The study was performed between September 2004 and September 2006 at the diabetes outpatient clinic at Stavanger University Hospital, Stavanger, Norway. The clinic serves an urban and nonurban population of approximately 310,000 people, and no other clinic in the area provides a similar specialized service. Most type 1 patients in the catchment area received their routine care at this clinic. When the patients attended regular diabetes visits with an endocrinologist, a diabetes nurse, or a podiatrist, they were recruited and randomized consecutively. The general design of the intervention was based on our own clinical experience and current SMBG recommendations by the American Diabetes Association (ADA)18
and the World Health Organization (WHO).19
The ADA states that SMBG should be an integrated part of diabetes care, be included in the management plan, and include evaluation of SMBG performance and technique to enable patients to use the data for therapy adjustment. The WHO recommends building up BG profiles by performing SMBG at specific times of the day/night. In Norway, an unlimited number of strips for SMBG are reimbursed, and patients can perform SMBG without financial costs.
Only type 1 diabetes patients were eligible for the 9-month study. Inclusion criteria were most recent measured glycated hemoglobin (A1C) ≥ 8%, treatment with multiple insulin injections or continuous subcutaneous insulin infusion pump (CSII), 18–70 years of age, and a SMBG user. Exclusion criteria were unstable condition with more than 5 kg weight variation or more than 1.5% variation in A1C within past 12 months, hypoglycemia unawareness, mental instability, or any condition limiting the patients ability to follow the study protocol. All patients had received comparable care and follow-up before inclusion in the study. Educational levels and social class were not assessed specifically. No survey for depression or general well-being was performed. Patients would have a set of reasons for insufficient metabolic control and complex explanations. All patients with elevated A1C received special attention on this issue to reach treatment targets. We included 134 patients: 69 randomized to the intervention and 65 to the control group. The patients in the intervention group were immediately scheduled for their first study visit after signing the informed consent form. The patients in the control group received regular diabetes care according to guidelines and were asked for participation and signed the consent form when returning for a regular visit approximately 9 months after randomization time. This design was carefully chosen to avoid disclosing the randomization code to the caregivers and their possible influence from the caregivers on study results. This was based on the fact that patients were included in a study focusing on the tools and targets already used in daily practice. We found this approach to be an advantage when performing the randomization in only one clinic involving relatively few professionals. Ten patients in the intervention group refused to participate for personal reasons and due to time limits or were excluded during the study due to mental disease and instability. One patient in the control group refused to participate.
The control group continued to receive regular diabetes care according to Norwegian guidelines. Norwegian guidelines recommend daily SMBG performance, weekly eight-point SMBG profiles, and an A1C goal of <7.0–7.5%.20
All patients performed a number of additional measurements for monitoring hypoglycemia. For consultations, patients usually brought their written BG results or their instrument where BG values are available in the instrument memory function. For a patient with insufficient metabolic control, all areas of possible intervention were assessed. A regular visit usually lasted approximately 30 min. The patients would normally attend a minimum of one clinical visit at the outpatient clinic in the period between randomization and the final 9-month study visit.
outlines the overall study design.
Intervention patients were scheduled for six visits (including inclusion and final visit) over the 9-month study period. At the first study visit, the intervention group was introduced to HemoCue Monitor (HemoCue AB, Ängelholm, Sweden), a new, accurate glucose instrument for daily SMBG performance (coefficient of variance [CV] 2.3% and bias of 2.4%, compared to a standardized comparison method). The consultation performed by a diabetes nurse and a biomedical laboratory scientist was strictly focused on correct SMBG performance, on knowledge about individual variations in BG values in daily life, and on actions to be taken based on the results. The patient SMBG performance with the instrument was assessed and reinforced at every visit. To make patients enhance their focus on BG self-management, the patients received and brought a BG diary for BG profiles at every visit, a “fasting BG map,” and a hypoglycemia registration. The 10-point BG profile (for three different days) included measurements before and after (1.5 h) every meal (usually four meals) and one 3:00 am value for each visit and also included corresponding insulin doses. The patients provided daily fasting BG values at every visit, marked and visualized on a “BG map” included in the BG diary. The diary also included registration of major (requiring assistance) and minor hypoglycemias (symptomatic or plasma glucose below 45 mg/dl [2.5 mmol/liter]). Meters were downloaded, but no comparison was done with logbooks, and the intervention was based on written logbooks, although some patients would use meter memory to add SMBG information and number of measurements to the discussion with the study nurse. At every visit, patterns of SMBG and BG values were discussed in depth in order for patients to make changes in insulin doses and profiles or in lifestyle to improve BG control. Algorithms were applied for changing both bolus and basal insulin dosing according to SMBG results. Application of the dosing algorithm was individualized in the discussion with the patients, taking individual differences into account. Target fasting BG and postprandial values were 72–108 mg/dl (4–6 mmol/liter), and deviations from this resulted in a focused therapy improvement discussion. Each visit would last up to 30 min, including all aspects described. The clinical research location and the study nurse were different and physically separated from the outpatient clinic with the outpatient clinic personnel caring for the control group and regular patients otherwise.
Regular A1C analysis at every visit was performed locally, and the patients in both study groups were informed about results consecutively as in regular clinical practice. In addition, a capillary blood sample for analyzing A1C on the study method was obtained at every visit and stored at −80 °C. At study end, A1C was then analyzed at the Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway, using High-Performance Liquid Chromatography Variant II, (Biorad Laboratories, Diagnostic Group, USA). Due to the inclusion procedure for the control group in which the patients were included in the study 9 months after randomization time, some of the initial samples were missed for this group. For these patients, we had to use the locally obtained A1C results. However, to be able to compare these results with results obtained using the frozen samples, we established an equation (based on local results compared with the results from the study method) to ensure correct estimates of results. The study method for A1C analysis was certified by the National Glycohemoglobin Standardization Program and was traceable to the Diabetes Control and Complications Trial reference method.21
The instrument showed good analytical quality with a CV of 1.2% and a bias of 2%.
Prestudy power calculations for the number of patients to be included in the study showed a need of 60 patients in each group in order to obtain a statistically significant result (95% confidence) with an absolute difference in A1C between groups at 9 months of 0.5%. The analysis was done based on the intention-to-treat principle. Chi-square test and Student's t-test were used for comparisons between groups. The statistical analysis was performed using Statistical Package for the Social Sciences software package (Version 15.0). A p-value < .05 was considered significant. The study design, informed consent form, and conduct were approved by the Regional Committee for Medical Research Ethics, Bergen, Norway.