Diabetes and obesity in Down Syndrome across the lifespan: a retrospective cohort study using UK electronic health records

Objective

Down Syndrome (DS) is the commonest form of chromosomal trisomy. Genetic factors in DS may increase the risk for diabetes. This study aimed to determine whether DS is associated with increased incidence of diabetes and the relationship with obesity across the lifespan compared to controls. 

Methods
Matched population-based cohort study (UK Clinical Practice Research Datalink, 1990-2020). 

Results
9,917 DS and 38,266 control patients were analysed. Diabetes rates were higher in DS individuals (incidence rate ratio 3.67; 95% CI 2.43 – 5.55; p<0.0001) and peaked at younger age; median age at diagnosis of 38 (28 to 49) years compared to 53 (43 to 61) years in controls. Incidence rates for T1DM were 0.44 per 1,000 patient years (0.31 to 0.61) in DS compared to 0.13 (0.09 to 0.17) in controls. T2DM rates were higher in DS compared to controls at age groups 5 years up to 34 years. In DS, peak mean BMI (kg/m2) was higher and at younger age (male=31.2 at 31 years; female=32.1 at 43 years) compared to controls (males=29.5 at 54 years; females 29.2 at 51 years); obesity was associated with an increased incidence of T2DM.

Conclusions
At younger ages, the incidence of diabetes in DS patients is up to four times that of controls. Peak mean BMI is higher and established earlier in DS, contributing to T2DM risk. Further investigation into the relationship between obesity and diabetes in DS is required to inform treatment and prevention measures.