Relationship of A1C to glucose concentrations in children with type 1 diabetes: assessments by high-frequency glucose determinations by sensors

Abstract

Objective: Despite the standing of A1C as the most validated and widely used measure for average glycemic control over time, the relationship between A1C and glucose concentrations is not completely understood. The purpose of this Diabetes Research in Children Network (DirecNet) study was to use continuous glucose monitoring data to examine the relationship between A1C and glucose in type 1 diabetes.

Research design and methods: Forty-eight youth enrolled in studies of the Navigator continuous glucose monitor were encouraged to wear the Navigator sensor at home continuously. A1C was measured at baseline, at 3 months, and at 6 months. Sensor glucose data were directly transmitted via the Internet, assuring that essentially all glucose values were analyzed.

Results: Subjects had a median of 112 h/week of Navigator data in the first 3 months and 115 h/week in the second 3 months. The slope of mean glucose over the previous 3 months versus A1C was only 18 mg/dl per 1.0% A1C. Individually, there was substantial variation in the relationship between mean glucose and A1C. A1C was not associated with glucose lability after controlling for mean glucose. Measures of an individual's rate of glycation were moderately correlated at the 3- and 6-month visits.

Conclusions: As the chemistry of glycation would predict, we found no evidence to contradict the simple hypothesis that A1C directly reflects mean glucose over time. There is, however, substantial variability in individual mean glucose concentrations for a given A1C. Transforming reliable A1C values into calculated mean glucose values would, when applied to an individual, introduce substantial error.

Figure 1. Mean glucose vs. A1c

Mean glucose measured by the Navigator sensor over a 3-month period prior to the A1c measurement (N=75 visits from 48 subjects). Regression line calculated from a repeated measures model accounting for correlated data from the same subject.

Figure 2. Measures of Glycation at 3 vs. 6-month Visits

N=27 subjects with data at both visits. The ratio of mean glucose to A1c (A) and the HGI index (B) are compared at the two visits. The diagonal represents the line of identity.