Investigating the presence and detectability of structural peripheral arterial changes in children with well-regulated type 1 diabetes versus healthy controls using ultra-high frequency ultrasound: a single-centre cross-sectional and case-control study.

Background: Children with type 1 diabetes have an increased risk of macrovascular complications. This study used ultra-high frequency ultrasound (UHFUS), enabling differentiation of intima thickness (IT), and media thickness (MT) in peripheral arteries, to examine early peripheral arterial changes in children with type 1 diabetes (CWD).

Methods: This cross-sectional and case-control study performed at the Queen Silvia Children's Hospital, Gothenburg, Sweden included CWD, aged 6-15.99 y/o, diabetes duration ≥5 years, compared to age and sex matched healthy controls. Exclusion criteria included other medical conditions or treatments besides insulin, abnormal examination findings or inability to handle extensive examinations. UHFUS measurements from the radial, dorsal pedal (DP), and carotid arteries as well as blood samples, blood pressure (BP)- and BMI z-score were collected from all study participants, and glucometrics from CWD.

Findings: Study inclusion was performed during 02/25/2019-06/28/2022, and a total of 50 CWD, and 41 healthy controls were included in the study. Of these, five CWD and four healthy controls were excluded, resulting in 45 (22 girls (49%), 23 boys (51%)) CWD (12.0 (2.3) y/o) and 37 (19 girls (51%), 18 boys (49%)) healthy controls (11.3 (2.5) y/o) included in data analysis. CWD had a mean HbA1c of 6.6% (48.1 mmol/mol), higher DBP z-scores (p = 0.019), DP IT, DP intima-media thickness (IMT), and radial IT compared with controls (p = 0.003, p = 0.008, and p = 0.002, respectively). Carotid IT was correlated with time in range (r = -0.47, p = 0.014), time in tight range (r = -0.64, p < 0.001), and glucose variability (r = 0.40, p = 0.004) in CWD. Time in tight range and longitudinal HbA1c were the strongest determinants for carotid IT in CWD, and type 1 diabetes diagnosis was the strongest determinant for IT across all arteries.

Interpretation: Children with well-regulated type 1 diabetes show early vascular changes in radial and DP arteries. Regression analyses indicate significant links between IT and hyperglycaemia and type 1 diabetes diagnosis respectively, indicating that structural arterial changes start in the intima. Our findings further emphasise increased time in normoglycemia as the most crucial action to prevent cardiovascular complications in type 1 diabetes. Additional larger studies are needed to confirm and further interpret the meaning of these results.

Funding: ALF-agreement, Child Diabetes Foundation, Swedish Diabetes Foundation, and the Sahlgrenska University Hospital Foundations.