Daily oral insulin improves metabolic markers in children at high risk for type 1 diabetes
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Daily oral insulin therapy may improve glucose and C-peptide measurements for a subset of children at high risk for type 1 diabetes, according to new TrialNet data presented at the American Diabetes Association Scientific Sessions.
“The main message is that, in the subset of participants with the highest risk for type 1 diabetes, one of the two doses of oral insulin that our study tested prevented deterioration of metabolic indices,” Maria Jose Redondo, MD, PhD, MPH, associate professor of pediatrics, diabetes and endocrinology at Texas Children's Hospital and Baylor College of Medicine, told Healio. “In a previous analysis, we had shown that this dose also causes favorable immunologic changes. Neither the immunologic nor the metabolic effects were seen with the other dose.”
As Healio previously reported, TrialNet data published in JAMA in 2017 showed that risk for type 1 diabetes development was not decreased in autoantibody-positive relatives of patients with type 1 diabetes randomly assigned to oral insulin, and oral insulin did not delay the time to diabetes progression. The annualized rate of diabetes did not significantly differ in the main study group between participants assigned oral insulin (8.8%) or placebo (10.2%). However, the annualized rate of diabetes was lower for secondary groups who received oral insulin with different autoantibody profiles and first-phase insulin release threshold combinations; the median time to diabetes was also longer for this subset in the oral insulin group (55.3 months) compared with the placebo group (24.3 months).
Researchers also observed a decline in insulin autoantibody titers associated with an increase in islet-specific CD4+ T-cell frequencies for a subset of participants who received a daily 67.5 mg oral insulin dose, but not for participants who received 500 mg oral insulin dose every 2 weeks.
“Here, we compared the two arms to assess whether metabolic effects also occur in the 67.5 mg per day treatment arm,” Redondo said during a presentation.
Researchers analyzed data from children aged 3 to 16 years with autoantibody positivity and a Diabetes Prevention Trial Risk Score (DPTRS) of at least 6.75, a subset where a metabolic effect of oral insulin has been demonstrated (mean age, 6 years). Participants received 67.5 mg daily oral insulin (n = 13), 500 mg biweekly oral insulin (n = 17) or placebo for 6 months. Researchers measured changes in mean glucose and C-peptide response curves during an oral glucose tolerance test at baseline and 6 and 12 months.
Researchers found that, compared with baseline measurements, glucose levels were higher and C-peptide levels were lower for each OGTT time point (30 to 120 minutes) at 12 months for the 500 mg biweekly dose group. Metabolic deterioration was not observed in the 67.5 mg daily dose group.
In an abstract, researchers wrote that the C-peptide to glucose ratio of centroid coordinates changed little in the 67.5 mg daily dose group but decreased in the 500 mg biweekly dose group (1.03 vs. –4.39; P < .05), after adjustment for baseline ratio, age and BMI z score.
“The better metabolic outcome of 67.5 mg daily dose of oral insulin than 500 mg every 2 weeks is consistent with the prior finding that immunologic change is associated with 67.5 mg daily dose, suggesting a linkage of immune and metabolic effects,” the researchers wrote.
Redondo said some may be surprised that the oral insulin benefit was observed in the participants at the highest risk for type 1 diabetes, as measured by DPTRS.
“The DPTRS includes C-peptide level, glucose level, BMI and age; high DPTRS is associated with high risk for progression to type 1 diabetes,” Redondo told Healio. “Our observation is surprising because it was previously believed that halting or reversing the autoimmune attack on beta cells would be easier in the cases where this process is less advanced.”
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Redondo MJ, et al. 12-OR. Presented at: American Diabetes Association Scientific Sessions, June 25-29, 2021 (virtual meeting).
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