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 ϭ 24) or premeal subcutaneous regular insulin (SC group; n ϭ 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 (ϮSD) IAB levels were 3.5 Ϯ 3.9 and 2.6 Ϯ 4.1 U/ml at baseline, respectively, compared with 101.4 Ϯ 140.4 and 4.3 Ϯ 9.4 U/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. B efore the introduction of highly purified porcine and recombinant human insulins into clinical practice, the use of less purified animal-derived insulin in patients with diabetes was associated with a near 100% prevalence of detectable insulin antibodies (IABs) (1). Although mean antibody levels are now lower in patients treated with subcutaneous human insulin, ϳ50% of such patients have measurable IABs (2). Since the initial description of IABs in the 1950s, the effect of antibody development, from low levels at baseline to levels commonly observed during clinical therapy, on key glycemic parameters has not been tested in a prospectively designed randomized controlled study.Multiple cross-sectional studies over the years have investigated whether IABs can cause alterations in insulin pharmacokinetics or pharmacodynamics. Although some studies have shown associations between IABs and delayed rises in free insulin concentrations (3,4) or prolonged half-life of free insulin (3,5) after insulin dosing, the clinical impact of these observations remains unclear (6). Using a standardized meal challenge test, one study showed a relationship between high-affinity IAB binding and impaired postprandial glucose tolerance (7), although such a relationship has not been consistently reported (8,9). Significantly, although some studies have reported a deleterious effect of IABs on long-term glycemic control (10 -12), most have not (8,(13)(14)(15)(16)(17)(18). Notably, the syndrome of immunologic insulin resistance has been reported in patients with high levels of maximum insulin binding (5).Furthermore, reports of prolongation of insulin half-life have not been associated with an increased incidence of clinical hypoglycemia (14), although rare cases of unusual hypoglycemic syndromes associated with insulin therapyrelated antibodies have been described (19 -21). In addition, hypoglycemia thought to be due primarily to high levels of low-affinity binding has been described in th...

IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects.

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The different proportions of soluble and protaminated IAsp result in differences in the pharmacokinetic and pharmacodynamic properties of BIAsp 30 and BIAsp 70. The pharmacokinetic and pharmacodynamic differences observed may allow for flexibility and individualised treatment regimens in patients with diabetes, while maintaining a limited number of daily injections.