Is HbA_1c Affected by Glycemic Instability?

Abstract

OBJECTIVE—HbA_1c is a standard clinical assessment of glycemia and the basis of most data relating glycemic control to complications. It remains unclear, however, whether HbA_1c is affected by glycemic variation and mean glycemia.

RESEARCH DESIGN AND METHODS—To test this question, we analyzed the statistical relationship between HbA_1c levels and glycemic variability as measured by self-monitoring of blood glucose (SMBG). The records of 256 subjects were studied. SMBG data for the preceding 3 months were downloaded, and HbA_1c was measured by ion-exchange high-performance liquid chromatography. Simple- and random-effects linear regression models were used to assess the independent contributions of mean blood glucose (BG) and SD of BG to HbA_1c, after adjusting for the mean BG.

RESULTS—Mean ± SD for HbA_1c was 7.66 ± 1.11% and for BG was 8.5 ± 1.9 mmol/l (153.3 ± 34.9 mg/dl); SD of BG for individual subjects was 3.5 mmol/l (63.3 mg/dl), varying from 0.4 mmol/l (8.1 mg/dl; very stable glycemia) to 8.4 mmol/l (152.5 mg/dl; very unstable glycemia). A close correlation between mean BG and HbA_1c was demonstrated (r = 0.62). Also, within-subject SD of BG correlated with HbA_1c (r = 0.375), indicating that people with poorer glycemic control had higher BG variance. After adjusting for mean BG in a linear regression model, however, the effect of the within-subject SD of BG on the HbA_1c was insignificant. Several further analyses confirmed the strength of the observation.

CONCLUSIONS—HbA_1c reflects mean glycemia and is not meaningfully affected by glycemic instability after adjusting for mean BG.