Diabetes and Obesity in Down Syndrome Across the Lifespan: A Retrospective Cohort Study Using U.K. Electronic Health Records

OBJECTIVE: Down syndrome (DS) is the most common form of chromosomal trisomy. Genetic factors in DS may increase the risk for diabetes. This study aimed to determine whether DS is associated with an increased incidence of diabetes and the relationship with obesity across the life span compared with control patients. RESEARCH DESIGN AND METHODS: This matched population–based cohort study analyzed UK Clinical Practice Research Datalink data from 1990 to 2020. RESULTS: A total of 9,917 patients with DS and 38,266 control patients were analyzed. Diabetes rates were higher in patients with DS (incidence rate ratio 3.67; 95% CI 2.43–5.55; P < 0.0001) and peaked at a younger age (median age at diagnosis 38 [interquartile range 28–49] years vs. 53 [43–61] years in control patients). Incidence rates (per 1,000 person-years) for type 1 diabetes mellitus were 0.44 (95% CI 0.31–0.61) in patients with DS vs. 0.13 (0.09–0.17) in control patients. Type 2 diabetes mellitus (T2DM) rates were higher in patients with DS versus control patients in age-groups from 5 years up to 34 years. In patients with DS, peak mean BMI was higher and at a younger age (males 31.2 kg/m(2) at age 31 years; females 32.1 kg/m(2) at 43 years) versus control patients (males 29.5 kg/m(2) at 54 years; females 29.2 kg/m(2) at 51 years). Obesity was associated with an increased incidence of T2DM. CONCLUSIONS: At younger ages, the incidence of diabetes in patients with DS is up to four times that of control patients. 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.