Cardiac Autonomic Dysfunction Is Associated With High-Risk Albumin-to-Creatinine Ratio in Young Adolescents With Type 1 Diabetes in AdDIT (Adolescent Type 1 Diabetes Cardio-Renal Interventional Trial)

Pathophysiology/Complications

Yoon Hi Cho¹,²,
Maria E. Craig¹,²,³,
Elizabeth A. Davis⁴,⁵,
Andrew M. Cotterill⁶,
Jennifer J. Couper⁷,
Fergus J. Cameron⁸,⁹,¹⁰,
Paul Z. Benitez-Aguirre¹,²,
R. Neil Dalton¹¹,
David B. Dunger¹²,
Timothy W. Jones⁴,⁵ and
Kim C. Donaghue¹,² ⇑
on behalf of the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)*

¹Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
²Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia
³School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
⁴Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia
⁵Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
⁶Department of Paediatric Endocrinology, Mater Children's Hospital, Brisbane, Queensland, Australia
⁷Endocrinology and Diabetes Centre, Women's and Children's Hospital, and Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia
⁸Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, Australia
⁹Murdoch Children’s Research Institute, Melbourne, Victoria, Australia
¹⁰The University of Melbourne, Melbourne, Victoria, Australia
¹¹WellChild Laboratory, St Thomas' Hospital, London, U.K.
¹²University Department of Paediatrics, Addenbrooke's Hospital, Cambridge, U.K.

Diabetes Care 2015 Apr; 38(4): 676-681. https://doi.org/10.2337/dc14-1848

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Figure 1
Heart rate (A) and overall RMSSD (B): marginal means from age 11 to 17 years (●, lower ACR tertiles; ■, upper ACR tertile.)

Table 1

Participant characteristics stratified by urine ACR tertiles

Data are presented as mean (SD), except as noted.
DBP, diastolic blood pressure; HDL-C, HDL-cholesterol; LDL-C, LDL-cholesterol; SBP, systolic blood pressure.

Table 2

Heart rate variability in adolescents with type 1 diabetes stratified by urine ACR tertiles

HRV parameter	Lower ACR tertiles	Upper ACR tertile	P value
HR (bpm)	73 (12)	76 (13)	<0.01
SDNN (ms)	76 (36)	68 (30)	0.02
RMSSD (ms)	71 (49)	63 (43)	0.04
LF power	1,839 (2,282)	1,363 (1,237)	<0.01
HF power	2,439 (3,751)	2,076 (3,229)	0.27
LF-to-HF ratio	1.3 (1.2)	1.5 (1.3)	0.14
TI	17 (7)	15 (6)	0.04

Table 3

Multivariable analysis of heart rate variability outcomes and ACR tertiles

HRV parameter	Factor^*	β (95% CI)	P value
HR	Upper ACR tertile⁺	2.5 (0.2–4.8)	0.03
	Age	−1.2 (−1.9 to −0.4)	<0.01
	HbA_1c	1.9 (1.0–2.8)	<0.001
SDNN	Upper ACR tertile	−6.6 (−12.7 to −0.4)	0.04
SDNN	HbA_1c	−3.8 (−6.2 to −1.4)	<0.01
RMSSD	Upper ACR tertile	−9.5 (−18.2 to −0.8)	0.03
	Age	−3.1 (−6.0 to −0.3)	0.03
	HbA_1c	−3.9 (−7.2 to −0.5)	0.02

HR, heart rate; HRV, heart rate variability.
↵* Diabetes duration, BMI SDS, and systolic or diastolic blood pressure SDS were not significant explanatory variables in the above models.
↵+ Reference group is lower tertiles.