Effectiveness of early intensive therapy on β-cell preservation in type 1 diabetes

Abstract

Objective: To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year.

Research design and methods: Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months.

Results: Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30).

Conclusions: In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

Trial registration: ClinicalTrials.gov NCT00760526.

Figures

Figure 1

Box plots for 2-h stimulated C-peptide AUC at each follow-up visit. The bottom and top of each box denote the 25th and 75th percentiles, respectively; the line inside the box denotes the median, and the dot is the geometric mean. The vertical axis is on a log(x + 1) scale.

Figure 2

HbA1c results. The bottom and top of each box denote the 25th and 75th percentiles, respectively; the line inside the box denotes the median, and the dot is the mean. The 6-week value is a local HbA1c measurement; others are from the central laboratory.

Figure 3

Insulin doses at each follow-up visit. The bottom and top of each box denote the 25th and 75th percentiles, respectively; the line inside the box denotes the median, and the dot is the mean.