OBJECTIVE -Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA 1c , prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.RESEARCH DESIGN AND METHODS -People with type 1 diabetes (n ϭ 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet mornϩbed ) or at a 12-h interval (IDet 12h ). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.RESULTS -With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet 12h vs. NPH, Ϫ1.5 mmol/l [95% CI Ϫ2.51 to Ϫ0.48], P ϭ 0.004; IDet mornϩbed vs. NPH, Ϫ2.3 mmol/l (Ϫ3.32 to Ϫ1.29), P Ͻ 0.001), as was self-measured prebreakfast plasma glucose (P ϭ 0.006 and P ϭ 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P ϭ 0.046; 32%, P ϭ 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet mornϩbed group (P Ͻ 0.001). Although HbA 1c for each insulin detemir group was not different from the NPH group, HbA 1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference Ϫ0.18% [Ϫ0.34 to Ϫ0.02], P ϭ 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P Ͻ 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet 12h vs. NPH, Ϫ0.8 kg [Ϫ1.44 to Ϫ0.24], P ϭ 0.006; IDet mornϩbed vs. NPH, Ϫ0.6 kg [Ϫ1.23 to Ϫ0.03], P ϭ 0.040).CONCLUSIONS -Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs. Diabetes Care 27:1081-1087, 2004L andmark studies show that intensive diabetes management delays progression of the late complications of type 1 diabetes (1,2). Although the introduction of rapid-acting insulin analogs has given improvement in postprandial blood glucose control, these analogs are not ideal for use with NPH insulin, which has inadequate duration of action to cover nighttime requirements and an undesirable peak effect ϳ5 h after administration (3). These problems, together with the high day-to-day variability in absorption (4,5), present a major barrier to achieving appropriate targets of blood glucose control.These limitations have stimulated the development of a soluble basal insulin analog that does not require resuspension before injection ...

OBJECTIVE -Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens.RESEARCH DESIGN AND METHODS -We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes.RESULTS -The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII Ϫ MDII) was 0.35% (95% CI Ϫ0.10 to 0.80, P ϭ 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII Ϫ MDII) (P ϭ 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events.CONCLUSIONS -When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.

When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.

According to the results of the Diabetes Control and Complications Trial (DCCT) (1), intensive diabetes management should be proposed for most type 1 diabetic patients to prevent long-term complications. However, the ideal insulin regimen should simultaneously achieve 2 goals: maintenance of near-euglycemia and avoidance of frequent and severe hypoglycemia.Several studies have suggested that continuous subcutaneous insulin infusion (CSII) could provide better glycemic control (2-4) with a lower risk of hypoglycemia (5,6) than multiple daily injections (MDI). But very few of these studies were randomized, and all used regular insulin. We and others (7-9) also reported that, when used in external pumps, the shortacting insulin analog lispro provided better glycemic control than regular insulin without increasing the frequency of hypoglycemic episodes.However, to the best of our knowledge, the benefits of lispro use in CSII and MDI have never been compared. Therefore, the aim of the present work was to compare the efficacy on glycemic control and hypoglycemia frequency of 2 new intensified insulin regimens, CSII and MDI, with insulin lispro in a randomized study. RESEARCH DESIGN AND METHODS -The study protocol was approved by the Ethics Committee of Toulouse, and all of the patients gave written consent. PatientsA total of 41 type 1 diabetic patients between 21 and 65 years of age participated in the study. At enrollment, 32 were treated by CSII with regular insulin and 9 by MDI with regular insulin or insulin lispro. The inclusion criteria were HbA 1c Ͻ10.0%, negative C-peptide, and experience of intensified Comparison of Continuous Subcutaneous Insulin Infusion and Multiple Daily Injection Regimens Using Insulin Lispro in Type 1 Diabetic Patients on Intensified TreatmentA randomized study O R I G I N A L A R T I C L EOBJECTIVE -To compare the efficacy of 2 intensified insulin regimens, continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), by using the short-acting insulin analog lispro in type 1 diabetic patients. RESEARCH DESIGN AND METHODS-A total of 41 C-peptide-negative type 1 diabetic patients (age 43.5 ± 10.3 years; 21 men and 20 women, BMI 24.0 ± 2.4 kg/m 2 , diabetes duration 20.0 ± 11.3 years) on intensified insulin therapy (MDI with regular insulin or lispro, n = 9; CSII with regular insulin, n = 32) were included in an open-label randomized crossover study comparing two 4-month periods of intensified insulin therapy with lispro: one period by MDI and the other by CSII. Blood glucose (BG) was monitored before and after each of the 3 meals each day.RESULTS -The basal insulin regimen had to be optimized in 75% of the patients during the MDI period (mean number of NPH injections per day = 2.65). HbA 1c values were lower when lispro was used in CSII than in MDI (7.89 ± 0.77 vs. 8.24 ± 0.77%, P Ͻ 0.001). BG levels were lower with CSII (165 ± 27 vs. 175 ± 33 mg/dl, P Ͻ 0.05). The SD of all the BG values (73 ± 15 vs. 82 ± 18 mg/dl, P Ͻ 0.01) was lower with CSII. The frequency of...