Association of diabetic ketoacidosis, severe hypoglycemia and glycemic control among children and young adults with type 1 diabetes mellitus treated with premixed versus basal-bolus insulin therapy

Background: This study compared event rates of diabetic ketoacidosis (DKA) and severe hypoglycemia, as well as glycemic control, among children, adolescents, and young adults with type 1 diabetes mellitus (T1DM) receiving basal-bolus or premixed insulin therapy. Methods: A total of 825 individuals aged ≤ 20 years with T1DM, using either basal-bolus or premixed insulin regimens, were retrospectively recruited from 2001 to 2015. Rates of DKA after diagnosis, severe hypoglycemia, and the level of glycated hemoglobin A1c (HbA1c) improvement during the follow-up period were analyzed. Results: Of the 825 patients, 226 receiving a premixed regimen were matched to the same number of patients receiving a basal-bolus regimen. In the matched cohort, DKA (10.62% vs. 5.31%; p = 0.037) and severe hypoglycemic episodes (25.22% vs. 10.62%; p < 0.001) were significantly higher in patients receiving a premixed regimen than those receiving a basal-bolus regimen. The median reduction of HbA1c, compared to the treatment-naive level, was better with the basal-bolus regimen than with the premixed regimen in both matched (2.2 vs. 2.1; p = 0.034) and the entire (3.1 vs. 1.9; p < 0.001) cohorts. Regardless of insulin regimen, a higher HbA1c level was significantly linked to higher risk of DKA development (hazard ratio [HR] 1.35 per 1% increase; p < 0.001) once the HbA1c level was ≥7.5%. Conclusions: A premixed insulin regimen may increase the DKA occurrence rate and severe hypoglycemic risk in children, adolescents, and young adults with TIDM, compared to a basal-bolus regimen. Tight glycemic control with HbA1c < 7.5% may prevent the increased risk of DKA.