Episodes of severe hypoglycemia became less frequent over a period of 26 years in patients with type 1 diabetes whose glucose was initially intensively managed to a hemoglobin A1c target of 7%, but, conversely, these problems increased in patients who had been managed to a conventional target of 9%, .

At the end of the 20-year-long Epidemiology of Diabetes Interventions and Complications (EDIC) study, which used an 8% HbA1c target for everyone, rates of severe hypoglycemia were 37 cases per 100 patient-years in patients managed intensively in the preceding Diabetes Control and Complications Trial (DCCT) – a significant decrease from the 61 cases per 100 patient-years observed when the DCCT concluded. However, rates of severe hypoglycemia also increased in the conventionally managed group, from 19 to 41 cases per 100 patient-years, according to Rose A. Gubitosi-Klug, MD, PhD, and her coauthors ( Diab Care. 2017;40[8]:1010-6 ).

“The equalization of rates between the two original treatment groups is largely attributable to their similar HbA1c levels during EDIC,” wrote Dr. Gubitosi-Klug, who is division chief of pediatric endocrinology at University Hospital, Cleveland Medical Center, and her coauthors. “[There was] a 13%-15% rise in severe hypoglycemia risk for every 10% decrement in HbA1c.”

The DCCT enrolled 1,441 patients with type 1 diabetes from 1983 to 1989. They were either managed intensively, with a target HbA1c of 7%, or, conventionally, with a 9% target. Specifically, during the DCCT, participants in the intensive group had lower current and mean HbA1c levels (~2% mean difference; P less than .001) as well as higher insulin doses than those in the conventional group (mean difference, 0.04 units/kg per day; P less than .001). During the DCCT, pump use across all quarterly visits averaged 35.7% in the intensive group versus 0.7% in the conventional group and rose to 41% and 1.6%, respectively, by the DCCT closeout (P less than .001).

Almost everyone in the DCCT then enrolled in the EDIC study, which ran from 1995 to 2013. EDIC used an 8% HbA1c target. During EDIC, diabetes management has evolved dramatically, with the introduction of rapid- and long-acting insulins and improved insulin pumps and blood glucose meters. Dr. Gubitosi-Klug and her colleagues examined how rates of severe hypoglycemia have changed with those advances.

During the DCCT, intensively managed patients were three times more likely than those conventionally managed to experience an episode of severe hypoglycemia, including seizure or coma. During EDIC, the frequency of severe hypoglycemia increased in patients who had been conventionally managed but decreased among those who had been intensively managed.

When the DCCT ended with an average 6.5 years follow-up, 65% of the intensive group and 35% of the conventional group had experienced at least one episode of severe hypoglycemia. But when the 20-year EDIC study ended, about half of everyone in the group had experienced at least one episode. Many experienced multiple events. In the DCCT, 54% of the intensive group and 30% of the conventional group had experienced at least four episodes. In EDIC, 37% of the intensive group and 33% of the conventional group had experienced at least four.

But the repeat events seemed to occur in a subset of patients, with 14% in the DCCT experiencing about half of the study’s severe hypoglycemic events, and 7% in EDIC experiencing about a third of them in that study.

The biggest risk factor for severe hypoglycemia was similar for both groups. A first incident doubled the risk for another in the conventional therapy group and tripled it in the intensive therapy group.

“The current data support the clinical perception that a small subset of individuals is more susceptible to severe hypoglycemia,” with 7% of patients with 11 or more episodes during EDIC representing 32% all the events in that study.

These events impart a risk of serious consequences, the authors said. There were 51 major accidents during the 6.5 years of the DCCT and 143 during the 20 years of EDIC, and these were similar between treatment groups. Most of these were motor vehicle accidents, and hypoglycemia was the possible, probable, or principal cause of 18 of the 28 in the DCCT and 23 of the 54 in EDIC.

Nevertheless, the finding that intensively managed patients did better over the years is encouraging, the authors noted. “Advancements in the tools for diabetes management and additional clinical trials have also demonstrated the importance of educational programs to support intensive diabetes therapy. Thus, with increasing years of experience, participants have likely benefitted from tailored educational efforts provided by treating physicians and certified diabetes educators to minimize hypoglycemia.”

None of the study authors reported any financial conflicts.

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