Continuous Subcutaneous Insulin Infusion (CSII) of Insulin Aspart Versus Multiple Daily Injection of Insulin Aspart/Insulin Glargine in Type 1 Diabetic Patients Previously Treated With CSII

Abstract

OBJECTIVE -Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII.RESEARCH DESIGN AND METHODS -One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48 -72 h.RESULTS -Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 Ϯ 47 vs. 355 Ϯ 50 mol/l, respectively; P ϭ 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose Ն80 mg/dl (1,270 Ϯ 742 vs. 1,664 Ϯ 1,039 mg ⅐ h ⅐ dl Ϫ1 ; P Ͻ 0.001) and AUC glucose Ն140 mg/dl (464 Ϯ 452 vs. 777 Ϯ 746 mg ⅐ h ⅐ dl Ϫ1 , CSII vs. MDI, respectively; P Ͻ 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 A.M. to 8:00 A.M.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes).CONCLUSIONS -In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine. Diabetes Care 28:533-538, 2005

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

“…Adult patients with type 1 diabetes mellitus-meta-analysis Of 17 selected studies we had to exclude five studies from this meta-analysis for the following reasons: (1) one study did not report any HbA 1c baseline and follow-up data [13]; (2) one study compared only treatment sequences (CSII-MDI vs MDI-CSII) at study endpoint [24]; (3) another trial provided no measure of variability [37]; (4) in one study [36] the discrepancies in the measurement of variability could not be resolved; and (5) another study [32] had an unacceptably high dropout rate immediately after randomisation assignment. Ultimately, 12 studies were included in the meta-analysis of the percentage of glycated haemoglobin at the end of treatment.…”

“…Adult patients with type 1 diabetes mellitus Of 14 studies reporting total insulin requirements at the end of treatment, 12 [13,19,22,24,28,30,[33][34][35][36][37]39] consistently found that the insulin doses were lower in CSII-treated patients. In seven [13,19,22,30,35,36,39] of these investigations, the difference was statistically significant.…”

“…Three others [33,35,36] reported that no severe hypoglycaemia was observed. Information on the number of patients with severe hypoglycaemic episodes could be found in six studies [13,21,22,24,28,34] and four [32,[37][38][39] at least reported on the rates or the number of severe hypoglycaemic events in the treatment groups. The proportion of patients with severe hypoglycaemic episodes ranged from 0 to 0.13 in the CSII group and from 0 to 0.4 in the MDI group.…”

“…Two other studies [30,37] presented results for overall hypoglycaemia only, but for the latter [37] the rate of mild/minor hypoglycaemic events could be calculated because exact numbers of severe events were available. Six studies [21,22,24,28,36,39] provided the event rates for mild/minor hypoglycaemia per patient per time period, which ranged from 0.9 to 3.1 weekly events per patient in the CSII groups and from 1.1 to 3.3 in the MDI groups (ranges include previously mentioned study [37]). The median rate per patient per week was 1.9 in the CSII groups and 1.7 in the MDI groups.…”

“…Ziegler et al [38] reported data on ketoacidosis indicating that the events per 100 patient-years were higher in the CSII group (intention to treat and per protocol analysis), but the difference was not statistically significant. All the other studies noted only a few ketotic events: in three studies there was one event in the CSII group only [24,33,36], another [21] reported one event in both treatment arms, yet another [39] reported four events in the CSII and none in the MDI group and the Oslo trial [28] found that two patients in the CSII vs no patients in the MDI group developed ketoacidosis. Data on hyperglycaemia were given in only one publication included in this review.…”