, duration of diabetes, and BMI percentiles. Daily insulin doses were available in …