Diabetic Ketoacidosis (DKA) is an acute complication of type 1 diabetes (T1D), and is the leading cause of hospitalizations and mortality (i.e., death) among children and younger adults with T1D in the US, UK and worldwide. DKA is also the presenting symptom of patients newly diagnosed with T1D, comprising between 30% to 40% of new cases in the US and UK, and 15% to 67% of the cases worldwide. However, due to limitations of current data, it is currently unclear whether patients presenting with DKA at diagnosis of T1D differ from those without presenting in DKA. Our specific aims are:
Aim 1: To estimate 20-year trends in incidence of T1D with and without DKA at presentation and to compare mortality rates in the two groups after T1D diagnosis. We will estimate the proportion of patients who present with DKA at diagnosis over the 20-year period, and estimate the 1-,3-, and 5-year mortality rates in both groups.
Aim 2: To ascertain the risk-factors associated with DKA at diagnosis. Using longitudinal clinical data, we will elucidate the key clinical (e.g., gastroenteritis) and non-clinical (e.g., healthcare access, social deprivation) risk-factors associated with a DKA presentation
Aim 3: To create models that predict patients and subgroups at highest risk of DKA at diagnosis. We will develop and validate statistical models that will help detect subgroups of patients that are at highest risk of presenting with DKA at diagnosis.
Diabetic Ketoacidosis (DKA) is an acute complication of type 1 diabetes (T1D), and is the leading cause of hospitalizations, morbidity and mortality among children and younger adults with T1D; it is also the presenting symptom of patients newly diagnosed with T1D, comprising between 30% to 40% of new cases in the US and UK. However, due to paucity of data, it is unclear whether patients presenting with DKA at diagnosis differ from those without DKA. We will use CPRD Gold and Aurum from 2000 to 2023 with linked information on hospitalizations, mortality, and social deprivation.
Aim 1: Among patients ≤21 years old newly diagnosed with T1D, we will describe the secular trends in incidence of DKA at diagnosis, as well as the short- and long-term mortality rates in the two groups after T1D diagnosis.
Aim 2: Among newly diagnosed T1D patients, we will create etiological models to elucidate the patient-level risk factors associated with the outcome of DKA at diagnosis. Multivariate modified Poisson regressions will be employed to directly model the adjusted relative risks associated with each risk factor of interest.
Aim 3: Among a cohort of patients who do not yet have T1D and using the risk-factors from Aim 2, we will create prognostic models to risk stratify patient subgroups according to their estimated probability of the outcome of DKA at diagnosis. We will use logistic regressions to model the outcome of DKA at diagnosis.
Hospitalization due to Diabetic Ketoacidosis (DKA) (all aims); all-cause and diabetic specific mortality (Aim 1 only)
Chintan Dave - Chief Investigator - Rutgers, The State University of New Jersey
Chintan Dave - Corresponding Applicant - Rutgers, The State University of New Jersey
Abner Nyandege - Collaborator - Rutgers, The State University of New Jersey
Brian Strom - Collaborator - Rutgers, The State University of New Jersey
Jason Roy - Collaborator - Rutgers, The State University of New Jersey
Sally Radovick - Collaborator - Rutgers Robert Wood Johnson Medical School
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation