Endocrine Abstracts

Background: Down Syndrome (DS) is the commonest form of chromosomal trisomy. Genetic factors in DS may increase the risk for diabetes. Obesity and type 2 diabetes mellitus (T2DM) rates have increased in the general populationbut it is not known whether this similarly affected people with DS.

Objective: 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). DS patients were identified using diagnostic codes for DS or Trisomy 21; up to 4 matched controls for each DS case was selected.

Results: 9,917 DS and 38,266 control patients were analysed. Diabetes rates were higher in DS individuals (incidence rate ratio 3.68; 95% CI 2.43 – 5.57; p<0.0001) and peaked at a younger age with over four times higher incidence per 1,000 patient years in children with DS aged 5-14 years old (1.55; 95% CI 0.95 - 2.39) compared to controls (0.38; 95% CI 0.25 – 0.57). There was over six times increased incidence of T1DM in patients with DS aged 15-24 years (1.13; 95% CI 0.62 - 1.90) compared to controls (0.18; 95% CI 0.09 - 0.33). T2DM rates were higher in DS compared to controls at age groups 5 years up to 34 years with over 10 times increased incidence in children aged 5-14 years with DS (0.62; 95% CI 0.27 - 1.22) compared to controls (0.06; 95% CI 0.02 - 0.16). 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.