Influence of glycaemic management and BMI on cardiac autonomic
markers in children with type 1 diabetes: a prospective cohort study
Ebba Bergdahl1 · Gun Forsander2 · Linda Milkovic3 · Frida Sundberg4 · Frida Dangardt1,5
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https://link.springer.com/article/10.1007/s00125-025-06592-3
Vol.:(0123456789)Diabetologia
https://doi.org/10.1007/s00125-025-06592-3
Abstract
Aims/hypothesis
Our aim was to examine the presence of subclinical cardiovascular autonomic neuropathy (CAN) in a
cohort of children with well-regulated type 1 diabetes by measuring baroreceptor sensitivity (BRS), QT variability index
(QTVI) and heart rate variability (HRV).
Methods
Forty-five children (aged 6–15.99 years) with a type 1 diabetes duration of ≥5 years, and 37 healthy control children
were included at baseline; and 28 and 18 children, respectively, were included at 2 year follow-up. Cardiac BRS, QTVI and
HRV were measured and anthropometrical data and blood samples were collected from all study participants. Longitudinal
HbA 1c values from 3 months after type 1 diabetes diagnosis and continuous glucose monitoring data from the children with
type 1 diabetes were also collected.
Results
Time in normoglycaemia (TING) increased significantly from 42% to 48% between baseline and 2 year follow-up
(p=0.042). No difference in BRS, QTVI or HRV were found between the study groups at baseline or follow-up. Children
with type 1 diabetes with a BMI z score ≥1 showed higher QTVI compared with either lean children with diabetes or healthy
control children. QTVI correlated with type 1 diabetes duration, longitudinal HbA 1c AUC and cystatin C in children with
type 1 diabetes at baseline, and with CV at follow-up. (r=−0.447 p=0.004, r=−0.376 p=0.017, r=−323 p=0.048, and
r=0.568 p=0.01, respectively). There was also a correlation between the increase in TING between the study visits and BRS
at follow-up in children with type 1 diabetes (r=0.524 p=0.031).
Conclusions/interpretation
In this well-regulated type 1 diabetes cohort we did not find manifest signs of CAN in children
with type 1 diabetes.
These are promising findings and should motivate further to keep striving for normoglycaemia in
paediatric diabetes care. Children with both type 1 diabetes and overweight seem more susceptible to early development of
CAN and might benefit from earlier and more intensive preventive targeting
Introduction
From the article
Diabetes autonomic neuropathy (DAN) includes disturbances
from the urogenital and gastrointestinal organs, the sudomo-
tor function and cardiovascular autonomic neuropathy
(CAN), the latter of which is the most studied form [1]. CAN
symptoms include tachycardia, orthostatism and exercise
intolerance, and CAN is a known risk factor for cardiovascu-
lar mortality in type 1 diabetes [2].
The presence of CAN is
also connected with hypoglycaemia unawareness and severe
hypoglycaemic events in individuals with type 1 diabetes [3].
CAN prevalence in children with type 1 diabetes varies sub-
stantially between different studies, possibly explained by the
lack of a gold-standard evaluation method [4, 5]. The SEARCH
for diabetes in youth study showed a 14.4% prevalence in young
individuals with type 1 diabetes with a mean duration of ill-
ness of 7.9 years, measured as impaired heart rate variability
(HRV) [6], and the DCCT/EDIC study found a CAN preva-
lence of 8.5% 6 years after diagnosis, measured as prolonged RR
interval [7].
CAN in children with diabetes has previously been
associated with type 1 diabetes duration, glycaemic manage-
ment [5] and a number of traditional cardiovascular risk factors
such as hypertension and obesity. It is even more pronounced in
young individuals with type 2 diabetes and also in the case of
lower HbA1c levels and shorter duration of illness [8]. Although
data on the prevalence of CAN in children with type 1 diabetes
are inconclusive, studies in adults with type 1 diabetes gener-
ally show a high prevalence of CAN (>30%) [9–11] associated
with type 1 diabetes duration, hypertension and diabetic kidney
disease (DKD) [9, 10, 12]. Hydroxy fatty acids and the tricar-
boxylic acid cycle are also associated with the development of
CAN and may constitute good targets for additional preventive
treatment in the future [13].
Hence, trustworthy markers associated with development
of CAN in children with type 1 diabetes are essential to
enable early detection and treatment before development of
manifest CAN [12]. We identify a need for reliable and sensi-
tive methods for early detection of CAN development in chil-
dren with diabetes, both for providing prevalence numbers
to help pathophysiological understanding and for enabling
early preventive treatment of CAN in children with diabetes.
Utdrag ur
Discussion
In this prospective cohort study, we used highly sensitive
methods for detection of subclinical CAN in children with
type 1 diabetes with low HbA 1c and no presence of other
traditional cardiovascular risk factors.
Children with type 1
diabetes were compared with age- and sex-matched healthy
control children, and we found no differences in BRS, QTVI
or HRV between the study groups at baseline or at 2 year
follow-up, nor any longitudinal changes in either of the study
groups.
There was an improvement in TING in children with
diabetes from baseline to follow-up, correlating with higher
BRS at follow-up, and QTVI was higher in children with
diabetes with BMIz ≥1 compared with children both with
and without diabetes and with normal weight. QTVI corre-
lated with type 1 diabetes duration and HbA1cAUC at baseline
and type 1 diabetes duration, cystatin C and age were inde-
pendent determinants for QTVI in children with diabetes in
multivariable regression.
Our results, especially the correla-
tions found for QTVI and BRS, as well as the results from
backwards multivariable regression suggest an association
between dysglycaemia and CAN, even in this study cohort
where children with diabetes display comparably low HbA1c
levels, even better lipid profiles than matched healthy control
children, and no other manifest cardiovascular complica-
tions. These quite unique glycaemic and metabolic manage-
ment results possibly explain the findings that there were no
significant differences in any of the measures of subclinical
CAN between children with and without diabetes.
Conclusion
In type 1 diabetes populations with access to
high technology and improved glycaemic management, data
on chronic complication development are still limited, and
our study adds to this knowledge gap.
Encouragingly, we
find no subclinical signs of CAN in this cohort of children
with well-regulated type 1 diabetes with normal weight.
Hence, sustaining low HbA1c and high TIR and TING might
delay or preferably prevent development of CAN. We further
confirm the additional risk of chronic complications that
comes with overweight/obesity in type 1 diabetes, suggest-
ing that intensified cardiovascular preventive focus in this
subgroup might be beneficial. Further studies with larger
study cohorts are essential to confirm our results and to
continue increasing the knowledge behind cardiovascular
complication development in children with well-regulated
type 1 diabetes.
Hopefully, this will result in even further
improvement of cardiovascular prevention in children with
diabetes, increasing both life expectancy and quality of life
for people living with type 1 diabetes in the future.
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