Mean Blood Glucose and Biological Variation Have Greater Influence on HbA1c Levels Than Glucose Instability

Abstract

OBJECTIVE—Mean blood glucose (MBG) over 2–3 months is a strong predictor of HbA1c (A1C) levels. Glucose instability, the variability of blood glucose levels comprising the MBG, and biological variation in A1C (BV) have also been suggested as predictors of A1C independent of MBG. To assess the relative importance of MBG, BV, and glucose instability on A1C, we analyzed patient data from the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS—A glucose profile set and sample for A1C were collected quarterly over the course of the DCCT from each participant (n = 1,441). The glucose profile set consisted of seven samples, one each drawn before and 90 min after breakfast, lunch, and dinner and one before bedtime. MBG and glucose instability (SD of blood glucose [SDBG]) were calculated as the arithmetic mean and SD of glucose profile set samples for each visit, respectively. A statistical model was developed to predict A1C from MBG, SDBG, and BV, adjusted for diabetes duration, sex, treatment group, stratum, and race. RESULTS—Data from 32,977 visits were available. The overall model was highly statistically significant (log likelihood = −41,818.75, likelihood ratio χ2[7] = 7,218.71, P > χ2 = 0.0000). MBG and BV had large influences on A1C based on their standardized coefficients. SDBG had only 1/14 of the impact of MBG and 1/10 of the impact of BV. CONCLUSIONS—MBG and BV have a large influence on A1C, whereas SDBG is relatively unimportant. Consideration of BV as well as MBG in the interpretation of A1C may enhance our ability to monitor diabetes management and predict complications.