Diabetes
Evolution of type 2 diabetes over 20 years and subsequent dementia incidence: an application of sequence and cluster analysis Scott C Zimmerman* Scott Zimmerman Jingxuan Wang Lucia Pacca Hyelee Kim Paola Gilsanz Sarah F Ackley Whitney Wells Anusha M Vable Melinda C Power Rachel Whitmer Catherine Schaefer M Maria Glymour
Type 2 diabetes (T2D) onset age, glucose control, treatment, and sequelae may be associated with dementia incidence. Electronic health records (EHRs) contain detailed histories of individuals’ diagnoses, labs and treatment over time, enabling analysis of complex T2D trajectories.
Using EHR and survey data from the Kaiser Permanente Northern California Research Program on Genes, Environment and Health measured 1996-2020, characterized individuals’ annual states as one of 14 states defined by KPNC membership, T2D diagnosis, and combinations of glucose control, treatment, and kidney dysfunction. Among T2D-free individuals at age 50, we characterized individuals’ state trajectories from age 50-69 and calculated clusters of similar trajectories using sequence and cluster analysis. Among individuals without dementia by age 70 we used Cox models to estimate associations between these clusters and subsequent dementia incidence after age 70, compared to individuals without a T2D diagnosis by age 70.
We summarized the 16,970 unique T2D-related trajectories experienced by 20,424 eligible individuals diagnosed with T2D by age 70 into 9 clusters (Figure). Clusters varied by T2D diagnosis timing and duration, HbA1c control, treatment, and kidney dysfunction. Dementia incidence over an average follow-up of 9.5 years varied across clusters relative to the group of 173,852 individuals without T2D at age 70, which had the lowest incidence. The lowest incidence for those with T2D was in a cluster characterized by long-term Kaiser membership, T2D onset typically after age 60, and moderate control of HbA1c with few drugs (cluster 6, HR=1.59 95%CI=(1.04, 2.42)). The highest risk cluster was characterized by onset of T2D typically before age 60 and chronic high HbA1c with low-to-moderate use of antihyperglycemic drugs (cluster 9, HR=4.26 95%CI=(3.13, 5.80)).
In these real-world data, dementia incidence varied substantially based on timing of T2D diagnosis, duration and treatment trajectories.
