Heterogeneity of hemoglobin A1d: assessment and partial characterization of two new minor hemoglobins, A1d3a and A1d3b, increased in uremic and diabetic patients, respectively.

We have separated and quantified two new minor hemoglobins named HbA1d3a and HbA1d3b. The level of HbA1d3a 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 HbA1d3a is an alpha-chain modified by carbamylation. The HbA1d3b level an 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 HbA1d3 modified by glycation. Indeed HbA1d3b correlated significantly with HbA1c (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.