Serial changes in glycosylated blood proteins and direct measures of glycemia were studied in 100 subjects with insulin-dependent diabetes mellitus (IDDM) over a 6-wk period while attempts were made to improve glycemic control. All measures of glycemic control improved significantly (P < .001). Mean ± SE glycosylated hemoglobin (HbA,) fell from 9.1 ± 0.2 to 8.0 ± 0.1%, glycosylated serum albumin (GSA) from 9.8 ± 0.4 to 7.3 ± 0.3%, and fructosamine from 3.92 ± 0.08 to 3.42 ± 0.07 mM. Fasting blood glucose levels fell from 11.1 ± 0.6 to 8.1 ± 0.7 mM, mean blood glucose levels from 12.5 ± 0.3 to 8.8 ± 0.3 mM, and the M value from 118 ± 7 to 40 ± 3 U. Mean percentage changes in direct measures of glycemia (32–66%) and GSA (29%) were greater than for fructosamine (11%) or HbA, (12%) levels (P < .001). Furthermore, the correlation between the change in GSA and changes in direct measures of glycemia over the initial 2-wk period was significantly different from the corresponding correlations between direct measures of glycemia and fructosamine over this period (P < .05-.01). Changes in GSA also correlated more closely than HbA, or fructosamine did with direct measures of glycemia after 4 and 6 wk. The Spearman rank-correlation coefficient (rs) of absolute changes in GSA, fructosamine, and HbA1 after 2–6 wk ranged from 0.27 to 0.57, confirming that the three measures responded differently to changing glycemic control. Cross-sectional analysis between different measures of glycemia demonstrated considerable variation in the degree of association at different times, with the closest correlations observed after 6 wk when glycemic control was relatively stable. GSA and fructosamine levels correlated with levels of mean blood glucose and M values estimated 2–4 wk earlier. GSA appears to be a more sensitive indicator of short-term improvement in glycemic control and glycemic instability in IDDM than fructosamine or HbA1.

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