medwireNews: Young people using hybrid closed-loop insulin therapy for type 1 diabetes have similar rates of severe hypoglycemia to those using sensor-augmented (open-loop) insulin pump therapy but are at increased risk for ketoacidosis, study findings indicate.
Other glycemic outcomes, including the rate of hypoglycemic coma, glycated hemoglobin (HbA1c) level, time spent in target glucose range, and glycemic variability were all significantly better among individuals using closed-loop systems than among those using open-loop therapy, report Beate Karges (RWTH Aachen University, Germany) and co-authors in The Lancet Diabetes & Endocrinology.
They say: “Our findings could influence future decisions regarding the use of automated insulin delivery with hybrid closed-loop systems in young people on pump therapy and CGM [continuous glucose monitoring] for reducing hypoglycaemic coma risk, reaching glycaemic targets, and identifying individual ketoacidosis risk.”
The study included data for 13,922 people aged 2–20 years (median age 13.2 years, 51.0% male) with a diabetes duration of more than 1 year, who participated in the Diabetes Prospective Follow-up initiative between 2021 and 2023. Of these, 7088 (50.9%) used closed-loop therapy and 6834 (49.1%) used open-loop therapy.
During a median 1.6 years of follow-up, the researchers found that the incidence of ketoacidosis was significantly higher among individuals using closed-loop therapy than those using open-loop therapy, at 1.74 versus 0.96 cases per 100 patient–years.
Furthermore, ketoacidosis rates increased significantly with increasing HbA1c levels in both groups, but the trend was more pronounced among closed-loop therapy users. Indeed, for individuals with a HbA1c level of 8.5% (69.4 mmol/mol) or higher, the incidence of ketoacidosis was 5.25 per 100 patient–years with closed-loop therapy versus 1.53 per 100 patient–years with open-loop therapy.
Karges and co-authors suggest “that increased ketoacidosis risk with closed-loop therapy is caused by insufficient insulin delivery, potentially resulting from system malfunctioning or user error.”
There was no significant difference between the closed-loop and open-loop groups in the rate of severe hypoglycemia, at 5.59 versus 6.63 cases per 100 patient–years, but individuals using closed-loop therapy had a significantly lower rate of hypoglycemic coma than those using open-loop therapy, at 0.62 and 0.91 cases per 100 patient–years, respectively.
The investigators say this indicates “that closed-loop therapy might reduce the progression to the most severe forms of hypoglycaemia,” possibly “due to the advanced algorithms for glucose-dependent regulation of insulin delivery with hybrid closed-loop systems, including predictions based on prior learning and subsequent reduction of insulin delivery.”
Of note, the difference in hypoglycemic coma rate between users of closed- and open-loop therapy was greatest in those with a HbA1c level of less than 6.5% (<47.5 mmol/mol; 0.43 vs 1.21 per 100 patient–years), “underlining the safety and effectiveness of current closed-loop therapy,” say Karges et al. “This finding supports a HbA1c target of less than 6.5% in populations with access to advanced technology.”
In addition, closed-loop therapy users had a significantly lower HbA1c level than open-loop users (7.34 vs 7.50%; 57 vs 58 mmol/mol), spent a significantly higher percentage of time in the target glucose range of 3.9–10.0 mmol/L (70.3–180.2 mg/dL; 64.0 vs 52.0%), and had significantly less glycemic variability as measured by the coefficient of variation (35.4 vs 38.3%).
“The effectiveness of hybrid closed-loop therapy to improve glycaemic outcomes and reduce hypoglycaemia coma risk provides evidence to advocate its use in individuals with pump therapy and CGM who do not reach glycaemic targets or who have experienced severe hypoglycaemia,” write Karges and co-authors.
“Of concern, people with above-target HbA1c levels who profit most from closed-loop therapy for glycaemic improvement in this and previous studies, are at highest ketoacidosis risk.”
Nonetheless, the researchers believe that “the overall benefit of improved glycaemia associated with hybrid closed-loop therapy would justify its use in the group of people with high HbA1c levels.”
They conclude: “A higher ketoacidosis risk with closed-loop therapy points to the current need for dedicated clinical care, including educational measures, increased alertness, and ketone monitoring to prevent this adverse event, particularly in those individuals with above-target HbA1c levels.”
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Lancet Diabetes Endocrinol 2024; doi:10.1016/S2213-8587(24)00284-5
