Starting insulin in type 2 diabetes: Continue oral hypoglycemic agents?

Exclusion criteria were severe comorbidity (ie, an illness that surpasses the impact of diabetes or was associated with a short life expectancy) and insufficient understanding of spoken Dutch to follow instructions. The final study population was 64 patients.

Study protocol

After randomization, patients were referred to the diabetes nurse of their family practice to receive usual education for patients starting on insulin therapy. This included information on diabetes (eg, symptoms of hypoglycemia) and dietary counseling as well as instructions on how to inject insulin and how to monitor blood glucose levels before breakfast, after meals, and before bedtime twice weekly.

Patients were also instructed to register any symptomatic hypoglycemic event, along with accompanying measurement of the blood glucose value if possible, and to report whether assistance from a third party was required. Blood glucose values and hypoglycemic events were to be recorded in a personal diabetes diary.

Insulin therapy was initiated with 8 IU before bedtime in the IC group, and with 12 and 6 IU before breakfast and dinner in the IM group, respectively. Insulin dosages were adjusted twice weekly by telephone contact with the diabetes nurse (adjusting phase), aiming for a target fasting blood glucose of 4.0–7.0 mmol/L and a target postprandial glucose of 4.0–10.0 mmol/L. When these targets were achieved and had proved stable, the insulin dose was fixed and telephone contacts were decreased to once monthly (stable phase).

Treatment failure was declared for patients in the IC group if glucose targets were not reached with a maximum daily dose of 40 IU NPH insulin. In the IM group, no ceiling was set for the insulin dose, but treatment was declared a failure when patients were switched to other treatment regimens due to unsatisfactory diurnal blood glucose profiles. Practice visits with the diabetes nurse or the family physician (according to local policy) were scheduled for 3, 6, 9, and 12 months after start of treatment.

Outcome measures

HbA_1c —measured by turbidimetric inhibition immunoassay (Hitachi 917; Roche Diagnostics, Basel, Switzerland; normal range 4%–6%)—and body weight were documented at randomization and at 3, 6, 9, and 12 months.

Frequency and severity of hypoglycemic events were monitored during telephone contacts and by checking patients’ diaries. At 3 and 12 months, patients completed a hypoglycemic symptoms checklist—including 18 autonomic, neuroglycopenic, and malaise symptoms—the severity of which was scored on a 7-point scale, ranging from 0 (not at all) to 6 (very intense), providing a potential range of 0 to 108.

Treatment satisfaction was measured at baseline and at 3 and 12 months, using the Dutch version of the Diabetes Treatment Satisfaction Questionnaire (DTSQ).⁹ The DTSQ is a validated self-report questionnaire; it consists of 8 questions, 6 of which refer to satisfaction with treatment. The answers were scored on a 0-to-6 Likert scale and added to produce a measure of satisfaction with diabetes treatment, providing a potential range of 0 (very dissatisfied) to 36 (very satisfied).

Well-being was measured at baseline and at 3 and 12 months with the Dutch version of the 12-item Well-Being Questionnaire (WBQ-12).¹⁰ The WBQ-12 consists of 12 assertions about the patients’ feelings, and is divided into 3 subscales from which a General Well-Being score is calculated, providing a potential range of 0 (low) to 36 (high).

Fear of self-injecting with insulin (FSI) and fear of self-testing for blood glucose levels (FST) was assessed at 3 and 12 months by the short version of the Diabetes Fear of Injecting and Self-Testing Questionnaire (D-FISQ), which has proved useful for research in insulin-treated diabetes patients.¹¹ This self-report questionnaire consists of a 6-item subscale for FSI, and a 9-item subscale for FST. The items were scored on a 4-point Likert scale, ranging from 0 (almost never) to 3 (almost always), referring to the past month.

Statistical methods

The primary outcome of the study was the difference in HbA_1c between the interventions. To detect a difference of at least 0.8%, 32 patients were needed in each group (standard deviation [SD]=1.1, α=0.05, power=80%). Data were expressed as means ± SD unless indicated otherwise. Analyses were based on intention to treat, and missing data were fitted by the last-observation-carried-forward principle. Last available measurements were used for patients reaching a study end point before 12 months of follow-up. Outcome measurements were compared between the 2 intervention groups by either analyses of covariance (ANCOVA) adjusting for baseline values,¹² unpaired t tests, or Mann-Whitney U test. The probability of treatment success was analyzed using Kaplan-Meier plots with the log-rank test. P<.05 was considered statistically significant. Data analyses were performed with SPSS release 11 (SPSS Inc, Chicago, Ill, USA).