THE EFFECT OF NORPLANT ON GLUCOSE-METABOLISM UNDER HYPERGLYCEMIC HYPERINSULINEMIC CONDITIONS

Objectives: To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism. Design: Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement. Setting: Yale University Clinical Research Center. Participants: Seven previously normally cycling, nonobese, nondiabetic women participated in the study. Interventions: Norplant insertion. Main Outcome Measures: Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion. Results: Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 mu U/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 mu U/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per mu U/mL. Conclusion: Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion.