Is HbA(1c) affected by glycemic instability?

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.

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.

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.

HbA(1c) reflects mean glycemia and is not meaningfully affected by glycemic instability after adjusting for mean BG.