Relative contributions of preprandial and postprandial glucose exposures, glycemic variability, and non-glycemic factors to HbA 1c in individuals with and without diabetes

Abstract Background/objective There is substantial interest in dietary approaches to reducing postprandial glucose (PPG) responses, but the quantitative contribution of PPG to longer-term glycemic control (reflected in glycated hemoglobin, HbA 1c ) in the general population is not known. This study quantified the associations of preprandial glucose exposure, PPG exposure, and glycemic variability with HbA 1c and estimated the explained variance in HbA 1c in individuals with and without type 2 diabetes (T2D). Subjects/methods Participants in the A1c-Derived Average Glucose (ADAG) study without T2D ( n = 77) or with non-insulin-treated T2D and HbA 1c <6.5% (T2D HbA1c < 6.5% , n = 63) or HbA 1c ≥ 6.5% (T2D HbA1c ≥ 6.5% , n = 34) were included in this analysis. Indices of preprandial glucose, PPG, and glycemic variability were calculated from continuous glucose monitoring during four periods over 12 weeks prior to HbA 1c measurement. In linear regression models, we estimated the associations of the glycemic exposures with HbA 1c and calculated the proportion of variance in HbA 1c explained by glycemic and non-glycemic factors (age, sex, body mass index, and ethnicity). Results The factors in the analysis explained 35% of the variance in HbA 1c in non-diabetic individuals, 49% in T2D HbA1c < 6.5% , and 78% in T2D HbA1c ≥ 6.5% . In non-diabetic individuals PPG exposure was associated with HbA 1c in confounder-adjusted analyses ( P < 0.05). In the T2D HbA1c < 6.5% group, all glycemic measures were associated with HbA 1c ( P < 0.05); preprandial glucose and PPG accounted for 14 and 18%, respectively, of the explained variation. In T2D HbA1c ≥ 6.5% , these glycemic exposures accounted for more than 50% of the variation in HbA 1c and with equal relative contributions. Conclusions Among the glycemic exposures, PPG exposure was most strongly predictive of HbA 1c in non-diabetic individuals, suggesting that interventions targeting lowering of the PPG response may be beneficial for long-term glycemic maintenance. In T2D, preprandial glucose and PPG exposure contributed equally to HbA 1c .