Injection of acidic or neutral insulin and pain: a single-center, prospective, controlled, noninterventional study in pediatric patients with type 1 diabetes mellitus

Abstract

Background: Pain resulting from injections has a potential influence on the acceptance and thus on the success of insulin treatment. Systematic investigation in humans has suggested that individuals perceive more pain during SC injection of acidic solutions than neutral solutions. Insulin glargine is a long-acting (up to 24-hour duration of effect), parenteral blood glucose-lowering agent. Unlike other insulins, it is injected as an acidic solution (pH 4).

Objective: The aim of this study was to assess whether the SC injection of insulin glargine is more painful than neutral insulin in a clinical setting.

Methods: This single-center, prospective, controlled, noninterventional study was performed in consecutively enrolled male and female pediatric patients (7-21 years) with type 1 diabetes mellitus who self-injected insulin >or=3 times per day and who had diabetes duration of >or=6 months. The study was conducted from September 1, 2005, to December 30, 2005, at the Diabetes Clinic, University Children's Hospital, Ulm, Germany. No changes to the patients' current insulin regimen were made. Based on their existing insulin treatment, patients were assigned to 1 of 2 treatment groups: (1) the acidic insulin group, which injected insulin glargine, and (2) the neutral insulin group, which injected neutral protamine Hagedorn or Semilente insulin. All patients also injected shortacting regular insulin or insulin analogs. Pain during SC insulin injection and during self-monitoring of blood glucose (SMBG) (the internal control) was assessed using a standardized, noninterventional protocol and optimized combined 10-cm visual analog scale and 5-point verbal rating scale (minimum = I cannot feel it at all; maximum = it hurts me). Patients were instructed to document pain immediately after insulin injection and SMBG at home 3 times a day on 3 different days.

Results: A total of 112 patients (mean [SD] age, 14.6 [3.0] years; sex, 60 [53.6%] male; mean [SD] glycosylated hemoglobin [HbA(1c)], 8.0% [1.4%]; mean [SD] diabetes duration, 6.1 [3.9] years) completed the study. Pain scores reported by the acidic group (n = 76) were not significantly different when compared with those of the neutral group (n = 36) (4.0 [2.0] vs 4.2 [1.9]). Pain scores were also similar for the injection of short-acting insulin in those from the acidic group when compared with those from the neutral group (3.7 [1.7] vs 4.1 [2.1]). Insulin injections were generally perceived as more painful than SMBG (3.9 [1.7] vs 2.9 [1.8]; P < 0.001). Using the Spearman rank correlation coefficient, pain perception was determined to be independent of age, gender, HbA(1c) level, and duration of diabetes.

Conclusion: Despite its acidic formulation (pH 4), insulin glargine was not perceived as more painful during SC injection than neutral long-acting or shortacting insulin in these pediatric patients with type 1 diabetes mellitus.