Heterogeneity of hemoglobin A(1d): Assessment and partial characterization of two new minor hemoglobins, A(1d3a) and A(1d3b), increased in uremic and diabetic patients, respectively

We have separated and quantified two new minor hemoglobins named HbA(1d3a) and HbA(1d3b). The level of HbA(1d3a) was significantly higher in uremic than in non-uremic patients (3.00 +/- 0.50% vs. 1.28 +/- 0.26% of total hemoglobin). It correlated well with carbamylated hemoglobin (r = 0.80, n = 81, p < 0.002) and with plasma urea concentration (r = 0.78, n = 81, p < 0.002). These data and the electrospray ionization mass spectrometric analysis provide strong evidence that HbA(1d3a) is an alpha-chain modified by carbamylation. The HbA(1d3a) level in diabetic patients was found to be 1.6-fold that in non-diabetic subjects (3.00 +/- 0.49 vs. 1.90 +/- 0.33). This was attributed to HbA(1d3) modified by glycation. Indeed HbA(1d3b) correlated significantly with HbA(1c) (r = 0.71, p < 0.002) and with serum glucose level (r = 0.62, p < 0.002). These two new minor hemoglobins may serve as complements for the objective assessment of averaged long-term uremia and glycemia in uremic and diabetic patients.