title: 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).
abstract: OBJECTIVE
  This study examined the association between cardiac autonomic dysfunction and high albumin-to-creatinine ratio (ACR) in adolescents with type 1 diabetes.
  
  
  METHODS
  Adolescents recruited as part of a multicenter screening study (n = 445, 49% female, aged 10-17 years, mean duration 6.9 years; mean HbA1c 8.4%, 68 mmol/mol) underwent a 10-min continuous electrocardiogram recording for heart rate variability analysis. Time-domain heart rate variability measures included baseline heart rate, SD of the R-R interval (SDNN), and root mean squared difference of successive R-R intervals (RMSSD). Spectral analysis included sympathetic (low-frequency) and parasympathetic (high-frequency) components. Standardized ACR were calculated from six early morning urine collections using an established algorithm, reflecting age, sex, and duration, and stratified into ACR tertiles, where the upper tertile reflects higher nephropathy risk.
  
  
  RESULTS
  The upper-tertile ACR group had a faster heart rate (76 vs. 73 bpm; P < 0.01) and less heart rate variability (SDNN 68 vs. 76 ms, P = 0.02; RMSSD 63 vs. 71 ms, P = 0.04). HbA1c was 8.5% (69 mmol/mmol) in the upper tertile vs. 8.3% (67 mmol/mol) in the lower tertiles (P = 0.07). In multivariable analysis, upper-tertile ACR was associated with faster heart rate (β = 2.5, 95% CI 0.2-4.8, P = 0.03) and lower RMSSD (β = -9.5, 95% CI -18.2 to -0.8, P = 0.03), independent of age and HbA1c.
  
  
  CONCLUSIONS
  Adolescents at potentially higher risk for nephropathy show an adverse cardiac autonomic profile, indicating sympathetic overdrive, compared with the lower-risk group. Longitudinal follow-up of this cohort will further characterize the relationship between autonomic and renal dysfunction and the effect of interventions in this population.
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yoon Hi
authors.initials: YH
authors.lastname: Cho
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Craig
authors.affiliation: Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Davis
authors.affiliation: Department of Paediatric Endocrinology, Mater Children's Hospital, Brisbane, Queensland, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Cotterill
authors.affiliation: Endocrinology and Diabetes Centre, Women's and Children's Hospital, and Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Couper
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, Australia Murdoch Children's Research Institute, Melbourne, Victoria, Australia The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Cameron
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Paul Z
authors.initials: PZ
authors.lastname: Benitez-Aguirre
authors.affiliation: WellChild Laboratory, St Thomas' Hospital, London, U.K.
authors.forename: R Neil
authors.initials: RN
authors.lastname: Dalton
authors.affiliation: University Department of Paediatrics, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.affiliation: Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Jones
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia kim.donaghue@health.nsw.gov.au.
authors.forename: Kim C
authors.initials: KC
authors.lastname: Donaghue
mesh_terms: D000293:Adolescent; D000418:Albumins / Q000378:metabolism*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D003404:Creatinine / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000294:innervation / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D000418:Albumins; D003404:Creatinine