A Randomized, Prospective Trial Comparing the Efficacy of Continuous Subcutaneous Insulin Infusion With Multiple Daily Injections Using Insulin Glargine

Abstract

OBJECTIVE -The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA 1c levels in children and adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODS -Thirty-two youth with type 1 diabetes (age 8 -21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA 1c . HbA 1c , total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy.RESULTS -While there was no significant change in the glargine group (HbA 1c 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA 1c levels, from 8.1 to 7.2% after 16 weeks of therapy (P Ͻ 0.02 vs. baseline and Ͻ0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P Ͻ 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group (P Ͻ 0.01).CONCLUSIONS -Lower HbA 1c and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes. Diabetes Care 27:1554 -1558, 2004T he Diabetes Control and Complications Trial (1,2) demonstrated the importance of lowering HbA 1c levels as close to normal as possible. The urgency to achieve strict diabetes control has contributed to a sharp increase in the use of continuous subcutaneous insulin infusion (CSII) in children with type 1 diabetes. Reports from our program (3,4) and others (5-7) have demonstrated that CSII can lower HbA 1c levels and rates of severe hypoglycemia in youth with type 1 diabetes. However, these findings can be questioned because prepump injection regimens varied in intensity and in the types of insulins that were used. Moreover, only the recent study of Weintrob et al. (7) was a randomized controlled trial of CSII versus multiple daily injections (MDIs) using NPH insulin.With intermediate-acting insulins, there are considerable dose-to-dose variations in the amount of insulin that is administered and absorbed (8). Additionally, the peaking actions of these insulins make them less than ideal for basal insulin replacement (8). These limitations have been overcome by the introduction of glargine insulin, the first soluble insulin analog that has a flat and prolonged timeaction profile. A disadvantage of MDIs with glargine is the large number of i...

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis

“…At the end of treatment HbA 1c /HbA 1 was significantly lower in the CSII group in each of the trials performed in adolescents [40,41]. In the trial including young children [43], glycated haemoglobin was slightly higher in CSII-treated patients but without reaching statistical significance (Table 1).…”

“…In the end, 33 publications with usable information were included in our systematic review. Of these, 17 studies (27 publications ) included mainly adult type 1 diabetic patients, three trials (four publications [40][41][42][43]) only children of up to 18 years and two studies (two publications [44,45]) examined patients with type 2 diabetes mellitus only.…”

“…Children with type 1 diabetes mellitus Of the randomised controlled trials found, one [41] used a crossover design, whereas the other two, far more recent investigations [40,43], were of parallel design. Altogether, 74 children took part in the three randomised controlled studies.…”

“…The duration of follow-up and treatment was 16 weeks in two trials and 52 weeks in the third trial. Two studies were performed in adolescents [40,41]. One study [43] included young children with a mean age of 4 years.…”

“…In the older study [41], regular insulin was used; in both recent studies [40,43] insulin analogues were used as pump insulin and as bolus insulin in the respective comparison groups. Insulin glargine was used as basal insulin in the MDI groups by all patients in one trial [40] and by 60% of patients at the end of the other study [43], while the other patients in that trial used NPH and ultralente as basal insulin. The quality of one study was assessed to be in category C and the other two studies were of higher quality (category B).…”