Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study

Abstract

The association of chronic glycemia, measured by HbA(1c), with long-term complications of type 1 diabetes has been well established in the Diabetes Control and Complications Trial (DCCT) and other studies. The role of intermediate-term and acute glycemia and of glucose variability on microvascular and cardiovascular disease (CVD) is less clear. In order to examine the interrelationships among long-term, intermediate-term, and acute measures of glucose and its daily variability, we compared HbA(1c), glycated albumin (GA), and seven-point glucose profile concentrations measured longitudinally in a case-cohort subpopulation of the DCCT. HbA(1c) and GA were closely correlated with each other and with the mean blood glucose (MBG) calculated from the seven-point profile. The associations of glucose variability and postprandial concentrations with HbA(1c) and GA were relatively weak and were further attenuated when MBG was included in multivariate models. In the case-cohort analyses, HbA(1c) and GA had similar associations with retinopathy and nephropathy, which were strengthened when both measures were considered together. Only HbA(1c) was significantly associated with CVD. The demonstrated interrelationships among different measures of glycemia will need to be considered in future analyses of their roles in the development of long-term complications of type 1 diabetes.

Figure 1

Scatterplot of all GA vs. HbA_1c values. The slope is a 3.37 increase in GA % per unit increase in HbA_1c % (SE = 0.118; P < 0.0001), with R² = 0.746.

Figure 2

Weighted estimates of the mean ± 95% CI of measures of glycemia at each annual visit during the DCCT in the aggregate cohort (N = 497) obtained from a longitudinal model with separate estimates for each group at each visit. A: GA. B: MBG. C: HbA_1c. Computed as the average of the values at each visit from the 10 imputed datasets with no missing values. Sample sizes at each year of 497, 497, 496, 494, 492, 446, 332, and 214. Observations weighted by the inverse sampling probabilities within strata defined by DCCT Treatment Group, primary vs. secondary cohort, and whether a case of retinopathy, nephropathy, or CVD. CONV, conventional group; INT, intensive group.