Intensive glucose control after the onset of type 1 diabetes has been suggested to preserve C-peptide production (1–3). In people with type 1 diabetes, sensor-augmented pump (SAP) use improved glycemic control, particularly when used >6 days/week (4). As previously reported, subjects with type 1 diabetes were randomized to either 3 days of in-hospital hybrid closed-loop therapy followed by SAP therapy or usual care (5). In the primary intent-to-treat analysis, no significant differences existed in HbA1c or C-peptide between the two groups at 1 year. In our post hoc analysis, we hypothesized that more frequent sensor use in the SAP group would be associated with lower HbA1c levels and preservation of C-peptide production at 1 year.
Subjects in the SAP group (n = 46) were stratified by median SAP use of 12.4 h/day. HbA1c and C-peptide levels were compared at baseline and 3, 6, 9, 12, and 24 months. At 12 months of follow-up, the median HbA1c values for those with SAP use above versus below the median were lower (7.0% [Q1, Q3 6.0, 7.5] vs. 7.7% [7.1, 8.5], P = 0.007).
All three C-peptide measures were 50–79% higher at 12 months in the above versus below median SAP use group. However, these nonsignificant trends were no longer present at 24 months. No statistically significant differences were seen in fasting, peak, or area under the curve C-peptide levels between the two groups at any time period over 2 years of follow-up. All three C-peptide measures declined >50% from 12 to 24 months in the high SAP use group, although HbA1c levels remained similar (Fig. 1).
Comparison over 2 years of those who used the SAP above the median compared with those who used the SAP below the median use in the first 12 months. A: HbA1c levels (%). B: Fasting C-peptide (nmol/L). C: Peak C-peptide (nmol/L). D: Area under the curve (AUC) C-peptide (nmol min/L). *P < 0.05 at 9 months and P < 0.01 at 12 and 24 months.
Comparison over 2 years of those who used the SAP above the median compared with those who used the SAP below the median use in the first 12 months. A: HbA1c levels (%). B: Fasting C-peptide (nmol/L). C: Peak C-peptide (nmol/L). D: Area under the curve (AUC) C-peptide (nmol min/L). *P < 0.05 at 9 months and P < 0.01 at 12 and 24 months.
As HbA1c levels remained similar at 12 and 24 months in the above median SAP use group, it can be concluded that factors other than glycemic control were likely related to the >50% reduction in C-peptide production during the second year after diagnosis. In subjects having type 1 diabetes for >1 year, only consistent (≥6 days/week) use of a SAP system was shown to improve glycemic control (2). In our analysis, we stratified subjects by the frequency of use of SAP over the year of follow-up (the primary end point), and median use (12.4 h) was about half the day. This frequency of SAP use may not have been sufficient to reduce HbA1c levels adequately to preserve β-cell function. The drop-off in frequency of continuous glucose monitor use in this and previous studies may be due to less sophisticated earlier-generation continuous glucose monitor technologies, such as the Medtronic Sof-sensor used in the initial study (5). Further studies with larger numbers of subjects who are followed for a longer time period and are using improved technology will be important to further evaluate this hypothesis in the future.
Article Information
Funding. This research was supported by National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants for the Diabetes Research in Children Network (DirecNet) Study Group (HD-41890-10, HD-41906-10, and HD-41908-10) and by grants for the Type 1 Diabetes TrialNet Study Group (U01-DK-085509, U01-DK-06104211, 5U01-DK-085466-05, U01-DK-085505-02, and 5U01-DK-085465-04). Other more complete information is available elsewhere (2,3).
Duality of Interest. D.M.M. is on the advisory board for Insulet, and his institution has received research funding from Medtronic and Dexcom. R.S. has received grant support from Medtronic MiniMed. B.B. received payment from Sanofi, GlySens, and Roche for serving on medical advisory boards; consulted for BD Biosciences; received payment for a lecture (symposium at the European Association for the Study of Diabetes) from Dexcom; received payment from Medtronic for serving on the Data and Safety Monitoring Board for Sensor-Augmented Pump Therapy for A1C Reduction (STAR 3) study; and received institutional payment from Medtronic for other principal investigator–initiated studies and sponsored research. S.A.W. is on the advisory board for Insulet and has received honoraria and grant support from Medtronic. H.P.C. has received grant support from Dexcom. No other potential conflicts of interest relevant to this article were reported.
Author Contributions. T.M.T., D.M.M., L.P., R.S., B.B., A.A.B., P.C., and H.P.C. researched the data and reviewed and edited the manuscript. T.M.T., D.M.M., L.P., and H.P.C. wrote the manuscript. L.A.D. and S.A.W. reviewed and edited the manuscript. H.P.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Prior Presentation. Data from this study were presented at the 75th Scientific Sessions of the American Diabetes Association, Boston, MA, 5–9 June 2015.
Clinical trial reg. no. NCT00760526, clinicaltrials.org.