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

OBJECTIVEThis study examined the association between cardiac autonomic dysfunction and high albumin-to-creatinine ratio (ACR) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODSAdolescents recruited as part of a multicenter screening study (n = 445, 49% female, aged 10-17 years, mean duration 6.9 years; mean HbA 1c 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. RESULTSThe 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). HbA 1c 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 (b = 2.5, 95% CI 0.2-4.8, P = 0.03) and lower RMSSD (b = 29.5, 95% CI 218.2 to 20.8, P = 0.03), independent of age and HbA 1c . CONCLUSIONSAdolescents at potentially higher risk for nephropathy show an adverse cardiac autonomic profile, indicating sympathetic overdrive, compared with the lowerrisk 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.

Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)

“…During the screening phase of the AdDIT study, we observed that young people (10-16 years) with an ACR in the highest tertile, although still within the normal range, already showed evidence of increased risk for CVD, as indicated by greater arterial stiffness and signs of impaired cardiac autonomic function, as well as higher rates of hyperfiltration, compared to adolescents in the lower/middle tertiles of ACR (11,13,14). The current longitudinal data from the AdDIT high-and low-ACR groups support these initial observations.…”

“…At baseline, AdDIT participants with an ACR in the upper tertile showed evidence of glomerular hyperfiltration, increased lipid levels and pulse wave velocity, and impaired autonomic function (11,13,14), despite similar HbA1c values across ACR tertiles. These data supported the hypothesis that risk stratification using ACR tertiles during early adolescence may be helpful for the early identification of patients at risk of developing vascular complications.…”

Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial

“…Adolescence is a particularly vulnerable period for the onset and priming of cardiovascular and renal complications (3,4), whereas the majority of young people with type 1 diabetes do not meet treatment targets (5,6). …”

Subclinical Myocardial Injury of Young Patients With Type1 Diabetes Mellitus Without Cardiovascular Disease

“…В связи с этим, терапия, направленная на за-медление прогрессирования сердечно-сосудистых заболеваний, не назначается своевременно [3,14]. Очень важно выявлять субклинические пораже-ния сердечно-сосудистой системы в этой группе пациентов для обнаружения факторов, предрас-полагающих к неблагоприятным осложнениям в дальнейшем [12].…”