Early ReportInadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens
Introduction
Modern insulin regimens aim to mimic physiological insulin profiles. Intermediate-acting insulin should provide basal insulin requirements, whereas short-acting insulin is given preprandially to cover food intake. This kind of insulin provision is deemed conventional intensified-insulin therapy and is highly effective in short-term and long-term diabetes control.1, 2, 3
For many patients with diabetes, insulin pens, which were developed to facilitate multiple daily injections of short-acting insulin in intensified treatment regimens, are the most convenient way to administer insulin.4, 5 With the introduction of pens with intermediate-acting insulin and premixed insulin combinations, insulin pens have become the most widely used device for insulin injection. The most commonly used intermediate-acting isophane insulin is neutral protamine Hagedorn (NPH). NPH cartridges for pens contain a predetermined ratio of NPH insulin and solvent or NPH in combination with a short acting soluble insulin—ie, these are two-phase solutions. The recommendation given to patients is to suspend NPH insulin by tipping the pen and gently rolling it in the palms of the hands before use until a complete suspension is achieved. However, the specific number of cycles is not provided by all manufacturers.6
We evaluated the completeness of insulin resuspension by NPH insulin-pen users and its effect on glycaemic control and hypoglycaemic events.
Section snippets
Methods
We assessed NPH insulin suspension in 109 insulin-dependent patients (39 with type 1 diabetes, 70 with type 2 diabetes). These patients were from seven medical practices (n=65) and the outpatient clinics of seven hospitals (n=44) in southern Germany. The study was approved by the local ethical committees. All patients had received a conventional education on the use of insulin pens and had used insulin for median of 10 years (interquartile range [IQR] 5–17).
After informed consent, patients
Results
Patient details and clinical data at baseline are shown in table 1. All patients with type 1 and 59 (84%) of patients with type 2 diabetes stated that they resuspended their NPH insulin before injection either by rolling and tipping or by shaking the pen at least five times; only ten patients tipped and rolled their pen more than ten times.
The NPH insulin content varied by more than 20% (range 5–214%) from the nominal value in the control cartridges in 71 (65%) of 109 patients (figure 1). Low
Discussion
We found that inadequate resuspension of NPH insulin before pen injection is common among diabetic patients treated with insulin. Patients who improved their technique for insulin resuspension had significantly fewer hypoglycaemic episodes than those that did not improve.
Other studies have reported impaired glycaemic control7, 8 and underdosing of insulin9 in patients using pen injectors. Hardy and colleagues10 reported a deterioration in glycaemic control in women who were changed to insulin
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