Diabetic ketoacidosis at diagnosis of type 1 diabetes and glycemic control over time: The SEARCH for diabetes in youth study

Abstract

Background: The diagnosis of type 1 diabetes (T1D) in youth is often associated with diabetic ketoacidosis (DKA). We aimed to evaluate if the presence of DKA at diagnosis of T1D is associated with less favorable hemoglobin A1c (HbA1c) trajectories over time.

Methods: The SEARCH for Diabetes in Youth study of 1396 youth aged <20 years with newly diagnosed T1D were followed for up to 13 (median 8 [interquartile range or IQR 6-9]) years after diagnosis. Of these, 397 (28%) had DKA (bicarbonate level < 15 mmol/L and/or pH < 7.25 (venous) or < 7.30 (arterial or capillary) or mention of DKA in medical records) at diabetes onset. Longitudinal HbA1c levels were measured at each follow-up visit (average number of HbA1c measures 3.4). A linear piecewise mixed effects model was used to analyze the effect of DKA status at diagnosis of T1D on long-term glycemic control, adjusting for age at diagnosis, diabetes duration at baseline, sex, race/ethnicity, household income, health insurance status, time-varying insulin regimen and glucose self-monitoring, study site, and baseline fasting C-peptide level.

Results: At baseline, HbA1c levels were significantly higher in youth with T1D diagnosed in DKA vs those who were not (9.9% ± 1.5% vs 8.5% ± 1.4%, respectively). After the first year with diabetes, there was a significant difference in the rate of change in HbA1c levels by DKA status: HbA1c was 0.16% higher each year in youth with DKA compared to those without (interaction P-value<0.0001), after adjusting for aforementioned covariates.

Conclusions: DKA at T1D diagnosis is associated with worsening glycemic control over time, independent of demographic, socioeconomic, and treatment-related factors and baseline fasting C-peptide.

Keywords: diabetic ketoacidosis; glycemic control; type 1 diabetes.

Figure 1:. Model-based HbA1c levels over time according to DKA status at diagnosis with Type 1 Diabetes

Data from piecewise linear mixed effects model with knot at 1 year diabetes duration (time 0 = diagnosis of type 1 diabetes). Time, as measured by diabetes duration, was assessed as a continuous variable and the shaded region corresponds to the 95% confidence interval. The number of data points contributing to each 1-year time interval are displayed in the table below the figure. Data are shown for up to 9 years post-diagnosis (the upper limit of the interquartile range). Model adjusted for: age at diagnosis, diabetes duration at baseline, sex, race/ethnicity, household income, insurance status, time varying insulin regimen and glucose self-monitoring, study site, and baseline fasting C-peptide. P-value <.0001 for the difference in slopes after year 1 between youth diagnosed with diabetes in DKA compared to those who were not. Predicted mean levels of HbA1c for youth presenting in DKA at diagnosis versus those who did not are: Year 1: 7.90% vs. 7.78%; Year 5: 9.21% vs. 8.59%; Year 9: 10.07% vs 8.89%, respectively. DKA = diabetic ketoacidosis; HbA1c = hemoglobin A_1c; T1D = type 1 diabetes.