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Pediatr Diabetes. 2016 Sep;17(6):398-406. doi: 10.1111/pedi.12300. Epub 2015 Sep 17.

High hemoglobin A1c variability is associated with early risk of microalbuminuria in children with T1D.

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Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Department of Pediatrics, University of Missouri-Kansas City, Kansas City, MO, USA.
University of Kansas Medical Center, Kansas City, KS, USA.
Department of Research Development and Clinical Investigations, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Department of Health Services and Outcomes Research, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
Department of Medicine, NU-Hospital Organization, Uddevalla, Sweden.
Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Cardiovascular Services, Saint Luke's Mid America Heart Institute, Kansas City, MO, USA.



To test the hypothesis that HbA1c variability, as measured by standard deviation (SD), is associated with increased risk for incident microalbuminuria and persistent microalbuminuria in pediatric type 1 diabetes (T1D).


A retrospective analysis using data from electronic health records was performed on 1195 patients from a pediatric diabetes clinic network in the Midwest USA from 1993 to 2009 with ≥1 yr of T1D, ≥4 total HbA1c values, ≥2 HbA1c values/yr, ≥1 urine microalbumin. Microalbuminuria, the main outcome was defined as albumin excretion rate ≥20 mcg/min or 2 of 3 consecutive urine microalbumin/creatinine ≥30 mg/gm. Patients who had persistently high microalbumin or who were treated with an angiotensin-converting-enzyme inhibitor within 1 yr were considered to have persistent microalbuminuria. Sex, race, age, diagnosis age, and duration were covariates.


Median numbers of per-patient HbA1c and microalbumin results were 14 and 3, respectively. Median intrapersonal mean HbA1c and SD were 8.62% (70.72 mol/mol) and 1.47% (16.07 mmol/mol), respectively. The median interquartile range (IQR) of diagnosis age was 9.4 yr (6.26-12.02) and diabetes duration was 4.97 yr (2.93-7.64). A total of 172 patients (14.4%) developed microalbuminuria; 55 (4.6%) had persistent microalbuminuria. Patients with higher SD of HbA1c had shorter time to microalbuminuria. In time-dependent Cox Proportional Hazard models, updated SD of HbA1c was significantly associated with microalbuminuria [univariate hazard ratio (HR) 1.48 (1.25-1.76); multivariable HR 1.28 (1.04-1.58)], whereas updated mean HbA1c was not [univariate HR 1.08 (0.97-1.22); multivariable HR 1.05 (0.92-1.2)]. Patients with persistent microalbuminuria had similar HRs.


HbA1c variability is independently associated with development of microalbuminuria in children with T1D, highlighting the importance of maintaining stable glycemic control in pediatric patients.


HbA1c variability; children; microalbuminuria; nephropathy; type 1 diabetes mellitus

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