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Early Vascular Changes in T1DM. Ebba Bergdahl et al. Göteborg

Ultrasound Detects Early Vascular Changes in Kids With T1D

eClinicalMedicine 2025:81:103097

Children with well-regulated type 1 diabetes (T1D) showed early vascular changes, with increased intima thickness in radial and dorsal pedal arteries as opposed to healthy control individuals without the condition.

METHODOLOGY:

Researchers conducted a case-control study to examine changes in the structure of peripheral arteries in children with well-regulated T1D vs healthy control individuals.
They included 45 children with T1D of at least 5 years’ duration (mean age, 12 years; 49% girls; mean A1c, 6.55%) and 37 healthy control individuals without the condition (mean age, 11.3 years; 49% girls).
Ultra-high–frequency ultrasound was used to scan the left radial and dorsal pedal arteries and both carotid arteries.
Primary outcomes were vascular wall measures such as intima thickness, media thickness, and intima-media thickness, assessed in the radial, dorsal pedal, and carotid arteries; secondary outcomes included glycaemic and metabolic markers associated with vascular wall measures.

TAKEAWAY:

Compared with healthy control individuals, children with T1D had increased dorsal pedal intima thickness, dorsal pedal intima-media thickness, and radial intima thickness (P = .003, .008, and .002, respectively).
In children with T1D, carotid intima thickness was negatively correlated with time in range (correlation coefficient [r], −0.518; P = .0057) and time in tight range (r, −0.609; P = .0008), whereas it was positively correlated with mean glucose (r, 0.477; P = .012) and longitudinal A1c (r, 0.457; P = .0027).
T1D diagnosis was identified as the strongest determinant of intima thickness across all examined arteries.

IN PRACTICE:

”Striving for normoglycaemia is essential in cardiovascular prevention in type 1 diabetes already in children, in addition to early monitoring and possibly pharmaceutical treatment for hypertension and hyperlipidaemia. When working with populations like this study cohort of CWD [children with T1D] with good glycaemic control, sensitive methods for detecting and assessing vascular impact over time are essential,” the authors wrote.

SOURCE:

This study was led by Ebba Bergdahl, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, and was published online on February 13, 2025, in eClinicalMedicine.

LIMITATIONS:

This study was conducted during the COVID-19 pandemic, which may have posed a significant limitation as the long-term effects of COVID-19 on the cardiovascular system remain unknown. The study did not collect data on the total daily insulin doses administered to children with T1D, which could have provided valuable insights into the relationship between insulin therapy and vascular health.

DISCLOSURES:

This study received financial support from the Swedish state, the Swedish Child Diabetes Foundation, and other sources. One author reported receiving funding from Vinnova, the Swedish Agency for Innovation Systems, and serving as an invited speaker at the International Society for Pediatric and Adolescent Diabetes (ISPAD) annual meeting in Lisbon, as well as heading the ISPAD special interest group on diabetes in schools.

From wwww.medscape.com

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

Ebba Bergdahl^a ebba.bergdahl@gu.se ∙ Gun Forsander^b ∙ Frida Sundberg^b ∙ Linda Milkovic^c ∙ Frida Dangardt^a,c

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https://www.thelancet.com/action/showPdf?pii=S2589-5370%2825%2900029-X

ABSTRACT

Summary

Background

Children with type 1 diabetes have an increased risk of macrovascular complications. This study usedultra-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 healthycontrols. Exclusion criteria included other medical conditions or treatments besides insulin, abnormalexaminationfindings or inability to handle extensive examinations. UHFUS measurements from the radial, dorsalpedal (DP), and carotid arteries as well as blood samples, blood pressure (BP)- and BMI z-score were collectedfrom 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 healthycontrols were included in the study. Of these,five CWD and four healthy controls were excluded, resulting in 45 (22girls (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 HbA1cwere the strongest determinants for carotid IT in CWD, and type 1 diabetes diagnosis was the strongestdeterminant 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 diagnosisrespectively, indicating that structural arterial changes start in the intima. Ourfindings further emphasiseincreased time in normoglycemia as the most crucial action to prevent cardiovascular complications in type 1diabetes. Additional larger studies are needed to confirm and further interpret the meaning of these results.

Funding

Research in context

Evidence before this studyWe searched PubMed during the period 1st of August 2022—31st of May 2024 using the following search terms (vascularOR cardiovascular) AND (children OR pediatric OR paediatric)AND (type 1 diabetes)filtering for humans, including articlesfrom 1990 up to the date of the literature search. Briefly,structural arterial changes have been previously described inboth the aorta and the carotid arteries in children with type 1diabetes (CWD). These changes are associated with glycaemicand metabolic control, and hyperglycaemia is considered themost important cardiovascular (CV) risk-factor in type 1diabetes, enhanced by traditional CV risk-factors. Studiesexploring structural changes to more peripheral arteries byusing ultra-high frequency ultrasound (UHFUS) has not yetbeen conducted in CWD. With an axial resolution of up to20μm, UHFUS enables differentiation of the intimal andmedial layers of the arterial wall. This allows for detection ofsmaller, likely earlier vascular changes, as well as more detailedpathophysiological considerations.

Added value of this study

CWD in this study show comparably very good glycaemiccontrol (HbA1c of 6.6 ± 0.6% (48.1 ± 6.0 mmol/mol)) and nopresence of other CV risk-factors. Regardless, peripheralarterial changes were found, predominately involving thedorsal pedal (DP) artery. To the best of our knowledge this isthefirst study to show detectible vascular changes in well-regulated paediatric type 1 diabetes. The UHFUS, allowingexamination of smaller arteries as well as differentiationbetween IT and MT, is likely the reason why what are believedto be earlier peripheral arterial changes than previously showncould be detected. The strong associations between carotid ITand glucometrics found in CWD in this study are interestingfindings in need of further confirmation suggesting animportant connection between hyperglycaemia and earlychanges to the intima.

Implications of all the available evidence

Our results confirm and further emphasise the importance ofglycaemic control to prevent CV complications in type 1diabetes. Wefind important associations between glycaemiccontrol and IT as well as blood pressure, indicating parallelprocesses affecting the vasculature by increasing both IT andMT. Our results show detectable vascular changes even in thiscohort of children with well-regulated type 1 diabetes.Hyperglycaemia plays a crucial role in complicationdevelopment, suggesting that striving for normoglycaemiaalready from type 1 diabetes diagnosis may be one of themost important cardio-preventive actions in paediatric type 1diabetes. When studying populations of CWD with well-controlled glycaemic levels—such as in Sweden, where 48% ofchildren aged 6–15.99 years with a diabetes duration of atleast 5 years maintain an HbA1c below 52 mmol/mol—data isessential to assess their current vascular risk

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