Unexplained hyperglycemic episodes in patients with type 1 diabetes (T1D) who are using automated insulin delivery (AID) systems may be a sign of undetected occlusions, new data showed.

In addition, the study found that alarms designed to alert patients of the occlusions only did so in a small fraction of cases, posing potential health risks and taking a toll on patients’ well-being.

“There is certainly a need for patient education and improved occlusion detection technology to address the gap between clinical [hyperglycemic] events and device notifications,” said first author Lori Laffel, MD, MPH, a professor of pediatrics at Joslin Diabetes Center, Harvard Medical School, in Boston, who presented the findings at 19th International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) 2026.

Unexplained Hyperglycemia

The study included 248 adults in a T1D Exchange community in the US who were using AID systems, who were surveyed between June and July 2025. As many as 220 (89%) reported experiencing at least one hyperglycemic event in the previous 4 weeks, defined as having glucose of 250 mg/dL or higher that could not be explained.

Of 122 participants who had more than one unexplained event and who changed their pod or set, 71% saw their glucose levels return to a target range within 3 hours of the pod or set change, while 7% took more than 6 hours to return to target.

Importantly, only four of the 122 participants (3%) received an occlusion alarm during the events. Most relied on continuous glucose monitoring (CGM) alarms (70%) or symptoms (20%) to detect unexplained hyperglycemia.

Other than the unexplained hyperglycemia, 44% of tubed pump users and 32% of pod users reported no physical signs, such as insulin leaking or a bent cannula, prior to changing their infusion set.

Of note, 71% had glucose values of 300 mg/dL or higher, and 21% had glucose values of 400 mg/dL or higher. Of those reporting events, 66% had more than two events over the previous month.

“This was really substantial hyperglycemia in some of these cases,” said Laffel. “This is a challenge and a recognized problem that we’re trying to overcome.”

A further inquiry into the impact of the hyperglycemic events on patients’ quality of life showed that, for approximately a quarter of patients, the events had a substantial disruption to their sleep; for about 70%, the events interfered with their daily activities and caused unpleasant physical symptoms; and about 75% experienced emotional distress due to the period of unrecognized hyperglycemia.

Ultimately, “the resolution of hyperglycemia after infusion set or pod changes, in the absence of other causes, suggests that unexplained hyperglycemia may serve as a clinical proxy for undetected occlusions,” Laffel told meeting attendees.

Insulin Infusion Site Failures Common

In a separate talk at the meeting, Irl B. Hirsch, MD, a professor of medicine at the University of Washington in Seattle, highlighted the extent of the problem. He cited recent research showing that as many as 41.4% of patients with T1D using AID systems, also from the TD Exchange, reported one or more insulin infusion site failures per month. The study also found that such failures are most commonly detected as the result of the development of hyperglycemia, rather than from a device’s occlusion alert.

“That is a lot of failures,” Hirsch asserted. It’s “a huge problem,” he added. “This is the true Achilles heel and while [there are] a lot of new insulin pumps, nobody talks about this.”

At the crux of the occlusions are the body’s responses to various components of the insulin systems, including repetitive microtraumas which trigger an immune response, leading to the activation of lipohypertrophy, and the formation of scar tissue, Hirsch explained.

“Chronic inflammation leads to fibrosis and fat necrosis, which cannot absorb insulin efficiently and increases the physical risk of catheter kinking,” he said. Furthermore, “the combination of inflammatory cell buildup and protein aggregation can clog the cannula, leading to total or partial occlusion.”

Factors Contributing to the Inflammation

Factors involved in the development of inflammation can include the pump’s catheter, Hirsch noted. Previous research has suggested Teflon catheters are associated with a more prolonged inflammatory response, as well as increased recruitment of macrophages and mast cells, and higher levels of TNF-alpha compared with polyurethan-based sensors.

And insulin itself has been linked to inflammatory responses related to preservatives, he added, citing results from the DERMIS study, conducted by Hirsch and his colleagues, in which skin biopsies of insulin pump sites showed differences compared with noninsulin controls in skin architecture, including fibrosis, inflammation, increased tissue eosinophils, and fat necrosis.

“These findings support allergic sensitization as a potentially common reaction at continuous subcutaneous insulin sites,” Hirsch and his colleagues concluded.

Data further supporting these results include findings from another study that showed the removal of phenolic preservative from insulin formulations had the effect of reducing inflammation without negatively affecting glucose levels.

These findings underscore that “these preservatives are a huge problem, and many reports replicate this,” said Hirsch. “The preservatives are needed for stability, but they’re cytotoxic, they often contribute to premature 3-day infusion set failure, not to mention the 7-day failure, skin irritation, and in some cases allergic reactions.”

The collective evidence suggests that “ideally, we need insulins without excipients, which appear to be a primary etiology of the inflammation,” he concluded.

The Cost of Catheters and Ketone Meters

Commenting on the issue, Satish K. Garg, MD, a professor of medicine and pediatrics and director of the Adult Program at the Barbara Davis Center for Diabetes, University of Colorado Anschutz, in Aurora, Colorado, said that in his experience, insulin pump occlusion cases are not at all uncommon.

“Whenever I am on call, the only significant calls that I get are early hyperglycemia and ketosis due to pump catheter occlusions,” he told Medscape Medical News.

Garg said his team typically advises that if patients have unexplained hyperglycemia, two small boluses, 45 minutes apart, should be administered through the pump, and if the glucose does not go down by more than 50 mg/dL, they should change the pump catheter.

“This is important to avoid ketosis and diabetic ketoacidosis,” he explained. “Unfortunately, patients often don’t change the pump catheters as recommended every 2-3 days,” instead they change every 4-5 days.

“This in part is due to the cost,” he added.

Patients are also advised to check ketones with a finger stick for beta hydroxybutyric acid, “however most don’t keep ketone meters at home due to the cost of strips,” Garg continued. “They may check urine ketones, which is not adequate.”

Advancing Technologies

A range of solutions are available or in the works that could address the problem, including a dual glucose ketone CGM system that addresses rising glucose and ketone levels resulting from a catheter’s occlusion, Garg said.

There’s also an already available extended wear infusion system (MiniMed), approved for 7 days, with other extended wear infusion systems in the works, he noted.

“I think the availability of the dual glucose ketone and extended wear infusion systems may help reduce such events in the future,” he said.

Of note, Laffel’s study was funded by Sequel Med Tech, that launched a new AID (Twiist) last year that the company says includes advanced occlusion detection.

Hirsch’s disclosures included consulting or other relationships with Sequel MedTech, CourPharmaceuticals, Abbott, Roche, and Hagar. Laffel’s study was funded by Sequel Med Tech, which has developed an AID system (Twiist) promoting advanced occlusion detection. Her disclosures included consulting or other relationships with Boehringer Ingelheim, Dexcom, Medtronic, Sequel Med Tech, Sinocare, Tandem Diabetes, Mannkind, Roche, Vertex, and Insulet Corp. Garg’s disclosures included relationships with Minimed, Dexcom, Lilly and Novo, with all funds and contracts through the University of Colorado.