Dietary Patterns and Lifestyle Factors as Determinants of Body Mass Index and Body Composition in Individuals with Down Syndrome—A Study Across Three Clinical Sites

Background/Objectives: It is often reported in the literature that the prevalence of obesity is high in individuals with Down Syndrome (DS). This study aims to assess how lifestyle factors—diet quality, nutrient intake or physical activity—contribute to weight gain. Methods: 230 males/females with DS, aged 12–45 years, were recruited across three geographically independent sites. A total of 185 participants were considered for this analysis and classified into normal-weight, overweight, and obese categories. Diet quality and nutrient intake were calculated using country-specific FFQs. Physical activity was assessed with the Minnesota Leisure Time Activity Questionnaire. Body composition measures were obtained with a bioimpedance scale. Results: The study corroborates a higher prevalence (%) of overweight/obesity in our DS cohort compared to the general population. Higher BMIs were significantly correlated with older age (p < 0.001), lower physical activity (p < 0.05), higher parental BMIs (p < 0.001, mother’s BMI; p < 0.05, father’s BMI), and increased adiposity indicators. Excess body weight showed an inverse association only with protein intake (p < 0.001). No significant differences emerged in total caloric or other macronutrients intake across BMI categories. However, notable differences in dietary patterns were observed among the three countries, reflecting cultural influences. A smaller exploratory sub-study suggested a potential relationship between higher IQ scores and better diet quality (p < 0.05). Conclusions: These findings provide new insights into contributors to overweight/obesity in DS people, indicating an influence of age, physical activity, familial factors, and body composition. Higher protein intake and culturally adapted lifestyle interventions may contribute to improving weight-related outcomes.