Both Continuous Subcutaneous Insulin Infusion and a Multiple Daily Insulin Injection Regimen With Glargine as Basal Insulin Are Equally Better Than Traditional Multiple Daily Insulin Injection Treatment

Diabetes Control and Complications Trial results showed that strict metabolic control may substantially reduce the risk of long-term microvascular complications (1). Over the study period, which averaged 7 years, the mean HbA_1c level in the intensive group treatment was 7.2%. Current guidelines of treatment for type 1 diabetes propose a goal of HbA_1c <7% (2). Nevertheless, in usual clinical practice, an acceptable metabolic control is achieved in a too low proportion of patients, even under multiple daily insulin injections (MDIs) (3). A recent meta-analysis of randomized trials concluded that continuous subcutaneous insulin infusion (CSII) permits a small improvement in blood glucose control with respect to MDIs (4). Glargine insulin is a human insulin analog that might mimic the effects of CSII at single basal infusion rate. Preliminary studies indicate that glargine may reduce the incidence of hypoglycemia and fasting blood glucose compared with NPH (5).

Whether an MDI treatment with glargine as long-acting insulin may offer similar results to those obtained with CSII is still unknown (6). For this purpose, we evaluated, in an open parallel group trial of 1-year duration involving 32 type 1 diabetic patients that had been treated with MDIs (regular or lispro insulin before each meal plus NPH as basal insulin) for at least 1 year, the efficacy of two regimens of intensive insulin treatment: CSII versus MDIs with lispro at each meal plus glargine as basal insulin. These patients were selected because of poor metabolic control (HbA_1c >8% in the previous year) despite MDI treatment. Two patients in both groups had a history of severe hypoglycemic episodes. Data are expressed as mean ± SD.

Sixteen type 1 diabetic patients (age 37.7 ± 11.2 years, 8 men, 8 women, duration of diabetes 19.6 ± 9.2 years) were treated with CSII, receiving lispro at multiple basal infusion rates plus boluses at meals, for a 1-year period (CSII group).

Sixteen type 1 diabetic patients (age 42.9 ± 15.6 years, 7 men, 9 women, duration of diabetes 14.7 ± 11.1 year) were treated with MDIs with lispro at each meal combined with glargine injected at dinner or at bedtime, for a 1-year period (glargine group).

In all patients, HbA_1c, fasting blood glucose, total cholesterol, HDL cholesterol, triglycerides, uric acid, insulin requirement, and severe hypoglycemic episodes (i.e., hypoglycemic event requiring assistance from another person or resulting in a seizure or coma) were evaluated every 3 months during the year before the study and during active treatment. We compared the mean ± SD of these parameters for the year preceding the study with those of active treatment (CSII or glargine) using the Student’s t test for paired data.

In the CSII group, compared with traditional MDI treatment, there was a significant decrease of HbA_1c (9.2 ± 1.6% during traditional MDI vs. 8.2 ± 1.2% during CSII, P < 0.001), fasting plasma glucose (11.9 ± 3.5 vs. 8.1 ± 2.8 mmol/l, P < 0.001), triglycerides (100.9 ± 41.6 vs. 85.5 ± 41.4 mg/dl, P < 0.05), severe hypoglycemic episodes (0.37 vs. 0.12 per patient/year, P < 0.05), and insulin requirement (50.4 ± 18 vs. 40.1 ± 13.1 units/day, P < 0.001). In the glargine group, compared with traditional MDI treatment, there was a significant decrease of HbA_1c (8.5 ± 1.3 vs. 7.9 ± 1.2%, P < 0.001), fasting plasma glucose (12.3 ± 3.9 vs. 10.5 ± 3.1 mmol/l, P < 0.001), triglycerides (90.6 ± 50.8 vs. 77.0 ± 39.3 mg/dl, P < 0.05), and severe hypoglycemic episodes (0.43 vs. 0.18 episodes per patient/year, P < 0.05). Insulin dose was unmodified (44.0 ± 11.1 vs. 43.1 ± 11.1 units/day, NS). There was no significant change in BMI in either the CSII (24.7 ± 4.2 vs. 24.6 ± 4 kg/m²) or glargine group (22.8 ± 2.9 vs. 22.9 ± 3 kg/m²).

We compared the responses to CSII and MDI with glargine by analyzing (using a nonpaired t test) the differences between measured variables before and after the two treatments. No significant difference between the two groups was present in the degree of improvement of HbA_1c, fasting plasma glucose, triglycerides, or severe hypoglycemic episodes. Only insulin requirement reduction was significantly greater in the CSII than in the glargine group (−10.3 ± 3.3 vs. −0.9 ± 0.3 units/day, respectively, P < 0.001).

The number of severe hypoglycemic episodes decreased both during pump treatment and during lispro plus glargine treatment, confirming the results of previous controlled trials (4). These findings are probably related to the lower variability in subcutaneous insulin absorption during CSII and to the unique profile of glargine biological action (5).

In our study, CSII was not associated with an increase in body weight. The presence of a dietitian specifically dedicated to this patient group may have helped to avoid this adverse effect of CSII (7).

In conclusion, we demonstrated that both CSII and MDIs with lispro plus glargine equally improve metabolic control and reduce severe hypoglycemia in type 1 diabetic patients that are unsatisfactorily controlled on MDIs using NPH as basal insulin.