Can Early Use of Closed-Loop System in T1D Save Pancreas Function?

Among adolescents with new-onset type 1 diabetes, tighter glucose control didn’t stave off a decline in endogenous insulin secretion, according to the randomized CLOuD trial.

Compared with standard insulin therapy, youth who started on a hybrid closed-loop system within 21 days of diagnosis didn’t have any less C-peptide secretion decline at 12 months (mean adjusted difference -0.06 pmol/mL, 95% CI -0.14 to 0.03), reported Roman Hovorka, PhD, of Addenbrooke’s Hospital in Cambridge, England, and colleagues.

Closed-loop therapy yielded an average geometric area under the curve (AUC) for the plasma C-peptide level after a mixed-meal tolerance test of 0.35 pmol/mL versus 0.46 pmol/mL with standard insulin therapy, the group reported in the New England Journal of Medicine.

Along with that miss on the primary endpoint, the same held true even after another year of follow-up. By 24 months, AUC for C-peptide was 0.18 pmol/mL with closed-loop therapy and 0.24 pmol/mL with standard insulin therapy.

Also, “total daily exogenous insulin requirements, a surrogate marker of residual insulin secretion, were similar in the two groups at all time points after diagnosis,” the researchers added.

Despite not preventing a decline in residual C-peptide secretion, closed-loop users did see a 0.4% lower HbA1c level at 12 months compared with the standard insulin group and spent more time in the target glucose range of 70 to 180 mg/dL. This benefit continued to grow, with closed-loop users seeing an average 1% lower HbA1c level after 24 months. Closed-loop therapy led to 2.4 more hours per day spent in the target range at 12 months and 3.4 hours more per day at 24 months.

“Hybrid closed-loop therapy currently is the most efficient treatment option in type 1 diabetes, so is it not surprising that superior glucose control was achieved in the closed-loop group,” commented Jan Bolinder, MD, PhD, of the Karolinska Institute in Stockholm, writing in an accompanying editorial.

However, Bolinder was quick to point out that despite this benefit, users of the closed loop system still weren’t able to achieve the recommended HbA1c target of 6.5% or below, instead hovering at 6.9% after 12 and 24 months.

“Hence, as the authors acknowledge, it might be too early to unquestionably rule out that a greater improvement in glucose control, getting closer to normoglycemia, may slow the decline in residual beta-cell function,” he suggested, adding that although the trial findings are “somewhat disappointing,” it was “good news” that closed-loop therapy aided in long-term glucose control after being introduced close to the time of diagnosis.

Adding to this, the researchers noted that it’s “likely that factors other than glycemic control, such as autoimmune response, affect the rate of C-peptide decline after diagnosis of type 1 diabetes and that closed-loop glucose control for 24 months after diagnosis is unable to preserve endogenous insulin secretion.”

A total of 97 newly diagnosed youth (average age 12 years) with type 1 diabetes were included in the CLOuD (Closed Loop From Onset in Type 1 Diabetes) trial — 51 assigned to a closed-loop system and 46 to standard insulin therapy. Of that group, 29% were in diabetic ketoacidosis at the time of diagnosis, HbA1c level was 10.6% at baseline, and 81% of the cohort was white.

The hybrid closed-loop system involved Medtronic insulin pumps and either Dexcom or Medtronic continuous glucose monitors fitted with the Cambridge model predictive control algorithm. Over the 24-month period, the the median percentage of time using continuous glucose monitoring was 81% and the percentage of time using the closed-loop system was 76%.

During the trial, there were five cases of severe hypoglycemia reported among three closed-loop users and one case reported in the standard insulin group. Additionally, there was one case of diabetic ketoacidosis in the closed-loop group.