Objective: This study examined subcutaneous tissue changes at sites used by continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and tested whether these changes, if any, were associated with glycated hemoglobin (HbA1c). Research Design and Methods: This prospective study investigated recently used CSII or CGM sites in 161 children and adolescents during the first year after initiation of a new diabetes device. Subcutaneous changes such as echogenicity, vascularization, and the distance from the skin surface to the muscle at CSII and CGM sites were assessed by ultrasound. Results: The distance from skin surface to muscle fascia at both the upper arm and abdomen was influenced by age, body mass index z-score, and sex. Especially in boys and the youngest, the depth of many devices outreached the mean distance. The mean distance for boys at the abdomen and upper arm ranged from 4.5-6.5 mm and 5-6.9 mm for all ages, respectively. Hyperechogenicity at CGM sites was 4.3% after 12 months. The frequency of subcutaneous hyperechogenicity and vascularization at CSII sites increased significantly over time (41.2% to 69.3% and 2% to 16% respectively, P < 0.001 and P = 0.009). Hyperechogenicity in the subcutis was not a predictor of elevated HbA1c (P = 0.11). Conclusion: There is large variation in the distance from the skin surface to the muscle fascia and many diabetes devices reach even deeper. Hyperechogenicity and vascularization increased significantly over time at CSII sites, but not CGM sites. The importance of hyperechogenicity for insulin absorption is unclear and further investigations are needed. Clinical Trial Registration number: NCT04258904.