Sustained Glucose Control Does Not Slow Decline of C-Peptide in Randomized T1D Study

This randomized, multicenter study of children and adolescents with new-onset type 1 diabetes (T1D) investigated the effect on glucose control of a closed-loop system, using C-peptide levels to gauge response

Sustained glucose control does not appear to prevent decline of residual C-peptide secretion, found the researchers of a new study published in The New England Journal of Medicine.

The randomized, multicenter study, comprising nearly 100 children and adolescents with new-onset type 1 diabetes (T1D), found that glucose control for 2 years with a closed-loop system did not slow the decline of C-peptide levels compared with control therapy consisting of standard insulin treatment. Treatment for both groups was initiated within 21 days of diagnosis.

“It is likely that factors other than glycemic control, such as autoimmune response, affect the rate of C-peptide decline after diagnosis of T1D and that closed-loop glucose control for 24 months after diagnosis is unable to preserve endogenous insulin secretion,” wrote the researchers. “It is possible that other factors act in concert with dysglycemia on C-peptide secretion.”

Both treatment groups saw declines in C-peptide levels by 12 months, and mean area under the curve (AUC) for plasma C-peptide levels at 12 months—the study’s primary end point—was not significantly different between the 2 groups (geometric mean, 0.35 pmol/mL with closed-loop therapy and 0.46 pmol/mL in the control group).

By 24 months, both groups continued to see declines and there continued to be no significant difference in AUC for C-peptide levels (mean adjusted difference, –0.04 pmol/mL).

Key secondary end points of the trial included the percentage of time in target glucose range, glycated hemoglobin level, and percentage of time with glucose levels below 70 mg/dL at 12 months.

“The mean time in the target glucose range was 10 percentage points higher, and the mean glycated hemoglobin level was 0.4 percentage points (4 mmol/mole) lower in the closed-loop group than in the control group at 12 months, but these results did not reach the pre- specified significance thresholds, and it is possible that a greater improvement in glucose control with attainment of normoglycemia could prevent the decline in C-peptide secretion,” detailed the researchers. “Further research is needed to definitively rule out a role of glycemic burden in the decline of C-peptide secretion.”

The mean adjusted difference in percentage of time with glucose levels under 70 mg/dL was 0.9 percentage points.

Despite not preventing the decline of C-peptide levels, the closed-loop system demonstrated benefits for patients and can safely accommodate variability in exogenous insulin requirements occurring with beta-cell recovery following diagnosis, the researchers noted. The closed-loop system continued to yield glycemic control for the 2-year period while glycemic control started to wean off 6 to 9 months after diagnosis.

A year following diagnosis, 78% of patients in the closed-loop group compared with 56% of patients in the control group were above national and international glycemic targets with a glycated hemoglobin level under 58 mmol/mole. By 2 years, this was maintained by 75% of patients in the closed-loop group compared with 39% of patients in the control group.


Boughton C, Allen J, Ware J, et al. Closed-loop therapy and preservation of C-peptide secretion in type 1 diabetes. New Engl J Med. 2022;387(10):882-893. doi:10.1016/j.semarthrit.2022.152076