The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin.

OBJECTIVE To assess the impact of the development of high- or low-affinity insulin antibodies (IABs) on postprandial glucose tolerance, duration of insulin action, and clinical safety in patients with type 1 diabetes receiving inhaled insulin (Exubera). RESEARCH DESIGN AND METHODS This study consisted of a prospective, randomized, open-label, parallel-group trial in which 47 patients with type 1 diabetes received NPH insulin twice daily plus either premeal inhaled insulin (INH group; n = 24) or pre-meal subcutaneous regular insulin (SC group; n = 23) for 24 weeks. Meal challenge and euglycemic clamp studies were performed on consecutive days at baseline, week 12, and week 24. Adverse events were monitored. RESULTS For the INH and SC groups, mean (+/-SD) IAB levels were 3.5 +/- 3.9 and 2.6 +/- 4.1 muU/ml at baseline, respectively, compared with 101.4 +/- 140.4 and 4.3 +/- 9.4 microU/ml at week 24. At week 24, the changes from baseline were similar for the INH and SC groups for maximal plasma glucose concentration (C(max)) (adjusted ratio for treatment group difference 0.99 [90% CI 0.95-1.03]), area under the plasma glucose concentration time curve (adjusted ratio for treatment group difference 0.98 [0.88-1.08]), and duration of insulin action (adjusted treatment group difference 29 min [-49 to 108]). No adverse events were attributed to IABs. CONCLUSIONS In patients with type 1 diabetes treated with inhaled insulin, development of high- or low-affinity IABs did not impair postprandial glucose tolerance, alter the time-action profile of insulin, or impact tolerability. No clinical relevance of IABs was identified in this study.